Research Briefing

This study presents a multimodal, systems-level map of the human brain histamine system, integrating transcriptomics, molecular imaging, developmental trajectories and cognitive meta-analysis. The findings link histaminergic system architecture to higher-order cognition and vulnerability to major psychiatric disorders.

Difficulty updating one’s beliefs to reflect changing circumstances — ‘belief stickiness’ — might underpin some forms of inflexibility. We found that increasing serotonin decreased belief stickiness and that obsessions were associated with increased belief stickiness. These findings uncover a new role for serotonin and could have implications for the treatment of obsessions.

Adolescence is a crucial period of brain maturation and rising risk for mental health. Using longitudinal neuroimaging and genetic data from over 11,000 youths, this study shows that genetic susceptibility to systemic inflammation is associated with accelerated cortical thinning and increased externalizing psychopathology, suggesting a neuroimmune pathway underlying psychiatric vulnerability.

We used artificial intelligence (AI) to map pan-disease dimensions — disease subtypes across an array of organ-specific disorders — from imaging data of the brain, eye and heart that captured shared and organ-specific heterogeneity. We then showed how these AI-derived dimensions can predict future risks of disease and mortality, provide insights into clinical trials, and inform potential drug targets.

Evidence from national medical records of over 8 million people in the Netherlands shows that autism is associated with increased risk of cardiometabolic conditions. These associations emerged in adolescents and young adults, suggesting earlier onset of such conditions in individuals with autism than in individuals without it.

A large-scale global meta-analysis highlights the efficacy of creative arts-based interventions in reducing symptoms of post-traumatic stress disorder (PTSD) among children and adolescents, especially those from underrepresented, non-Western populations.

Residents of low-latitude megacities face rising humid-heat vulnerability as climate warms. We reveal that humid heat — especially at night — worsens the current morbidity burden of mental and behavioral disorders (MBDs) in Shanghai more than high temperatures alone. We project that high greenhouse gas emissions will sharply increase the morbidity burden of MBDs by the 2090s, stressing the need for mitigation.

This precision medicine trial shows that guanfacine, a selective α_2A adrenoreceptor agonist, restores the function of the cognitive control circuit in patients with the cognitive biotype of depression. Circuit engagement was accompanied by improved cognition and high response and remission rates. Thus, targeted treatments show potential to accelerate personalized psychiatric care.

Our analyses of multimodal data from brain magnetic resonance imaging and body dual-energy X-ray absorptiometry in adults reveal that fat accumulation in specific body regions contributes to differential neural vulnerabilities and cognitive aging, independently of body mass index.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment for depression. However, few studies have explored whether pretreatment functional neuroimaging can be used to predict rTMS-induced changes in depressive symptoms. Using machine learning, we identified that changes in a distinct symptom cluster of core mood and anhedonia, could be predicted more accurately than overall symptom severity.

Restrictive eating disorders, including anorexia nervosa and avoidant/restrictive food intake disorder, present with severe underweight but differ in their clinical presentations and psychiatric comorbidities. Distinguishing brain alterations primarily driven by low BMI from those associated with eating disorder and comorbidity-related pathophysiology remains a crucial challenge that we aimed to address in this study.

One in three stroke survivors experience depression or anxiety, but no large-scale studies of real-world clinical practice have assessed whether psychological therapies are beneficial for these patients. We analyzed national healthcare records in England to evaluate the effectiveness of primary care psychological therapies for stroke survivors with common mental disorders.

Genetic variants and regions associated with cannabis use disorder (CanUD) and cannabis use also influence a range of psychiatric traits. We used genetic methods to demonstrate increased risk caused by CanUD of developing several psychiatric disorders, and that psychiatric disorders also increase CanUD risk. There were genetic differences between cannabis use and CanUD.

Greater genetic susceptibility to schizophrenia is associated with thinner retinal structures — the macula, as well as both the outer retina and the inner retina. Biological pathways associated with neuroinflammation, which play a part in schizophrenia, might be involved in retinal thinning mechanisms.

The role and effects of traumatic brain injury (TBI) on the development of chronic long-term health conditions are unclear. This umbrella review of existing systematic reviews and meta-analyses synthesizes the effects of TBI on risk of physical and mental health disorders and discusses implications for research and clinical management.

We showed, in multiple population-based birth cohorts, that blood-based DNA methylation partially explains the relationship between childhood adversity and adolescent depressive symptoms. DNA-methylation sites across the epigenome could explain an increased risk of depression but, unexpectedly, other sites also served as markers of resilience against the effects of childhood adversity on depression risk.

Using multimodal brain imaging and organ-specific physiological markers from more than 18,000 adult participants of the UK Biobank database, this study reveals integrated pathways that explain the interplay between brain, body, environment and lifestyle, and their collective influence on mental health outcomes.

Analyses of functional MRI brain images of young people with depression revealed that altered brain connectivity associated with this disorder is circumscribed to specific networks and hub regions, including the default mode and attentional networks. The magnitude of these connectivity changes is a reliable predictor of depression symptom severity.

Mood dysfunction is more common in people with brain tumors than in those with other tumor types, but the reasons for this association are unclear. Using various methods for lesion–symptom mapping, we identified brain locations in patients with diffuse glioma that are related to severe depressive symptoms or an absence of depressive symptoms.

Postpartum depression (PPD) is a major public health concern, yet we lack tools to predict PPD during pregnancy. We found that lower sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle response, can predict risk of PPD in women who were not depressed during their pregnancy.