Structural Brain Imaging Studies Offer Clues about the Effects of the Shared Genetic Etiology among Neuropsychiatric Disorders

Abstract

WordsBackground: Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. Methods:From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD) and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. Results:The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were significantly correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494; p = 0.025). Conclusions:Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 3,004 Individuals Assessed in a Worldwide ENIGMA Study

“…Our cross-disorder whole-brain cortical mapping revealed a strong link between morphometric signatures of schizotypy with schizophrenia, along a SZ-BD-MDD axis. These findings partly resemble previous genetic [95] and neuroanatomical correlations [70, 96] observed between schizophrenia, bipolar disorder and major depression [97]. Interestingly, the relationship between the cortical patterns of schizotypy and schizophrenia revealed regional discordant and concordant effect sizes.…”

“…These findings partly resemble previous genetic [95] and neuroanatomical correlations [70,96] observed between schizophrenia, bipolar disorder and major depression [97]. Interestingly, the relationship between the cortical patterns of schizotypy and schizophrenia revealed regional discordant and concordant effect sizes.…”

Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

“…ADHD and ASD often co-occur (Leitner, 2014) and are known to share genetic influences (Ghirardi et al, 2019;Stergiakouli et al, 2017), such that the two diagnostic labels are likely to capture a partly overlapping spectrum of related disorders (Demopoulos, Hopkins, & Davis, 2013;van der Meer et al, 2012). Studies that aimed to identify shared brain structural traits between ADHD and ASD have found mixed results (Boedhoe et al, 2019;Radonjić et al, 2019), with perhaps the greatest overlap involving regions of the 'social brain', including orbitofrontal cortex (Baribeau et al, 2019). However, laterality has not been specifically studied in this regard, so that our finding of reduced rightward medial orbitofrontal cortex surface area in both disorders may be a new insight into shared neurobiology between ADHD and ASD.…”

“…Studies that aimed to identify shared brain structural traits between ADHD and ASD have found mixed results (Boedhoe et al, 2019;Radonjić et al, 2019), with perhaps the greatest overlap involving regions of the 'social brain', including orbitofrontal cortex (Baribeau et al, 2019). However, laterality has not been specifically studied in this regard, so that our finding of reduced rightward medial orbitofrontal cortex surface area in both disorders may be a new insight into shared neurobiology between ADHD and ASD.…”

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study

“…Therefore, overlap in neuropathology between our epilepsy cohort and major neuropsychiatric disorders could, in part, underlie the high rates of co-morbidity observed among these disorders. Increasing evidence suggests that neuropsychiatric disorders themselves are not separated by sharp neurobiological boundaries (Baker et al, 2019), but have overlapping of genetic influences and brain dysfunction (Brainstorm Consortium et al, 2018;Radonjić et al, 2019). Although genetic overlap between these neuropsychiatric disorders and epilepsy is low, overlap in dysfunctional brain networks may be partly due to comorbidities, and warrants further investigation.…”