Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder (BD) (BO) are at higher risk of BD than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC. METHOD: BO (n = 29; mean age = 13.8 years; 14 female), NBO (n = 28; mean age = 13.9 years; 12 female) and HC (n = 23; mean age = 13.7 years; 11 female) were scanned while performing a number-guessing reward task. Of the participants, 11 BO and 12 NBO had current non-BD psychopathology; five BO and four NBO were taking psychotropic medications. RESULTS: A 3 (group) × 2 (conditions: win-control/loss-control) analysis of variance revealed a main effect of group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster-p < 0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses. CONCLUSIONS: This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO v. healthy NBO v. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.

The relationship between the size and asymmetry of the lateral ventricles and cortical myelin content in individuals with mood disorders.

Background: Although enlargement of the lateral ventricles was previously observed in individuals with mood disorders, the link between ventricular size and asymmetry with other indices of brain structure remains underexplored. In this study, we examined the association of lateral ventricular size and asymmetry with cortical myelin content in individuals with bipolar (BD) and depressive (DD) disorders compared to healthy controls (HC). Methods: Magnetic resonance imaging (MRI) was used to obtain T1w and T2w images from 149 individuals (age=27.7 (SD=6.1) years, 78% female, BD=38, DD=57, HC=54). Cortical myelin content was calculated using the T1w/T2w ratio. Elastic net regularized regression identified brain regions whose myelin content was associated with ventricular size and asymmetry. A post-hoc linear regression examined how participants' diagnosis, illness duration, and current level of depression moderated the relationship between the size and asymmetry of the lateral ventricles and levels of cortical myelin in the selected brain regions. Results: Individuals with mood disorders had larger lateral ventricles than HC. Larger ventricles and lower asymmetry were observed in individuals with BD who had longer lifetime illness duration and more severe current depressive symptoms. A greater left asymmetry was observed in participants with DD than in those with BD (p<0.01). Elastic net revealed that both ventricular enlargement and asymmetry were associated with altered myelin content in cingulate, frontal, and sensorimotor cortices. In BD, but not other groups, ventricular enlargement was related to altered myelin content in the right insular regions. Conclusions: Lateral ventricular enlargement and asymmetry are linked to myelin content imbalance, thus, potentially leading to emotional and cognitive dysfunction in mood disorders.

The interaction between depression diagnosis and BMI is related to altered activation pattern in the right inferior frontal gyrus and anterior cingulate cortex during food anticipation.

BACKGROUND: Depression and overweight/obesity often cooccur but the underlying neural mechanisms for this bidirectional link are not well understood. METHODS: In this functional magnetic resonance imaging study, we scanned 54 individuals diagnosed with depressive disorders (DD) and 48 healthy controls (HC) to examine how diagnostic status moderates the relationship between body mass index (BMI) and brain activation during anticipation and pleasantness rating of food versus nonfood stimuli. RESULTS: We found a significant BMI-by-diagnosis interaction effect on activation in the right inferior frontal gyrus (RIFG) and anterior cingulate cortex (ACC) during food versus nonfood anticipation (p < .0125). Brain activation in these regions was greater in HC with higher BMI than in HC with lower BMI. Individuals with DD showed an opposite pattern of activation. Structural equation modeling revealed that the relationship between BMI, activation in the RIFG and ACC, and participants' desire to eat food items shown in the experiment depended on the diagnostic status. CONCLUSIONS: Considering that food anticipation is an important component of appetitive behavior and that the RIFG and ACC are involved in emotion regulation, response inhibition and conflict monitoring necessary to control this behavior, we propose that future clinical trials targeting weight loss in DD should investigate whether adequate mental preparation positively affects subsequent food consumption behaviors in these individuals.