Trait and state alterations in excitatory connectivity between subgenual anterior cingulate cortex and cerebellum in patients with current and remitted depression

ABSTRACTHow do differences in onset, symptoms, and treatment response arise between various mental illnesses despite substantial overlap of genetic risk factors? To address this question, we carried out deep RNA sequencing of human postmortem subgenual anterior cingulate cortex, a key component of limbic circuits linked to mental illness. Samples were obtained from 200 individuals diagnosed with bipolar disorder, schizophrenia, or major depression, and controls. Differential expression analysis in cases versus controls detected modest differences that were similar across disorders, although transcript-level differences were more pronounced. Case-case comparisons revealed greater expression differences between disorders, including many genes and transcripts that were expressed in opposite directions in each diagnostic group, compared to controls. Relative transcript abundances were associated with common genetic variants that accounted for disproportionate fractions of diagnosis-specific heritability. Inherited genetic risk factors shape the brain transcriptome and contribute to diagnostic differences between broad classes of mental illness.

Download Full-text

Testing a Developmental Model of Parental Warmth, Amygdala–Subgenual Anterior Cingulate Cortex Connectivity, and Depressive Symptoms in Adolescents During the COVID-19 Pandemic

10.31234/osf.io/4xv8s ◽

2021 ◽

Author(s):

Jonas G. Miller ◽

Tiffany C. Ho ◽

Jaclyn Schwartz Kirshenbaum ◽

Rajpreet Chahal ◽

Anthony Gifuni ◽

...

Keyword(s):

Depressive Symptoms ◽

Anterior Cingulate Cortex ◽

Family Environment ◽

Mental Health Problems ◽

Predictive Marker ◽

Cingulate Cortex ◽

Developmental Model ◽

Anterior Cingulate ◽

Parental Warmth ◽

Subgenual Anterior Cingulate Cortex

Background: Neurobiological measures may serve as predictive markers of risk for and resilience to depressive symptoms during the COVID-19 pandemic. We tested a developmental model linking variation in amygdala–subgenual anterior cingulate cortex (sgACC) resting-state connectivity both to earlier experiences in the family environment and to subsequent vulnerability to depressive symptoms during the pandemic.Methods: We used data from a longitudinal study that included three waves (N=214 adolescents; ages 9-15 years at Time 1 (T1), 11-17 years at Time 2 (T2), and 12-19 years during the pandemic at Time 3 [T3]). We assessed parental warmth (T1), depressive symptoms (T1 to T3), and functional connectivity between the sgACC and basolateral (BLA) and centromedial amygdala (CMA) (T1 and T2). We modeled associations among early parental warmth, amygdala–sgACC connectivity, and depressive symptoms before and during the pandemic.Results: Less parental warmth was associated prospectively with stronger BLA–sgACC connectivity approximately two years later (=-.23, p=.021) over and above the effect of BLA–sgACC connectivity at T1. Stronger BLA–sgACC connectivity, in turn, was associated with heightened depressive symptoms, both before (r=.21, p=.031) and during the pandemic (=.22, p=.031; independent of the effect of pre-pandemic symptoms). Conclusion: Adolescents who experience less parental warmth may develop a pattern of BLA–sgACC connectivity that increases their risk for mental health problems during the pandemic. BLA–sgACC connectivity in early to middle adolescence may be a predictive marker of risk for depressive symptoms in general and specifically during periods of heightened stress.

Download Full-text