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Aim: Genome‐wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD‐associated loci. Methods: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders. Results: A meta‐analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10−8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over‐represented in categories including long‐term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling. Conclusion: The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis. [ABSTRACT FROM AUTHOR]

Aim: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. Methods: A nested, case–control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age‐matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three‐generation cohort. Concentrations of nine plasma cytokines (IFN‐γ, IL‐1β, IL‐4, IL‐6, IL‐10, IL‐12p40, IL‐12p70, IL‐13, and TNF‐α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. Results: Cross‐sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL‐4 levels during pregnancy and after delivery than the control group, and that plasma IL‐4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL‐10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL‐10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN‐γ, IL‐6, IL‐12p40, and TNF‐α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. Conclusions: These results suggest a potential protective effect of the anti‐inflammatory cytokines IL‐4 and IL‐10 during pregnancy against the development of PPD. [ABSTRACT FROM AUTHOR]

This document is a response to a previous article discussing the potential role of anti-inflammatory cytokines in postpartum depression. The response focuses on a case study of a young woman who developed tardive dystonia after taking brexpiprazole for 1.5 years. The patient experienced improvement in her dystonia and returned to her job after starting clozapine. The exact mechanisms behind antipsychotic-induced dystonia remain unclear, but it is suggested that an imbalance in the basal ganglia pathways and serotonin involvement may contribute to its development. The case highlights the need for vigilance in monitoring for tardive dystonia when using brexpiprazole, even in patients with few risk factors. [Extracted from the article]

In summary, we showed the ITIH3 rs2535629 risk allele is not significantly related to either cognitive function or traits, but is associated with increase in CSFV, reduction of task-induced deactivation, and decrease of fALFF, which is a measure of brain activity at rest. The inter-alpha-trypsin inhibitor heavy chain H3 I (ITIH3) i gene contains 24 exons and spans 14.2 kb of the genome. [Extracted from the article]

Aim: Glial fibrillary acidic protein (GFAP), the intermediate filament protein expressed in astrocytes, plays a key role in many aspects of brain function through communication with neurons or blood vessels. A common single nucleotide polymorphism (SNP), GFAP –250 C/A (rs2070935), is associated with the transcriptional regulation of GFAP, which can potentially result in the genotype‐specific brain structure. This study aimed to verify the biological effects of the GFAP variants on brain structure and function. Methods: We investigated the associations between the GFAP variants and magnetic resonance imaging findings, including gray and white matter volumes, white matter integrity, and resting arterial blood flow, from 1212 healthy Japanese subjects. Results: The GFAP –250 C/A genotype was significantly associated with total gray matter volume, total white matter volume, average mean diffusivity, and mean cerebral blood flow. In voxel‐by‐voxel analyses, the GFAP genotype showed significant associations with the regional gray and white matter volumes in the inferior frontal lobe and corpus callosum, the regional mean diffusivity in the left posterior region, and the regional cerebral blood flow throughout the brain. Conclusion: This study revealed a common SNP that is significantly associated with multiple global brain structure parameters. [ABSTRACT FROM AUTHOR]

Aim: Tissue pH and RNA integrity are crucial quality‐control indicators of human post‐mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post‐mortem tissues. Methods: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post‐mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 μL/10 mg tissue) and 10 volumes (1000 μL/100 mg tissue) of nuclease‐free water and subjected to pH measurements using an InLab Ultra micro pH electrode. Results: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. Conclusion: The proposed protocol used one‐tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post‐mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post‐mortem brain studies by diminishing confounding factors. [ABSTRACT FROM AUTHOR]

Aim: CX3CR1, a G‐protein‐coupled receptor, is involved in various inflammatory processes. Two non‐synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1‐expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia. Methods: Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals. Results: The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators. Conclusion: This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells. [ABSTRACT FROM AUTHOR]