Formal thought disorder in unipolar depression: Prevalence and functional brain correlates from a multimodal MRI study

Formal thought disorder (FTD), involving disruptions in language and thought, is commonly linked to schizophrenia but is also prevalent and debilitating in Major Depressive Disorder (MDD). Despite its clinical relevance, few studies have comprehensively examined FTD in MDD using operationalized rating scales and MR neuroimaging. FTD was assessed in 379 acute MDD patients using the Scales for the Assessment of Positive and Negative Symptoms. Whole-brain MRI was used to examine associations between FTD severity and gray and white matter structures, as well as resting-state functional connectivity (seed-to-voxel analysis) with CAT12, FSL, and CONN toolboxes. Overall, 37.5% of patients presented with FTD symptoms (29% negative; 14.5% positive; 6.1% both). Negative FTD was more common and driven by increased response latency and poverty of speech. FTD severity correlated negatively with gray matter volume of the right posterior cingulate gyrus and with white matter integrity of the right corticospinal tract. Functional resting state analyses showed FTD severity positively correlated with connectivity between the amygdala-hippocampus complex and the right pre- and postcentral gyri. Positive FTD was correlated with decreased connectivity between the orbitofrontal cortex and left occipital, temporal, and subgenual cingulate regions. Negative FTD was correlated with increased connectivity between the inferior frontal and middle frontal gyri. Neural correlates were unrelated to depression severity, illness duration, or psychotropic medication. This study highlights the prevalence and importance of FTD in acute MDD with structural and functional brain correlates being linked to language-related areas previously reported in schizophrenia.