Biological Psychiatry

BACKGROUND: Understanding the biological processes underlying individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. Yet it remains unclear how FKBP5 DNA methylation (DNAm) in peripheral blood relates to individual differences in measures of neural structure and function, and their relevance to daily-life stress responsivity...

BACKGROUND: Symptoms of borderline personality disorder (BPD) often manifest in adolescence, yet the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents. METHODS: We used functional Magnetic Resonance Imaging (fMRI) data from young adults and adolescents from the Human Connectome Project: Young Adults (HCP-YA; N=870, ages 22-37 years, 457 female) and Development (HCP-D; N=223, ages 16-21 years, 121 female)...

BACKGROUND: Psychomotor disturbances are observed across psychiatric disorders and often present as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries. METHODS: We analyzed data from the Human Connectome Project for Early Psychosis, a multi-site study of 125 people with early psychosis and 58 healthy participants with resting-state fMRI and clinical characterization...

BACKGROUND: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence. METHODS: We performed a two-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (n = 18,340) and intelligence (n = 269,867)...

BACKGROUND: Abnormal reward sensitivity is a risk factor for psychiatric disorders, including eating disorders such as overeating and binge-eating disorder, but the brain structural mechanisms underlying it are not completely understood. Here, we sought to investigate the relationship between multi-modal whole-brain structural features and reward sensitivity in nonhuman primates. METHODS: Reward sensitivity was evaluated through behavioral economic analysis in which monkeys (adult rhesus macaques, 5 males; 7 females) responded for sweetened-condensed milk (10,30,56%), Gatorade, or water using an operant procedure in which the response requirement increased incrementally across sessions (i...

The use of clinical prediction models to produce individualised risk estimates can facilitate the implementation of precision psychiatry. As a source of data from large, clinically representative patient samples, electronic health records (EHRs) provide a platform to develop and validate clinical prediction models, as well as potentially implementing them in routine clinical care. The present review describes promising use cases for the application of precision psychiatry to EHR data and considers their performance in terms of discrimination (ability to separate individuals with and without the outcome) and calibration (extent to which predicted risk estimates correspond to observed outcomes), as well as their potential clinical utility (weighing benefits and costs associated with the model compared to different approaches across different assumptions of the number-needed-to-test)...

BACKGROUND: Bipolar disorder (BPD) is a debilitating mood disorder with an unclear aetiology. A better understanding of the underlying pathophysiological mechanisms will help to identify novel targets for improved treatment options and prevention strategies. In this metabolome-wide Mendelian randomization study, we screened for metabolites that may have a causal role in BPD. METHODS: We tested a total of 913 circulating metabolite exposures assessed in 14,296 Europeans using a mass spectrometry-based platform...

BACKGROUND: The zona incerta (ZI) is a subcortical structure primarily investigated in rodents, that is implicated in various behaviors from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In our study, we used diffusion MRI tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. METHODS: We performed probabilistic tractography in 7T on 178 subjects from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts...

BACKGROUND: Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated (1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC), and (2) how such effects related to gene expression and receptor maps. METHODS: Across 115 participants (37 controls, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task...

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BACKGROUND: Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic interneurons (PVINs) within the NAc are required for this process. Perineuronal nets (PNNs) are extracellular matrix structures enriched around PVINs that arise during development and are proposed to mediate brain circuit stability. However, their function in adult NAc is largely unknown. Here we study the developmental emergence and adult regulation of PNNs in the NAc of male and female mice and test the cellular and behavioral consequences of reducing the PNN component Brevican in NAc PVINs...

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