Translational Psychiatry

http://www.nature.com/tp

List of Papers (Total 517)

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities

The mu opioid receptor (MOR) plays a critical role in modulating social behavior in humans and animals. Accordingly, MOR null mice display severe alterations in their social repertoire as well as multiple other behavioral deficits, recapitulating core and secondary symptoms of autism spectrum disorder (ASD). Such behavioral profile suggests that MOR dysfunction, and beyond this...

Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the...

Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression

Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British...

Lithium and fluoxetine regulate the rate of phosphoinositide synthesis in neurons: a new view of their mechanisms of action in bipolar disorder

Lithium is widely used to treat bipolar disorder, but its primary mechanism of action is uncertain. One proposal has been that lithium’s ability to inhibit the enzyme inositol monophosphatase (IMPase) reduces the supply of recycled inositol used for membrane phosphoinositide (PIns) synthesis. This 28-year-old hypothesis is still widely debated, however, largely because total...

MiR-9, miR-153 and miR-124 are down-regulated by acute exposure to cocaine in a dopaminergic cell model and may contribute to cocaine dependence

Cocaine is one of the most used psychostimulant drugs worldwide. MicroRNAs are post-transcriptional regulators of gene expression that are highly expressed in brain, and several studies have shown that cocaine can alter their expression. In a previous study, we identified several protein-coding genes that are differentially expressed in a dopaminergic neuron-like model after an...

Common and differential transcriptional responses to different models of traumatic stress exposure in rats

The effect of six different traumatic stress protocols on the transcriptome of the rat adrenal gland was examined using RNA sequencing. These protocols included chronic variable stress, chronic shock, social defeat and social isolation. The response of the transcriptome to stress suggested that there are genes that respond in a universal or stress modality-independent manner, as...

Convergence of evidence from a methylome-wide CpG-SNP association study and GWAS of major depressive disorder

DNA methylation is an epigenetic modification that provides stability and diversity to the cellular phenotype. It is influenced by both genetic sequence variation and environmental factors, and can therefore potentially account for variation of heritable phenotypes and disorders. Therefore, methylome-wide association studies (MWAS) are promising complements to genome-wide...

Proteomics for blood biomarker exploration of severe mental illness: pitfalls of the past and potential for the future

Recent improvements in high-throughput proteomic approaches are likely to constitute an essential advance in biomarker discovery, holding promise for improved personalized care and drug development. These methodologies have been applied to study multivariate protein patterns and provide valuable data of peripheral tissues. To highlight findings of the last decade for three of the...

Effect of valproate and pregabalin on human anxiety-like behaviour in a randomised controlled trial

Valproate is an anticonvulsant drug with strong preclinical evidence for reducing anxiety behaviour in rodents but no clear clinical evidence. To motivate clinical trials, we here investigate the use of valproate in a translational human model of anxiety behaviour. In a double-blind, randomised, placebo-controlled trial, n = 118 healthy participants played a previously validated...

Peripubertal stress increases play fighting at adolescence and modulates nucleus accumbens CB1 receptor expression and mitochondrial function in the amygdala

Play fighting is a highly rewarding behavior that helps individuals to develop social skills. Early-life stress has been shown to alter play fighting in rats and hamsters as well as to increase aggressive behaviors at adulthood. However, it is not known whether individual differences in stress-induced play fighting are related to differential developmental trajectories towards...

Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders

Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity...

PSD95 and nNOS interaction as a novel molecular target to modulate conditioned fear: relevance to PTSD

Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR...

Riluzole reduces amyloid beta pathology, improves memory, and restores gene expression changes in a transgenic mouse model of early-onset Alzheimer’s disease

Alzheimer’s disease (AD) represents a major healthcare burden with no effective treatment. The glutamate modulator, riluzole, was shown to reverse many AD-related gene expression changes and improve cognition in aged rats. However, riluzole’s effect on amyloid beta (Aβ) pathology, a major histopathological hallmark of AD, remains unclear. 5XFAD transgenic mice, which harbor...

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)

A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS...

Brain-computer-interface-based intervention re-normalizes brain functional network topology in children with attention deficit/hyperactivity disorder

A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations...

Investigating the genetic architecture of general and specific psychopathology in adolescence

Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling...

Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations

Previous genome-wide association studies (GWAS) suggest that rs10489202 in the intron of MPC2 (mitochondrial pyruvate carrier 2) is a risk locus for schizophrenia in Han Chinese populations. To validate this discovery, we conducted a replication analysis in an independent case-control sample of Han Chinese ancestry (437 cases and 2031 controls), followed by a meta-analytic...

Relationship between white matter integrity and serum inflammatory cytokine levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics

Recently, accumulated evidence has indicated a role of inflammation in the pathogenesis of major depressive disorder (MDD). Therefore, we evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode in drug-naive MDD patients, using a tract-based spatial statistics (TBSS) method. A total of 35 drug-naive MDD patients with...

Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory

Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). Given that polycystic ovary syndrome (PCOS) is also associated with elevated prenatal testosterone and its precursor sex steroids, a hypothesis from the prenatal sex steroid theory is that women with PCOS should have elevated autistic traits and a higher rate of autism among...

Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling

The ankyrin 3 gene (ANK3) is a well-established risk gene for psychiatric illness, but the mechanisms underlying its pathophysiology remain elusive. We examined the molecular effects of disrupting brain-specific Ank3 isoforms in mouse and neuronal model systems. RNA sequencing of hippocampus from Ank3+/− and Ank3+/+ mice identified altered expression of 282 genes that were...

Altered cerebellar–insular–parietal–cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network–based statistic analysis

To date, few functional magnetic resonance imaging (fMRI) studies have explored resting-state functional connectivity (RSFC) in long-lasting anorexia nervosa (AN) patients via graph analysis. The aim of the present study is to investigate, via a graph approach (i.e., the network-based statistic), RSFC in a sample of adolescents at the earliest stages of AN (i.e., AN duration less...

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

Definitive data are lacking on the mechanism of action and biomarkers of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression. Low-intensity rTMS (LI-rTMS) has demonstrated utility in preclinical models of rTMS treatments but the effects of LI-rTMS in murine models of depression are unknown. We examined the behavioral and neurobiologic changes in...

Development and validation of a new rating scale for perimenopausal depression—the Meno-D

The menopause transition is a time when women experience an increased risk for new onset depression, as well as relapse of depression. While there are overlapping symptoms between major depression and depression during menopause, differences suggest ‘perimenopausal depression’ may be a unique subtype of depression associated with characteristic symptoms. There is currently no...

Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics

Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive...