Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [ 11 C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (V T). [ 11 C]UCB-J V T was significantly lower in the frontal and anterior cingulate cortices in schizophrenia with large effect sizes (Cohen's d = 0.8-0.9), but there was no significant difference in the hippocampus. We also investigated the effects of antipsychotic drug administration on SV2A levels in Sprague-Dawley rats using western blotting, [ 3 H]UCB-J autoradiography and immunostaining with confocal microscopy, finding no significant effects on any measure. These findings indicate that there are lower synaptic terminal protein levels in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for them.

Objectives:Sleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraine patients. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI), and objective sleep architecture measured using polysomnography between adult and pediatric patients, and healthy controls.Methods:This review was pre-registered on PROSPERO (CRD42020209325). A systematic search of five databases (Embase, MEDLINE®, Global Health, APA PsycINFO, APA PsycArticles, last searched: 12/17/2020) was conducted to find case-controlled studies which measured polysomnography and/or PSQI in patients with migraine. Pregnant participants and those with other headache disorders were excluded. Effect sizes (Hedges’ g) were entered into a random effects model meta-analysis. Study quality was evaluated with the Newcastle Ottawa Scale, and publication bias with Egger’s regression test.Results:32 studies were eligible, of which 21 measured PSQI and/MIDAS in adults, 6 measured PSG in adults and 5 in children. The overall mean study quality score was 5/9, and this did not moderate any of the results, and there was no risk of publication bias. Overall, adults with migraine had higher PSQI scores than healthy controls (g=0.75, p < .001, 95% confidence interval [95%CI]: 0.54 - 0.96). This effect was larger in those with chronic rather than episodic condition (g=1.03, p < .001, 95%CI: 0.37 - 1.01, g = 0.63, p < .001, 95%CI: 0.38 - 0.88 respectively). For polysomnographic studies, adults and children with migraine displayed a lower percentage of REM sleep (g=-0.22, p = 0.017, 95%CI: -0.41 - -0.04, g = -0.71, p = 0.025, 95%CI: -1.34 - -0.10 respectively) than controls. Pediatric patients displayed less total sleep time (g=-1.37, p = 0.039, 95%CI: -2.66 - -0.10), more wake (g=0.52, p < .001, 95%CI: 0.08 – 0.79) and shorter sleep onset latency (g=-0.37, p < .001, 95%CI: -0.54 - -0.21) than controls.Discussion:People with migraine have significantly poorer subjective sleep quality and altered sleep architecture compared to healthy individuals. Further longitudinal empirical studies are required to enhance our understanding of this relationship.