Biological Psychiatry

BACKGROUND: Psychotic experiences are thought to emerge from various interrelated patterns of disrupted belief updating, such as overestimating the reliability of sensory information and misjudging task volatility. Yet, these substrates have never been jointly addressed under one computational framework and it is not clear to what degree they reflect trait-like computational patterns. METHODS: We introduced a novel hierarchical Bayesian model that describes how individuals simultaneously update their beliefs about the task volatility and noise in observation...

BACKGROUND: Glutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy (MRS) using the MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders. METHODS: By combining MRS using the MEGA-PRESS and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex (mPFC) and precuneus and explore relationships between the GSH levels and intrinsic neuronal activity as well as clinical symptoms among the three groups of healthy controls (HCs, N=30), major depressive disorder (MDD, N=28), and obsessive-compulsive disorder (OCD, N=28)...

Cognitive impairment associated with schizophrenia (CIAS) and related deficits in learning (plasticity) are amongst the leading causes of disability in schizophrenia. Despite this, there are no FDA approved treatments for CIAS, and the development of treatments has been limited by numerous Phase II/III failures of compounds that showed initial promise in small-scale studies. N-methyl-d-aspartate-type glutamate receptors (NMDAR) have been proposed to play an important role in schizophrenia; moreover, NMDAR has a well characterized role in cognition, learning and neuroplasticity...

BACKGROUND: Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms underlying regional SC-FC coupling patterns are not well understood. METHODS: We enrolled 182 patients with MDD and 157 healthy control (HC) subjects, quantifying the intergroup differences in regional SC-FC coupling...

BACKGROUND: Rather than a passive reflection of nociception, pain is shaped by the interplay between one's experiences, current cognitive-affective states, and expectations. The placebo-response, a paradoxical yet reliable phenomenon, is postulated to reduce pain by engaging mechanisms shared with "active" therapies. It has been assumed that mindfulness meditation, practiced by sustaining nonjudgmental awareness of arising sensory events, merely reflects mechanisms evoked by placebo. Recently, brain-based multivariate pattern analysis (MVPA) has been validated to successfully disentangle nociceptive-specific, negative-affective, and placebo-based dimensions of the subjective pain experience...

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluate the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). METHODS: This phase I single center open label study recruited treatment-resistant OCD and MDD. Outcomes were measured 6mo, 12mo, and 18-24months (long-term) after MRgFUS capsulotomy...

BACKGROUND: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. METHODS: We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2...

Persisting symptoms and disability remain a problem for an appreciable proportion of people with schizophrenia despite treatment with antipsychotic medication. Improving outcomes requires an understanding of the nature and mechanisms of the pathological processes underlying persistence. Classical features of schizophrenia, which include disorganization and impoverishment of mental activity, are well recognised early clinical features that predict poor long-term outcome. Substantial evidence indicates that these features reflect imprecise predictive coding...

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition. Over the past decade, a considerable number of approaches have been developed to identify potential neuroimaging-based biomarkers of ASD and have uncovered specific neural mechanisms underlying behaviors associated with ASD. However, the substantial heterogeneity among those diagnosed with ASD hinders the development of biomarkers. Disentangling the heterogeneity of ASD is pivotal to improve quality of life for individuals with ASD by facilitating early diagnosis and individualized interventions for those who need support...

BACKGROUND: Brain serotonin 4 receptor (5-HT4 R) levels are lower in untreated patients with Major Depressive Disorder (MDD) and are linked to verbal memory. We here investigate the relationship between 5-HT4 R, clinical outcomes, and cognitive function in patients with MDD who initiate SSRI drug treatment. METHODS: Ninety moderately to severely depressed patients underwent molecular brain imaging to measure 5-HT4 R binding prior to antidepressant treatment with escitalopram...

BACKGROUND: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning. METHODS: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (Nmice ≥ 3), tract tracing (Nmice = 5), ex vivo electrophysiology (Ncells ≥ 30), in vivo calcium imaging with fiber photometry (Nmice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (Nmice ≥ 4)...

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development...

BACKGROUND: Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers improving the prediction of AD and adverse child birth, neurodevelopmental, and mental health outcomes remains unexplored. METHODS: In a cohort of 331 mother-child dyads, we studied associations between AD (history of medical register diagnoses and/or Center of Epidemiological Studies Depression Scale score during pregnancy≥20) and 95 metabolic measures analyzed three times during pregnancy...

BACKGROUND: Sleep deprivation (SD) negatively affects brain function. Most brain imaging studies have investigated the effects of SD on 'static' brain function. SD effects on functional brain dynamics and their relationship with molecular changes remain relatively unexplored. METHODS: We used functional MRI to examine resting brain state dynamics after one night of SD compared to rested wakefulness (RW) and assessed their association with striatal brain dopamine D2 receptor availability (D2R) measured by PET-[11C]raclopride using network control theory...

Maternal prenatal depression can affect child brain and behavioural development. Specifically, altered limbic network structure and function is a likely mechanism through which prenatal depression impacts the life-long mental health of exposed children. While developmental trajectories are influenced by many factors that exacerbate risk or promote resiliency, the role of child age and sex in the relationship between prenatal depression and the child brain remains unclear. Here, we review studies of associations between prenatal depression and brain structure and function, with a focus on the role of age and sex in these relationships...

BACKGROUND: Numerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, there is still a dearth of literature examining brain network localization of gray matter atrophy, neurocognitive and social cognitive dysfunction in schizophrenia. METHODS: To address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 schizophrenia individuals and 9275 healthy controls...

No abstract text is available yet for this article.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following three different rTMS stimulation protocols, all combined with exposure and response prevention (ERP). METHODS: In this three-arm proof-of-concept randomized trial, 61 treatment-refractory adult OCD patients received 16 sessions of rTMS immediately prior to ERP over 8 weeks, with task-based functional MRI (tb-fMRI) scans and clinical assessments pre- and post-treatment...

BACKGROUND: Different types of early-life adversity have been associated with children's brain structure and function. However, understanding the disparate influence of distinct adversity exposures on the developing brain remains a major challenge. METHODS: This study investigates the neural correlates of 10 robust dimensions of early-life adversity identified through exploratory factor analysis in a large community sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study...

Major depressive disorder (MDD) is a common psychiatric disorder and has been a leading cause of disability worldwide. Astrocytes play a role in the maintenance of the function of the central nervous system (CNS), both physiologically and pathologically. Accumulated evidence indicates that the astrocyte is an important contributor to the pathophysiology of MDD including blood-brain barrier (BBB) integrity, gap junctions, gliotransmission, glutamate homeostasis, and energy metabolism. Here, we comprehensively summarize an astroglial basis for MDD based on molecular, cellular, and circuit properties, suggesting that astrocytes appear to be highly sensitive to stress and are likely to be uniquely positioned to integrate peripheral and central stress responses...