Yale Psychiatry

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences. In this article, we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry. Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease, cerebrovascular disease, glioma, psychiatric disease, traumatic brain injury, and myelin deficit. In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases. Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood, the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications. However, the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications. This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

JOURNAL/nrgr/04.03/01300535-202502000-00033/figure1/v/2024-05-28T214302Z/r/image-tiff There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson's disease after diagnosis. Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids, such as docosahexaenoic acid, and exercise in Parkinson's disease, we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway. First, mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation. Four weeks after lesion, animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks. During this period, the animals had access to a running wheel, which they could use or not. Docosahexaenoic acid treatment, voluntary exercise, or the combination of both had no effect on (i) distance traveled in the open field test, (ii) the percentage of contraversive rotations in the apomorphine-induction test or (iii) the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta. However, the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum. Compared to docosahexaenoic acid treatment or exercise alone, the combination of docosahexaenoic acid and exercise (i) improved forelimb balance in the stepping test, (ii) decreased the striatal DOPAC/dopamine ratio and (iii) led to increased dopamine transporter levels in the lesioned striatum. The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson's disease.

The worldwide spread of novel psychoactive substances (NPS) in the illicit drug market and their continuous increase in number and type, for the purpose of bypassing controlled substance legislation, represents a continuing challenge for forensic scientists, clinicians and enforcement authorities. We aim to provide information regarding the most urgent harms related to NPS consumption in different world regions and the current state of the art for NPS analysis.

Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West.

Symptoms of cancer-related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample.

Frailty is a complex trait. Twin studies and high-powered Genome Wide Association Studies conducted in the UK Biobank have demonstrated a strong genetic basis of frailty. The present study utilized summary statistics from a Genome Wide Association Study on the Frailty Index to create and test the predictive power of frailty polygenic risk scores (PRS) in two independent samples - the Lothian Birth Cohort 1936 (LBC1936) and the English Longitudinal Study of Ageing (ELSA) aged 67-84 years. Multiple regression models were built to test the predictive power of frailty PRS at five time points. Frailty PRS significantly predicted frailty, measured via the FI, at all-time points in LBC1936 and ELSA, explaining 2.1% (β = 0.15, 95%CI, 0.085-0.21) and 1.8% (β = 0.14, 95%CI, 0.10-0.17) of the variance, respectively, at age ~ 68/ ~ 70 years (p < 0.001). This work demonstrates that frailty PRS can predict frailty in two independent cohorts, particularly at early ages (~ 68/ ~ 70). PRS have the potential to be valuable instruments for identifying those at risk for frailty and could be important for controlling for genetic confounders in epidemiological studies.

New sleep-inducing drugs (eg, ramelteon, suvorexant, and lemborexant) have been shown to prevent delirium in high-risk groups. However, no single study has simultaneously evaluated the delirium-preventing effects of all novel sleep-inducing drugs in hospitalized patients. Therefore, this study aimed to clarify the relationship between sleep-inducing drugs and delirium prevention in patients hospitalized in general medical-surgical settings for nonpsychiatric conditions who underwent liaison interventions for insomnia.

The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the last ∼35 years detailed information has accrued about the redundant and unique expression and function of the six mammalian Dlx family genes. DLX proteins interact with general transcriptional regulators, and co-bind with other transcription factors to enhancer elements with highly specific activity in the developing forebrain. Integration of the genetic and biochemical data has yielded a foundation for a gene regulatory network governing the differentiation of forebrain GABAergic neurons. In this Primer, we describe the discovery of vertebrate Dlx genes and their crucial roles in embryonic development. We largely focus on the role of Dlx family genes in mammalian forebrain development revealed through studies in mice. Finally, we highlight questions that remain unanswered regarding vertebrate Dlx genes despite over 30 years of research.

Homelessness is associated with adverse health and social outcomes. People experiencing homelessness have been found to have a high risk of violent crime victimisation as well as high prevalence of psychiatric disorders. It is poorly understood whether experiencing homelessness is associated with additional risks of violent offending and whether psychiatric disorders contribute to these risks. We examined the association between homelessness, psychiatric disorders, and first violence offence leading to conviction.

Research on the impact of the COVID-19 pandemic on mothers/childbearing parents has mainly been cross-sectional and focused on psychological symptoms. This study examined the impact on function using ongoing, systematic screening of a representative Ontario sample.

With dual focus on structured, objective quantification of parent observations of child's behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them.

Traumatic brain injury (TBI) occurs at the highest rate in older adulthood and increases risk for cognitive impairment and dementia.

Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine.

Mobile health (mHealth) apps have the potential to enhance health care service delivery. However, concerns regarding patients' confidentiality, privacy, and security consistently affect the adoption of mHealth apps. Despite this, no review has comprehensively summarized the findings of studies on this subject matter.

Depression accounts for a high proportion of neuropsychiatric disorders and is associated with abnormal states of neurons in specific brain regions. Microglia play a pivotal role in the inflammatory state during depression development; however, the exact mechanism underlying chronic mood states remains unknown. Thus, the present study aimed to determine whether microRNAs (miRNAs) alleviate stress-induced depression-like behavior in mice by regulating the expression levels of their target genes, explore the role of neuroinflammation induced by microglial activation in the pathogenesis and progression of depression, and determine whether the role of the miR-29a-5p/transmembrane protein 33 (TMEM33) axis.

Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum.

Reducing harm from combustible cigarette use among women of reproductive age (WRA) is critical given their potential vulnerability to multigenerational adverse impacts of cigarette smoking. Although electronic nicotine delivery systems (ENDS) are not approved smoking cessation aids in the US, many WRA who smoke report using ENDS to help quit smoking. Associations between ENDS use patterns and smoking-cessation efforts among US WRA remain unclear.

Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin (5-HT) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT receptors and VGSCs. Towards this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT receptors and blocks sodium current. The new compound, -(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, G-mediated, calcium flux at 5-HT receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT, 5-HT, and 5-HT receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons. Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the treatment of psychiatric disorders that are increasingly being found to benefit from the simultaneous targeting of multiple receptors. We synthesized a novel small molecule (XOB) that simultaneously antagonizes two key therapeutic targets of bipolar disorder, 5-HT receptors and voltage-gated sodium channels (VGSCs), in heterologous cells, and inhibits the intrinsic excitability of mouse prefrontal cortex layer V pyramidal neurons in brain slices. XOB represents a valuable new proof-of-principle tool for future preclinical investigations and provides a novel molecular approach to the pharmacological treatment of complex neuropsychiatric disease, which often requires a combination of therapeutics for sufficient patient benefit.

TSPO ligands are promising alternatives to benzodiazepines in the treatment of anxiety, as they display less pronounced side effects such as sedation, cognitive impairment, tolerance development and abuse potential. In a randomized double-blind repeated-measures study we compare a benzodiazepine (alprazolam) to a TSPO ligand (etifoxine) by assessing side effects and acquiring resting-state fMRI data from 34 healthy participants after 5 days of taking alprazolam, etifoxine or a placebo. To study the effects of the pharmacological interventions in fMRI in detail and across different scales, we combine in our study complementary analysis strategies related to whole-brain functional network connectivity, local connectivity analysis expressed in regional homogeneity, fluctuations in low-frequency BOLD amplitudes and coherency of independent resting-state networks. Participants reported considerable adverse effects such as fatigue, sleepiness and concentration impairments, related to the administration of alprazolam compared to placebo. In resting-state fMRI we found a significant decrease in functional connection density, network efficiency and a decrease in the networks rich-club coefficient related to alprazolam. While observing a general decrease in regional homogeneity in high-level brain networks in the alprazolam condition, we simultaneously could detect an increase in regional homogeneity and resting-state network coherence in low-level sensory regions. Further we found a general increase in the low-frequency compartment of the BOLD signal. In the etifoxine condition, participants did not report any significant side effects compared to the placebo, and we did not observe any corresponding modulations in our fMRI metrics. Our results are consistent with the idea that sedation globally disconnects low-level functional networks, but simultaneously increases their within-connectivity. Further, our results point towards the potential of TSPO ligands in the treatment of anxiety and depression.

Although the relationship between schizophrenia and disability is well established, the association between the symptoms of the disorder and functional domains remains unclear. The current study explored the nuances of the relationship between symptoms and domains of functioning in a sample of 1127 patients with schizophrenia. We assessed the symptoms of schizophrenia with the Positive and Negative Syndrome Scale (PANSS) and psychosocial functioning with the mini-ICF-APP (mini-International Classification of Functioning Rating for Limitations of Activities and Participation in Psychological Disorders). The mean PANSS score was 94.28 (27.20), and the mean mini-ICF-APP score was 25.25 (8.96), both of which are indicative of severe symptom load and impairment. We were able to show a strong relationship and overlap between symptoms and disability in patients with schizophrenia. We identified several symptoms related to functional impairment. Deficits in judgment and abstract thinking contribute to impairment through poor adherence (to routines and compliance with rules) and difficulties in planning and organizing. We believe that in schizophrenia, symptoms and their interactions constitute a disorder beyond any single manifestation. Furthermore, we suggest that cognitive testing and cognitive treatment should become part of the standard of care for patients with schizophrenia.

Persons with substance use disorders (SUDs) have a greater risk of suicide compared with the general population. Adjustment Disorder (AD) has been under-researched in SUD populations.

Previous research indicates an association of body dysmorphic disorder (BDD) with suicidal thoughts and behaviours, but has largely relied on small cohorts drawn from specialist clinics.

This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors.

One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS).

Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal methodology to implement and synthesize these techniques.

Applying effort-based decision-making tasks provides insights into specific variables influencing choice behaviors. The current review summarizes the structural and functional neuroanatomy of effort-based decision-making. Across 39 examined studies, the review highlights the ventromedial prefrontal cortex in forming reward-based predictions, the ventral striatum encoding expected subjective values driven by reward size, the dorsal anterior cingulate cortex for monitoring choices to maximize rewards, and specific motor areas preparing for effort expenditure. Neuromodulation techniques, along with shifting environmental and internal states, are promising novel treatment interventions for altering neural alterations underlying decision-making. Our review further articulates the translational promise of this construct into the development, maintenance and treatment of psychiatric conditions, particularly those characterized by reward-, effort- and valuation-related deficits.

ABSTRACT: Purpose: Emergency department (ED) visits for suicidal ideation and self-harm are more prevalent in autistic than non-autistic youth. However, providers are typically offered insufficient guidance for addressing suicide risk in autistic youth, likely impacting confidence and care.

To describe temporal trends in inpatient care use for adult mental disorders in Czechia from 1994 until 2015.

Habits are familiar behaviors triggered by cues, not outcome predictability, and are insensitive to changes in the environment. They are adaptive under many circumstances but can be considered antecedent to compulsions and intrusive thoughts that drive persistent, potentially maladaptive behavior. Whether compulsive-like and habitual behaviors share neural substrates is still being determined. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences. We found that these mice demonstrate habitual response biases and compulsive-like grooming behavior that was reversible by fluoxetine and ketamine. They also suffer dendritic spine attrition on excitatory neurons in the orbitofrontal cortex (OFC). Nevertheless, synaptic melanocortin 4 receptor (MC4R), a factor implicated in compulsive behavior, is preserved, leading to the hypothesis that Mc4r+ OFC neurons may drive aberrant behaviors. Repeated chemogenetic stimulation of Mc4r+ OFC neurons triggered compulsive and not inflexible or habitual response biases in otherwise typical mice. Thus, Mc4r+ neurons within the OFC appear to drive compulsive-like behavior that is dissociable from habitual behavior. Understanding which neuron populations trigger distinct behaviors may advance efforts to mitigate harmful compulsions.

Alzheimer's disease (AD) is characterized by an initial decline in declarative memory, while non-declarative memory processing remains relatively intact. Error-based motor adaptation is traditionally seen as a form of non-declarative memory, but recent findings suggest that it involves both fast, declarative and slow, non-declarative adaptive processes. If the declarative memory system shares resources with the fast process in motor adaptation, it can be hypothesized that the fast, but not the slow, process is disturbed in AD patients. To test this, we studied 20 early-stage AD patients and 21 age-matched controls of both sexes using a reach adaptation paradigm that relies on spontaneous recovery after sequential exposure to opposing force fields. Adaptation was measured using error clamps and expressed as an adaptation index (AI). Although patients with AD showed slightly lower adaptation to the force field than the controls, both groups demonstrated effects of spontaneous recovery. The time course of the AI was fitted by a hierarchical Bayesian two-state model in which each dynamic state is characterized by a retention and learning rate. Compared to controls, the retention rate of the fast process was the only parameter that was significantly different (lower) in the AD patients, confirming that the memory of the declarative, fast process is disturbed by AD. The slow adaptive process was virtually unaffected. Since the slow process learns only weakly from error, our results provide neurocomputational evidence for the clinical practice of errorless learning of everyday tasks in people with dementia. Experimental and modeling studies of motor adaptation suggest a dual-rate process of motor memory formation. We examined force-field motor adaptation in patients diagnosed with impaired declarative memory due to early-stage Alzheimer's disease. Using hierarchical Bayesian modeling, we show that their fast, but not slow process of adaptation is affected, suggesting that the fast process in motor adaptation shares resources with the declarative memory system.

To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth.

COVID-19 necessitated a shift to virtual data collection for many research projects, providing the opportunity for novel approaches to carrying out multi-site clinical trials. Virtual multiteam systems (VMTS) are a type of team structure in which multiple geographically dispersed teams collaborate using technology-mediated communication. The article presents a case study of our use of VMTS, in response to COVID-19, to carry out a multisite randomized hybrid effectiveness-implementation trial of a caregiver-mediated intervention.

This study is original in that it assesses various types of care needs, barriers to care, and factors associated with higher unmet needs among 308 permanent supportive housing (PSH) residents in Quebec (Canada). Data from structured interviews that featured the Perceived Need for Care Questionnaire were collected from 2020 to 2022, controlling for the COVID-19 pandemic period. Eight types of care (e.g., information, counseling) were accounted for. Based on the Behavioral Model for Vulnerable Populations, predisposing, need, and enabling factors associated with higher unmet care needs were assessed using a negative binomial regression model. The study found that 56% of adult PSH residents, even those who had lived in PSH for 5 + years, had unmet care needs. Twice as many unmet needs were due to structural (e.g., care access) rather than motivational barriers. Living in single-site PSH, in healthier neighborhoods, having better quality of life and self-esteem, and being more satisfied with housing and outpatient care were associated with fewer unmet care needs. PSH residents with co-occurring mental disorders (MD) and substance use disorders (SUD), and with moderate or severe psychological distress were likely to have more unmet needs. Better access to care, counseling and integrated treatment for co-occurring MD-SUD might be improved, as well as access to information on user rights, health and available support. Welfare benefits could be increased, with more peer support and meaningful activities, especially in single-site PSH. The quality of the neighborhoods where PSH are located might also be better monitored.

Adverse childhood experiences (ACEs) increase risk for mental illness in women and their children, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role. The impact of ACEs on the HPA axis may be strongest when ACEs occur prepubertally and in those exposed to abuse ACEs.

Suicide is the second leading cause of death in U.S. adolescents and young adults, and generally associated with a psychiatric disorder. Suicidal behavior has a complex etiology and pathogenesis. Moderate heritability suggests genetic causes. Associations between childhood and recent life adversity indicate contributions from epigenetic factors. Genomic contributions to suicide pathogenesis remain largely unknown. This paper is based on a workshop held to design strategies to identify molecular drivers of suicide neurobiology that would be putative new treatment targets. The panel determined that, while bulk tissue studies provide comprehensive information, single-nucleus approaches identifying cell-type specific changes are needed. While single nuclei techniques lack information on cytoplasm, processes, spines, and synapses, spatial multiomic technologies on intact tissue detect cell alterations specific to brain tissue layers and subregions. Because suicide has genetic and environmental drivers, multiomic approaches combining cell-type specific epigenome, transcriptome, and proteome provide a more complete picture of pathogenesis. To determine the direction of effect of suicide risk gene variants on RNA and protein expression, and how these interact with epigenetic marks, single nuclei and spatial multiomics quantitative trait loci maps should be integrated with whole genome sequencing and genome-wide association databases. The workshop concluded with the recommendation for the formation of an international suicide biology consortium that will bring together brain banks and investigators with expertise in cutting-edge omics technologies to delineate the biology of suicide and identify novel potential treatment targets to be tested in cellular and animal models for drug and biomarkers discovery, to guide suicide prevention.

Women have a two-fold increased rate of stress-associated psychiatric disorders such as depression and anxiety, but the mechanisms of this increased susceptibility remain incompletely understood. Female subjects were historically excluded from preclinical studies and clinical trials. Additionally, chronic stress paradigms used to study psychiatric pathology in animal models were developed for use in males. However, recent changes in NIH policy encourage inclusion of female subjects, and considerable work has been performed in recent years to understand biological sex differences that may underlie differences in susceptibility to chronic stress associated psychiatric conditions. We here review the utility as well as current challenges of using the framework of the NIH's research domain criteria as a transdiagnostic approach to study sex differences in rodent models of chronic stress including recent progress in the study of sex differences in the neurobehavioral domains of negative valence, positive valence, cognition, social processes, arousal, and social processes.

Affective temperaments have been shown to robustly affect infertility treatment success. However, identification of possible mediating factors through which they exert their influence is still lacking. A growing number of results suggest that adherence to recommended treatments may be such a mediator, on the one hand, because affective temperaments are known to influence adherence and, on the other hand, because non-adherence negatively influences the treatment outcome. Recommended treatment of infertility involves, beyond medications, dietary and lifestyle changes. The aim of this retrospective cohort study was to evaluate whether adherence to physician-prescribed diet and physical activity recommendations mediates the effect of affective temperaments on infertility treatment outcomes. Among 308 women who underwent infertility treatment in an Assisted Reproduction Center, affective temperaments, adherence to diet, adherence to physical exercise, and infertility treatment success (clinical pregnancy) were assessed besides detailed medical history and demographic parameters. Associations between affective temperaments, adherence to diet and recommended physical activity, and assisted reproduction outcomes were analyzed using generalized linear models and causal mediation analysis. Adherence to physical activity didn't have an effect, but diet adherence increased the odds of infertility treatment success by 130% suggesting its role as a potential mediator. Based on causal mediation analysis, higher depressive and anxious temperament scores were directly associated with 63% and 45% lower odds of achieving clinical pregnancy, respectively, with effects not mediated by diet adherence. Higher irritable temperament scores indirectly decreased the odds of achieving clinical pregnancy by 14%, mediated by diet adherence; while higher cyclothymic temperament scores decreased the odds of achieving clinical pregnancy both directly by 51% and indirectly, mediated by diet adherence by 11%. Our results suggest that diet adherence mediates the mechanism by which irritable and cyclothymic affective temperaments influence IVF treatment success. Since adherence is a modifiable risk factor of infertility treatment success, screening for affective temperaments may help to identify potentially high-risk non-adherent patient groups and offer patient-tailored treatment, which may help increase the chances of a successful pregnancy and live birth in women undergoing IVF treatment.

As organisms age, the activity of the endocannabinoid system in the brain declines, coinciding with increased neuroinflammation and disrupted hypothalamic functions. Notably, cannabinoid type 1 (CB1) receptors are highly expressed in the ventromedial hypothalamic nucleus within the mediobasal hypothalamus, a central area of neuroendocrine regulation. This study investigates whether the CB1 receptor influences age-related changes in a brain region-dependent manner. Therefore, we performed stereotaxic injections of rAAV1/2 expressing Cre recombinase in 2-month-old CB1 male animals to delete the CB1 gene and in CB1-deficient (CB1-STOP) mice to induce its re-expression. The intensity of pro-inflammatory glial activity, gonadotropin-releasing hormone (GnRH) and insulin-like growth factor-1 receptor (IGF-1R) expression was assessed in the hypothalamus of mice at 18-19 months of age. Site-specific CB1 receptor deletion induced pro-inflammatory glial activity and increased hypothalamic Igf1r mRNA expression. Unexpectedly, GnRH levels remained unaltered. Importantly, rescue of the receptor in null mutant animals had the opposite effect: it reduced pro-inflammatory glial activation and decreased Igf1r mRNA expression without affecting GnRH production. Overall, the study highlights the important role of the CB1 receptor in the VMH in reducing age-related inflammation and modulating IGF-1R signaling.

Social anxiety disorder (SAD) and panic disorder (PD) are prevalent anxiety disorders characterized by a complex interplay of genetic and environmental factors. Both disorders share overlapping features and often coexist, despite displaying distinct characteristics. Childhood life adversity, overall stressful life events, and genetic factors contribute to the development of these disorders. DNA methylation, an epigenetic modification, has been implicated in the pathogenesis of these diseases. In this study, we investigated whether whole-genome DNA methylation risk scores (MRSs) for SAD risk, severity of social anxiety, childhood life adversity, PD risk, and overall stressful life events were associated with SAD or PD case‒control status. Preliminary epigenome-wide association studies (EWASs) for SAD risk, severity of social anxiety, and childhood life adversity were conducted in 66 SAD individuals and 77 healthy controls (HCs). Similarly, EWASs for PD risk and overall stressful life events were performed in 182 PD individuals and 81 HCs. MRSs were calculated from these EWASs. MRSs derived from the EWASs of SAD risk and severity of social anxiety were greater in PD patients than in HCs. Additionally, MRSs derived from the EWASs of overall stressful life events, particularly in PD individuals, were lower in SAD individuals than in HCs. In contrast, MRSs for childhood life adversity or PD risk were not significantly associated with PD or SAD case‒control status. These findings highlight the epigenetic features shared in both disorders and the distinctive epigenetic features related to social avoidance in SAD patients, helping to elucidate the epigenetic basis of these disorders.

Latent classes are a useful tool in developmental research, however there are challenges associated with embedding them within a counterfactual mediation model. We develop and test a new method "updated pseudo class draws (uPCD)" to examine the association between a latent class exposure and distal outcome that could easily be extended to allow the use of any counterfactual mediation method. UPCD extends an existing group of methods (based on pseudo class draws) that assume that the true values of the latent class variable are missing, and need to be multiply imputed using class membership probabilities. We simulate data based on the Avon Longitudinal Study of Parents and Children, examine performance for existing techniques to relate a latent class exposure to a distal outcome ("one-step," "bias-adjusted three-step," "modal class assignment," "non-inclusive pseudo class draws," and "inclusive pseudo class draws") and compare bias in parameter estimates and their precision to uPCD when estimating counterfactual mediation effects. We found that uPCD shows minimal bias when estimating counterfactual mediation effects across all levels of entropy. UPCD performs similarly to recommended methods (one-step and bias-adjusted three-step), but provides greater flexibility and scope for incorporating the latent grouping within any commonly-used counterfactual mediation approach.

Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence.

The purpose of this study was to determine the extent to which patient's perspective of symptom improvement, as indexed by the Patient Global Impression of Change (PGIC) survey, is associated with symptom improvement on common measures of neurobehavioral and mental health symptoms following concussion.

This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA). The paper appraises the extant literature on mandatory clozapine haematological monitoring.

Both trio and population designs are popular study designs for identifying risk genetic variants in genome-wide association studies (GWASs). The trio design, as a family-based design, is robust to confounding due to population structure, whereas the population design is often more powerful due to larger sample sizes. Here, we propose KnockoffHybrid, a knockoff-based statistical method for hybrid analysis of both the trio and population designs. KnockoffHybrid provides a unified framework that brings together the advantages of both designs and produces powerful hybrid analysis while controlling the false discovery rate (FDR) in the presence of linkage disequilibrium and population structure. Furthermore, KnockoffHybrid has the flexibility to leverage different types of summary statistics for hybrid analyses, including expression quantitative trait loci (eQTL) and GWAS summary statistics. We demonstrate in simulations that KnockoffHybrid offers power gains over non-hybrid methods for the trio and population designs with the same number of cases while controlling the FDR with complex correlation among variants and population structure among subjects. In hybrid analyses of three trio cohorts for autism spectrum disorders (ASDs) from the Autism Speaks MSSNG, Autism Sequencing Consortium, and Autism Genome Project with GWAS summary statistics from the iPSYCH project and eQTL summary statistics from the MetaBrain project, KnockoffHybrid outperforms conventional methods by replicating several known risk genes for ASDs and identifying additional associations with variants in other genes, including the PRAME family genes involved in axon guidance and which may act as common targets for human speech/language evolution and related disorders.

The extent to which the neural systems underlying semantic processes degrade with advanced age remains unresolved, which motivated the current study of neural activation on functional magnetic resonance imaging (fMRI) during semantic judgments of associated vs. unassociated, semantic vs. rhyme, and abstract vs. rhyme word pairs. Thirty-eight older adults, 55-85 years of age, performed semantic association decision tasks in a mixed event-related block fMRI paradigm involving binary judgments as to whether word pairs were related (i.e., semantically associated). As hypothesized, significantly greater activation was evident during processing of associated (vs. unassociated) word pairs in cortical areas implicated in semantic processing, including the angular gyrus, temporal cortex, and inferior frontal cortex. Cortical areas showed greater activation to unassociated (vs. associated) word pairs, primarily within a large occipital cluster. Greater activation was evident in cortical areas when response to semantic vs. phonemic word pairs. Contrasting activation during abstract vs. concrete semantic processing revealed areas of co-activation to both semantic classes, and areas that had greater response to either abstract or concrete word pairs. Neural activation across conditions did not vary as a function of greater age, indicating only minimal age-associated perturbation in neural activation during semantic processing. Therefore, the response of the semantic hubs, semantic control, and secondary association areas appear to be largely preserved with advanced age among older adults exhibiting successful cognitive aging. These findings may provide a useful clinical contrast if compared to activation among adults experiencing cognitive decline due Alzheimer's, frontal-temporal dementia, and other neurodegenerative diseases.

To examine patient and provider perspectives on privacy and security considerations in telemedicine during the COVID-19 pandemic.

Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity.

Dog ownership has been associated with several complex traits and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through meta-analysis of 31,566 Swedish twins in five discovery cohorts and additional 65,986 European-ancestry individuals in three replication cohorts from Sweden, Norway, and the UK. Association test with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified two suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphisms-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002, 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence the dog ownership among European-ancestry individuals.

Cannabis and nicotine/tobacco products (NTP) are commonly co-used in adolescence and young adulthood; however, limited research has been done on predictive health behaviors to co-use. The current study is a preliminary investigation into the relationships of modifiable health behaviors on cannabis and NTP co-use in adolescents and young adults.

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

Foundational mathematical abilities, acquired in early childhood, are essential for success in our technology-driven society. Yet, the neurobiological mechanisms underlying individual differences in children's mathematical abilities and learning outcomes remain largely unexplored. Leveraging one of the largest multicohort datasets from children at a pivotal stage of knowledge acquisition, we first establish a replicable mathematical ability-related imaging phenotype (MAIP). We then show that brain gene expression profiles enriched for candidate math ability-related genes, neuronal signaling, synaptic transmission, and voltage-gated potassium channel activity contributed to the MAIP. Furthermore, the similarity between MAIP gene expression signatures and brain structure, acquired before intervention, predicted learning outcomes in two independent math tutoring cohorts. These findings advance our knowledge of the interplay between neuroanatomical, transcriptomic, and molecular mechanisms underlying mathematical ability and reveal predictive biomarkers of learning. Our findings have implications for the development of personalized education and interventions.

Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC.

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.

Impaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear.

Increasing interest has centered on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioral therapy (bCBT) intervention for depression.

Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers.

Presentation to the emergency department (ED) with self-harm provides an important opportunity for intervention.

Lesbian, gay, bisexual, transgender, queer, intersex, aromantic and asexual (LGBTQIA+) communities in the United States experience higher rates of alcohol use than the general population. While experiencing intimate partner violence (IPV) is thought to lead to increased alcohol use in LGBTQIA+ people, little research has investigated the temporal relationship between IPV and alcohol use in this population.

Therapist anxious distress when delivering child mental health treatment has been understudied as a factor that contributes to the underuse of some evidence-based interventions (EBIs), such as time-out for children with disruptive behaviors. This study investigated therapist anxious avoidance of time-out using a three-part, vignette-based survey design. Therapists (n = 198) read a vignette of an in-session time-out and reported on their personal anxious distress and likelihood of discontinuing the implementation of time-out. Therapists also provided open-ended descriptions of challenges to delivering time-out. Therapists reported moderate anxious distress at time points 1 and 2 and lower anxious distress at time 3 when the time-out had resolved. Most therapists endorsed some avoidance of time-out. Binomial logistic regression analyses indicated that increased anxious distress corresponded with an increased probability of avoiding time-out delivery in the future. Qualitative reports expanded on challenges to implementing time-out. Findings suggest the importance of addressing therapist anxious distress when implementing children's mental health treatments.

To determine whether sub-clinical levels of drinking may contribute to suicide risk, and whether the risk differs by sex, we aimed to evaluate the relationship between average amount of alcohol consumed per day and death by suicide.

The unmet need for mental health care is a global concern. There is a lack of cross-cultural studies examining adolescent help-seeking behavior from both formal and informal sources, including both high-and lower-income countries. This study investigates mental health help-seeking behavior in eight Asian and European countries. Data from 13,184 adolescents aged 13-15 (51% girls) was analysed using mixed-effects logistic regression with school-wise random intercepts to compare countries and genders. Although a significant proportion of adolescents considered getting or sought informal help, formal help-seeking remained exceptionally low, especially in middle-income countries (< 1%), while it ranged from 2 to 7% in high-income countries. Among adolescents with high emotional and behavioral problems (scoring above the 90th percentile on the Strengths and Difficulties Questionnaire), 1-2% of those in middle-income countries and 6-25% of those in high-income countries sought formal help. Girls generally seek more help than boys. The study shows the most adolescents do not receive formal help for mental health problems. The unmet need gap is enormous, especially in lower-income countries. Informal sources of support, including relatives, peers, and teachers, play a crucial role, especially in lower-income countries.

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.

Postpartum depression (PPD) is a psychiatric condition affecting women post-childbirth. Medication combined with psychotherapy, is the current protocol for its treatment. A meta-analysis was conducted using RevMan 5.4 to explore the efficacy and safety of peri-partum administration of esketamine for preventing PPD. After searching several databases to retrieve the relevant RCTs, seven were included in this analysis, with dichotomous data presented as risk ratio and continuous data as mean difference. The study found a lower incidence of PPD in the esketamine group compared to the control group (RR= 0.37), with significant difference in EPDS scores between the two groups (MD= -1.23) in the first week postpartum. The esketamine group reported a lower prevalence of PPD 4-6 weeks postpartum (RR= 0.48), and no significant difference in EPDS scores after 4 weeks postpartum (MD = -0.10). The esketamine group had a significantly higher incidence of hallucination (RR= 13.85). Other adverse effects, such as dizziness (RR= 4.09), nausea (RR= 0.88), vomiting (RR=0.74), headache (RR=1.52), nightmares (RR=1.22), pruritus (RR=0.29), and drowsiness (RR=1.57) did not show significant differences between the two groups. The study found that esketamine, with manageable side effects, reduces the prevalence of post-partum depression (PPD) after one week as well as after four to six weeks. However, the findings are limited by the limited number of available RCTs, and future research should determine the ideal dosage, the most effective method of administration and the long-term safety profile of esketamine so that it may be considered as an adjunct therapy or a potential sole treatment option.

Cocaine Use Disorder (CUD) is an important health issue, associated with structural brain abnormalities. However, the impact of the route of administration and their predictive value for relapse remain unknown.

To examine the differences in mental health problems by sexual orientation and gender identity in first-year university students in Chile during the pandemic.

Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke.

Since the onset of the COVID-19 pandemic, most research has focused on the management of the acute symptoms of the disease. Yet some people tend to experience symptoms beyond the acute phase, defined as Post-COVID-19 Condition (PCC). This study aims to assess the impact of COVID-19 and PCC on anxiety and depression.

Serotonin (5-HT) syndrome (SS) consists of changes in mental status as well as autonomic and neuromuscular changes. Though not well understood, serotonergic pathways have been implicated in the mechanism of action of electroconvulsive therapy (ECT). Ketamine has been used as an induction agent in ECT and as therapy for treatment-resistant depression. Utilizing a case report and literature review, we explored the underlying serotonergic mechanisms of ECT and ketamine by which a syndrome of serotonin toxicity may be precipitated. We describe the case of a 72-year-old woman who developed recurrent SS on 2 occasions in similar circumstances involving the administration of ketamine for ECT. In our literature review, we found 5 cases in which SS was associated with ECT and 1 case linking ketamine to SS. There is emerging evidence that the mechanism of ECT involves 5-HT1A and 5-HT2A receptors, the same receptors that are involved in SS. ECT can transiently increase the permeability of the blood-brain barrier, leading to increased levels of antidepressants in the brain. ECT can, therefore, enhance 5-HT transmission and the likelihood of SS in the presence of serotonergic agents. The effect of ketamine on 5-HT transmission is mediated by the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Ketamine increases α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid activity in the medial prefrontal cortex, which leads to downstream 5-HT release through glutamate. Through this mechanism, ketamine can increase 5-HT transmission, leading to SS. To our knowledge, this is the only case report of recurrent SS with concurrent use of ECT and ketamine. As ketamine is frequently used in ECT and many patients undergoing ECT are on serotonergic medications, it is important to recognize ketamine as a potential risk factor for SS. There is no evidence for added efficacy when combining ECT and ketamine. Thus, one should proceed with caution when combining these treatments. The burgeoning use of ketamine in ambulatory settings makes it necessary to elucidate the risks, which we discuss further. More research is needed into the mechanisms of ketamine and ECT, specifically how the combination of these treatments influence 5-HT levels.

This study aimed to develop a patient-centered survivorship care plan (SCP) for US military Veteran bladder cancer (BC) survivors in accordance with the National Academy of Medicine recommendation that survivors receive an SCP at treatment completion. BC, which differentially impacts older men, is a costly and highly recurrent cancer associated with invasive procedures and long-term surveillance. Veteran BC survivors may face challenges navigating the patient-to-survivor transition due to their age and comorbidities.

Interpersonal hypersensitivity (IHS) is a core organizing concept of Good Psychiatric Management, a generalist treatment for borderline personality disorder (BPD) that relies on basic tools most clinicians already employ yet is informed by an organized and evidence-based framework, developed for dissemination in various mental health care settings. We work in an inpatient psychiatric unit that specializes in the management of suicidal crises at the University Hospitals of Geneva, Switzerland. Because we see numerous patients with previously undiagnosed BPD during their first hospitalization, we have developed techniques and instruments to promote efficient and easy-to-implement psychoeducation. In this article, we propose a practical and user-friendly measure of IHS that is well-suited for use by multidisciplinary inpatient staff or outpatient nursing-based staff, the IHS Ruler, which is based on a visual analog scale. It is a pragmatic tool for preliminary psychoeducation for patients with BPD and their caregivers. Its ease of use and structured way of presenting the inner experience of these patients in relation to their current interpersonal environment allows caregivers to establish a framework for internal reflection and sharing, discuss the causes of current transactions, and illuminate larger patterns in the causes of the patient's crises. Ultimately, this process can help patients and the clinical staff supporting them anticipate future problems.

Metabolites disruptions in tryptophan (TRP) and kynurenine pathway (KP) are believed to disturb neurotransmitter homeostasis and contribute to depressive symptoms. This study aims to investigate serum levels of KP metabolites in adolescent major depressive disorder (AMDD), and examine their relationship with depression severities. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze serum levels of TRP, kynurenic acid (KYNA), kynurenine (KYN), and 3-hydroxy-kynurenine (3-HK) in 143 AMDD participants and 98 healthy controls (HC). Clinical data, including Children's Depression Inventory (CDI) scores, were collected and analyzed using statistical methods, such as ANOVA, logistic regression, Receiver operating characteristic curve analysis and a significance level of p < 0.05 was used for all analyses. AMDD showed significantly decreased serum levels of KYNA (-25.5%), KYN (-14.2%), TRP (-11.0%) and the KYNA/KYN ratio (-11.9%) compared to HC (p < 0.01). Conversely, significant increases were observed in 3-HK levels (+50.4%), the 3-HK/KYNA ratio (+104.3%) and the 3-HK/KYN ratio (+93.0%) (p < 0.01). Logistic regression analysis identified increased level of 3-HK as a contributing factor to AMDD, while increased level of KYNA acted as a protective factor against AMDD. The 3-HK/KYNA ratio demonstrated an area under the curve (AUC) of 0.952. This study didn't explore AMDD's inflammatory status and its metabolites relationship explicitly. These findings indicate that metabolites of TRP and KP may play a crucial role in the pathogenesis of AMDD, emphasizing the potential of the 3-HK/KYNA ratio as a laboratory biomarker for early detection and diagnosis of AMDD.

Health care workers experience high rates of burnout and psychiatric distress. A large health care system in the southwest United States developed a comprehensive mental health service model for employees. Services offered range from traditional benefits (eg, Employee Assistance Program), resiliency and well-being initiatives, and innovative technology solutions, to access to peer support services for professional practice issues. The latest innovation in services is a free, self-insured outpatient mental health clinic designed exclusively for health care workers and their dependents. In this article, the authors describe the development of expanded mental health programming for health care workers and discuss how this unique service model proactively reduces common barriers to the receipt of high-quality care. This approach to caring for the workforce may serve as a model for other health care organizations across the United States. By providing mental health support to employees, health care organizations are mitigating the risk of burnout and related consequences to the system.

CDKL5 deficiency disorder (CDD), an epileptic encephalopathy for which novel therapeutics are under development, lacks valid and reliable measures of therapeutic efficacy. We aimed to elucidate the neurophysiological and brain structural features of CDD patients and identify objective indicators reflecting the clinical severity.

Drug addiction therapies commonly fail because continued drug use promotes the release of excessive and pleasurable dopamine levels. Because the connection between pleasure and drug use becomes hard-wired in the nucleus accumbens (NAc), which interfaces motivation, effective therapies need to modulate this mesolimbic reward system. Here, we report that mice with knockdown of the cation channel TRPA1 (transient receptor potential ankyrin 1) were resistant to the drug-seeking behavior and reward effects of cocaine compared to their wildtype litter mates. In our study, we demonstrate that TRPA1 inhibition in the NAc reduces cocaine activity and dopamine release, and conversely, that TRPA1 is critical for cocaine-induced synaptic strength in dopamine receptor 1-expressing medium spiny neurons. Taken together, our data support that cocaine-induced reward-related behavior and synaptic release of dopamine in the NAc are controlled by TRPA1 and suggest that TRPA1 has therapeutic potential as a target for drug misuse therapies.

Catatonia is a complex syndrome with unique cognitive, psychomotor, and mood features. Mannerisms and stereotypies are catatonic signs that have been extensively observed and described in the literature, mostly in the context of movements or motor acts. Stereotypies are commonly described as repetitive psychomotor or verbal acts with the abnormality not inherent in the act but in its frequency. Mannerisms, like stereotypies, are repetitive psychomotor or verbal acts, but they are fundamentally odd in nature. Recently, several reports have described these phenomena in the context of complex behaviors, such as eating and drinking. Identification and appreciation of personal and cultural norms, in addition to a careful analysis of behavioral processes and actions, are important tools for clinicians to identify these potentially elusive and often missed patterns of behavior in patients with catatonia. We present the case of a 30-year-old male with a psychiatric history of treatment-resistant, recurrent major depressive disorder with psychotic features who presented to the inpatient psychiatric unit with signs of catatonia, including repeated, purposeless eating. The patient's chart was reviewed, and a literature review was conducted using PubMed with the keywords catatonia, stereotypies, mannerisms, and hyperphagia. The patient, who was diagnosed with catatonia and expressed hyperphagia as a stereotypy, responded to lorazepam. This case shows that hyperphagia may present as a stereotypy in patients with catatonia.

Chronic stress lead to dysregulation of metabolic hormones, creating risk for obesity and type 2 diabetes. Based on previous work suggesting the potential for sexual activity to relieve psychological stress and reduce stress-related neuroendocrine activity, the present research explored sexual activity as a protective factor. We focused on chronic stress in the form of caregiving stress, comparing premenopausal mothers of a child with an autism spectrum disorder vs. a neurotypical child, in relation to metabolic hormones - insulin (and insulin resistance as assessed by HOMA), leptin, and ghrelin. Then, we explored the moderating role of sexual activity. Our results showed that high-stress mothers showed higher levels of insulin, insulin resistance, and lower levels of ghrelin compared to low-stress mothers. However, sexual activity modulated these associations such that among mothers who were sexually active (as coded from their daily diaries), no significant differences in these outcomes were observed between groups. This buffering effect of sexual activity was distinguishable from the buffering effect of physical activity and independent of global relationship satisfaction. Together, our findings provide novel evidence supporting the potential protective effects of sexual activity from chronic stress-related metabolic disease risk.

Prescriptions for atypical antipsychotics in children and adolescents are increasing globally. However, a precise understanding of the clinical variables and evidence that prescribers consider before using these agents is lacking. While empirical literature on the long-term safety and efficacy of these medications is available, the literature concerning their use in these younger age groups is relatively sparse. In this study, we examined the current prescribing patterns of medical professionals employed by a public health service in Australia.

There are individual effects of alexithymia, childhood maltreatment, impulsivity, and some biological markers on aggression and psychological distress in schizophrenia. However, the combined effects of these psychological and biological markers have not yet been fully studied. This study therefore aimed to investigate the influence of these psychological and biological markers on aggression and psychological distress (e.g., depression and anxiety) in inpatients with schizophrenia (n = 355). Participants completed self-report and clinician-rated scales, and blood samples were collected. There were no significant differences between patients with and without alexithymia regarding biological markers. Patients with childhood maltreatment exhibited higher levels of free triiodothyronine (FT3) and C-reactive protein (CRP), as well as lower total cholesterol (TC) levels, compared to non-traumatized individuals. Aggression was positively predicted by psychological distress, alexithymia, childhood maltreatment, impulsivity, CRP, and FT3, and negatively by TC and low-density lipoprotein cholesterol. Negative symptoms, childhood maltreatment, alexithymia, aggression, and CRP positively, and high-density lipoprotein cholesterol negatively emerged as predictors of psychological distress. The study highlights the connections between childhood maltreatment, alexithymia, impulsivity, and potentially related biological dysregulation in explaining aggression and negative mood states as a bio-psychological model of aggression and mood in schizophrenia.

This column is the first of a 3-part series illustrating the importance of medical knowledge, including clinical pharmacology, in a forensic context. This first case involved an 18-year-old high school student who suffered an anoxic brain injury and remained in a state of permanent decorticate posture, unresponsive except for grunts and primitive movements until he died several years later. Our investigation began by ruling out plausible causes that were suggested by the defense in the malpractice suit. Once those possibilities were eliminated, the focus was on what accounted for the damage to the patient using general medical knowledge and clinical pharmacology. The 4 Ds of forensic psychiatry (duty, damages, dereliction, and direct cause) are the 4 elements that the plaintiff is required to prove in civil court to prevail in a malpractice suit and are applied to this case with a special focus on dereliction and direct cause. This catastrophic outcome was due to 3 factors. First, the patient had physiologically significant dehydration to the point that he had developed a reflex tachycardia to maintain his blood pressure. Second, the patient had been switched from extended to immediate-release quetiapine, resulting in a doubling of the peak concentration of the drug, which produced higher occupancy of alpha-1 adrenergic, histamine-1, and dopamine-2 receptors, causing a further drop in his blood pressure as well as increased sedation and impairment of his gag reflex. These effects occurred quickly because of the faster absorption of the IR formulation of the drug. Third, the patient had gone to sleep in a reclining chair so that his brain was above his heart and his lower extremities were below his heart, resulting in an increased "steal" of cardiac output going to his brain. These 3 factors together led the patient to aspirate and suffer a hypoxic brain injury after an episode of vomitus. This column explains the process by which the cause of this sad outcome was determined, how it was related to a dereliction of duty to the patient, and how other proposed causes were ruled out.

Epilepsy, a chronic neurological condition characterized by unpredictable seizures, poses considerable challenges, including disability, stigma, and increased mortality. Psychiatric comorbidities are prevalent in 20-30% of epilepsy patients, notably mood or anxiety disorders, psychotic symptoms, and personality disorders. Trauma and childhood adversities are pivotal risk factors for psychopathology, yet the link between Post-Traumatic Stress Disorder (PTSD) and epilepsy remains underexplored. This meta-analysis is aimed to establish updated estimates of PTSD prevalence among individuals with epilepsy. Fifteen studies, comprising 996 epilepsy patients, were included. The overall pooled prevalence of PTSD in epilepsy patients was 18%. Notably, patients with epilepsy exhibited a three-fold increased risk of developing PTSD compared to the general population. Subgroup analysis revealed a higher PTSD prevalence in uncontrolled studies (25%) compared to controlled studies (14%). Additionally, patients with Psychogenic Non-Epileptic Seizures (PNES) demonstrated higher PTSD prevalence than epilepsy patients, with a threefold higher risk in healthy controls compared to PNES controls. While gender prevalence did not significantly affect PTSD occurrence, drug resistant epilepsy did not correlate with PTSD prevalence. Moreover, age of epilepsy onset showed no significant correlation with PTSD prevalence. This meta-analysis underscores the substantial burden of PTSD among epilepsy patients, potentially attributable to the traumatic nature of seizures and the chronic stigma associated with epilepsy. Improved recognition and management of psychiatric conditions, particularly PTSD, are crucial in epilepsy care pathways to enhance patients' quality of life. Further research and comprehensive diagnostic tools are imperative to better understand and address the prevalence of PTSD in epilepsy patients.

The shortage and distribution of nurses affect healthcare access in aging societies. Limited research has explored the nursing workforce in clinics, which is vital for healthcare delivery. This study aimed to investigate the shortage and distribution of nurses in clinics in Taiwan, considering geographical, institutional, and specialty variations.

This paper analyzed the role of depression as a mediator in the association between bullying, cyberbullying, and suicide risk in adolescent females. A total of 751 Colombian adolescent females (M= 13.71, SD=1.897), who were administered the Plutchik Suicide Risk Scale, the Beck Depression Inventory, the European Bullying Intervention Project Questionnaire and Cyberbullying. Bullying victimization and aggression and cyberbullying victimization were found to contribute statistically significant effects that explaining 22 % of the variance in depression. The variables of victimization in bullying and cyberbullying and depression explained 64 % of the variance in suicidal risk, and depression mediated the association between victim and aggressor roles in bullying and cyberbullying in predicting suicidal risk, whose total direct and indirect effects are statistically significant. The findings support the role of depression as a mediating variable between bullying and cyberbullying and suicidal risk in female adolescents and highlight the importance of focusing prevention and intervention efforts on risk factors for depression and suicidal behavior in cases of bullying and cyberbullying.

The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden in patients with schizophrenia. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.

As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when combined with smartphone apps, enable secure text messaging. As an adjunct to such internet-based CBT (ICBT) approaches, text messaging has been associated with increased adherence and therapeutic alliance.

Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status.

There has been a longstanding effort to integrate behavioral health and HIV care for people with comorbid HIV and behavioral health needs, including those with severe mental illness (SMI). As this population frequents both behavioral health and HIV care settings, they were likely to experience new obstacles to the quality and availability of care during the COVID-19 pandemic. This study aims to describe how clinics for HIV services or behavioral healthcare-as well as co-located sites providing both-sought to rapidly shift protocols to maintain a standard of patient care for people with comorbid HIV and SMI while adapting to the unprecedented circumstances of the pandemic.

The current study aimed to investigate the impact of oxytocin on emotion recognition, trust, body image, affect, and anxiety and whether eating disorder (ED) symptoms moderated any of these relationships.

The increased prevalence of visual impairment among diabetes patients has become a major global public health problem. Although numerous primary studies have been conducted to determine the prevalence of visual impairment and its associated factors among diabetes patients in Ethiopia, these studies presented inconsistent findings. Therefore, this review aimed to determine the pooled prevalence of visual impairment and identify associated factors among diabetes patients.

Young women who are not in education, employment, or training (NEET) experience poorer health and social outcomes compared to non-NEET young women and to NEET young men, especially in deprived areas with intersecting inequalities. The evidence on effective public health approaches is scarce. Interventions that target hope, which NEET young women notably lack, offer a promising theory-driven and intuitive means to prevent mental health problems and improve social outcomes. Hope can be defined as a goal-focused mindset comprising self-agency (motivation and self-belief) and pathways (identifying routes to achieving goals). Hope is implicated in a variety of evidence-based psychosocial interventions for young people, but is not directly targeted by existing prevention programmes for NEET populations. The current study used a phased qualitative research design and participatory methods to model a hope-focused intervention for NEET young women. Phase 1 investigated population needs and intervention parameters through semi-structured interviews with 28 key informants living or working in disadvantaged coastal communities in South-East England. The sample comprised eight NEET young women, four family members, and 16 practitioners from relevant support organisations. Phase 2 refined intervention parameters and outcomes through co-design sessions with four NEET young women, followed by a theory of change workshop with 10 practitioners. The resulting intervention model is articulated as a mentor-supported, in-person psychosocial intervention that builds hope by enhancing positive sense of self and time spent in meaningful activities, before explicitly teaching the skills needed to identify, set, and pursue personally meaningful goals.