Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Negative symptoms in schizophrenia have been associated with structural and functional alterations of the amygdala. We hypothesised that there would be between-group differences in amygdala volume and neural activation patterns during processing of affective stimuli among patients with schizophrenia and healthy controls. We further hypothesised correlations between neuroimaging metrics and clinical ratings of negative symptoms in patients with schizophrenia.

We used structural and functional magnetic resonance imaging to assess volume and neural activation of the amygdala in 28 patients with schizophrenia and 28 healthy controls.

We found no between-group differences in amygdala volume or neural activation. However, we found a significant negative correlation between emotional blunting and neural activation in the left amygdala during processing of positive affect. We also found a significant negative correlation between stereotyped thinking and the volume of right amygdala.

Our findings implicate the amygdala in a subgroup of negative symptoms in schizophrenia that are characterised by reduced expression with blunted affect and stereotyped thinking.

Motor retardation is a characteristic feature of bipolar depression, and is also a core feature of Parkinson's disease. Within the framework of the functional deafferentiation theory in Parkinson's disease, we hypothesised that motor retardation in bipolar depression is mediated by disrupted subcortical activation, leading to decreased activation of cortical motor areas during finger tapping.

We used functional magnetic resonance imaging to investigate neural activity during self-paced finger tapping to elucidate whether brain regions that mediate preparation, control and execution of movement are activated differently in subjects with bipolar depression (n = 9) compared to healthy controls (n = 12).

An uncorrected whole-brain analysis revealed significant group differences in dorsolateral and ventromedial prefrontal cortex. Corrected analyses showed non-significant differences in patients compared to controls: decreased and less widespread activation of the left putamen and left pallidum; increased activity in the left thalamus and supplementary motor area; decreased activation in the left lateral pre- and primary motor cortices; absence of activation in the pre-supplementary motor area; activation of the bilateral rostral cingulate motor area.

Both movement preparation and execution may be affected in motor retardation, and the activity in the whole left-side motor circuit is altered during self-initiated motor performance in bipolar depression.