Dopamine release during psychological stress in euthymic bipolar I disorder: a Positron Emission Tomography study with [11C]raclopride.

BACKGROUND: Neurochemical mechanisms underlying stress induced relapse of mood episodes in Bipolar I Disorder (BD) remain unknown. This study investigated whether euthymic BD patients have a greater dopamine release in ventral striatum, caudate and putamen in response to psychological stress using Positron Emission Tomography (PET) scanning with the radiotracer [11C]raclopride. METHODS: Euthymic patients with BD (n = 10) and 10 matched healthy controls underwent two [11C]raclopride PET scans, one during a "stress" and the other in a "no stress" condition separated by at least 24 h. Montreal Imaging Stress Test (MIST) was used to induce stress during stress condition. Participants received an injection of [11C]raclopride over one minute followed by PET scan for 60 min. Participants were assessed for mood symptom severity at baseline, and before and after each scan. The reduction in [11C]raclopride binding in stress condition compared with non-stress rest condition for each subject provided an estimate of dopamine release due to stress. RESULTS: There was a significant effect of stress in reducing the [11C]raclopride binding in the ventral striatum, caudate and putamen; however, no significant effects of group or condition x group interaction were found. LIMITATIONS: Small sample size and recruitment of euthymic patients who may be less vulnerable to stress may limit the generalizability of findings. CONCLUSIONS: Our findings showed that psychological stress led to dopamine release in the basal ganglia for all participants but the magnitude of dopamine release during a stress task was not different between euthymic BD patients and healthy controls.

Longitudinal grey matter changes following first episode mania in bipolar I disorder: A systematic review.

BACKGROUND: While widespread grey matter (GM) changes are seen in bipolar I disorder (BD-I), it is unclear how early in the illness such changes emerge. To date there has been little synthesis of findings regarding longitudinal grey matter changes early in the course of BD-I. We conducted a systematic review to examine the evolution of GM changes in BD-I patients following the first episode of mania (FEM). METHODS: Following PRISMA guidelines, we conducted a systematic review of studies examining longitudinal changes in GM volume (GMV), cortical thickness and/or surface area in BD-I patients following FEM. We qualitatively synthesized results regarding longitudinal GM changes in BD-I patients. RESULTS: Fifteen studies met inclusion criteria, all examining GMV changes. Longitudinal ACC volume decrease following FEM was the most replicated finding, but was only reported in 4 out of 7 studies that examined this region as part of a whole brain/region of interest analysis, with 2 of these positive studies using an overlapping patient sample. The impact of episode recurrence, medications, and other clinical factors was inconsistently examined. LIMITATIONS: The literature regarding GM changes early in BD-I is highly inconsistent, likely due to heterogeneity in participant characteristics, imaging methodology/analysis and duration of follow up. CONCLUSIONS: Though there was some suggestion that structural ACC changes may represent a marker for neuroprogression following FEM, results were too inconsistent to draw any conclusions. Larger longitudinal studies examining cortical thickness/surface area, and the influence of relevant clinical factors, are needed to better understand neuroprogression in early BD-I.

Diffusion properties of the fornix assessed by deterministic tractography shows age, sex, volume, cognitive, hemispheric, and twin relationships in young adults from the Human Connectome Project.

The fornix is the primary efferent pathway of the hippocampus and plays a central role in memory circuitry. Diffusion tensor imaging has shown changes in the fornix with typical development and aging. Here, the fornix was investigated in 903 healthy young adult participants aged 22-36 years old from the high-spatial resolution 1.25 mm isotropic Human Connectome Project (HCP) diffusion dataset. Manual deterministic tractography was used to assess relationships between fornix diffusion parameters and age, sex, laterality, hippocampus volume, memory scores, and genetic effects in a subgroup of mono- and dizygotic twins. Fornix diffusion metrics were weakly correlated with age over the given age span. While significant hemispheric and sex differences were observed (greater fractional anisotropy (FA) and volume in the right hemisphere; greater FA and volume in females), there was great overlap between the groups. Hippocampus volume measurements showed greater volume in the right hemisphere, were found to be larger in males, and were weakly correlated with fornix FA and volume. Interestingly, all fornix diffusion measurements correlated strongly with fornix volume, suggesting the presence of partial volume effects despite the high-spatial resolution of the data. Both fornix diffusion parameters and hippocampal volumes were able to explain some variance (0.6-5.5%) in the memory tests evaluated. The fornix diffusion parameters were influenced by both genetic and shared environmental factors, displaying greater variability in dizygotic than in monozygotic twins. These findings provide a comprehensive depiction of the fornix in healthy, young individuals, upon which future typical development/aging and pathological studies could anchor.