Translational Psychiatry

Dysregulation of copper (Cu) metabolism may contribute to the pathogenesis of major depressive disorder (MDD) by disrupting hippocampal function. The aim of this study is to elucidate the neurobiological mechanisms through integrated clinical and animal experiments. A total of 85 MDD patients and 65 healthy controls (HCs) were recruited for this study. Serum Cu, ceruloplasmin (Cp) levels, and the…

Abstract The widespread and increasing prevalence of excess body mass represents a major public health concern and has been hypothesized to involve dysfunction of the dopaminergic reward system. However, a detailed, systems-level understanding of interactions between the dopamine system and body mass regulation in humans has been elusive. To address this knowledge gap, we employed positron emissi…

Traumatic brain injury (TBI) can result in chronic functional disability and is associated with persistent psychiatric symptoms, including posttraumatic stress disorder (PTSD), depression, and anxiety. Ibogaine, an oneirogenic alkaloid with unique pharmacological properties, has shown initial promise as a potential treatment for TBI-related sequelae. We previously observed large improvements in f…

Major depressive disorder (MDD) exhibits substantial heterogeneity, posing challenges for its diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for delineating cellular programs in neuronal and immune populations implicated in MDD pathogenesis. Advances in large language models (LLMs) are now enhancing single-cell analysis by improving annotation, clus…

Cannabis use has been consistently associated with increased risks of depression, suicidal ideation, and suicide attempt. We aimed to compare the trajectories of depression and suicide attempt risk among individuals who used cannabis before or concomitantly with the onset of depressive symptoms, relative to depressed individuals who did not use cannabis. We used data from 24,446 participants of C…

Cognitive impairment in patients with major depressive disorder (MDD) and a history of childhood trauma (CT) may be associated with microstructural abnormalities in the neostriatum, including the caudate and putamen. However, the nature of these alterations and their role in cognitive dysfunction remain unclear. This study aimed to characterise neostriatal microstructural alterations and examine …

Chronic psychological stress has been implicated as a risk factor for Alzheimer’s disease (AD), potentially through cortisol-mediated acceleration of disease progression. However, the molecular pathways underlying this relationship remain poorly understood. Epigenetic regulation of the glucocorticoid and mineralocorticoid receptor genes ( NR3C1 and NR3C2 ), which encode receptors for cortisol, ma…

In the context of the microbiota-gut-brain axis, diet represents a critical yet still debated component of translational psychiatry. However, population-based evidence linking microbiota-supportive dietary patterns to depressive symptoms remains limited. This research leverages the Dietary Index for Gut Microbiota (DI-GM) to examine the associations between a gut-microbiota-friendly diet and depr…

Abstract Detecting schizophrenia (SZ) from electroencephalography (EEG) signals using machine- and deep learning models gained traction lately due to potential utility in early disease detection and differential diagnosis. Classification performance reports in the range of 95% accuracy and above are common; however, review of state-of-the-art literature indicates that ~65% of published works invo…

Autism spectrum disorder (ASD) shows high variability in brain structure and behavior, complicating identification of biologically meaningful subtypes and their neuroanatomical and molecular bases. To address this, we analyzed structural MRI data from 1055 ASD and 1164 typically developing (TD) individuals. Gray matter volume (GMV) values from regions showing significant ASD–TD differences were e…

People with severe mental illness (SMI), including schizophrenia (SCZ) and bipolar disorder (BD), show elevated risk for somatic conditions and premature mortality. Both genetic liability and modifiable lifestyle factors have been implicated in this comorbidity, yet large-scale studies examining their independent and combined effects across multiple somatic conditions are lacking. We therefore ex…

Psychopathy is a personality construct characterized by emotional detachment, impulsivity, and antisocial tendencies. Despite a clinical prevalence of 1%, the biological underpinnings of psychopathy remain poorly understood. Emerging evidence suggests a role for the microbiota-brain axis in personality and behavior, yet its relevance to psychopathy remains unexplored. This study investigated the …

Abstract The putamen plays a key role in motor control, learning, and cognition, with abnormal putamen volumes associated with neuropsychiatric disorders. Using data from the ABCD study, we performed a genome wide association study (GWAS) of putamen volumes, followed by replication and pathway enrichment analyses. We next evaluated the shared genetic architecture of putamen volume and neuropsychi…

Abstract Depressive and anxiety symptoms prevalent in major depressive disorder (MDD), that affects millions globally, with many patients showing incomplete response to standard treatments. This open-label pilot study evaluated the effects of a 12-week multi-strain probiotic supplementation on depressive and anxiety symptoms in 30 adults with depressive and anxiety symptoms (e.g., MDD, adjustment…

Premature epigenetic aging has been linked to poorer cognitive performance, but the neuroanatomical pathways underlying this association remain unclear. Therefore, we tested whether premature epigenetic aging predicts deviations from normative brain development and cognition in young adulthood. We followed 254 young adults from the ELSPAC prenatal birth cohort. Epigenetic aging was estimated usin…

Abstract Clozapine is the most effective antipsychotic drug, while also causing the most severe metabolic side effects. The underlying mechanisms of these side effects appear multifactorial and are not entirely understood. We hypothesized that liver sinusoidal endothelial cells (LSEC) dysfunction is linked to the metabolic side effects of clozapine, based on known association between reduced LSEC…

BACKGROUND: Maladaptive self-beliefs are a core symptom of major depressive disorder. These beliefs are perpetuated by a negatively biased integration of self-related feedback. Understanding the neurocomputational mechanisms of biased belief updating may help to counteract maladaptive beliefs and the maintenance of depression. METHODS: The present study uses a belief-updating task and functional …

Background: Treatment-resistant depression (TRD) affects 30-50% of patients with major depressive disorder (MDD). Electroconvulsive therapy (ECT) and sub-anesthetic ketamine treatment can relieve TRD, yet their antidepressant mechanisms remain unclear. Peripheral blood gene expression offers a non-invasive proxy to examine potential treatment-response biomarkers. Methods: We conducted a transcrip…

Abstract Excitation/inhibition (E/I) balance is crucial for maintaining healthy brain function and can be disrupted in various neurological and psychiatric disorders. Despite its importance, there are few tools to study E/I balance non-invasively in humans. Here, we propose a canonical microcircuit model to estimate E/I balance from non-invasive magneto- and electroencephalography (M/EEG) recordi…