Neural circuit basis of pathological anxiety.

Anxiety disorders are the most prevalent mental health conditions worldwide. Unfortunately, the understanding of the precise neurobiological mechanisms that underlie these disorders remains limited. Current diagnostic classifications, based on observable symptoms rather than underlying pathophysiology, do not capture the heterogeneity within and across anxiety disorders.

Psychiatric Symptoms, Cognition, and Symptom Severity in Children.

Importance: Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms.

Objective: To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children.

Neuroimaging for precision medicine in psychiatry.

Although the lifetime burden due to mental disorders is increasing, we lack tools for more precise diagnosing and treating prevalent and disabling disorders such as major depressive disorder. We lack strategies for selecting among available treatments or expediting access to new treatment options. This critical review concentrates on functional neuroimaging as a modality of measurement for precision psychiatry, focusing on major depressive and anxiety disorders.

Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety.

There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy.

Brain Circuit-Derived Biotypes for Treatment Selection in Mood Disorders: A Critical Review and Illustration of a Functional Neuroimaging Tool for Clinical Translation.

Although the lifetime burden due to major depressive disorder is increasing, we lack tools for selecting the most effective treatments for each patient. One-third to one-half of patients with major depressive disorder do not respond to treatment, and we lack strategies for selecting among available treatments or expediting access to new treatment options. This critical review concentrates on functional neuroimaging as a modality of measurement for precision psychiatry.

Transdiagnostic Mood, Anxiety, and Trauma Symptom Factors in Alcohol Use Disorder: Neural Correlates Across 3 Brain Networks.

Background: Alcohol use disorder (AUD) is associated with high rates of trauma, mood, and anxiety disorders. Across these diagnoses, individual symptoms substantially overlap, highlighting the need for a transdiagnostic approach. Furthermore, there is limited research on how transdiagnostic psychopathology impacts the neural correlates of AUD.

Heritability of cognitive and emotion processing during functional MRI in a twin sample.

Despite compelling evidence that brain structure is heritable, the evidence for the heritability of task-evoked brain function is less robust. Findings from previous studies are inconsistent possibly reflecting small samples and methodological variations. In a large national twin sample, we systematically evaluated heritability of task-evoked brain activity derived from functional magnetic resonance imaging.

A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder.

Background: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible.

Features of immunometabolic depression as predictors of antidepressant treatment outcomes: pooled analysis of four clinical trials.

Background: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

Aims: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Method: Data on 2551 individuals with depression across the iSPOT-D ( = 967), CO-MED ( = 665), GENDEP ( = 773) and EMBARC ( = 146) clinical trials were used.

Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans.

Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.

Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice.

Psychiatric disorders are associated with significant social and economic burdens, many of which are related to issues with current diagnosis and treatments. The coronavirus (COVID-19) pandemic is estimated to have increased the prevalence and burden of major depressive and anxiety disorders, indicating an urgent need to strengthen mental health systems globally. To date, current approaches adopted in drug discovery and development for psychiatric disorders have been relatively unsuccessful.

Negative association between anterior insula activation and resilience during sustained attention: an fMRI twin study.

Background: While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.

Methods: The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure.

A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Cognitive deficits in depression have been associated with poor functional capacity, frontal neural circuit dysfunction, and worse response to conventional antidepressants. However, it is not known whether these impairments combine together to identify a specific cognitive subgroup (or "biotype") of individuals with major depressive disorder (MDD), and the extent to which these impairments mediate antidepressant outcomes.

Objective: To undertake a systematic test of the validity of a proposed cognitive biotype of MDD across neural circuit, symptom, social occupational function, and treatment outcome modalities.

UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice.

The effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged iDISCO+ cleared tissue with light sheet fluorescence microscopy (LSFM) to examine the impact of environmental context on psilocybin-elicited neural activity at cellular resolution. Voxel-wise analysis of c-Fos-immunofluorescence revealed clusters of neural activity associated with main effects of context and psilocybin-treatment, which were validated with c-Fos cell density measurements.

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis.

Introduction: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking.

Predicting wellbeing over one year using sociodemographic factors, personality, health behaviours, cognition, and life events.

Various sociodemographic, psychosocial, cognitive, and life event factors are associated with mental wellbeing; however, it remains unclear which measures best explain variance in wellbeing in the context of related variables. This study uses data from 1017 healthy adults from the TWIN-E study of wellbeing to evaluate the sociodemographic, psychosocial, cognitive, and life event predictors of wellbeing using cross-sectional and repeated measures multiple regression models over one year. Sociodemographic (age, sex, education), psychosocial (personality, health behaviours, and lifestyle), emotion and cognitive processing, and life event (recent positive and negative life events) variables were considered.

Associations between mental wellbeing and fMRI neural bases underlying responses to positive emotion in a twin sample.

Background: Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment.

Methods: We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task.

Association of Changes in Neural Targets and Dietary Outcomes among Patients with Comorbid Obesity and Depression: Post hoc Analysis of ENGAGE-2 Mechanistic Clinical Trial.

Background: Disruptions in brain circuits that regulate cognition and emotion can hinder dietary change and weight loss among individuals with obesity and depression.

Objective: The study aimed to investigate whether changes in brain targets in the cognitive control, negative affect, and positive affect circuits after 2-mo problem-solving therapy (PST) predict changes in dietary outcomes at 2 and 6 mo.

Methods: Adults with obesity and depression from an academic health system were randomly assigned to receive PST (7-step problem-solving and behavioral activation strategies) over 2 mo or usual care.