Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing.

A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle–Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results.

Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact.

Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.

The differential diagnosis of psychiatric disorders is relatively challenging for several reasons. In this context, we believe that task-based magnetic resonance imaging (MRI) can serve as a tool for differential diagnosis. The aim of this study was to explore the commonalities in brain activities among individuals with psychiatric disorders and to identify the key brain regions that can distinguish between these disorders.

The PubMed, MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO, and Google Scholar databases were searched for whole-brain functional MRI studies that compared psychiatric patients and normal controls. The psychiatric disorders included schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Studies using go–nogo paradigms were selected, we then conducted activation likelihood estimation (ALE) meta-analysis, factor analysis, and regression analysis on these studies subsequently.

A total of 152 studies (108 with patients) were selected and a consistent pattern was found, that is, decreased activities in the same brain regions across six disorders. Factor analysis clustered six disorders into three pairs: SCZ and ASD, MDD and BD, and ADHD and BD. Furthermore, the heterogeneity of SCZ and ASD was located in the left and right thalamus; and the heterogeneity of MDD and BD was located in the thalamus, insula, and superior frontal gyrus.

The results can lead to a new classification method for psychiatric disorders, benefit the differential diagnosis at an early stage, and help to understand the biobasis of psychiatric disorders.