Neurostructural and neurocognitive correlates of APOE ε4 in youth bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a clinical risk factor for Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4), a genetic risk factor for AD, has been associated with brain structure and neurocognition in healthy youth. AIMS: We evaluated whether there was an association between APOE ε4 with neurostructure and neurocognition in youth with BD. METHODS: Participants included 150 youth (78 BD:19 ε4-carriers, 72 controls:17 ε4-carriers). 3T-magnetic resonance imaging yielded measures of cortical thickness, surface area, and volume. Regions-of-interest (ROI) and vertex-wise analyses of the cortex were conducted. Neurocognitive tests of attention and working memory were examined. RESULTS: Vertex-wise analyses revealed clusters with a diagnosis-by-APOE ε4 interaction effect for surface area (p = 0.002) and volume (p = 0.046) in pars triangularis (BD ε4-carriers > BD noncarriers), and surface area (p = 0.03) in superior frontal gyrus (controls ε4-carriers > other groups). ROI analyses were not significant. A significant interaction effect for working memory (p = 0.001) appeared to be driven by nominally poorer performance in BD ε4-carriers but not control ε4-carriers; however, post hoc contrasts were not significant. CONCLUSIONS: APOE ε4 was associated with larger neurostructural metrics in BD and controls, however, the regional association of APOE ε4 with neurostructure differed between groups. The role of APOE ε4 on neurodevelopmental processes is a plausible explanation for the observed differences. Future studies should evaluate the association of APOE ε4 with pars triangularis and its neurofunctional implications among youth with BD.

The Effects of Psilocybin in Adults with Major Depressive Disorder and the General Population: Findings from Neuroimaging Studies.

The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and potentially other psychedelics. We assessed neuroimaging observations with psilocybin among participants with MDD and healthy populations. A systematic search was conducted on PubMed, Google Scholar and PsycINFO from database inception to November 17th, 2021. The study quality (i.e., risk of bias) was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A total of ten studies evaluated psilocybin in healthy populations and three studies assessed psilocybin in MDD participants using neuroimaging techniques. Following psilocybin administration, a decrease in amygdala activity and a reduction in depressive symptoms was observed in two studies. Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, was seen in healthy populations. There was high heterogeneity in methodology (e.g., dosing schedule and imaging methods) amongst included studies. Longitudinal studies are needed to further elucidate psilocybin treatment for MDD, its long-term effects and the possibility of sustained therapeutic effects.