Psychological Medicine

BackgroundAnhedonia is a core symptom of major depressive disorder (MDD). While its narrow definition as a hedonic or consummatory deficit evolved to encompass anticipatory and motivational reward facets, it remains unclear where reward deficits manifest. As evidence accumulates for metabolic hormones affecting reward processing, studying their role in mitigating reward deficits could yield crucial insights. Here, we compare food reward ratings between patients with MDD and healthy control parti...

BackgroundDepressive (DD) and bipolar (BD) disorders are characterized by biases in anticipating and encoding emotional information. Depressive traits are linked to negative affective biases, while hypomanic features are associated with heightened responsiveness to positive stimuli. The vividness of visual imagery may further modulate these biases. This study examined how lifetime dimensional symptoms of depression and hypomania across diagnoses interact with imagery vividness to modulate brain ...

Eating disorders--including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder--are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge-eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six loci associated with BE, including loci associat...

ImportanceAnxiety disorders are often comorbid with general medical conditions, but the extent and directionality of these associations and shared genetic risk factors are not well understood. ObjectiveTo investigate the potential associations and the directionality between anxiety disorders and general medical conditions, and to explore the underlying shared genetic risk. DesignWe used FinnGen data since the beginning of the registries or in Cox regression analyses between 2011 and 2022. Set...

BackgroundAnorexia Nervosa (AN) has a high mortality rate and often a chronic illness course, yet few existing treatments are effective. AN is heritable and shares genetic architecture with cardiometabolic traits, while the relationship to metabolomic markers is unknown. MethodsWe analyzed genome-wide association studies (GWAS) of 249 circulating plasma metabolomic biomarkers and AN to map their shared genetic architecture and compare with related mental health, anthropometric and cardiometabol...

BackgroundKetamine is increasingly used as a therapeutic option for treatment-resistant depression (TRD) due to its rapid antidepressant properties, yet the mechanisms underlying these effects remain elusive. Preclinical evidence suggests ketamine acts on neural pathways implicated in reward processing, but translational efforts have proven challenging, due to a lack of paradigms allowing for analogous assessment of depressive phenotypes across species. Here, we investigated the effects of a sin...

BackgroundFatigue is a central symptom of major depressive disorder (MDD). Research in healthy individuals has shown that heightened feelings of fatigue are associated with a reduced willingness to exert effort. However, it remains unclear how fatigue affects effort-based decision-making in individuals with MDD. In this study, we explore how cognitive effort is traded for rewards in MDD and how feelings of fatigue and depressed mood symptoms influence this decision-making process. MethodsHealth...

BackgroundThe sense of agency, or the belief in action causality, is an elusive construct that impacts day-to-day experience and decision-making. Despite its relevance in a range of neuropsychiatric disorders, it is widely under-studied and remains difficult to measure objectively in patient populations. We developed and tested a novel cognitive measure of valence-modulated agency perception in an in-person and online cohort. MethodsThe in-person cohort consisted of 52 healthy control subjects ...

BackgroundTranscranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex has mild to moderate antidepressant effects. Little is known about the mechanisms of action. Other antidepressant treatments have been shown to act in part by reducing negative biases, which are thought to play a causal role in the maintenance of depression. Negative biases are hypothesized to stem from aberrant reinforcement learning processes, more precisely from overestimation of the informative...

Eating disorders (EDs) are complex psychiatric conditions that often emerge during adolescence, and affected individuals frequently demonstrate high rates of psychiatric comorbidity, particularly with depressive and anxiety disorders. Although risk for EDs reflects both genetic and neurobiological factors, knowledge of how genetic risk for EDs relates to neurobiology and psychiatric symptoms during critical developmental periods remains limited. We therefore implemented a novel multivariate fram...

BackgroundEating disorders are severe psychiatric conditions associated with high mortality rates, particularly among young people. These disorders often co-occur with self-harm and suicidal ideation, yet the temporal dynamics between these variables remain poorly understood. AimsThis study aims to elucidate the longitudinal associations between eating disorder symptoms, self- harm, and suicidal ideation using structural equation modelling. MethodRepeated measures of these phenotypes were used...

Impulsivity can be a risk factor for serious complications for those with mood disorders. To understand intra-individual impulsivity variability, we analyzed longitudinal data of a novel gamified digital Go/No-Go (GNG) task in a clinical sample (n=43 mood disorder participants, n=17 healthy controls) and an open-science sample (n=121, self-reported diagnoses). With repeated measurements within-subject, we disentangled two aspects of GNG: reaction time and accuracy in response inhibition (i.e., i...

BackgroundEven though anxious depression is among the most prevalent psychiatric conditions; its underlying neural and behavioral characteristics remain not well understood. This may be important to break down heterogeneity in depression. This study investigated the unique profile of individuals with anxious depression using affective startle modulation, a process known to independently probe appetitive/defensive systems and known to be affected by mood and anxiety disorders Methods236 depresse...

BackgroundEating disorder treatment is most successful when delivered at first onset, underscoring the importance of early intervention. UK patients transition from child to adult services at age 18, a process often poorly supported. Genetic factors may contribute to earlier onset, but molecular genetic research into symptom onset and severity remains limited. AimsWe investigated (1) age at onset of behavioural symptoms and low weight, including sex differences, (2) the SNP-based heritability a...

Constitutional thinness and anorexia nervosa are both characterised by persistent, extremely low weight with body mass indices (BMI) below 18.5 kg/m2. Individuals with anorexia nervosa concurrently show distorted perceptions of their own body and engage in weight-loss behaviours, whereas individuals with constitutional thinness typically wish to gain weight. Both are heritable, share genomics with BMI, but have not been shown to be genetically correlated with each other. We aim to differentiate ...

Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetic factors in the expression of eating disorders and OCD/anxiety phenotypes. We examined whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorders, OCD, and anxiety symptoms in a large population-based developmental cohort. Using summary...

BackgroundOvergeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and were previously associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal areas. In a previous study, remitted MDD patients successfully modulated guilt-selective rSATL-subgenual cingulate connectivity using real-time functional magnetic resonance imaging (rtfMRI) neurofeedback training, thereby increasing th...

Major depressive disorder (MDD) exhibits psychomotor retardation which concerns abnormal slowness of both thoughts and movements. In the current study, we investigated whether such psychomotor disturbance also disrupts the MDD subjects ability to synchronize their movements to a rhythmic tone sequence. We found that the timing between finger taps and tones is altered for MDD subjects (N=38), compared with healthy controls (N=65), mainly when tones are presented at a low frequency below 1 Hz. No ...

IMPORTANCEElectroconvulsive therapy (ECT) is an effective medical procedure for patients with treatment-resistant depression. However, quantitative neural and behavioral measures that characterize how patients respond to ECT treatment are largely lacking. OBJECTIVEDetermine whether neurocomputational models that integrate information about adaptive learning behavior and associated affective experiences can characterize neurobehavioral changes in patients whose depression improves following ECT ...

Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism. To investigate fundamental links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to pu...