The psychopathology of mood disorders: implications for identifying neurocognitive intervention targets

J Affect Disord. 2025 May 16:119423. doi: 10.1016/j.jad.2025.119423. Online ahead of print.

ABSTRACT

BACKGROUND: Neurofeedback and neuromodulation treatments are of increasing clinical interest, but their neurocognitive targets are poorly understood.

METHODS: In this review, we will use Jaspers’ phenomenological psychopathology combined with modern network analysis to identify neurocognitive treatment targets by focussing on distinctive and necessary symptoms of mood disorders as well as their subsyndromal and prognostic variations.

RESULTS: We discuss the early descriptions of Kraepelin’s mixed affective states and suggest a model of four mood states (depressed, anxious, irritable, and elated) and their dynamic evolution and mixing. Blame and praise internalisation and externalisation biases are proposed as key mechanisms underpinning mood states, together with approach/withdrawal-related action tendencies. Whilst self-worth and interest emerge as the most distinctive symptom dimensions, that are necessary for bipolar and recurrent unipolar depressive disorders, we also discuss anxiety as a potential primary symptom in a subgroup of chronic depression. Based on a neuroanatomical model of the conceptual self, anterior temporal and subgenual networks and their importance for self-blame and worthlessness, as well as the hypothesised role of septo-hypothalamic networks for affiliative interest are discussed. The latter is distinguished from ventral striatal networks as relevant for more general approach-related action tendencies and hedonic interest (anticipatory anhedonia). Finally, recent target validation from early-stage fMRI neurofeedback trials are reviewed.

LIMITATIONS: It was not feasible to employ a systematic review approach.

CONCLUSIONS: Neurofeedback studies are not only of interest as new treatments, but also for enhancing our pathophysiological understanding and could gain clinical impact with ongoing advances in scalable neurotechnologies.

PMID:40383302 | DOI:10.1016/j.jad.2025.119423