Structural connectivity associated with familial risk for mental illness: A meta‐analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders

Abstract

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable conditions with overlapping genetic liability. Transdiagnostic and disorderspecific brain changes associated with familial risk for developing these disorders remain poorly understood. We carried out a meta-analysis of diffusion tensor imaging (DTI) studies to investigate white matter microstructure abnormalities in relatives that might correspond to shared and discrete biomarkers of familial risk for psychotic or mood disorders. A systematic search of PubMed and Embase was performed to identify DTI studies in relatives of SCZ, BD, and MDD patients. Seed-based d Mapping software was used to investigate global differences in fractional anisotropy (FA) between overall and disorder-specific relatives and healthy controls (HC). Our search identified 25 studies that met full inclusion criteria. A total of 1,144 relatives and 1,238 HC were included in the meta-analysis. The overall relatives exhibited decreased FA in the genu and splenium of corpus callosum (CC) compared with HC. This finding was found highly replicable in jack-knife analysis and subgroup analyses. In disorder-specific analysis, compared to HC, relatives of SCZ patients exhibited the same changes while those of BD showed reduced FA in the left inferior longitudinal fasciculus (ILF). The present study showed decreased FA in the genu and splenium of CC in relatives of SCZ, BD, and MDD patients, which might represent a shared familial vulnerability marker of severe mental illness. The white matter abnormalities in the left ILF might represent a specific familial risk for bipolar disorder.

Systematic Review: White Matter Microstructural Organization in Adolescents With Depression

“… 57 A meta-analysis of white matter correlates of relatives of patients with severe mental disorders (MDD, bipolar disorder, and/or schizophrenia) showed decreased FA in the genu and splenium of the corpus callosum in relatives of patients as compared to controls, although a specific effect size was not reported. 56 Lim et al 54 concluded, in a meta-analysis, that history of childhood maltreatment was associated with reduced FA in the anterior corpus callosum, along with the fornix, anterior thalamic radiation, optic radiations, the inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus. Notably, these regions are similarly implicated in MDD in our current systematic review.…”

Autism is Associated within vivoChanges in Gray Matter Neurite Architecture

“…Diffusion weighted imaging (DWI) has consistently identified measures indicative of decreased fiber integrity throughout the brain of those with ASD (Conti et al, 2017; Groen, 2011; Libero et al, 2016). However, decreased fiber integrity is associated with many other neurodevelopmental and psychiatric diagnoses and may simply be a non-specific indicator of global perturbation (Benedetti et al, 2014; Stojanovski et al, 2019; Xu et al, 2022). Increased cortical hemispheric symmetry appears to be more specific to ASD but has proven difficult to replicate (Carper et al, 2016; Deng & Wang, 2021; Postema et al, 2019; Sha et al, 2021).…”

Moment-to-moment affective dynamics in schizophrenia and bipolar disorder

“…There is a high level of comorbidity of psychotic and affective symptoms across both disorders [3][4][5][6][7][8]. Common DNA variants and brain changes that appear to influence the risk of both schizophrenia and bipolar disorder have been identified [9,10], and an individual's risk of suffering from either schizophrenia or bipolar disorder is elevated if a firstdegree relative has one of the disorders [11], indicating a significant overlap in genetic factors underlying the two disorders [12]. Therefore, it would be of theoretical and clinical value to examine similarities and differences in psychological processes across disorders [13,14].…”