Psychopathological Syndromes Across Affective and Psychotic Disorders Correlate With Gray Matter Volumes

Abstract

Introduction More than a century of research on the neurobiological underpinnings of major psychiatric disorders (major depressive disorder [MDD], bipolar disorder [BD], schizophrenia [SZ], and schizoaffective disorder [SZA]) has been unable to identify diagnostic markers. An alternative approach is to study dimensional psychopathological syndromes that cut across categorical diagnoses. The aim of the current study was to identify gray matter volume (GMV) correlates of transdiagnostic symptom dimensions. Methods We tested the association of 5 psychopathological factors with GMV using multiple regression models in a sample of N = 1069 patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MDD (n = 818), BD (n = 132), and SZ/SZA (n = 119). T1-weighted brain images were acquired with 3-Tesla magnetic resonance imaging and preprocessed with CAT12. Interactions analyses (diagnosis × psychopathological factor) were performed to test whether local GMV associations were driven by DSM-IV diagnosis. We further tested syndrome specific regions of interest (ROIs). Results Whole brain analysis showed a significant negative association of the positive formal thought disorder factor with GMV in the right middle frontal gyrus, the paranoid-hallucinatory syndrome in the right fusiform, and the left middle frontal gyri. ROI analyses further showed additional negative associations, including the negative syndrome with bilateral frontal opercula, positive formal thought disorder with the left amygdala-hippocampus complex, and the paranoid-hallucinatory syndrome with the left angular gyrus. None of the GMV associations interacted with DSM-IV diagnosis. Conclusions We found associations between psychopathological syndromes and regional GMV independent of diagnosis. Our findings open a new avenue for neurobiological research across disorders, using syndrome-based approaches rather than categorical diagnoses.

Identifying Changes of Brain Regional Homogeneity and Cingulo-Opercular Network Connectivity in First-Episode, Drug-Naïve Depressive Patients With Suicidal Ideation

“…Our findings are consistent with previous studies that demonstrated that MDD is a degenerative mental illness dominated by disrupted ReHo ( Späti et al, 2015 ) and GMV atrophy ( Schmaal et al, 2020 ; Zhang et al, 2020 ; Stein et al, 2021 ). By using ReHo and SCN analysis ( Lerch et al, 2006 ; Alexander-Bloch et al, 2013 ), we found that compared with healthy people, MDD patients had functional and structural defects in the CON and showed disrupted ReHo and GMV atrophy in the ACC.L and abnormal structural connectivity of the ACC.L–SFG.L ( Boes et al, 2018 ; Crowell et al, 2019 ; Cole et al, 2020 ; Rappaport et al, 2020 ).…”

Reduced Gray Matter Volume in Orbitofrontal Cortex Across Schizophrenia, Major Depressive Disorder, and Bipolar Disorder: A Comparative Imaging Study

“…A recent study found the associations between psychopathological syndromes and regional GMV across affective and psychotic disorders. Especially found positive formal thought disorder was correlated with the GMV of bilateral OFC (Stein et al, 2021). There was also a followup study in SZ that showed the important role of OFC in SZ.…”

Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders

“…Given that mental disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorder (SSD) exhibit high overlap in many domains (e.g., psychopathology, genetics, neuropsychology, regional brain volume alterations), the research question has emerged whether they are characterized by more communalities rather than differences [1][2][3][4][5][6]. In the domain of brain morphometry, previous work has attempted, but failed, to find a unique neural correlate (i.e., biomarker) specific to one such disorder [2].…”

“…Since there is first evidence for significant GMV overlap across affective and psychotic disorders [2], it raises the question whether there are common, underlying factors that are responsible for these transdiagnostic findings. From previous structural brain imaging research, we know that the following four domains, among others, have been associated with brain structure in patients and healthy controls (HC): (1) early risk and protective factors: childhood maltreatment, urbanicity, familial risk, gestational age, birth weight, and parental bonding [12,[17][18][19][20], (2) current risk and protective factors: life events, resilience, and social support [21][22][23], (3) psychopathology: global functioning, positive, negative, depressive, and manic symptoms [3,24], and (4) neuropsychological performance [25]. To the best of our knowledge, it has not been investigated whether transdiagnostic morphometric alterations are related to transdiagnostic phenotypical or risk patterns.…”