Psychological Medicine

The present study focuses on the role of amygdala reactivity to negative facial expressions in major depressive disorder (MDD). A number of studies have found amygdala hyperreactivity in depressed patients compared with control subjects. This has been interpreted in terms of a negative depressive bias in attention and memory, given the amygdalas role in attending to and remembering negatively valenced stimuli. However, failure to find amygdala hyperreactivity in depression is not uncommon, and a...

BackgroundExercise therapy reduces depressive and anxiety symptoms, but its neural mechanisms are not fully understood. We examined whether and how running therapy reorganizes dynamic brain functional connectivity in affective disorders. MethodsAt baseline, resting-state fMRI was collected from 66 healthy controls and 50 individuals with affective disorders. Co-activation patterns analyses (CAPs) identified recurring whole-brain network states characterized by spatial patterns of regional co-ac...

BackgroundAntidepressants exert their therapeutic effects through ameliorating negative emotional biases that underpin depression. However, therapeutic gains may depend upon restructuring how emotional information is processed. This can be achieved through Cognitive Bias Modification (CBM), a technique for positively shifting recognition of emotional facial expressions. Here, we examined how CBM modifies emotional processing circuits in individuals with depression who were taking Selective Serot...

BackgroundBorderline personality disorder (BPD) involves emotional instability and stress sensitivity linked to oxytocinergic and HPA-axis dysregulation. This study examined oxytocin and cortisol responses to acute psychosocial stress and the modulatory effects of SSRIs and hormonal contraception. Methods93 female participants (45 with BPD with/without SSRIs and 48 healthy controls) underwent the Trier Social Stress Test. Linear and generalized linear mixed-effects models were applied to assess...

ObjectiveIn response to a clinical observation of an Anorexia Nervosa (AN) patient with family history of Parkinsons Disease (FHoPD), and evidence of similarities in dopamine function, personality, anxiety and weight loss symptoms between AN and PD, we completed a pilot study to estimate FHoPD in families of those with eating disorders (EDs). MethodWe ascertained FHoPD among ED patients and community participants, and estimated relative risks (RRs) for AN, Bulimia Nervosa (BN) and Binge Eating ...

Isolating specific cognitive effects of antidepressant drugs is crucial to develop targeted and individualized treatment selection in psychiatry. In this double-blind, placebo-controlled study in healthy controls, we used computational modeling to characterize the cognitive effects of two classes of drugs for depression, escitalopram, a typical SSRI which increases serotonergic transmission, and agomelatine, which activates melatonin receptors and antagonizes 5-HT2C serotonergic receptors. 128 h...

BackgroundBipolar disorder (BIP) frequently co-occurs with heightened substance use (SU) and substance use disorders (SUDs). Although the strong co-occurrence of these heritable traits points to shared genetic susceptibility, the extent to which there are differences in how SU and SUD overlap with BIP genetic architecture remains unclear. MethodsWe quantified the polygenic overlap between BIP and SUDs (alcohol, cannabis, opioid, and tobacco), and BIP and SU traits (drinks per week, lifetime can...

BackgroundMajor depressive disorder (MDD) involves immune-metabolic dysregulation, psychosocial adversity, and multidomain cognitive disturbances, yet single cognitive indices often show small and inconsistent effects. We derived a multivariate Cambridge Neuropsychological Test Automated Battery (CANTAB)-based cognitive phenotype ("cognitype") and tested whether it adds explanatory value beyond adverse childhood experiences (ACEs) and an acute-phase protein (APP) index in acute-phase MDD. Metho...

Deficits in inhibitory control are common across a wide range of psychiatric disorders and are closely linked to symptom severity, including emotional dysregulation, anxiety, substance misuse, and self-harm, making them an appealing target for intervention. Cognitive training offers a low-cost, scalable, and non-invasive strategy to strengthen inhibitory control; however, most existing paradigms target only a single facet of inhibition and rarely account for environmental influences, such as aff...

BackgroundImpairments in cognitive functioning (CF) contribute to the onset, severity, and persistence of psychiatric symptoms. While specific CF domains may relate differentially to psychopathology, evidence also supports a general factor of cognitive impairment (the C-factor). We aimed to examine how general and domain-specific CF impairments relate to psychopathology using both diagnosis-specific and transdiagnostic symptom frameworks. MethodsData were drawn from five cognitive tasks adminis...

BackgroundTransdiagnostic genetic factor models organize shared liability across psychiatric disorders, but they may leave systematic pairwise genetic overlap unexplained. MethodsUsing publicly available PGC cross-disorder LD score regression genetic correlations and published five-factor genomic SEM parameters, we computed model-implied disorder correlations and derived edge-level residual genetic correlations (observed minus model-implied) for all disorder pairs. We summarized residual misfit...

ObjectiveTo identify immunomodulatory drug targets with genetic evidence in major depressive disorder (MDD), probe symptom-level heterogeneity in their effects, and identify drug repurposing opportunities. MethodsWe used cis-Mendelian randomisation to evaluate the targets of 204 immunomodulatory compounds, including immunosuppressants, cytokine inhibitors, and anti-infectives. As exposures, we selected genetic instruments from nine genome-wide association studies (GWASs) of protein or gene tran...

Bullying is an adverse childhood experience affecting up to one-third of the global population and linked to psychosis-like experiences (PLEs), which increase the risk of psychotic disorders. This study aimed to investigate the association between the severity and persistence of bullying and PLEs and the neurobiological pathways from bullying to psychosis-like experiences by assessing multiscale brain functional network connectivity (msFNC). We used data from the ABCD Study, a large, ongoing, mu...

Evidence-based psychotherapies are first-line treatments for psychiatric disorders, yet response rates remain suboptimal. Noninvasive brain stimulation (NIBS) may augment psychotherapy by modulating treatment-engaged circuits. We conducted a systematic review and meta-analysis of randomized controlled trials comparing active NIBS plus evidence-based psychotherapy versus sham NIBS plus psychotherapy. Following Cochrane methods, we searched six databases through February 2025, screening 1,017 reco...

Trauma is an established risk factor for a diverse range of psychiatric disorders. This effect on risk is widely thought to be mediated, at least partially, by the deleterious impact of trauma on brain structure and function. We tested this neurobiological mediation hypothesis in 670 adults (40% male; age 18-45 years, M = 29.60, SD = 7.67) with diverse psychiatric histories who undertook self-reported and interview-based assessment of psychopathology along with magnetic resonance imaging (MRI). ...

Numerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of this study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show...

BackgroundAdolescents with a parental history of bipolar disorder (BD; High-Risk) are more likely to develop BD than those without such history (Low-Risk). Actigraphy studies in adults indicate that instability in sleep and rest-activity rhythms (RAR) may be associated with progression to BD. However, it remains unclear whether High-and Low-Risk adolescents are differentially affected by sleep/RAR instability and their impact on emerging mood symptoms. MethodsWe recruited 50 adolescents unaffec...

BackgroundAn accelerated schedule of intermittent theta burst stimulation (aiTBS) has been shown to improve clinical efficacy of transcranial magnetic stimulation for bipolar disorder (BD) and major depressive disorder (MDD). We investigated the functional connectivity changes underpinning clinical effects of aiTBS on transdiagnostic treatment-resistant depression (TRD). MethodsData were collected from two studies: an open-label active aiTBS study for MDD and a double-blind, randomized control ...

BackgroundEmerging evidence suggests that cognitive impairment cuts across traditional psychiatric diagnoses and may reflect a shared underlying cognitive liability. We examined whether a general cognitive factor (gFc) accounts for transdiagnostic deficits across schizophrenia (SZ), bipolar disorder (BD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD). MethodsA total of 472 affected individuals and 253 population healthy controls (HC) completed a standardized cognitive bat...

Background and aimsGambling-related cognitive distortions (GRCD) are closely linked to problem gambling symptom severity (PGSI) and are associated with superstitious and delusional ideation, as well as indirectly with conspiracy beliefs. Although conceptually distinct, these different belief domains share core features (e.g., erroneous beliefs about causal structure) and may be related to compulsivity. The latent factor structure underlying these belief domains is poorly understood. This preregi...