Identification of common spontaneous brain activity alterations across psychiatric disorders

Many mental illnesses share behavioral, genetic and imaging features. However, common resting-state functional abnormalities across diagnoses remain unclear. This study aimed to investigate shared spontaneous functional alterations in neural circuitry across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data. A voxel-wise meta-analysis was conducted to investigate amplitude of low-frequency fluctuation (ALFF) differences between patients with major psychiatric disorders (including bipolar disorders, major depressive disorders, schizophrenia, obsessive-compulsive disorder, posttraumatic stress disorder, and anxiety disorders) and healthy controls (HCs). Further analyses explored transcriptional profiles, neurotransmitter systems, and cognitive functions associated with ALFF alterations to uncover potential molecular mechanisms underlying spontaneous neural activity signatures. A total of 254 experiments from 210 ALFF studies (10456 patients; 11014 HCs) were included. We found increased ALFF mainly in the bilateral inferior frontal gyrus (IFG), insula, anterior cingulate gyrus/medial prefrontal cortex (ACC/mPFC), amygdala, striatum, right orbitofrontal cortex, and decreased ALFF in the right precentral gyrus and postcentral gyrus in patients across major psychiatric disorders. The abnormal pattern of ALFF across psychiatric disorders was spatially associated with transmembrane transport and ion channel, and dopaminergic, serotonergic, noradrenaline, opioid, and acetylcholine neurotransmission, as well as cognitive terms mainly involved rewards, mood, and fear. Common alteration of spontaneous brain activity across major psychiatric disorders are underpinned by disrupted gene expression, neurotransmitter activity, and cognitive functions. These findings highlight transdiagnostic neurobehavioral phenotypes that extend beyond discrete diagnostic categories, offering insights into shared pathophysiological mechanisms in psychiatric disorders.