Reviews & Analysis

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.

In this Perspective, Singh et al. examine the growing role of patient and public participation, involvement and engagement in discovery science, highlighting the need for clearer guidance in the context of youth mental health research.

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.

This Review provides a critical assessment of current mechanistic and clinical evidence on the interaction between the gut microbiota and mental health to differentiate causative, correlative and bidirectional roles of the gut microbiota in psychiatric disorders. It highlights current priority questions and provides recommendations for the standardization of future studies.

This Perspective presents the developmental origins of mental health and disorders (DOMHaD) framework, emphasizing genetic, environmental and epigenetic influences on psychiatric conditions. It highlights interactions over time, revealing pathways for understanding, preventing and treating these complex disorders effectively.

The authors of this Perspective discuss the impact of SSRIs on child development during maternal depression, addressing methodological challenges and emphasizing the necessity of considering various intersecting factors influencing perinatal mental health, treatment and developmental outcomes for offspring.

This Perspective challenges the traditional approaches to suicide prevention research, which are often rooted in studies from high-income countries. It advocates for culturally informed, community-based strategies, drawing on successful examples from the global south.

Major depressive disorder (MDD) exhibits sex-specific differences in onset, symptoms and treatment response, yet biomarkers for guiding sex-specific interventions remain unidentified. Here the authors propose the use of resting-state functional magnetic resonance imaging to uncover sex-based neural differences in MDD, advocating for larger studies to enhance diagnostic tools and personalized treatments.

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.

Adolescents and young adults face unique ethical challenges in digital health interventions due to their developmental and technological needs. Here the authors identify critical ethical gaps in digital health interventions research for this population and emphasize the need to co-design ethical guidelines with youth, particularly those from marginalized backgrounds, rooted in core principles, such as autonomy, beneficence and justice.

In this Perspective, the authors review evidence suggesting that stimulating posterior regions such as the occipital cortex and cerebellum could offer new therapeutic avenues, potentially enhancing TMS efficacy across various psychiatric conditions.

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.

Adolescence marks a critical period for the onset of depression, yet the neurobiological mechanisms remain unclear. Here the authors review literature linking adolescent brain development to depression risk, emphasizing the need for both large-scale and focused studies to refine methodologies and enhance understanding of neural influences on youth depression.

This Perspective highlights the important role of energy metabolism in psychiatric disorders and sets the groundwork for future studies in the emerging field of metabolic psychiatry.

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.

In this Perspective, the authors cover what is known about anxiety and depression symptoms and sleep disturbance in relation to Alzheimer disease pathology and cognitive decline.

In this Perspective, the authors discuss the need to address the women’s brain health gap and its link to the concept of brain capital.

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.

Whiskey et al. discuss the reasons for the underuse of clozapine among Black individuals with treatment-resistant schizophrenia and propose changes to enhance clinicians’ confidence in prescribing it to this population.