Psychological Medicine最新文献

Major depressive disorder (MDD), smoking, and drinking frequently co-occur, with evidence suggesting these relationships may differ by sex. However, the direction of causality and the extent of sex-specific associations remain unclear. We investigated sex-specific genetic relationships between MDD and substance use phenotypes using genome-wide association studies (GWAS) from the UK Biobank and publicly available sex-stratified GWAS for MDD and problematic alcohol use (PAU). Causal effects were assessed using bidirectional, sex-stratified Mendelian randomization (MR). We further applied multivariable MR (MVMR) to evaluate the influence of socioeconomic status (SES). Genetic correlation analyses indicated significant shared genetic architecture between MDD and all substance use traits in sex-combined GWAS. In sex-specific analyses, the correlation between cigarettes per day and MDD was significantly stronger in females, and drinks per week were correlated with MDD only in females. MR analyses showed that genetic liability to MDD increased the risk of smoking initiation and PAU in females, and was associated with reduced alcohol drinking frequency in males. In contrast, no tested substance use trait showed evidence of a causal effect on MDD in either sex. MVMR adjusting for SES attenuated the association between MDD and smoking initiation. The effect on PAU in females remained. In males, the negative association between MDD and drinking frequency became non-significant after SES adjustment. These findings reveal sex-specific genetic and causal relationships between smoking, drinking, and MDD, and highlight the role of SES as a potential confounder. Incorporating sex and socioeconomic context is critical when examining these associations.

Background: Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing.

Methods: A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle-Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results.

Results: Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact.

Conclusions: Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.

Background: People suffering from common mental disorders (CMDs), such as depression and anxiety, are more likely to be inactive in the labor market. Psychological therapies are highly effective at treating CMDs, but less is known about their impact on long-term labor market outcomes.

Methods: Using national treatment program data in England, NHS Talking Therapies (NHSTT), with unique linkage to administration data on employment and census records, we estimated the effects of NHSTT on employment and earnings. We used an event study approach using individual fixed effects to capture time-invariant confounders and natural recovery.

Results: Overall, completing treatment led to a maximum average increase of £17 in monthly earnings (year 2) and a likelihood of paid employment by 1.5 percentage points (year 7). Those 'Not working, seeking work' saw a maximum average increase in pay of £63 per month (year 7) and a likelihood of paid employment by 3.1 percentage points (year 4). Patients in the younger age groups (25-34 years) saw the largest effect on the likelihood of paid employment by 2.3 percentage points (year 7), followed by those aged 35-44 years with 2.0 percentage points (year 5).

Conclusions: Completion of psychological treatment for CMDs through the national NHSTT program leads to sustained increases in both employment and earnings up to 7 years after the start of treatment. Our findings demonstrate the economic benefits of treating CMDs and how investing in mental health can impact labor market participation.

Background: There is evidence that the two most common subtypes of functional neurological disorder, functional seizures (FSs) and functional motor symptoms (FMDs), have differences between them beyond symptom type, creating debate as to whether they may best be considered distinct disorders. However, most research has studied FS or FMD separately, and the few studies that have directly compared them have been relatively small. We used the large TriNetX electronic health database to see whether the differences previously identified would be confirmed in a larger sample of both subtypes.

Methods: All cases of FMD without FS were compared with cases of FS without FMD, extracted from the TriNetX electronic health records database. Previously identified between-group differences in demographics, comorbidity, and antecedents were compared between groups.

Results: Over 120,000 cases of FMD and FS were extracted. They confirmed that people with FS were significantly younger and had a younger onset than those with FMD, were more likely to be Black and less likely to be Asian, and had higher rates of all comorbid mental health diagnoses, other than somatoform diagnoses, which were more common in FMD. The onset of FS was more commonly preceded by psychological injury, as measured by preceding depression or stress reactions.

Conclusion: The differences between FMD and FS previously identified in small studies were confirmed in this much larger dataset. They provide indirect support for differences in etiology and mechanism, which may in turn support a nosological distinction between FMD and FS.

Background: Neuroimaging studies have consistently revealed neuroanatomical abnormalities in individuals with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). However, it remains unknown whether and to what extent disorder-selective gray matter variations occur in these prominent psychiatric disorders. This study conducted a meta-analysis of 25 years of published voxel-based morphometry (VBM) research to assess the presence of selective and robust neuroanatomical substrates of gray matter variation in BD, MDD, and SZ.

Methods: Peer-reviewed experiments encompassing subjects with target disorders were systematically searched in the MEDLINE database. Additionally, peer-reviewed data on 30 other psychiatric disorders and 65 neurological diseases were obtained from the BrainMap database. Experiments reporting whole-brain group comparisons between patients and healthy controls were included if they identified significant reductions in gray matter morphometry.

Results: The data were analyzed using the Bayes fACtor mOdeliNg algorithm. A total of 1,021 VBM experiments were included, comprising 29,540 patients and 28,177 healthy controls. Primary analyses of psychiatric data revealed strong evidence of gray matter reduction in the right middle temporal gyrus for BD and the posterior dorsal anterior cingulate cortex for SZ (P ≥ 95% selectivity). The robustness of these findings was confirmed using the fail-safe method tailored to the neuroimaging meta-analytic environment. No selective findings were observed in additional analyses that included neurological diseases.

Conclusions: Taken together, these findings offer a framework that underscores the significance of diagnosis-selective neural substrates in psychopathology, a new perspective that could inform distinct pathophysiological processes and assist in diagnosis and treatment.

Maternal depressive symptoms during pregnancy have consequences for offspring brain development, likely mediated via biological signals. However, gestational biological correlates of maternal depression may differ depending on childhood maltreatment (CM) history. We investigated the association of maternal depressive symptoms in pregnancy and CM history with newborn global white matter microstructure. In a sample of N = 90 mother-infant dyads from two cohorts, maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. CM was assessed with the Childhood Trauma Questionnaire or the Adverse Childhood Experiences scale. Diffusion-weighted imaging was performed in the infants within 90 days of birth. Fiber profiles of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were determined, and a global mean for each metric was computed. In adjusted models, there was a significant interaction effect of maternal depression and CM on newborn global FA (β = -0.523, p = .029) and RD (β = 0.590, p = .014) but not AD (β = 0.367, p = .120). In infants of women with CM history, maternal depressive symptoms were correlated negatively with FA and positively with RD. In contrast, infants of women without CM exhibited the reverse pattern of associations between depressive symptoms and diffusion metrics. These findings suggest that the impact of prenatal exposures, such as maternal depressive symptoms, on offspring brain development may be conditional on the presence or absence of maltreatment history. These findings highlight the importance of assessing trauma history and monitoring psychosocial well-being during pregnancy.

Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder. While existing studies have revealed abnormalities in brain structure and function associated with OCD, there is a paucity of research integrating these two aspects, and the transcriptional patterns underlying these abnormalities remain unclear. This study is a multiscale, exploratory investigation designed to generate hypotheses rather than to test causal mechanisms. We aimed to investigate aberrations in brain structure-function coupling (SFC) in OCD patients and, by integrating gene expression profiles and neurotransmitter maps, to explore the potential molecular and genetic bases of these changes. We recruited 100 medication-free OCD patients and 90 healthy controls, and employed multimodal imaging techniques to systematically analyze abnormalities in static SFC in OCD patients. Subsequently, we conducted transcriptomic analysis to identify genes associated with SFC abnormalities and performed spatial correlation analysis with neurotransmitter atlases to investigate potential links between SFC dysregulation and transcriptional patterns. Our findings demonstrated that OCD patients exhibit significant SFC abnormalities in the right temporoparietal junction (rTPJ). These SFC abnormalities are significantly associated with 2,421 gene expression profiles and the serotonin neurotransmitter system. Gene enrichment analysis revealed that these aberrant genes are primarily involved in key biological processes, such as brain development, synaptic signaling, cell projection development, and regulation of neuronal processes. By integrating multimodal imaging, transcriptomic, and neurotransmitter data, this study provides multiscale evidence for the potential molecular basis of SFC abnormalities in the rTPJ of OCD patients, offering preliminary insights into a possible pathological pathway of OCD.

Background: Children with attention-deficit/hyperactivity disorder (ADHD) frequently exhibit impairing emotional dysregulation along with inattention and hyperactivity. We aim to parse the heterogeneity of behavioral and emotional dysregulation in ADHD using latent brain factors based on cortical thickness (CT), and examine associated differences in intrinsic functional connectivity (iFC).

Methods: Data were collected from 123 children (39 ADHD, 47 ADHD with impairing emotional outbursts [ADHD + IEO], 37 neurotypical controls [NT], 5-9.9 years old). First, exploratory factor analysis revealed latent behavioral factors. Using Latent Dirichlet allocation, we decomposed heterogeneous CT patterns into parsimonious latent brain factors. We further investigated the functional relevance of brain regions showing structural differences in the ADHD + IEO group and examined associations between brain and behavioral latent factors.

Results: Among the four behavioral factors identified (Externalizing, Emotion Dysregulation, Internalizing, and Surgency/Impulsivity), the dominant factor - Externalizing behavior - significantly differentiated the ADHD + IEO from the ADHD and NT groups. A conjunction analysis of the three brain factors revealed significantly thicker CT in the dorsolateral prefrontal cortex for ADHD + IEO compared to NT. Using this region as a seed, we found reduced functional connectivity primarily in the default mode network, which differentiated ADHD + IEO and ADHD groups. Structural brain and iFC measures showed significant associations with the Externalizing behavior factor.

Conclusions: Parsing the neurobiology underlying the heterogeneous presentation of ADHD requires integrating multiple modalities and analytical methods. This study demonstrates that combining behavioral, structural, and functional data reveals unique neural features associated with behavioral and emotional dysregulation.