Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects biological processes in the early stages of brain development. As studying the changes that occur in the early stages of life is important to prevent age-related neurological and psychiatric disorders, we aim to focus on these changes. The transcriptomic markers of ageing that are common to the analysed brain regions of C57Bl/6J mice were identified after conducting two-way ANOVA tests and effect size analysis on the time courses of gene expression profiles in various mouse brain regions. A total of 16,374 genes (59.9%) significantly changed their expression level, among which 7600 (27.8%) demonstrated tissue-dependent differences only, and 1823 (6.7%) displayed time-dependent and tissue-independent responses. Focusing on genes with at least a large effect size gives the list of potential biomarkers 12,332 (45.1%) and 1670 (6.1%) genes, respectively. There were 305 genes that exhibited similar significant time response trends (independently of the brain region). Samples from an 11-day-old mouse embryo validated the identified early-stage brain ageing markers. The overall functional analysis revealed tRNA and rRNA processing in the mitochondrion and contact activation system (CAS), as well as the kallikrein/kinin system (KKS), together with clotting cascade and defective factor F9 activation being affected by ageing. Most ageing-related pathways were significantly enriched, especially those that are strongly connected to development processes and neurodegenerative diseases.

UNASSIGNED: Epidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear.
UNASSIGNED: We assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis.
UNASSIGNED: We found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, P=7.35×10-12; HDL: rg=0.304, P=4.14×10-17). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ (P values are 6.59×10-11 and 2.10×10-12, respectively) and the 6p22.1 locus was identified in both MDD and SCZ (P values are 1.05×10-8 and 5.75×10-14, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (P<0.05/18776 = 2.66×10-6). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels.
UNASSIGNED: Our findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.

BACKGROUND: The ketogenic diet (KD) has been highly developed in the past for the treatment of epileptic pathological states in children and adults. Recently, the current re-emergence in its popularity mainly focuses on the therapy of cardiometabolic diseases. The KD can also have anti-inflammatory and neuroprotective activities which may be applied to the prevention and/or co-treatment of a diverse range of psychiatric disorders.
OBJECTIVE: This is a comprehensive literature review that intends to critically collect and scrutinize the pre-existing research basis and clinical data of the potential advantageous impacts of a KD on stress, anxiety, depression, schizophrenia and bipolar disorder.
METHODS: This literature review was performed to thoroughly represent the existing research in this topic, as well as to find gaps in the international scientific community. In this aspect, we carefully investigated the ultimate scientific web databases, e.g., PubMed, Scopus, and Web of Science, to derive the currently available animal and clinical human surveys by using efficient and representative keywords.
RESULTS: Just in recent years, an increasing amount of animal and clinical human surveys have focused on investigating the possible impacts of the KD in the prevention and co-treatment of depression, anxiety, stress, schizophrenia, and bipolar disorder. Pre-existing basic research with animal studies has consistently demonstrated promising results of the KD, showing a propensity to ameliorate symptoms of depression, anxiety, stress, schizophrenia, and bipolar disorder. However, the translation of these findings to clinical settings presents a more complex issue. The majority of the currently available clinical surveys seem to be moderate, usually not controlled, and have mainly assessed the short-term effects of a KD. In addition, some clinical surveys appear to be characterized by enormous dropout rates and significant absence of compliance measurement, as well as an elevated amount of heterogeneity in their methodological design.
CONCLUSIONS: Although the currently available evidence seems promising, it is highly recommended to accomplish larger, long-term, randomized, double-blind, controlled clinical trials with a prospective design, in order to derive conclusive results as to whether KD could act as a potential preventative factor or even a co-treatment agent against stress, anxiety, depression, schizophrenia, and bipolar disorder. Basic research with animal studies is also recommended to examine the molecular mechanisms of KD against the above psychiatric diseases.

UNASSIGNED: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration.
UNASSIGNED: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA.
UNASSIGNED: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r = 0.400, p = 0.005).
UNASSIGNED: Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.

UNASSIGNED: There may be an interaction between viral hepatitis and psychiatric disorders during disease progression. Herein, we conducted Mendelian randomization (MR) to explore the causal associations and mediators between viral hepatitis and psychiatric disorders.
UNASSIGNED: Genome-wide association studies summary data for viral hepatitis [including chronic hepatitis B (CHB) and chronic hepatitis C (CHC)] and psychiatric disorders (including depression, anxiety, schizophrenia, obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder) were obtained. Two-sample MR was performed to assess the causal associations between viral hepatitis and psychiatric disorders. Further, a mediation analysis was conducted to evaluate the potential mediators. Inverse-variance weighted, MR-Egger, and weighted median were used as the main methods, while a sensitivity analysis was performed to evaluate pleiotropy and heterogeneity.
UNASSIGNED: There was no causal effect of CHB/CHC on psychiatric disorders, as well as psychiatric disorders on CHB. However, schizophrenia presented a causal effect on increased CHC risk [odds ratio (OR)=1.378, 95%CI: 1.012-1.876]. Further, a mediation analysis identified coffee consumption and body mass index as mediators in the effect of schizophrenia on CHC, mediating 3.75% (95%CI: 0.76%-7.04%) and 0.94% (95%CI: 0.00%-1.70%) proportion, respectively.
UNASSIGNED: We revealed that schizophrenia patients faced a high risk of CHC, and insufficient coffee consumption and underweight could mediate the causal effect of schizophrenia on CHC. The prevention of hepatitis C might be a beneficial strategy for patients with schizophrenia. The right amount of nutrition supplements and coffee consumption might be part of a beneficial lifestyle in preventing the high CHC risk in patients with schizophrenia.

This Commentary describes the 20th Anniversary of VasCog 2023, held in Gothenburg, Sweden.

UNASSIGNED: Yokukansan is a Japanese herbal medicine used in psychiatry to treat behavioral and psychological symptoms of dementia and other psychiatric symptoms. However, the glycyrrhizic acid included in this medicine can cause pseudoaldosteronism and hypokalemia. We aimed to identify the risk factors for hypokalemia due to yokukansan.
UNASSIGNED: A retrospective cohort study was conducted on patients previously treated with yokukansan. The risk factors were determined by comparing the hypokalemia group with the non-hypokalemia group for each parameter.
UNASSIGNED: This study included 304 patients who received yokukansan treatment between April 2009 and March 2019. We found that 17.4% (n = 53) of the patients experienced yokukansan-induced hypokalemia. Risk factors detected as significantly different between patients with and without yokukansan-associated hypokalemia were low serum potassium concentration before yokukansan administration, dose 7.5 g /day or more, and dementia. Hypokalemia occurred earlier in patients with low albumin, low potassium, and dementia.
UNASSIGNED: It is necessary to pay attention to hypokalemia onset when administering yokukansan at 7.5 g or more to patients with low potassium levels and dementia. Our findings suggest that potassium levels must be checked early after yokukansan administration, especially in patients with low albumin, low potassium, and dementia.

BACKGROUND: Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project.
METHODS: The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain.
CONCLUSIONS: Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

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OBJECTIVE: Access to psychiatry services in Kashmir is challenging because of active enduring conflict, insecurity and a fundamental role played by the traditional health workers. We aimed to assess the main pathways to mental health services in Kashmir, India.
METHODS: This cross-sectional hospital-based study was performed from March 2012 to June 2017 in the outpatient psychiatry department at a psychiatric disease hospital in Kashmir. A convenience sampling method was used to select newly referred patients to the services. A survey was developed to collect information on demographic data and the main pathways for patients when seeking care for mental disorders.
RESULTS: A total of 518 patients were interviewed. About half of the respondents (48.8 %) attended clinical consultation from a general pathway like a physician or a neurologist, while 31.8% were visiting a psychiatrist for a significant psychiatric disorder. For some patients (17.8%), their initial pathway to mental health services is traditional healers.
CONCLUSIONS: The current study revealed different pathways to seeking psychiatric care in Kashmir India. Further studies are needed to address the treatment gap and ways to improve access to mental health services for the Kashmir population.