Psychological Medicine最新文献

Background: Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.

Method: The sample (N = 9350; age 8-21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology ('p') factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors.

Results: The final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively).

Conclusion: By modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.

Background: Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD).

Method: Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (¹H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test.

Results: euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068).

Conclusions: Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Background: Shame is experienced as a threat to social self, and so activates threat-protective responses. There is evidence that shame has trauma-like characteristics, suggesting it can be understood within the same conceptual framework as trauma and dissociation. Evidence for causal links among trauma, dissociation, and psychosis thus warrant the investigation of how shame may influence causal mechanisms for psychosis symptoms.

Methods: This study tested the interaction between dissociation and shame, specifically external shame (feeling shamed by others), in predicting psychotic-like experiences (PLEs) six months later in a general population sample (N = 314). It also tested if social safeness moderates these effects. A longitudinal, online questionnaire design tested a moderation model (dissociation-shame) and a moderated moderation model (adding social safeness), using multiple regressions with bootstrap procedures.

Results: Although there was no direct effect of dissociation on PLEs six months later, there was a significant interaction effect with shame, controlling for PLEs at baseline. There were complex patterns in the directions of effects: For high-shame-scorers, higher dissociation predicted higher PLE scores, but for low-shame-scorers, higher dissociation predicted lower PLE scores. Social safeness was found to significantly moderate these interaction effects, which were unexpectedly more pronounced in the context of higher social safeness.

Conclusions: The results demonstrate evidence for an interaction between dissociation and shame on its impact on PLEs, which manifests particularly for those experiencing higher social safeness. This suggests a potential role of social mechanisms in both the etiology and treatment of psychosis, which warrants further testing in clinical populations.

Background: Attention deficit hyperactivity disorder (ADHD) is increasingly diagnosed in adults. People with intellectual disability have higher rates of ADHD yet there is little evidence on the presentation and pharmacological treatment of ADHD in this population or how this differs from the general population.

Methods: Retrospective cohort study using data from electronic health records. Adults with intellectual disability newly diagnosed with ADHD between 2007 and 2022 were matched to adults with ADHD without intellectual disability and their clinical features and treatments were compared.

Results: A total of 159 adults with ADHD and intellectual disability and 648 adults with ADHD without intellectual disability formed the dataset. Adults with intellectual disability had higher rates of psychiatric co-morbidity and spent more time under mental health services than those without intellectual disability. They were more likely to have recorded agitation, aggression, hostility, and mood instability, and less likely to have poor concentration recorded in the 12 months prior to the diagnosis of ADHD. Following diagnosis, people with intellectual disability were significantly less likely to be prescribed any medication for ADHD than controls without intellectual disability (adjusted odds ratio 0.60, 95% confidence interval 0.38-0.91), and were less likely to be prescribed stimulants (27.7% v 46.0%, p < 0.001).

Conclusions: The presence of behaviors that challenge in adults with intellectual disability may indicate co-occurring ADHD. Further work to define the safety and efficacy of medication for ADHD in adults with intellectual disability is needed to understand differences in prescription rates and to avoid inequities in care outcomes.

Background: We investigated (a) whether polygenic risk for schizophrenia predicts different trajectories of social development among those who have not developed psychoses and (b) whether possible associations are PRS_SCZ-specific or evident also for any polygenic risk for mental disorders, e.g. for major depression.

Methods: Participants came from the population-based Young Finns Study (n = 2377). We calculated a polygenic risk score for schizophrenia (PRS_SCZ) and for major depression (PRS_DEP). Diagnoses of psychotic disorders were derived from the hospital care register. Social development from adolescence to middle age was measured by (a) perceived social support from friends, family, and a close other, (b) perceived sociability, and (c) family structure (partnership status, number of children, age of first-time parenthood).

Results: Among those without manifest psychoses, high PRS_SCZ predicted lower experienced support from friends (B = -0.04, p = 0.009-0.035) and family (B = -0.04, p = 0.009-0.035) especially after early adulthood, and also lower perceived sociability (B = -0.05, p = 0.010-0.026). PRS_SCZ was not related to family structure. PRS_DEP did not predict any domain of social development.

Conclusions: Individuals at high PRS_SCZ (not converted to psychosis) seem to experience a lower preference to be with others over being alone. Individuals with high (v. low) PRS_SCZ seem to have a similar family structure in terms of partnership status or number of children but, nevertheless, they experience less support from their family. Among those not converted to psychosis in a typical age period, high PRS_SCZ may predict a 'later risk phase' and reduced functional resilience when approaching middle age.

Background: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation.

Methods: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls.

Results: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results.

Conclusions: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Background: Adolescence is a key developmental period for the emergence of psychopathology. Reward-related brain activity increases across adolescence and has been identified as a potential neurobiological mechanism of risk for different forms of psychopathology. The reward positivity (RewP) is an event-related potential component that indexes reward system activation and has been associated with both concurrent and family history of psychopathology. However, it is unclear whether the RewP is also associated with higher-order psychopathology subfactors and whether this relationship is present across different types of reward.

Methods: In a sample of 193 adolescent females and a biological parent, the present study examined the association between adolescent and parental psychopathology subfactors and adolescent RewP to monetary and social reward.

Results: Results indicated that the adolescent and parental distress subfactors were negatively associated with the adolescent domain-general RewP. The adolescent and parental positive mood subfactors were negatively associated with the adolescent domain-general and domain-specific monetary RewP, respectively. Conversely, the adolescent and parental fear/obsessions subfactors were positively associated with the adolescent domain-general RewP. The associations between parental and adolescent psychopathology subfactors and the adolescent RewP were independent of each other.

Conclusions: The RewP in adolescent females is associated with both concurrent and parental psychopathology symptoms, suggesting that it indexes both severity and risk for higher-order subfactors.

Background: A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target.

Method: 190 cycling individuals (M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1-6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms.

Results: The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity.

Conclusions: An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.

Background: Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders.

Methods: Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473).

Results: Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVW_forward = 0.13, 95% CI 0.01-0.24).

Conclusions: Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.

Background: A large and accumulating body of evidence shows that loneliness is detrimental for various health and well-being outcomes. However, less is known about potentially modifiable factors that lead to decreased loneliness.

Methods: We used data from the Health and Retirement Study to prospectively evaluate a wide array of candidate predictors of subsequent loneliness. Importantly, we examined if changes in 69 physical-, behavioral-, and psychosocial-health factors (from t₀;2006/2008 to t₁;2010/2012) were associated with subsequent loneliness 4 years later (t₂;2014/2016).

Results: Adjusting for a large range of covariates, changes in certain health behaviors (e.g. increased physical activity), physical health factors (e.g. fewer functioning limitations), psychological factors (e.g. increased purpose in life, decreased depression), and social factors (e.g. greater number of close friends) were associated with less subsequent loneliness.

Conclusions: Our findings suggest that subjective ratings of physical and psychological health and perceived social environment (e.g. chronic pain, self-rated health, purpose in life, anxiety, neighborhood cohesion) are more strongly associated with subsequent loneliness. Yet, objective ratings (e.g. specific chronic health conditions, living status) show less evidence of associations with subsequent loneliness. The current study identified potentially modifiable predictors of subsequent loneliness that may be important targets for interventions aimed at reducing loneliness.