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Algorithms and Psychiatry

A machine-learning approach for differentiating borderline personality disorder from community participants with brain-wide functional connectivity
Lahnakoski JM, Nolte T, Solway A, Vilares I, Hula A, Feigenbaum J, Lohrenz T, King-Casas B, Fonagy P, Montague PR and Schilbach L
Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci.
Temporal prediction of suicidal ideation in an ecological momentary assessment study with recurrent neural networks
Choo TH, Wall M, Brodsky BS, Herzog S, Mann JJ, Stanley B and Galfalvy H
Ecological Momentary Assessment (EMA) holds promise for providing insights into daily life experiences when studying mental health phenomena. However, commonly used mixed-effects linear statistical models do not fully utilize the richness of the ultidimensional time-varying data that EMA yields. Recurrent Neural Networks (RNNs) provide an alternative data analytic method to leverage more information and potentially improve prediction, particularly for non-normally distributed outcomes.
Graph convolutional network with attention mechanism improve major depressive depression diagnosis based on plasma biomarkers and neuroimaging data
Jiang C, Lin B, Ye X, Yu Y, Xu P, Peng C, Mou T, Yu X, Zhao H, Zhao M, Li Y, Zhang S, Chen X, Pan F, Shang D, Jin K, Lu J, Chen J, Yin J and Huang M
The absence of clinically-validated biomarkers or objective protocols hinders effective major depressive disorder (MDD) diagnosis. Compared to healthy control (HC), MDD exhibits anomalies in plasma protein levels and neuroimaging presentations. Despite extensive machine learning studies in psychiatric diagnosis, a reliable tool integrating multi-modality data is still lacking.
Exploring the potential of representation and transfer learning for anatomical neuroimaging: Application to psychiatry
Dufumier B, Gori P, Petiton S, Louiset R, Mangin JF, Grigis A and Duchesnay E
The perspective of personalized medicine for brain disorders requires efficient learning models for anatomical neuroimaging-based prediction of clinical conditions. There is now a consensus on the benefit of deep learning (DL) in addressing many medical imaging tasks, such as image segmentation. However, for single-subject prediction problems, recent studies yielded contradictory results when comparing DL with Standard Machine Learning (SML) on top of classical feature extraction. Most existing comparative studies were limited in predicting phenotypes of little clinical interest, such as sex and age, and using a single dataset. Moreover, they conducted a limited analysis of the employed image pre-processing and feature selection strategies. This paper extensively compares DL and SML prediction capacity on five multi-site problems, including three increasingly complex clinical applications in psychiatry namely schizophrenia, bipolar disorder, and Autism Spectrum Disorder (ASD) diagnosis. To compensate for the relative scarcity of neuroimaging data on these clinical datasets, we also evaluate three pre-training strategies for transfer learning from brain imaging of the general healthy population: self-supervised learning, generative modeling and supervised learning with age. Overall, we find similar performance between randomly initialized DL and SML for the three clinical tasks and a similar scaling trend for sex prediction. This was replicated on an external dataset. We also show highly correlated discriminative brain regions between DL and linear ML models in all problems. Nonetheless, we demonstrate that self-supervised pre-training on large-scale healthy population imaging datasets (N≈10k), along with Deep Ensemble, allows DL to learn robust and transferable representations to smaller-scale clinical datasets (N≤1k). It largely outperforms SML on 2 out of 3 clinical tasks both in internal and external test sets. These findings suggest that the improvement of DL over SML in anatomical neuroimaging mainly comes from its capacity to learn meaningful and useful abstract representations of the brain anatomy, and it sheds light on the potential of transfer learning for personalized medicine in psychiatry.
BrainDAS: Structure-aware domain adaptation network for multi-site brain network analysis
Song R, Cao P, Wen G, Zhao P, Huang Z, Zhang X, Yang J and Zaiane OR
In the medical field, datasets are mostly integrated across sites due to difficult data acquisition and insufficient data at a single site. The domain shift problem caused by the heterogeneous distribution among multi-site data makes autism spectrum disorder (ASD) hard to identify. Recently, domain adaptation has received considerable attention as a promising solution. However, domain adaptation on graph data like brain networks has not been fully studied. It faces two major challenges: (1) complex graph structure; and (2) multiple source domains. To overcome the issues, we propose an end-to-end structure-aware domain adaptation framework for brain network analysis (BrainDAS) using resting-state functional magnetic resonance imaging (rs-fMRI). The proposed approach contains two stages: supervision-guided multi-site graph domain adaptation with dynamic kernel generation and graph classification with attention-based graph pooling. We evaluate our BrainDAS on a public dataset provided by Autism Brain Imaging Data Exchange (ABIDE) which includes 871 subjects from 17 different sites, surpassing state-of-the-art algorithms in several different evaluation settings. Furthermore, our promising results demonstrate the interpretability and generalization of the proposed method. Our code is available at https://github.com/songruoxian/BrainDAS.
An explainable machine learning framework for predicting the risk of buprenorphine treatment discontinuation for opioid use disorder among commercially insured individuals
Al Faysal J, Noor-E-Alam M, Young GJ, Lo-Ciganic WH, Goodin AJ, Huang JL, Wilson DL, Park TW and Hasan MM
Buprenorphine is an effective evidence-based medication for opioid use disorder (OUD). Yet premature discontinuation undermines treatment effectiveness, increasing the risk of mortality and overdose. We developed and evaluated a machine learning (ML) framework for predicting buprenorphine care discontinuity within 12 months following treatment initiation.
Data harmonization and federated learning for multi-cohort dementia research using the OMOP common data model: A Netherlands consortium of dementia cohorts case study
Mateus P, Moonen J, Beran M, Jaarsma E, van der Landen SM, Heuvelink J, Birhanu M, Harms AGJ, Bron E, Wolters FJ, Cats D, Mei H, Oomens J, Jansen W, Schram MT, Dekker A and Bermejo I
Establishing collaborations between cohort studies has been fundamental for progress in health research. However, such collaborations are hampered by heterogeneous data representations across cohorts and legal constraints to data sharing. The first arises from a lack of consensus in standards of data collection and representation across cohort studies and is usually tackled by applying data harmonization processes. The second is increasingly important due to raised awareness for privacy protection and stricter regulations, such as the GDPR. Federated learning has emerged as a privacy-preserving alternative to transferring data between institutions through analyzing data in a decentralized manner.
Symptoms of a feather flock together? An exploratory secondary dynamic time warp analysis of 11 single case time series of suicidal ideation and related symptoms
de Beurs D, Giltay EJ, Nuij C, O'Connor R, de Winter RFP, Kerkhof A, van Ballegooijen W and Riper H
Suicidal ideation fluctuates over time, as does its related risk factors. Little is known about the difference or similarities of the temporal patterns. The current exploratory secondary analysis examines which risk symptoms have similar time dynamics using a mathematical algorithm called dynamic time warping (DTW). Ecological momentary assessment data was used of 11 depressed psychiatric outpatients with suicidal ideation who answered three daytime surveys at semi-random sampling points for a period of three to six months. Patients with 45 assessments or more were included. Results revealed significant inter-individual variability in symptom dynamics and clustering, with certain symptoms often clustering due to similar temporal patterns, notably feeling sad, hopelessness, feeling stuck, and worrying. The directed network analyses shed light on the temporal order, highlighting entrapment and worrying as symptoms strongly related to suicide ideation. Still, all patients also showed unique directed networks. While for some patients changes in entrapment directly preceded change in suicide ideation, the reverse temporal ordering was also found. Relatedly, within some patients, perceived burdensomeness played a pivotal role, whereas in others it was unconnected to other symptoms. The study underscores the individualized nature of symptom dynamics and challenges linear models of progression, advocating for personalized treatment strategies.
Efficacy and cost-effectiveness of a digital guided self-management intervention to support transition from intensive care to community care in anorexia nervosa (TRIANGLE): pragmatic multicentre randomised controlled trial and economic evaluation
Cardi V, Rowlands K, Ambwani S, Lord J, Clark-Bryan D, McDaid D, Schmidt U, Macdonald P, Arcelus J, Landau S and Treasure J
There is uncertainty regarding how best to support patients with anorexia nervosa following inpatient or day care treatment. This study evaluated the impact of augmenting intensive treatment with a digital, guided, self-management intervention (ECHOMANTRA) for patients with anorexia nervosa and their carers.
Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1
Pan Y, Zhang X, Wen X, Yuan N, Guo L, Shi Y, Jia Y, Guo Y, Hao F, Qu S, Chen Z, Yang L, Wang X and Liu Y
Major depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1.
Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders
Hilbert K, Böhnlein J, Meinke C, Chavanne AV, Langhammer T, Stumpe L, Winter N, Leenings R, Adolph D, Arolt V, Bischoff S, Cwik JC, Deckert J, Domschke K, Fydrich T, Gathmann B, Hamm AO, Heinig I, Herrmann MJ, Hollandt M, Hoyer J, Junghöfer M, Kircher T, Koelkebeck K, Lotze M, Margraf J, Mumm JLM, Neudeck P, Pauli P, Pittig A, Plag J, Richter J, Ridderbusch IC, Rief W, Schneider S, Schwarzmeier H, Seeger FR, Siminski N, Straube B, Straube T, Ströhle A, Wittchen HU, Wroblewski A, Yang Y, Roesmann K, Leehr EJ, Dannlowski U and Lueken U
Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.
Machine-learning-based feature selection to identify attention-deficit hyperactivity disorder using whole-brain white matter microstructure: A longitudinal study
Chiang HL, Wu CS, Chen CL, Tseng WI and Gau SS
We aimed to identify important features of white matter microstructures collectively distinguishing individuals with attention-deficit/hyperactivity disorder (ADHD) from those without ADHD using a machine-learning approach.
Multimodal brain-derived subtypes of Major depressive disorder differentiate patients for anergic symptoms, immune-inflammatory markers, history of childhood trauma and treatment-resistance
Colombo F, Calesella F, Bravi B, Fortaner-Uyà L, Monopoli C, Tassi E, Carminati M, Zanardi R, Bollettini I, Poletti S, Lorenzi C, Spadini S, Brambilla P, Serretti A, Maggioni E, Fabbri C, Benedetti F and Vai B
An estimated 30 % of Major Depressive Disorder (MDD) patients exhibit resistance to conventional antidepressant treatments. Identifying reliable biomarkers of treatment-resistant depression (TRD) represents a major goal of precision psychiatry, which is hampered by the clinical and biological heterogeneity. To uncover biologically-driven subtypes of MDD, we applied an unsupervised data-driven framework to stratify 102 MDD patients on their neuroimaging signature, including extracted measures of cortical thickness, grey matter volumes, and white matter fractional anisotropy. Our novel analytical pipeline integrated different machine learning algorithms to harmonize data, perform data dimensionality reduction, and provide a stability-based relative clustering validation. The obtained clusters were characterized for immune-inflammatory peripheral biomarkers, TRD, history of childhood trauma and depressive symptoms. Our results indicated two different clusters of patients, differentiable with 67 % of accuracy: one cluster (n = 59) was associated with a higher proportion of TRD, and higher scores of energy-related depressive symptoms, history of childhood abuse and emotional neglect; this cluster showed a widespread reduction in cortical thickness (d = 0.43-1.80) and volumes (d = 0.45-1.05), along with fractional anisotropy in the fronto-occipital fasciculus, stria terminalis, and corpus callosum (d = 0.46-0.52); the second cluster (n = 43) was associated with cognitive and affective depressive symptoms, thicker cortices and wider volumes. Multivariate analyses revealed distinct brain-inflammation relationships between the two clusters, with increase in pro-inflammatory markers being associated with decreased cortical thickness and volumes. Our stratification of MDD patients based on structural neuroimaging identified clinically-relevant subgroups of MDD with specific symptomatic and immune-inflammatory profiles, which can contribute to the development of tailored personalized interventions for MDD.
Discriminative analysis of schizophrenia and major depressive disorder using fNIRS
Diao Y, Wang H, Wang X, Qiu C, Wang Z, Ji Z, Wang C, Gu J, Liu C, Wu K and Wang C
Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions.
An interpretable machine learning-based cerebrospinal fluid proteomics clock for predicting age reveals novel insights into brain aging
Melendez J, Sung YJ, Orr M, Yoo A, Schindler S, Cruchaga C and Bateman R
Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to predict the chronological age of individuals with a 0.79 Pearson correlation and mean estimated error (MAE) of 4.30 years in our validation cohort. Additionally, we analyzed proteins highly weighted by the algorithm to gain insights into changes in CSF and uncover novel insights into brain aging. We also demonstrate a novel method to create a minimal protein clock that uses just 109 protein features from the original clock to achieve a similar accuracy (0.75 correlation, MAE 5.41). Finally, we demonstrate that our clock identifies novel proteins that are highly predictive of age in interactions with other proteins, but do not directly correlate with chronological age themselves. In conclusion, we propose that our CSF protein aging clock can identify novel proteins that influence the rate of aging of the central nervous system (CNS), in a manner that would not be identifiable by examining their individual relationships with age.
A novel blood-based epigenetic biosignature in first-episode schizophrenia patients through automated machine learning
Karaglani M, Agorastos A, Panagopoulou M, Parlapani E, Athanasis P, Bitsios P, Tzitzikou K, Theodosiou T, Iliopoulos I, Bozikas VP and Chatzaki E
Schizophrenia (SCZ) is a chronic, severe, and complex psychiatric disorder that affects all aspects of personal functioning. While SCZ has a very strong biological component, there are still no objective diagnostic tests. Lately, special attention has been given to epigenetic biomarkers in SCZ. In this study, we introduce a three-step, automated machine learning (AutoML)-based, data-driven, biomarker discovery pipeline approach, using genome-wide DNA methylation datasets and laboratory validation, to deliver a highly performing, blood-based epigenetic biosignature of diagnostic clinical value in SCZ. Publicly available blood methylomes from SCZ patients and healthy individuals were analyzed via AutoML, to identify SCZ-specific biomarkers. The methylation of the identified genes was then analyzed by targeted qMSP assays in blood gDNA of 30 first-episode drug-naïve SCZ patients and 30 healthy controls (CTRL). Finally, AutoML was used to produce an optimized disease-specific biosignature based on patient methylation data combined with demographics. AutoML identified a SCZ-specific set of novel gene methylation biomarkers including IGF2BP1, CENPI, and PSME4. Functional analysis investigated correlations with SCZ pathology. Methylation levels of IGF2BP1 and PSME4, but not CENPI were found to differ, IGF2BP1 being higher and PSME4 lower in the SCZ group as compared to the CTRL group. Additional AutoML classification analysis of our experimental patient data led to a five-feature biosignature including all three genes, as well as age and sex, that discriminated SCZ patients from healthy individuals [AUC 0.755 (0.636, 0.862) and average precision 0.758 (0.690, 0.825)]. In conclusion, this three-step pipeline enabled the discovery of three novel genes and an epigenetic biosignature bearing potential value as promising SCZ blood-based diagnostics.
Proceedings of PRINCETON IV: PDE5 inhibitors and cardiac health symposium
Rosen RC, Miner M, Burnett AL, Blaha MJ, Ganz P, Goldstein I, Kim N, Kohler T, Lue T, McVary K, Mulhall J, Parish SJ, Sadeghi-Nejad H, Sadovsky R, Sharlip I and Kloner RA
Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023.
CMRxRecon: A publicly available k-space dataset and benchmark to advance deep learning for cardiac MRI
Wang C, Lyu J, Wang S, Qin C, Guo K, Zhang X, Yu X, Li Y, Wang F, Jin J, Shi Z, Xu Z, Tian Y, Hua S, Chen Z, Liu M, Sun M, Kuang X, Wang K, Wang H, Li H, Chu Y, Yang G, Bai W, Zhuang X, Wang H, Qin J and Qu X
Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The 'CMRxRecon' dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.
Evaluation of machine learning-based classification of clinical impairment and prediction of clinical worsening in multiple sclerosis
Noteboom S, Seiler M, Chien C, Rane RP, Barkhof F, Strijbis EMM, Paul F, Schoonheim MM and Ritter K
Robust predictive models of clinical impairment and worsening in multiple sclerosis (MS) are needed to identify patients at risk and optimize treatment strategies.
Impact of HCV cure on subsequent hospitalizations in people with mental disorders: Results from the French claims database
Rolland B, Hallouche N, Lada O, Rabiéga P, Fouad F, Benabadji E and Pol S
Although HCV cure after direct-acting antiviral (DAA) treatment is associated with hepatic and extrahepatic benefits, few studies have assessed the impact of HCV treatment in people with mental disorders (PWMDs). Using quasi-exhaustive national data from the French administrative health care databases (SNDS), we explored whether DAA treatment in PWMDs affected hospitalizations in both psychiatric and non-psychiatric settings.
Retraction Note: Microbiome analyses of blood and tissues suggest cancer diagnostic approach
Poore GD, Kopylova E, Zhu Q, Carpenter C, Fraraccio S, Wandro S, Kosciolek T, Janssen S, Metcalf J, Song SJ, Kanbar J, Miller-Montgomery S, Heaton R, Mckay R, Patel SP, Swafford AD and Knight R
End-to-end pseudonymization of fine-tuned clinical BERT models : Privacy preservation with maintained data utility
Vakili T, Henriksson A and Dalianis H
Many state-of-the-art results in natural language processing (NLP) rely on large pre-trained language models (PLMs). These models consist of large amounts of parameters that are tuned using vast amounts of training data. These factors cause the models to memorize parts of their training data, making them vulnerable to various privacy attacks. This is cause for concern, especially when these models are applied in the clinical domain, where data are very sensitive. Training data pseudonymization is a privacy-preserving technique that aims to mitigate these problems. This technique automatically identifies and replaces sensitive entities with realistic but non-sensitive surrogates. Pseudonymization has yielded promising results in previous studies. However, no previous study has applied pseudonymization to both the pre-training data of PLMs and the fine-tuning data used to solve clinical NLP tasks. This study evaluates the effects on the predictive performance of end-to-end pseudonymization of Swedish clinical BERT models fine-tuned for five clinical NLP tasks. A large number of statistical tests are performed, revealing minimal harm to performance when using pseudonymized fine-tuning data. The results also find no deterioration from end-to-end pseudonymization of pre-training and fine-tuning data. These results demonstrate that pseudonymizing training data to reduce privacy risks can be done without harming data utility for training PLMs.
Brainstem raphe hypoechogenicity is an independent predictor of post-stroke depression
Richter D, Ebert A, Mazul L, Ruland Q, Charles James J, Gold R, Tsivgoulis G, Palaiodimou L, Juckel G and Krogias C
Post-stroke depression (PSD) is a common complication after stroke and has a substantial effect on the quality of life of patients. Nevertheless, reliable individual prediction of PSD is not possible. As depressive symptoms have been associated with brainstem raphe (BR) hypoechogenicity on transcranial sonography (TCS), we aimed to explore the association of BR hypoechogenicity and the occurrence of PSD.
Neural Decoding and Feature Selection Techniques for Closed-Loop Control of Defensive Behavior
Liu J, Younk R, Drahos LM, Nagrale SS, Yadav S, Widge AS and Shoaran M
Many psychiatric disorders involve excessive avoidant or defensive behavior, such as avoidance in anxiety and trauma disorders or defensive rituals in obsessive-compulsive disorders. Developing algorithms to predict these behaviors from local field potentials (LFPs) could serve as foundational technology for closed-loop control of such disorders. A significant challenge is identifying the LFP features that encode these defensive behaviors.
The Machine Speaks: Conversational AI and the Importance of Effort to Relationships of Meaning
Hartford A and Stein DJ
The focus of debates about conversational artificial intelligence (CAI) has largely been on social and ethical concerns that arise when we speak to machines-what is gained and what is lost when we replace our human interlocutors, including our human therapists, with AI. In this viewpoint, we focus instead on a distinct and growing phenomenon: letting machines speak for us. What is at stake when we replace our own efforts at interpersonal engagement with CAI? The purpose of these technologies is, in part, to remove effort, but effort has enormous value, and in some cases, even intrinsic value. This is true in many realms, but especially in interpersonal relationships. To make an effort for someone, irrespective of what that effort amounts to, often conveys value and meaning in itself. We elaborate on the meaning, worth, and significance that may be lost when we relinquish effort in our interpersonal engagements as well as on the opportunities for self-understanding and growth that we may forsake.
Chemical signatures delineate heterogeneous amyloid plaque populations across the Alzheimer's disease spectrum
Koutarapu S, Ge J, Dulewicz M, Srikrishna M, Szadziewska A, Wood J, Blennow K, Zetterberg H, Michno W, Ryan NS, Lashley T, Savas J, Schöll M and Hanrieder J
Amyloid plaque deposition is recognized as the primary pathological hallmark of Alzheimer's disease(AD) that precedes other pathological events and cognitive symptoms. Plaque pathology represents itself with an immense polymorphic variety comprising plaques with different stages of amyloid fibrillization ranging from diffuse to fibrillar, mature plaques. The association of polymorphic Aβ plaque pathology with AD pathogenesis, clinical symptoms and disease progression remains unclear. Advanced chemical imaging tools, such as functional amyloid microscopy combined with MALDI mass spectrometry imaging (MSI), are now enhanced by deep learning algorithms. This integration allows for precise delineation of polymorphic plaque structures and detailed identification of their associated Aβ compositions. We here set out to make use of these tools to interrogate heterogenic plaque types and their associated biochemical architecture. Our findings reveal distinct Aβ signatures that differentiate diffuse plaques from fibrilized ones, with the latter showing substantially higher levels of Aβx-40. Notably, within the fibrilized category, we identified a distinct subtype known as coarse-grain plaques. Both in sAD and fAD brain tissue, coarse grain plaques contained more Aβx-40 and less Aβx-42 compared with cored plaques. The coarse grain plaques in both sAD and fAD also showed higher levels of neuritic content including paired helical filaments (PHF-1)/phosphorylated phospho Tau-immunopositive neurites. Finally, the Aβ peptide content in coarse grain plaques resembled that of vascular Aβ deposits (CAA) though with relatively higher levels of Aβ1-42 and pyroglutamated Aβx-40 and Aβx-42 species in coarse grain plaques. This is the first of its kind study on spatial biochemical characterization of different plaque morphotypes demonstrating the potential of the correlative imaging techniques used that further increase the understanding of heterogeneous AD pathology. Linking the biochemical characteristics of amyloid plaque polymorphisms with various AD etiologies and toxicity mechanisms is crucial. Understanding the connection between plaque structure and disease pathogenesis can enhance our insights. This knowledge is particularly valuable for developing and advancing novel, amyloid-targeting therapeutics.
Computer-vision analysis of craniofacial dysmorphology in 22q11.2 deletion syndrome and psychosis spectrum disorders
Roalf DR, McDonald-McGinn DM, Jee J, Krall M, Crowley TB, Moberg PJ, Kohler C, Calkins ME, Crow AJD, Fleischer N, Gallagher RS, Gonzenbach V, Clark K, Gur RC, McClellan E, McGinn DE, Mordy A, Ruparel K, Turetsky BI, Shinohara RT, White L, Zackai E and Gur RE
Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders.
Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer
Kicman A, Gacuta E, Kulesza M, Będkowska EG, Marecki R, Klank-Sokołowska E, Knapp P, Niczyporuk M and Ławicki S
Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.
The bispectral electroencephalography (BSEEG) method quantifies post-operative delirium-like states in young and aged male mice after head mount implantation surgery
Nishiguchi T, Shibata K, Yamanishi K, Dittrich MN, Islam NY, Patel S, Phuong NJ, Marra PS, Malicoat JR, Seki T, Nishizawa Y, Yamanashi T, Iwata M and Shinozaki G
Delirium, a syndrome characterized by an acute change in attention, awareness, and cognition, is commonly observed in older adults, although there are few quantitative monitoring methods in the clinical setting. We developed a bispectral electroencephalography (BSEEG) method capable of detecting delirium and can quantify the severity of delirium using a novel algorithm. Pre-clinical application of this novel BSEEG method can capture a delirium-like state in mice following LPS administration. However, its application to postoperative delirium (POD) has not yet been validated in animal experiments. This study aimed to create a POD model in mice with the BSEEG method by monitoring BSEEG scores following EEG head-mount implantation surgery and throughout the recovery. We compared the BSEEG scores of C57BL/6J young (2-3 months old) with aged (18-19 months old) male mice for quantitative evaluation of POD-like states. Postoperatively, both groups displayed increased BSEEG scores and a loss of regular diurnal changes in BSEEG scores. In young mice, BSEEG scores and regular diurnal changes recovered relatively quickly to baseline by postoperative day 3. Conversely, aged mice exhibited prolonged increases in postoperative BSEEG scores and it reached steady states only after postoperative day 8. This study suggests that the BSEEG method can be utilized as a quantitative measure of POD and assess the effect of aging on recovery from POD in the pre-clinical model.
Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models
Ohanyan H, van de Wiel M, Portengen L, Wagtendonk A, den Braver NR, de Jong TR, Verschuren M, van den Hurk K, Stronks K, Moll van Charante E, van Schoor NM, Stehouwer CDA, Wesselius A, Koster A, Ten Have M, Penninx BWJH, van Wier MF, Motoc I, Oldehinkel AJ, Willemsen G, Boomsma DI, Beenackers MA, Huss A, van Boxtel M, Hoek G, Beulens JWJ, Vermeulen R and Lakerveld J
Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors.
Involuntary psychiatric hospitalisation - differences and similarities between patients detained under the mental health act and according to the legal guardianship legislation
Peters SJ, Schmitz-Buhl M, Zielasek J and Gouzoulis-Mayfrank E
Involuntary psychiatric hospitalisation occurs under different legal premises. According to German law, detention under the Mental Health Act (MHA) is possible in cases of imminent danger of self-harm or harm to others, while detention according to the legal guardianship legislation (LGL) serves to prevent self-harm if there is considerable but not necessarily imminent danger. This study aims to compare clinical, sociodemographic and environmental socioeconomic differences and similarities between patients hospitalised under either the MHA or LGL.
GEN-RWD Sandbox: bridging the gap between hospital data privacy and external research insights with distributed analytics
Gottardelli B, Gatta R, Nucciarelli L, Tudor AM, Tavazzi E, Vallati M, Orini S, Di Giorgi N and Damiani A
Artificial intelligence (AI) has become a pivotal tool in advancing contemporary personalised medicine, with the goal of tailoring treatments to individual patient conditions. This has heightened the demand for access to diverse data from clinical practice and daily life for research, posing challenges due to the sensitive nature of medical information, including genetics and health conditions. Regulations like the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. and the General Data Protection Regulation (GDPR) in Europe aim to strike a balance between data security, privacy, and the imperative for access.
Use of Machine-Learning Algorithms Based on Text, Audio and Video Data in the Prediction of Anxiety and Post-Traumatic Stress in General and Clinical Populations: A Systematic Review
Ciharova M, Amarti K, van Breda W, Peng X, Lorente-Català R, Funk B, Hoogendoorn M, Koutsouleris N, Fusar-Poli P, Karyotaki E, Cuijpers P and Riper H
Research in machine-learning (ML) algorithms using natural behavior (i.e., text, audio, and video data) suggests that these techniques could contribute to personalization in psychology and psychiatry. However, a systematic review of the current state-of-the-art is missing. Moreover, individual studies often target ML experts, and may overlook potential clinical implications of their findings. In a narrative accessible to mental health professionals, we present a systematic review, conducted in 5 psychology and 2 computer-science databases. We included 128 studies assessing the predictive power of ML algorithms using text, audio, and/or video data in the prediction of anxiety and post-traumatic stress (PTSD). Most studies (n = 87) aimed at predicting anxiety, the remainder (n = 41) focused on PTSD. They were mostly published since 2019, in computer science journals, and tested algorithms using text (n = 72), as opposed to audio or video. They focused mainly on general populations (n = 92), less on laboratory experiments (n = 23) or clinical populations (n = 13). Methodological quality varied, as did reported metrics of the predictive power, hampering comparison across studies. Two thirds of studies, focusing on both disorders, reported acceptable to very good predictive power (including high-quality studies only). Results of 33 studies were uninterpretable, mainly due to missing information. Research into ML algorithms using natural behavior is in its infancy, but shows potential to contribute to diagnostics of mental disorders, such as anxiety and PTSD, in the future, if standardization of methods, reporting of results, and research in clinical populations are improved.
Black-white differences in chronic stress exposures to predict preterm birth: interpretable, race/ethnicity-specific machine learning model
Kim S, Brennan PA, Slavich GM, Hertzberg V, Kelly U and Dunlop AL
Differential exposure to chronic stressors by race/ethnicity may help explain Black-White inequalities in rates of preterm birth. However, researchers have not investigated the cumulative, interactive, and population-specific nature of chronic stressor exposures and their possible nonlinear associations with preterm birth. Models capable of computing such high-dimensional associations that could differ by race/ethnicity are needed. We developed machine learning models of chronic stressors to both predict preterm birth more accurately and identify chronic stressors and other risk factors driving preterm birth risk among non-Hispanic Black and non-Hispanic White pregnant women.
A multivariate to multivariate approach for voxel-wise genome-wide association analysis
Wu Q, Zhang Y, Huang X, Ma T, Hong LE, Kochunov P and Chen S
The joint analysis of imaging-genetics data facilitates the systematic investigation of genetic effects on brain structures and functions with spatial specificity. We focus on voxel-wise genome-wide association analysis, which may involve trillions of single nucleotide polymorphism (SNP)-voxel pairs. We attempt to identify underlying organized association patterns of SNP-voxel pairs and understand the polygenic and pleiotropic networks on brain imaging traits. We propose a bi-clique graph structure (ie, a set of SNPs highly correlated with a cluster of voxels) for the systematic association pattern. Next, we develop computational strategies to detect latent SNP-voxel bi-cliques and an inference model for statistical testing. We further provide theoretical results to guarantee the accuracy of our computational algorithms and statistical inference. We validate our method by extensive simulation studies, and then apply it to the whole genome genetic and voxel-level white matter integrity data collected from 1052 participants of the human connectome project. The results demonstrate multiple genetic loci influencing white matter integrity measures on splenium and genu of the corpus callosum.
Re-evaluating the prognosis of schizophrenia: tackling the issue of inadequate treatment
Agid O
Neural connectivity patterns explain why adolescents perceive the world as moving slow
Ghorbani F, Zhou X, Talebi N, Roessner V, Hommel B, Prochnow A and Beste C
That younger individuals perceive the world as moving slower than adults is a familiar phenomenon. Yet, it remains an open question why that is. Using event segmentation theory, electroencephalogram (EEG) beamforming and nonlinear causal relationship estimation using artificial neural network methods, we studied neural activity while adolescent and adult participants segmented a movie. We show when participants were instructed to segment a movie into meaningful units, adolescents partitioned incoming information into fewer encapsulated segments or episodes of longer duration than adults. Importantly, directed communication between medial frontal and lower-level perceptual areas and between occipito-temporal regions in specific neural oscillation spectrums explained behavioral differences between groups. Overall, the study reveals that a different organization of directed communication between brain regions and inefficient transmission of information between brain regions are key to understand why younger people perceive the world as moving slow.
Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers
Çelik MH, Gagneur J, Lim RG, Wu J, Thompson LM and Xie X
The high heritability of ALS contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone ChIP-seq and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers. Across different omics levels, outliers are robustly replicated, and chromatin accessibility outliers are reliable predictors of gene expression outliers and aberrant protein levels. When promoter accessibility does not align with gene expression, our results indicate that molecular aberrations are more likely to be linked to post-transcriptional regulation rather than transcriptional regulation. Our findings demonstrate that the outlier detection paradigm can uncover dysregulated regions in rare diseases. EpiOut is available at github.com/uci-cbcl/EpiOut.
Machine learning applied to prediction of relapse, hospitalization, and suicide in bipolar disorder using neuroimaging and clinical data: A systematic review
Amanollahi M, Jameie M, Looha MA, Basti FA, Cattarinussi G, Moghaddam HS, Di Camillo F, Akhondzadeh S, Pigoni A, Sambataro F, Brambilla P and Delvecchio G
Bipolar disorder (BD) is a mental disorder associated with increased morbidity/mortality. Adverse outcome prediction helps with the management of patients with BD.
Neuroadaptive Bayesian optimisation to study individual differences in infants' engagement with social cues
Gui A, Throm E, da Costa PF, Penza F, Aguiló Mayans M, Jordan-Barros A, Haartsen R, Leech R and Jones EJH
Infants' motivation to engage with the social world depends on the interplay between individual brain's characteristics and previous exposure to social cues such as the parent's smile or eye contact. Different hypotheses about why specific combinations of emotional expressions and gaze direction engage children have been tested with group-level approaches rather than focusing on individual differences in the social brain development. Here, a novel Artificial Intelligence-enhanced brain-imaging approach, Neuroadaptive Bayesian Optimisation (NBO), was applied to infant electro-encephalography (EEG) to understand how selected neural signals encode social cues in individual infants. EEG data from 42 6- to 9-month-old infants looking at images of their parent's face were analysed in real-time and used by a Bayesian Optimisation algorithm to identify which combination of the parent's gaze/head direction and emotional expression produces the strongest brain activation in the child. This individualised approach supported the theory that the infant's brain is maximally engaged by communicative cues with a negative valence (angry faces with direct gaze). Infants attending preferentially to faces with direct gaze had increased positive affectivity and decreased negative affectivity. This work confirmed that infants' attentional preferences for social cues are heterogeneous and shows the NBO's potential to study diversity in neurodevelopmental trajectories.
Development of a differential treatment selection model for depression on consolidated and transformed clinical trial datasets
Perlman K, Mehltretter J, Benrimoh D, Armstrong C, Fratila R, Popescu C, Tunteng JF, Williams J, Rollins C, Golden G and Turecki G
Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via "trial and error". Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining data across trials poses numerous challenges. There is also persistent concern that machine learning models can propagate harmful biases. We have created a methodology for organizing and preprocessing depression clinical trial data such that transformed variables harmonized across disparate datasets can be used as input for feature selection. Using Bayesian optimization, we identified an optimal multi-layer dense neural network that used data from 21 clinical and sociodemographic features as input in order to perform differential treatment benefit prediction. With this combined dataset of 5032 individuals and 6 drugs, we created a differential treatment benefit prediction model. Our model generalized well to the held-out test set and produced similar accuracy metrics in the test and validation set with an AUC of 0.7 when predicting binary remission. To address the potential for bias propagation, we used a bias testing performance metric to evaluate the model for harmful biases related to ethnicity, age, or sex. We present a full pipeline from data preprocessing to model validation that was employed to create the first differential treatment benefit prediction model for MDD containing 6 treatment options.
Neuroimaging epicenters as potential sites of onset of the neuroanatomical pathology in schizophrenia
Jiang Y, Palaniyappan L, Luo C, Chang X, Zhang J, Tang Y, Zhang T, Li C, Zhou E, Yu X, Li W, An D, Zhou D, Huang CC, Tsai SJ, Lin CP, Cheng J, Wang J, Yao D, Cheng W, Feng J and
Schizophrenia lacks a clear definition at the neuroanatomical level, capturing the sites of origin and progress of this disorder. Using a network-theory approach called epicenter mapping on cross-sectional magnetic resonance imaging from 1124 individuals with schizophrenia, we identified the most likely "source of origin" of the structural pathology. Our results suggest that the Broca's area and adjacent frontoinsular cortex may be the epicenters of neuroanatomical pathophysiology in schizophrenia. These epicenters can predict an individual's response to treatment for psychosis. In addition, cross-diagnostic similarities based on epicenter mapping over of 4000 individuals diagnosed with neurological, neurodevelopmental, or psychiatric disorders appear to be limited. When present, these similarities are restricted to bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. We provide a comprehensive framework linking schizophrenia-specific epicenters to multiple levels of neurobiology, including cognitive processes, neurotransmitter receptors and transporters, and human brain gene expression. Epicenter mapping may be a reliable tool for identifying the potential onset sites of neural pathophysiology in schizophrenia.
DDN3.0: determining significant rewiring of biological network structure with differential dependency networks
Fu Y, Lu Y, Wang Y, Zhang B, Zhang Z, Yu G, Liu C, Clarke R, Herrington DM and Wang Y
Complex diseases are often caused and characterized by misregulation of multiple biological pathways. Differential network analysis aims to detect significant rewiring of biological network structures under different conditions and has become an important tool for understanding the molecular etiology of disease progression and therapeutic response. With few exceptions, most existing differential network analysis tools perform differential tests on separately learned network structures that are computationally expensive and prone to collapse when grouped samples are limited or less consistent.
Is the Caudate, Putamen, and Globus Pallidus the Delusional Disorder's Trio? A Texture Analysis Study
Baykara M and Baykara S
The neurobiological basis of delusional disorder is less explored through neuroimaging techniques than in other psychotic disorders. This study aims to provide information about the neural origins of delusional disorder (DD) by examining the neuroanatomical features of some basal nuclei with magnetic resonance imaging (MRI) texture analysis.
Towards reliable forecasting of healthcare capacity needs: A scoping review and evidence mapping
Grøntved S, Jørgine Kirkeby M, Paaske Johnsen S, Mainz J, Brink Valentin J and Mohr Jensen C
The COVID-19 pandemic has highlighted the critical importance of robust healthcare capacity planning and preparedness for emerging crises. However, healthcare systems must also adapt to more gradual temporal changes in disease prevalence and demographic composition over time. To support proactive healthcare planning, statistical capacity forecasting models can provide valuable information to healthcare planners. This systematic literature review and evidence mapping aims to identify and describe studies that have used statistical forecasting models to estimate healthcare capacity needs within hospital settings.
A Second Space Age Spanning Omics, Platforms, and Medicine Across Orbits
Mason CE, Green J, Adamopoulos KI, Afshin EE, Baechle JJ, Basner M, Bailey SM, Bielski L, Borg J, Borg J, Broddrick JT, Burke M, Caicedo A, Castañeda V, Chatterjee S, Chin C, Church G, Costes SV, De Vlaminck I, Desai RI, Dhir R, Diaz JE, Etlin SM, Feinstein Z, Furman D, Garcia-Medina JS, Garrett-Bakelman F, Giacomello S, Gupta A, Hassanin A, Houerbi N, Irby I, Javorsky E, Jirak P, Jones CW, Kamal KY, Kangas BD, Karouia F, Kim J, Kim JH, Kleinman A, Lam T, Lawler JM, Lee JA, Limoli CL, Lucaci A, MacKay M, McDonald JT, Melnick AM, Meydan C, Mieczkowski J, Muratani M, Najjar D, Othman MA, Overbey EG, Paar V, Park J, Paul AM, Perdyan A, Proszynski J, Reynolds RJ, Ronca AE, Rubins K, Ryon KA, Sanders LM, Glowe PS, Shevde Y, Schmidt MA, Scott RT, Shirah B, Sienkiewicz K, Sierra M, Siew K, Theriot CA, Tierney BT, Venkateswaran K, Hirschberg JW, Walsh SB, Walter C, Winer DA, Yu M, Zea L, Mateus J and Beheshti A
The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.
Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study
Camporesi S, Xin L, Golay P, Eap CB, Cleusix M, Cuenod M, Fournier M, Hashimoto K, Jenni R, Ramain J, Restellini R, Solida A, Conus P, Do KQ and Khadimallah I
This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials.
Mitigating Racial Bias in Health Care Algorithms: Improving Fairness in Access to Supportive Housing
Noam KR, Schmutte T, Bory C and Plant RW
Algorithms for guiding health care decisions have come under increasing scrutiny for being unfair to certain racial and ethnic groups. The authors describe their multistep process, using data from 3,465 individuals, to reduce racial and ethnic bias in an algorithm developed to identify state Medicaid beneficiaries experiencing homelessness and chronic health needs who were eligible for coordinated health care and housing supports. Through an iterative process of adjusting inputs, reviewing outputs with diverse stakeholders, and performing quality assurance, the authors developed an algorithm that achieved racial and ethnic parity in the selection of eligible Medicaid beneficiaries.
Taming the chaos ?! - part 2: limitations of using eXplainable Artificial Intelligence (XAI) to tackle the complexity in psychotherapy of children and adolescents
Roessner V, Uhlmann A, Ehrlich S and Waltereit R
Opioid Maintenance Therapy: A Review of Methadone, Buprenorphine, and Naltrexone Treatments for Opioid Use Disorder
Fipps DC, Oesterle TS and Kolla BP
The rates of opioid use and opioid related deaths are escalating in the United States. Despite this, evidence-based treatments for Opioid Use Disorder are underutilized. There are three medications FDA approved for treatment of Opioid Use Disorder: Methadone, Buprenorphine, and Naltrexone. This article reviews the history, criteria, and mechanisms associated with Opioid Use Disorder. Pertinent pharmacology considerations, treatment strategies, efficacy, safety, and challenges of Methadone, Buprenorphine, and Naltrexone are outlined. Lastly, a practical decision making algorithm is discussed to address pertinent psychiatric and medical comorbidities when prescribing pharmacology for Opioid Use Disorder.
Validation of MyFORTA: An Automated Tool to Improve Medications in Older People Based on the FORTA List
Wehling M, Weindrich J, Weiss C, Heser K, Pabst A, Luppa M, Bickel H, Weyerer S, Pentzek M, König HH, Lühmann D, van der Leeden C, Scherer M, Riedel-Heller SG, Wagner M and Pazan F
Listing tools have been developed to improve medications in older patients, including the Fit fOR The Aged (FORTA) list, a clinically validated, positive-negative list of medication appropriateness. Here, we aim to validate MyFORTA, an automated tool for individualized application of the FORTA list.
Modeling intra-individual inter-trial EEG response variability in autism
Dong M, Telesca D, Guindani M, Sugar C, Webb SJ, Jeste S, Dickinson A, Levin AR, Shic F, Naples A, Faja S, Dawson G, McPartland JC and Şentürk D
Autism spectrum disorder (autism) is a prevalent neurodevelopmental condition characterized by early emerging impairments in social behavior and communication. EEG represents a powerful and non-invasive tool for examining functional brain differences in autism. Recent EEG evidence suggests that greater intra-individual trial-to-trial variability across EEG responses in stimulus-related tasks may characterize brain differences in autism. Traditional analysis of EEG data largely focuses on mean trends of the trial-averaged data, where trial-level analysis is rarely performed due to low neural signal to noise ratio. We propose to use nonlinear (shape-invariant) mixed effects (NLME) models to study intra-individual inter-trial EEG response variability using trial-level EEG data. By providing more precise metrics of response variability, this approach could enrich our understanding of neural disparities in autism and potentially aid the identification of objective markers. The proposed multilevel NLME models quantify variability in the signal's interpretable and widely recognized features (e.g., latency and amplitude) while also regularizing estimation based on noisy trial-level data. Even though NLME models have been studied for more than three decades, existing methods cannot scale up to large data sets. We propose computationally feasible estimation and inference methods via the use of a novel minorization-maximization (MM) algorithm. Extensive simulations are conducted to show the efficacy of the proposed procedures. Applications to data from a large national consortium find that children with autism have larger intra-individual inter-trial variability in P1 latency in a visual evoked potential (VEP) task, compared to their neurotypical peers.
Behavioral health and generative AI: a perspective on future of therapies and patient care
Sezgin E and McKay I
There have been considerable advancements in artificial intelligence (AI), specifically with generative AI (GAI) models. GAI is a class of algorithms designed to create new data, such as text, images, and audio, that resembles the data on which they have been trained. These models have been recently investigated in medicine, yet the opportunity and utility of GAI in behavioral health are relatively underexplored. In this commentary, we explore the potential uses of GAI in the field of behavioral health, specifically focusing on image generation. We propose the application of GAI for creating personalized and contextually relevant therapeutic interventions and emphasize the need to integrate human feedback into the AI-assisted therapeutics and decision-making process. We report the use of GAI with a case study of behavioral therapy on emotional recognition and management with a three-step process. We illustrate image generation-specific GAI to recognize, express, and manage emotions, featuring personalized content and interactive experiences. Furthermore, we highlighted limitations, challenges, and considerations, including the elements of human emotions, the need for human-AI collaboration, transparency and accountability, potential bias, security, privacy and ethical issues, and operational considerations. Our commentary serves as a guide for practitioners and developers to envision the future of behavioral therapies and consider the benefits and limitations of GAI in improving behavioral health practices and patient outcomes.
The stability of slow-wave sleep and EEG oscillations across two consecutive nights of laboratory polysomnography in cognitively normal older adults
Mullins AE, Pehel S, Parekh A, Kam K, Bubu OM, Tolbert TM, Rapoport DM, Ayappa I, Varga AW and Osorio RS
Laboratory polysomnography provides gold-standard measures of sleep physiology, but multi-night investigations are resource intensive. We assessed the night-to-night stability via reproducibility metrics for sleep macrostructure and electroencephalography oscillations in a group of cognitively normal adults attending two consecutive polysomnographies. Electroencephalographies were analysed using an automatic algorithm for detection of slow-wave activity, spindle and K-complex densities. Average differences between nights for sleep macrostructure, electroencephalography oscillations and sleep apnea severity were assessed, and test-retest reliability was determined using two-way intraclass correlations. Agreement was calculated using the smallest real differences between nights for all measures. Night 2 polysomnographies showed significantly greater time in bed, total sleep time (6.3 hr versus 6.8 hr, p < 0.001) and percentage of rapid eye movement sleep (17.5 versus 19.7, p < 0.001). Intraclass correlations were low for total sleep time, percentage of rapid eye movement sleep and sleep efficiency, moderate for percentage of slow-wave sleep and percentage of non-rapid eye movement 2 sleep, good for slow-wave activity and K-complex densities, and excellent for spindles and apnea-hypopnea index with hypopneas defined according to 4% oxygen desaturation criteria only. The smallest real difference values were proportionally high for most sleep macrostructure measures, indicating moderate agreement, and proportionally lower for most electroencephalography microstructure variables. Slow waves, K-complexes, spindles and apnea severity indices are highly reproducible across two consecutive nights of polysomnography. In contrast, sleep macrostructure measures all demonstrated poor reproducibility as indicated by low intraclass correlation values and moderate agreement. Although there were average differences in percentage of rapid eye movement sleep and total sleep time, these were numerically small and perhaps functionally or clinically less significant. One night of in-laboratory polysomnography is enough to provide stable, reproducible estimates of an individual's sleep concerning measures of slow-wave activity, spindles, K-complex densities and apnea severity.
Using random forest to identify correlates of depression symptoms among adolescents
Gohari MR, Doggett A, Patte KA, Ferro MA, Dubin JA, Hilario C and Leatherdale ST
Adolescent depression is a significant public health concern, and studying its multifaceted factors using traditional methods possess challenges. This study employs random forest (RF) algorithms to determine factors predicting adolescent depression scores.
[Brain check-up: a structured approach diagnosing mild cognitive impairment in the primary care setting]
Wolski L, Bopp AK, Schwientek AK, Langer S, Dogan V and Grimmer T
The reason-related identification of mild cognitive impairment (MCI) in primary care is helpful to treat reversible causes or decelerate progression to dementia by optimal management of existing risk factors. In this process general practitioners are in a key position. The present feasibility study investigated the practicability of a diagnostic algorithm (brain check-up), comprising neuropsychological examinations, differential diagnoses and follow-up measures.
Multimodal cross-examination of progressive apraxia of speech by diffusion tensor imaging-based tractography and Tau-PET scans
Gatto RG, Pham NTT, Duffy JR, Clark HM, Utianski RL, Botha H, Machulda MM, Lowe VJ, Schwarz CG, Jack CR, Josephs KA and Whitwell JL
Progressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech-language-related WM tracts identified using DTI tractography in PAOS. Twenty-two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir-PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non-fluent variant/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole-brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI-studio) and specific tracts were identified using an automatic fiber tracking atlas-based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal-occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (p < .0001) and elevated flortaucipir SUVR (p = .0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC] = 0.83), followed by the left arcuate fasciculus (AUROC = 0.75) and left frontal aslant tract (AUROC = 0.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech/language difficulties in PAOS.
Generalized genetic liability to substance use disorders
Miller AP, Bogdan R, Agrawal A and Hatoum AS
Lifetime and temporal co-occurrence of substance use disorders (SUDs) is common and compared with individual SUDs is characterized by greater severity, additional psychiatric comorbidities, and worse outcomes. Here, we review evidence for the role of generalized genetic liability to various SUDs. Coaggregation of SUDs has familial contributions, with twin studies suggesting a strong contribution of additive genetic influences undergirding use disorders for a variety of substances (including alcohol, nicotine, cannabis, and others). GWAS have documented similarly large genetic correlations between alcohol, cannabis, and opioid use disorders. Extending these findings, recent studies have identified multiple genomic loci that contribute to common risk for these SUDs and problematic tobacco use, implicating dopaminergic regulatory and neuronal development mechanisms in the pathophysiology of generalized SUD genetic liability, with certain signals demonstrating cross-species and translational validity. Overlap with genetic signals for other externalizing behaviors, while substantial, does not explain the entirety of the generalized genetic signal for SUD. Polygenic scores (PGS) derived from the generalized genetic liability to SUDs outperform PGS for individual SUDs in prediction of serious mental health and medical comorbidities. Going forward, it will be important to further elucidate the etiology of generalized SUD genetic liability by incorporating additional SUDs, evaluating clinical presentation across the lifespan, and increasing the granularity of investigation (e.g., specific transdiagnostic criteria) to ultimately improve the nosology, prevention, and treatment of SUDs.
Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study
Bhuyan G and Rabha A
Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.
Machine learning cryptography methods for IoT in healthcare
Chinbat T, Madanian S, Airehrour D and Hassandoust F
The increased application of Internet of Things (IoT) in healthcare, has fueled concerns regarding the security and privacy of patient data. Lightweight Cryptography (LWC) algorithms can be seen as a potential solution to address this concern. Due to the high variation of LWC, the primary objective of this study was to identify a suitable yet effective algorithm for securing sensitive patient information on IoT devices.
Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis
Dennis EL, Vervoordt S, Adamson MM, Houshang A, Bigler ED, Caeyenberghs K, Cole JH, Dams-O'Connor K, Deutscher EM, Dobryakova E, Genova HM, Grafman JH, Håberg AK, Hellstrøm T, Irimia A, Koliatsos VE, Lindsey HM, Livny A, Menon DK, Merkley TL, Mohamed AZ, Mondello S, Monti MM, Newcombe VF, Newsome MR, Ponsford J, Rabinowitz A, Smevik H, Spitz G, Venkatesan UM, Westlye LT, Zafonte R, Thompson PM, Wilde EA, Olsen A and Hillary FG
The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression.
Neural markers of reduced arousal and consciousness in mild cognitive impairment
Estarellas M, Huntley J and Bor D
People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI.
Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study
Chan K, Wahome E, Tsiachristas A, Antonopoulos AS, Patel P, Lyasheva M, Kingham L, West H, Oikonomou EK, Volpe L, Mavrogiannis MC, Nicol E, Mittal TK, Halborg T, Kotronias RA, Adlam D, Modi B, Rodrigues J, Screaton N, Kardos A, Greenwood JP, Sabharwal N, De Maria GL, Munir S, McAlindon E, Sohan Y, Tomlins P, Siddique M, Kelion A, Shirodaria C, Pugliese F, Petersen SE, Blankstein R, Desai M, Gersh BJ, Achenbach S, Libby P, Neubauer S, Channon KM, Deanfield J, Antoniades C and
Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population.
Artificial Intelligence in Eye Movements Analysis for Alzheimer's Disease Early Diagnosis
Maleki SF, Yousefi M, Sobhi N, Jafarizadeh A, Alizadehsani R and Gorriz-Saez JM
As the world's population ages, Alzheimer's disease is currently the seventh most common cause of death globally; the burden is anticipated to increase, especially among middle-class and elderly persons. Artificial intelligence-based algorithms that work well in hospital environments can be used to identify Alzheimer's disease. A number of databases were searched for English-language articles published up until March 1, 2024, that examined the relationships between artificial intelligence techniques, eye movements, and Alzheimer's disease. A novel non-invasive method called eye movement analysis may be able to reflect cognitive processes and identify anomalies in Alzheimer's disease. Artificial intelligence, particularly deep learning, and machine learning, is required to enhance Alzheimer's disease detection using eye movement data. One sort of deep learning technique that shows promise is convolutional neural networks, which need further data for precise classification. Nonetheless, machine learning models showed a high degree of accuracy in this context. Artificial intelligence-driven eye movement analysis holds promise for enhancing clinical evaluations, enabling tailored treatment, and fostering the development of early and precise Alzheimer's disease diagnosis. A combination of artificial intelligence-based systems and eye movement analysis can provide a window for early and non-invasive diagnosis of Alzheimer's disease. Despite ongoing difficulties with early Alzheimer's disease detection, this presents a novel strategy that may have consequences for clinical evaluations and customized medication to improve early and accurate diagnosis.
Comparing Human-Smartphone Interactions and Actigraphy Measurements for Circadian Rhythm Stability and Adiposity: Algorithm Development and Validation Study
Chuang HH, Lin C, Lee LA, Chang HC, She GJ and Lin YH
This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions.
Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson's Disease
Kumari S, Rana B, Senthil Kumaran S, Chaudhary S, Jain S, Srivastava AK and Rajan R
Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses.
Enhancing post-traumatic stress disorder patient assessment: leveraging natural language processing for research of domain criteria identification using electronic medical records
Miranda O, Kiehl SM, Qi X, Brannock MD, Kosten T, Ryan ND, Kirisci L, Wang Y and Wang L
Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities.
Candidate Genes from an FDA-Approved Algorithm Fail to Predict Opioid Use Disorder Risk in Over 450,000 Veterans
Davis CN, Jinwala Z, Hatoum AS, Toikumo S, Agrawal A, Rentsch CT, Edenberg HJ, Baurley JW, Hartwell EE, Crist RC, Gray JC, Justice AC, Gelernter J, Kember RL and Kranzler HR
Recently, the Food and Drug Administration gave pre-marketing approval to algorithm based on its purported ability to identify genetic risk for opioid use disorder. However, the clinical utility of the candidate genes comprising the algorithm has not been independently demonstrated.
Research on clinical aspects of bipolar disorder: A review of Indian studies
Narula S, Pal A, Reddy MS and Mahajan SL
Bipolar disorder is one of the severe mental disorders that are associated with significant morbidity of the patients. Despite advancements in our understanding about the disorder, it remains a challenging proposition to treat bipolar disorder, largely since the prophylactic treatment of the disorder requires assessment of complex clinical algorithms. The revisions of the classificatory systems have also changed the conceptualization of the disorder. In this background, we conducted a review of the Indian studies conducted on the clinical aspects of bipolar disorder.
Metabolic features of adolescent major depressive disorder: A comparative study between treatment-resistant depression and first-episode drug-naive depression
Gan X, Li X, Cai Y, Yin B, Pan Q, Teng T, He Y, Tang H, Wang T, Li J, Zhu Z, Zhou X and Li J
Major depressive disorder (MDD) is a psychiatric illness that can jeopardize the normal growth and development of adolescents. Approximately 40% of adolescent patients with MDD exhibit resistance to conventional antidepressants, leading to the development of Treatment-Resistant Depression (TRD). TRD is associated with severe impairments in social functioning and learning ability and an elevated risk of suicide, thereby imposing an additional societal burden. In this study, we conducted plasma metabolomic analysis on 53 adolescents diagnosed with first-episode drug-naïve MDD (FEDN-MDD), 53 adolescents with TRD, and 56 healthy controls (HCs) using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) and reversed-phase liquid chromatography-mass spectrometry (RPLC-MS). We established a diagnostic model by identifying differentially expressed metabolites and applying cluster analysis, metabolic pathway analysis, and multivariate linear support vector machine (SVM) algorithms. Our findings suggest that adolescent TRD shares similarities with FEDN-MDD in five amino acid metabolic pathways and exhibits distinct metabolic characteristics, particularly tyrosine and glycerophospholipid metabolism. Furthermore, through multivariate receiver operating characteristic (ROC) analysis, we optimized the area under the curve (AUC) and achieved the highest predictive accuracy, obtaining an AUC of 0.903 when comparing FEDN-MDD patients with HCs and an AUC of 0.968 when comparing TRD patients with HCs. This study provides new evidence for the identification of adolescent TRD and sheds light on different pathophysiologies by delineating the distinct plasma metabolic profiles of adolescent TRD and FEDN-MDD.
Predicted Brain Age in First-Episode Psychosis: Association with Inexpressivity
Salisbury DF, Wulf BM, Seebold D, Coffman BA, Curtis MT and Karim HT
Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a "younger" PBA was associated with higher vocabulary scores among all individuals, while an "older" PBA was associated with more severe negative symptom "Inexpressivity" component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode.
The copy number variant architecture of psychopathology and cognitive development in the ABCD study
Sha Z, Sun KY, Jung B, Barzilay R, Moore TM, Almasy L, Forsyth JK, Prem S, Gandal MJ, Seidlitz J, Glessner JT and Alexander-Bloch AF
Childhood is a crucial developmental phase for mental health and cognitive function, both of which are commonly affected in patients with psychiatric disorders. This neurodevelopmental trajectory is shaped by a complex interplay of genetic and environmental factors. While common genetic variants account for a large proportion of inherited genetic risk, rare genetic variations, particularly copy number variants (CNVs), play a significant role in the genetic architecture of neurodevelopmental disorders. Despite their importance, the relevance of CNVs to child psychopathology and cognitive function in the general population remains underexplored.
Large Language Models for Social Determinants of Health Information Extraction from Clinical Notes - A Generalizable Approach across Institutions
Keloth VK, Selek S, Chen Q, Gilman C, Fu S, Dang Y, Chen X, Hu X, Zhou Y, He H, Fan JW, Wang K, Brandt C, Tao C, Liu H and Xu H
The consistent and persuasive evidence illustrating the influence of social determinants on health has prompted a growing realization throughout the health care sector that enhancing health and health equity will likely depend, at least to some extent, on addressing detrimental social determinants. However, detailed social determinants of health (SDoH) information is often buried within clinical narrative text in electronic health records (EHRs), necessitating natural language processing (NLP) methods to automatically extract these details. Most current NLP efforts for SDoH extraction have been limited, investigating on limited types of SDoH elements, deriving data from a single institution, focusing on specific patient cohorts or note types, with reduced focus on generalizability. This study aims to address these issues by creating cross-institutional corpora spanning different note types and healthcare systems, and developing and evaluating the generalizability of classification models, including novel large language models (LLMs), for detecting SDoH factors from diverse types of notes from four institutions: Harris County Psychiatric Center, University of Texas Physician Practice, Beth Israel Deaconess Medical Center, and Mayo Clinic. Four corpora of deidentified clinical notes were annotated with 21 SDoH factors at two levels: level 1 with SDoH factor types only and level 2 with SDoH factors along with associated values. Three traditional classification algorithms (XGBoost, TextCNN, Sentence BERT) and an instruction tuned LLM-based approach (LLaMA) were developed to identify multiple SDoH factors. Substantial variation was noted in SDoH documentation practices and label distributions based on patient cohorts, note types, and hospitals. The LLM achieved top performance with micro-averaged F1 scores over 0.9 on level 1 annotated corpora and an F1 over 0.84 on level 2 annotated corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. To foster collaboration, access to partial annotated corpora and models trained by merging all annotated datasets will be made available on the PhysioNet repository.
Using AI-Based Technologies to Help Nurses Detect Behavioral Disorders: Narrative Literature Review
Fernandes S, von Gunten A and Verloo H
The behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia and have multiple negative consequences. Artificial intelligence-based technologies (AITs) have the potential to help nurses in the early prodromal detection of BPSD. Despite significant recent interest in the topic and the increasing number of available appropriate devices, little information is available on using AITs to help nurses striving to detect BPSD early.
Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England
Copland E, Patone M, Saatci D, Handunnetthi L, Hirst J, Hunt DPJ, Mills NL, Moss P, Sheikh A, Coupland CAC, Harnden A, Robertson C and Hippisley-Cox J
The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.
Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells
Peres N, Lepski GA, Fogolin CS, Evangelista GCM, Flatow EA, de Oliveira JV, Pinho MP, Bergami-Santos PC and Barbuto JAM
Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.
A multimodal machine learning model for predicting dementia conversion in Alzheimer's disease
Lee MW, Kim HW, Choe YS, Yang HS, Lee J, Lee H, Yong JH, Kim D, Lee M, Kang DW, Jeon SY, Son SJ, Lee YM, Kim HG, Kim REY and Lim HK
Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.
A machine learning approach using conditional normalizing flow to address extreme class imbalance problems in personal health records
Kim Y, Choi W, Choi W, Ko G, Han S, Kim HC, Kim D, Lee DG, Shin DW and Lee Y
Supervised machine learning models have been widely used to predict and get insight into diseases by classifying patients based on personal health records. However, a class imbalance is an obstacle that disrupts the training of the models. In this study, we aimed to address class imbalance with a conditional normalizing flow model, one of the deep-learning-based semi-supervised models for anomaly detection. It is the first introduction of the normalizing flow algorithm for tabular biomedical data.
Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study
Gao PY, Ma LZ, Wang XJ, Wu BS, Huang YM, Wang ZB, Fu Y, Ou YN, Feng JF, Cheng W, Tan L and Yu JT
Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.
Digital phenotyping data and anomaly detection methods to assess changes in mood and anxiety symptoms across a transdiagnostic clinical sample
Cohen A, Naslund J, Lane E, Bhan A, Rozatkar A, Mehta UM, Vaidyam A, Byun AJS, Barnett I and Torous J
Clinical assessment of mood and anxiety change often relies on clinical assessment or self-reported scales. Using smartphone digital phenotyping data and resulting markers of behavior (e.g., sleep) to augment clinical symptom scores offers a scalable and potentially more valid method to understand changes in patients' state. This paper explores the potential of using a combination of active and passive sensors in the context of smartphone-based digital phenotyping to assess mood and anxiety changes in two distinct cohorts of patients to assess the preliminary reliability and validity of this digital phenotyping method.
The blind spots of psychiatric reform in Greece
Stylianidis S
According to international experience, the conditions for the successful outcome of a psychiatric reform are the following: (a) Existence of political will (supporting a national plan with assessment, monitoring, and corrective intervention procedures for structural dysfunctions, etc.). (b) Strong mental health leadership (executive expertise and skills that advance the public health agenda). (c) Challenging the dominance of the biomedical model in therapeutic practice through the promotion of holistic care practices, evidence-based innovative actions, collaborative care, the promotion of recovery culture, and the and the use of innovative digital tools. (d) Ensuring necessary resources over time, so that resources from the transition of the asylum model to a model of sectorial community mental health services "follow" the patient. (e) Strengthening the participation of service recipients and their families in decision-making processes and evaluation of care quality. (f) Practices based on ethical principles (value-based practice) and not only on the always necessary documentation (evidence-based practice).1- 4 Convergent evidence from the "ex post" evaluation of the implementation of the national plan Psychargos 2000-20095 and from the recent rapid assessment of the psychiatric reform by the Ministry of Health and the WHO Athens office (SWOT analysis)6 indicates "serious fragmentation of services, an uncoordinated system that often results in inappropriate service provision, a lack of epidemiological studies and studies concerning the local needs of specific populations, uneven development of services between different regions of the country, a large number of specialized professionals with significant deficits in community psychiatry expertise, a lack of personnel in supportive roles, significant gaps in specialized services (for individuals with autism spectrum disorders, intellectual disabilities, eating disorders, old and new addictions, and community forensic psychiatry services)". We would also like to highlight lack of coordination and collaboration among different mental health service systems (public primary and secondary service providers, NGOs, municipal services, mental health services of the armed forces, private sector), complete absence of systematic evaluation and monitoring (lack of quality of care indicators, clinical outcomes, epidemiological profile of each service), lack of quality assurance mechanisms and clinical management systems, insufficient number of beds mainly for acute cases, unclear protocols for discharge issuance and ensuring continuity of care, deficient budget for Mental Health in relation to the overall healthcare expenditure (currently 3.3%), and finally, one of the highest rates of involuntary hospitalizations in Europe, which is linked to serious issues concerning the protection of the rights of service users. After the pandemic and the emergence of the silent but expected mental health pandemic, WHO, EU, and the Greek Ministry of Health emphasized the need to adopt a public mental health agenda with an emphasis on community psychiatry in order to address both the old structural dysfunctions and inadequacies of psychiatric reform (regulation 815/1984, Leros I-Leros II plan, Psychargos A & B, incomplete implementation of laws 2071/1992 & 2716/1999, incomplete deinstitutionalization of the remaining psychiatric hospitals). However, it is time to reflect that it is not possible to talk today about the need to update and implement a new national plan to upgrade mental health in the country without answering basic questions, both old and new, about the wider context of its implementation. The transformation of the deficient psychiatric care in the country cannot be completed without the urgent restructuring of the National Health System7 and the reform of the Greek welfare state itself, which is also characterized by irrationality, inequalities, bureaucratic inefficiency, and fragmentation.8 As we should have learned from the bankruptcy and the prolonged economic, social, and cultural crisis in our country, reforms usually pay off in the long term, while the time horizon of the applied policies is narrow and usually reaching the next election. The fact is that in any reform effort, including psychiatry, the political system does not demonstrate the ability to promote transparency, evaluation, stable rules of regulation, reference to a universally applicable legal and institutional framework, the limitation of clientelism and guild resistances. From this point of view, it is necessary to give meaning in the context of Greek psychiatric reform to the professional burnout of the National Health System workers, the lack of motivation and vision, the intrusion into the NGO space by new entities without any connection to the culture of psychiatry reform, the guild resistances of all relevant specialties, the selective use of psychotherapeutic techniques, as trends of discrediting the relief of social and psychological suffering in the field of public mental health. There is an urgent need to understand new pathologies (narcissistic disorders, new forms of addiction, eating disorders, "pathology of emptiness", adolescent delinquency and suicide, psychosomatic manifestations due to high stress, pathology of fluid social ties, deficient socialization of young people "outside of their algorithms") through a solid and coherent analysis of the toxic postmodernity culture. In addition to the social determinants of mental health,9 it is necessary in clinical work to also assess the psychological factors, such as uncertainty, conflict, loss of control, and incomplete information, that burden human health.10 In order to reduce the gap between declarations and real life, there is an urgent need to overcome the blind spots of psychiatric reform in the country by establishing internal and external evaluation processes, training young professionals in holistic care and community networking and communication skills, retraining leaders for organizational change, and strengthening the participation of service users in the context of deepening democracy in mental health. As mental health professionals, the object of our work in the community should be the reconstruction of meaning and the fragile or non-existent social bond in subjects who have been cut off from any possible production of meaning and participation in their history. Why should our therapeutic responses be stereotypically repetitive in the face of these complex, radical changes in the meta-context and the new demands of our patients? After all, as the philosopher Ernst Bloch puts it, utopia is "that which does not exist yet.".
Interdisciplinary approach to identify language markers for post-traumatic stress disorder using machine learning and deep learning
Quillivic R, Gayraud F, Auxéméry Y, Vanni L, Peschanski D, Eustache F, Dayan J and Mesmoudi S
Post-traumatic stress disorder (PTSD) lacks clear biomarkers in clinical practice. Language as a potential diagnostic biomarker for PTSD is investigated in this study. We analyze an original cohort of 148 individuals exposed to the November 13, 2015, terrorist attacks in Paris. The interviews, conducted 5-11 months after the event, include individuals from similar socioeconomic backgrounds exposed to the same incident, responding to identical questions and using uniform PTSD measures. Using this dataset to collect nuanced insights that might be clinically relevant, we propose a three-step interdisciplinary methodology that integrates expertise from psychiatry, linguistics, and the Natural Language Processing (NLP) community to examine the relationship between language and PTSD. The first step assesses a clinical psychiatrist's ability to diagnose PTSD using interview transcription alone. The second step uses statistical analysis and machine learning models to create language features based on psycholinguistic hypotheses and evaluate their predictive strength. The third step is the application of a hypothesis-free deep learning approach to the classification of PTSD in our cohort. Results show that the clinical psychiatrist achieved a diagnosis of PTSD with an AUC of 0.72. This is comparable to a gold standard questionnaire (Area Under Curve (AUC) ≈ 0.80). The machine learning model achieved a diagnostic AUC of 0.69. The deep learning approach achieved an AUC of 0.64. An examination of model error informs our discussion. Importantly, the study controls for confounding factors, establishes associations between language and DSM-5 subsymptoms, and integrates automated methods with qualitative analysis. This study provides a direct and methodologically robust description of the relationship between PTSD and language. Our work lays the groundwork for advancing early and accurate diagnosis and using linguistic markers to assess the effectiveness of pharmacological treatments and psychotherapies.
Security Analysis for Smart Healthcare Systems
Ibrahim M, Al-Wadi A and Elhafiz R
The healthcare industry went through reformation by integrating the Internet of Medical Things (IoMT) to enable data harnessing by transmission mediums from different devices, about patients to healthcare staff devices, for further analysis through cloud-based servers for proper diagnosis of patients, yielding efficient and accurate results. However, IoMT technology is accompanied by a set of drawbacks in terms of security risks and vulnerabilities, such as violating and exposing patients' sensitive and confidential data. Further, the network traffic data is prone to interception attacks caused by a wireless type of communication and alteration of data, which could cause unwanted outcomes. The advocated scheme provides insight into a robust Intrusion Detection System (IDS) for IoMT networks. It leverages a honeypot to divert attackers away from critical systems, reducing the attack surface. Additionally, the IDS employs an ensemble method combining Logistic Regression and K-Nearest Neighbor algorithms. This approach harnesses the strengths of both algorithms to improve attack detection accuracy and robustness. This work analyzes the impact, performance, accuracy, and precision outcomes of the used model on two IoMT-related datasets which contain multiple attack types such as Man-In-The-Middle (MITM), Data Injection, and Distributed Denial of Services (DDOS). The yielded results showed that the proposed ensemble method was effective in detecting intrusion attempts and classifying them as attacks or normal network traffic, with a high accuracy of 92.5% for the first dataset and 99.54% for the second dataset and a precision of 96.74% for the first dataset and 99.228% for the second dataset.
Guidelines for the assessment and management of residual sleepiness in obstructive apnea-hypopnea syndrome: Endorsed by the French Sleep Research and Medicine Society (SFRMS) and the French Speaking Society of Respiratory Diseases (SPLF)
Barateau L, Baillieul S, Andrejak C, Bequignon É, Boutouyrie P, Dauvilliers Y, Gagnadoux F, Geoffroy PA, Micoulaud-Franchi JA, Montani D, Monaca C, Patout M, Pépin JL, Philip P, Pilette C, Tamisier R, Trzepizur W, Jaffuel D and Arnulf I
Excessive daytime sleepiness (EDS) is frequent among patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and can persist despite the optimal correction of respiratory events (apnea, hypopnea and respiratory efforts), using continuous positive airway pressure (CPAP) or mandibular advancement device. Symptoms like apathy and fatigue may be mistaken for EDS. In addition, EDS has multi-factorial origin, which makes its evaluation complex. The marketing authorization [Autorisation de Mise sur le Marché (AMM)] for two wake-promoting agents (solriamfetol and pitolisant) raises several practical issues for clinicians. This consensus paper presents recommendations of good clinical practice to identify and evaluate EDS in this context, and to manage and follow-up the patients. It was conducted under the mandate of the French Societies for sleep medicine and for pneumology [Société Française de Recherche et de Médecine du Sommeil (SFRMS) and Société de Pneumologie de Langue Française (SPLF)]. A management algorithm is suggested, as well as a list of conditions during which the patient should be referred to a sleep center or a sleep specialist. The benefit/risk balance of a wake-promoting drug in residual EDS in OSAHS patients must be regularly reevaluated, especially in elderly patients with increased cardiovascular and psychiatric disorders risks. This consensus is based on the scientific knowledge at the time of the publication and may be revised according to their evolution.
Integrating Alcohol Biosensors With Ecological Momentary Intervention (EMI) for Alcohol Use: a Synthesis of the Latest Literature and Directions for Future Research
Wang Y, Porges EC, DeFelice J and Fridberg DJ
Excessive alcohol use is a major public health concern. With increasing access to mobile technology, novel mHealth approaches for alcohol misuse, such as ecological momentary intervention (EMI), can be implemented widely to deliver treatment content in real time to diverse populations. This review summarizes the state of research in this area with an emphasis on the potential role of wearable alcohol biosensors in future EMI/just-in-time adaptive interventions (JITAI) for alcohol use.
The Use of Generative Adversarial Network and Graph Convolution Network for Neuroimaging-Based Diagnostic Classification
Huynh N, Yan D, Ma Y, Wu S, Long C, Sami MT, Almudaifer A, Jiang Z, Chen H, Dretsch MN, Denney TS, Deshpande R and Deshpande G
Functional connectivity (FC) obtained from resting-state functional magnetic resonance imaging has been integrated with machine learning algorithms to deliver consistent and reliable brain disease classification outcomes. However, in classical learning procedures, custom-built specialized feature selection techniques are typically used to filter out uninformative features from FC patterns to generalize efficiently on the datasets. The ability of convolutional neural networks (CNN) and other deep learning models to extract informative features from data with grid structure (such as images) has led to the surge in popularity of these techniques. However, the designs of many existing CNN models still fail to exploit the relationships between entities of graph-structure data (such as networks). Therefore, graph convolution network (GCN) has been suggested as a means for uncovering the intricate structure of brain network data, which has the potential to substantially improve classification accuracy. Furthermore, overfitting in classifiers can be largely attributed to the limited number of available training samples. Recently, the generative adversarial network (GAN) has been widely used in the medical field for its generative aspect that can generate synthesis images to cope with the problems of data scarcity and patient privacy. In our previous work, GCN and GAN have been designed to investigate FC patterns to perform diagnosis tasks, and their effectiveness has been tested on the ABIDE-I dataset. In this paper, the models will be further applied to FC data derived from more public datasets (ADHD, ABIDE-II, and ADNI) and our in-house dataset (PTSD) to justify their generalization on all types of data. The results of a number of experiments show the powerful characteristic of GAN to mimic FC data to achieve high performance in disease prediction. When employing GAN for data augmentation, the diagnostic accuracy across ADHD-200, ABIDE-II, and ADNI datasets surpasses that of other machine learning models, including results achieved with BrainNetCNN. Specifically, in ADHD, the accuracy increased from 67.74% to 73.96% with GAN, in ABIDE-II from 70.36% to 77.40%, and in ADNI, reaching 52.84% and 88.56% for multiclass and binary classification, respectively. GCN also obtains decent results, with the best accuracy in ADHD datasets at 71.38% for multinomial and 75% for binary classification, respectively, and the second-best accuracy in the ABIDE-II dataset (72.28% and 75.16%, respectively). Both GAN and GCN achieved the highest accuracy for the PTSD dataset, reaching 97.76%. However, there are still some limitations that can be improved. Both methods have many opportunities for the prediction and diagnosis of diseases.
Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight
Shen FX, Wolf SM, Lawrenz F, Comeau DS, Dzirasa K, Evans BJ, Fair D, Farah MJ, Han SD, Illes J, Jackson JD, Klein E, Rommelfanger KS, Rosen MS, Torres E, Tuite P, Vaughan JT and Garwood M
Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.
Pattern transitions in diary data of MDD patients: a mixed-methods multiple case study of psychotherapy dynamics
Nordholt S, Garrison P, Aichhorn W, Ochs M and Schiepek G
Mixed-methods approaches promise a deep understanding of psychotherapeutic processes. This study uses qualitative and quantitative data from daily diary entries and daily self-assessments during inpatient treatment. The aim of the study is to get an insight into the similarities and differences between both types of data and how they represent self-organized pattern transitions in psychotherapy. While a complete correlation of results is not expected, we anticipate observing amplifying and subsidiary patterns from both perspectives.
Brain Disorder Detection and Diagnosis using Machine Learning and Deep Learning - A Bibliometric Analysis
Chaki J and Deshpande G
Brain disorders are one of the major global mortality issues, and their early detection is crucial for healing. Machine learning, specifically deep learning, is a technology that is increasingly being used to detect and diagnose brain disorders. Our objective is to provide a quantitative bibliometric analysis of the field to inform researchers about trends that can inform their Research directions in the future.
[Posttraumatic stress disorder clinical guidelines and treatment standards: focus on the symptoms of the psychophysiological arousal]
Vasileva AV
The article describes the main diagnostic criteria and principles of posttraumatic stress disorder (PTSD) diagnostic with the consideration of risk factors and specific clinical features. The main biomarkers search trends and existing limitations are considered. The role of the psychophysiological arousal symptoms claster is highlighted in the clinical picture of PTSD as well as in connection with the main cluster of re-experiencing symptoms activation and slowing of sanogenesis process. The necessity of PTSD detection in somatic medicine is thoroughly described. The article presents therapeutic algorithms of the latest international and Russian PTSD treatment clinical guidelines based on the individual combination of psychotherapy and psychopharmacotherapy treatment choice. Additionally the accumulated during the last decades national clinical experience of the anxiety disorders treatment, including the symptoms of psychophysiological arousal is highlighted that determined the list of the recommended drugs indicating the evidence level, in the PTSD treatment standards and guidelines. The treatment choices possibilities with the consideration of different PTSD symptoms cluster expression and comorbid states and individual case distress level specific are presented. Main evidence based psychotherapeutic methods are described.
Genes associated with cellular senescence as diagnostic markers of major depressive disorder and their correlations with immune infiltration
Chen J, Xie X, Lin M, Han H, Wang T, Lei Q and He R
Emerging evidence links cellular senescence to the pathogenesis of major depressive disorder (MDD), a life-threatening and debilitating mental illness. However, the roles of cellular senescence-related genes in MDD are largely unknown and were investigated in this study using a comprehensive analysis.
Outcomes following hip fracture surgery in adults with schizophrenia in Ontario, Canada: A 10-year population-based retrospective cohort study
Ansari H, Fung K, Cheung AM, Jaglal S, Bogoch ER and Kurdyak PA
To understand immediate and long-term outcomes following hip fracture surgery in adults with schizophrenia.
Cardiovascular disease risk: it is complicated, but race and ethnicity are key, a Bayesian network analysis
Bowles NP, He Y, Huang YH, Stecker EC, Seixas A and Thosar SS
Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures).
Decoding imagined speech with delay differential analysis
Carvalho VR, Mendes EMAM, Fallah A, Sejnowski TJ, Comstock L and Lainscsek C
Speech decoding from non-invasive EEG signals can achieve relatively high accuracy (70-80%) for strictly delimited classification tasks, but for more complex tasks non-invasive speech decoding typically yields a 20-50% classification accuracy. However, decoder generalization, or how well algorithms perform objectively across datasets, is complicated by the small size and heterogeneity of existing EEG datasets. Furthermore, the limited availability of open access code hampers a comparison between methods. This study explores the application of a novel non-linear method for signal processing, delay differential analysis (DDA), to speech decoding. We provide a systematic evaluation of its performance on two public imagined speech decoding datasets relative to all publicly available deep learning methods. The results support DDA as a compelling alternative or complementary approach to deep learning methods for speech decoding. DDA is a fast and efficient time-domain open-source method that fits data using only few strong features and does not require extensive preprocessing.
Estimating classification consistency of machine learning models for screening measures
Gonzalez O, Georgeson AR and Pelham WE
This article illustrates novel quantitative methods to estimate classification consistency in machine learning models used for screening measures. Screening measures are used in psychology and medicine to classify individuals into diagnostic classifications. In addition to achieving high accuracy, it is ideal for the screening process to have high classification consistency, which means that respondents would be classified into the same group every time if the assessment was repeated. Although machine learning models are increasingly being used to predict a screening classification based on individual item responses, methods to describe the classification consistency of machine learning models have not yet been developed. This article addresses this gap by describing methods to estimate classification inconsistency in machine learning models arising from two different sources: sampling error during model fitting and measurement error in the item responses. These methods use data resampling techniques such as the bootstrap and Monte Carlo sampling. These methods are illustrated using three empirical examples predicting a health condition/diagnosis from item responses. R code is provided to facilitate the implementation of the methods. This article highlights the importance of considering classification consistency alongside accuracy when studying screening measures and provides the tools and guidance necessary for applied researchers to obtain classification consistency indices in their machine learning research on diagnostic assessments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Zero Suicide Quality Improvement: Developmental and Pandemic-Related Patterns in Youth at Risk for Suicide Attempts
Asarnow JR, Clarke GN, Miranda JM, Edelmann AC, Sheppler CR, Firemark AJ, Zhang L, Babeva K, Venables C and Comulada S
The Zero Suicide (ZS) approach to health system quality improvement (QI) aspires to reduce/eliminate suicides through enhancing risk detection and suicide-prevention services. This first report from our randomized trial evaluating a stepped care for suicide prevention intervention within a health system conducting ZS-QI describes 1) our screening and case identification process, 2) variation among adolescents versus young adults; and 3) pandemic-related patterns during the first COVID-19 pandemic year. Between April 2017 and January 2021, youths aged 12-24 with elevated suicide risk were identified through an electronic health record (EHR) case-finding algorithm followed by direct assessment screening to confirm risk. Eligible/enrolled youth were evaluated for suicidality, self-harm, and risk/protective factors. Case finding, screening, and enrollment yielded 301 participants showing suicide risk-indicators: 97% past-year suicidal ideation, 83% past suicidal behavior; 90% past non-suicidal self-injury (NSSI). Compared to young adults, adolescents reported: more past-year suicide attempts (47% vs 21%, p<.001) and NSSI (past 6-months, 64% vs 39%, p<.001); less depression, anxiety, posttraumatic stress, and substance use; and greater social connectedness. Pandemic-onset was associated with lower participation of racial-ethnic minority youths (18% vs 33%, p<.015) and lower past-month suicidal ideation and behavior. Results support the value of EHR case-finding algorithms for identifying youths with potentially elevated risk who could benefit from suicide-prevention services, which merit adaptation for adolescents versus young adults. Lower racial-ethnic minority participation after the COVID-19 pandemic-onset underscores challenges for services to enhance health equity during a period with restricted in-person health care, social distancing, school closures, and diverse stresses.
Anxiety and depression in patients with non-site-specific cancer symptoms: data from a rapid diagnostic clinic
Monroy-Iglesias MJ, Russell B, Martin S, Fox L, Moss C, Bruno F, Millwaters J, Steward L, Murtagh C, Cargaleiro C, Bater D, Lavelle G, Simpson A, Onih J, Haire A, Reeder C, Jones G, Smith S, Santaolalla A, Van Hemelrijck M and Dolly S
Rapid diagnostic clinics (RDCs) provide a streamlined holistic pathway for patients presenting with non-site specific (NSS) symptoms concerning of malignancy. The current study aimed to: 1) assess the prevalence of anxiety and depression, and 2) identify a combination of patient characteristics and symptoms associated with severe anxiety and depression at Guy's and St Thomas' Foundation Trust (GSTT) RDC in Southeast London. Additionally, we compared standard statistical methods with machine learning algorithms for predicting severe anxiety and depression.
A few theoretical results for Laplace and arctan penalized ordinary least squares linear regression estimators
John M and Vettam S
Two new nonconvex penalty functions - Laplace and arctan - were recently introduced in the literature to obtain sparse models for high-dimensional statistical problems. In this paper, we study the theoretical properties of Laplace and arctan penalized ordinary least squares linear regression models. We first illustrate the near-unbiasedness of the nonzero regression weights obtained by the new penalty functions, in the orthonormal design case. In the general design case, we present theoretical results in two asymptotic settings: (a) the number of features, fixed, but the sample size, , and (b) both and tend to infinity. The theoretical results shed light onto the differences between the solutions based on the new penalty functions and those based on existing convex and nonconvex Bridge penalty functions. Our theory also shows that both Laplace and arctan penalties satisfy the oracle property. Finally, we also present results from a brief simulations study illustrating the performance of Laplace and arctan penalties based on the gradient descent optimization algorithm.
A machine learning approach for differentiating bipolar disorder type II and borderline personality disorder using electroencephalography and cognitive abnormalities
Nazari MJ, Shalbafan M, Eissazade N, Khalilian E, Vahabi Z, Masjedi N, Ghidary SS, Saadat M and Sadegh-Zadeh SA
This study addresses the challenge of differentiating between bipolar disorder II (BD II) and borderline personality disorder (BPD), which is complicated by overlapping symptoms. To overcome this, a multimodal machine learning approach was employed, incorporating both electroencephalography (EEG) patterns and cognitive abnormalities for enhanced classification. Data were collected from 45 participants, including 20 with BD II and 25 with BPD. Analysis involved utilizing EEG signals and cognitive tests, specifically the Wisconsin Card Sorting Test and Integrated Cognitive Assessment. The k-nearest neighbors (KNN) algorithm achieved a balanced accuracy of 93%, with EEG features proving to be crucial, while cognitive features had a lesser impact. Despite the strengths, such as diverse model usage, it's important to note limitations, including a small sample size and reliance on DSM diagnoses. The study suggests that future research should explore multimodal data integration and employ advanced techniques to improve classification accuracy and gain a better understanding of the neurobiological distinctions between BD II and BPD.
A Bayesian multilevel model for populations of networks using exponential-family random graphs
Lehmann B and White S
The collection of data on populations of networks is becoming increasingly common, where each data point can be seen as a realisation of a network-valued random variable. Moreover, each data point may be accompanied by some additional covariate information and one may be interested in assessing the effect of these covariates on network structure within the population. A canonical example is that of brain networks: a typical neuroimaging study collects one or more brain scans across multiple individuals, each of which can be modelled as a network with nodes corresponding to distinct brain regions and edges corresponding to structural or functional connections between these regions. Most statistical network models, however, were originally proposed to describe a single underlying relational structure, although recent years have seen a drive to extend these models to populations of networks. Here, we describe a model for when the outcome of interest is a network-valued random variable whose distribution is given by an exponential random graph model. To perform inference, we implement an exchange-within-Gibbs MCMC algorithm that generates samples from the doubly-intractable posterior. To illustrate this approach, we use it to assess population-level variations in networks derived from fMRI scans, enabling the inference of age- and intelligence-related differences in the topological structure of the brain's functional connectivity.
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Psychiatry AI RAISR 4D System Psychiatry + Mental Health