Psychological Medicine最新文献

Background: Repetitive negative thinking (RNT) and neuroticism are risk factors for internalizing psychopathology. However, their interaction has only been investigated at the self-report level, and studies elucidating their interrelationship at the neural level are lacking. We therefore investigated the interaction of trait RNT and neuroticism with respect to the dynamics of neural networks during negative self-referential processing.

Methods: A sample of 110 healthy subjects reported trait RNT and neuroticism, followed by an RNT induction paradigm during fMRI. Dynamic coactivation pattern (CAP) analysis was used to identify a set of recurring coactivation patterns and to quantify their persistence and count rates. Next, the effects of trait RNT, neuroticism, and their interaction on brain dynamics were tested using regression models.

Results: Negative interactions between RNT and neuroticism were found for persistence and counts of the canonical default mode network (DMN) as well as salience network (SAL) CAP. Simple slope analysis revealed that subjects scoring high on neuroticism exhibited a negative association between trait RNT and DMN as well as canonical SAL dynamics. Furthermore, trait RNT was positively associated with persistence and count rates of a hybrid FPN+DMN coactivation state.

Conclusions: Our results suggest that individuals with high neuroticism who spend more time in SAL and DMN CAPs may be less vulnerable to RNT, potentially reflecting more adaptive network configurations. Furthermore, less segregated CAPs, evident by the concurrent activation of functionally antagonistic networks (FPN+DMN), emerge more often in individuals prone to RNT, likely reflecting disrupted network interactions.

Background: Unpredictability in the child's environment has recently emerged as a significant and unique form of early life adversity (ELA). Cross-sectional studies have linked childhood unpredictability with increased post-traumatic stress disorder (PTSD) symptoms in adults; however, no prospective studies have tested the link between childhood unpredictability and PTSD risk in later life, nor what processes, such as increased anhedonia symptoms, might mediate such risk. Here, we leveraged three distinct prospective, longitudinal cohorts to test the hypothesis that unpredictability during childhood contributes to adult PTSD via worsening anhedonia symptoms.

Methods: Participants were male service members (n=314), adult females (n=170), and adolescents (n=137) recruited for separate longitudinal investigations. All completed dimensional assessments of anhedonia symptoms and PTSD; childhood trauma and childhood unpredictability were measured by the Questionnaire for Unpredictability in Childhood (QUIC). Pearson correlations tested relations between QUIC, anhedonia symptoms, and PTSD symptoms. Mediational models tested whether the link between childhood unpredictability and PTSD is mediated by increased anhedonia symptoms by estimating indirect effects via bootstrapped path analysis.

Results: Childhood unpredictability was associated with increased adult PTSD symptoms in all three cohorts (rs>.19, ps<.016). Further, in all three cohorts, the relationship was partially mediated by higher anhedonia symptoms (bs>0.046, 95% confidence intervals = 0.01-0.12). All effects remained significant when controlling for levels of childhood trauma and removing anhedonia-related PTSD items.

Conclusions: Unpredictability during childhood may confer risk for adult PTSD, and this increased risk may occur via alterations in anhedonia symptoms. Efforts to increase predictability during childhood could enhance resilience to later traumatic events.

Background: DNA methylation influences gene-environment interactions and brain development in bipolar disorder (BD). We aimed to identify BD-associated epigenetic loci and examine their associations with brain structural variation.

Methods: We conducted an epigenome-wide association study (BD group, n = 90; healthy controls group, n = 161) to identify BD-associated DNA methylation loci, and we additionally performed copy number alteration and functional enrichment analyses. The correlations between epigenetic loci and cortical thickness (CT) were assessed using Pearson's partial correlation analysis, and the co-methylation effect of the epigenetic loci identified in the neuroimaging-epigenetic analysis was investigated.

Findings: A total of 156 differentially methylated positions (DMPs) and 7 differentially methylated regions were identified, and the genes associated with them were observed to be enriched in biological processes related to muscle hypertrophy and neuronal activity. Significant correlations between the methylation levels of 13 DMPs associated with three genes (miR886, PLEC1, and ICAM5) and the CT of the right postcentral gyrus and inferior frontal gyrus were identified. Specifically, 10 DMPs associated with the CpG island in the upstream region of the miR886 gene showed negative correlations with the right postcentral gyrus CT, implicating miR886-associated CpG-island methylation in regional cortical thinning.

Conclusion: Epigenetic changes might play an important role in brain structural changes in BD. These multimodal findings nominate miR886-related methylation as a candidate molecular correlate of cortical thinning and warrant replication and mechanistic follow-up in larger, state-diverse cohorts.

Background: Oxytocin (OT) exerts widely modulatory effects on socio-emotional functions in humans, which can be achieved via enhancing the salience of social cues by interacting with the dopaminergic attention system. However, there is a lack of direct evidence for OT modulating attentional processing, with its underlying neural mechanisms remaining to be elucidated.

Methods: In a double-blind, placebo-controlled, between-subject design, 60 healthy male participants were recruited. We combined pharmaco-electroencephalography with two modified tasks (a cue-target visual search [CTVS] task and a face distractor interference [FDI] task) to investigate whether intranasal OT can modulate attentional processing of social cues in top-down versus bottom-up task sets.

Results: In the CTVS task, OT accelerated participants' response time to target faces, which was paralleled by a larger N170 and stronger theta power, suggesting that OT promoted early top-down attentional processing of social cues. In the FDI task, OT inhibited the distractive effect of task-irrelevant emotional faces in the first half of the task via facilitating top-down attentional control to targets as reflected by enhanced attentional selection (increased N2pc) and more efficient attentional processing (decreased P300). However, in the second half, OT switched from facilitating top-down attentional control to potentiating bottom-up attentional capture by emotional face distractors, as evidenced by OT reducing response accuracy but having no effects on the N2pc and P300.

Conclusions: Our findings not only provide evidence for the role of OT in modulating attentional processing of social cues but also lend support to its therapeutic potential in normalizing such attentional deficits.

Background: Cognitive symptoms are common in functional neurological disorder (FND), yet evidence of impaired neurocognitive test performance is variable. We aimed to assess self-reported cognitive symptoms, neurocognitive test performance, and metacognitive confidence in patients with functional seizures (FS) and functional motor symptoms (FMS).

Methods: Participants with FS (n = 50) and FMS (n = 50) were compared to age- and gender-matched healthy controls (HC, n = 50), and clinical controls with depression and/or anxiety disorders (CC, n = 50). The Cambridge Neuropsychological Test Automated Battery was used to examine response speed, working memory, executive functions, and social-emotional processing, with subjective confidence rated for each test. Intellectual functioning, performance validity, and self-reported cognitive symptoms were also assessed.

Results: The FND groups reported elevated cognitive symptoms compared to HC and CC (p-values<0.001). Impaired performance was demonstrated in both FND groups on tests of sustained attention (p-values = 0.03- < 0.001) and set-shifting (p-values = 0.01-0.001). Performance validity was comparable between groups (p = 0.64). The FND groups reported reduced post-diction confidence for sustained attention (p < 0.001). Executive performance deficits correlated with reduced test-specific confidence in FS/FMS (p-values = 0.02- < 0.001). In FMS, post-diction confidence for sustained attention performance correlated negatively with cognitive symptoms (p = 0.002). Cognitive symptoms were associated with psychological/physical symptom load, quality-of-life, and/or general functioning in FND and CC groups (p-values = 0.04- < 0.001).

Conclusions: Patients with FS and FMS displayed localized deficits on tests of executive functioning, with reduced domain-specific metacognitive confidence, alongside significant cognitive symptoms. These neurocognitive features were associated with poorer clinical status, warranting interventions targeting cognitive control and/or cognitive symptoms in everyday life.

Background: Schizophrenia (SZ) is a debilitating psychiatric disorder where patients experience cognitive decline. Antipsychotic drugs alleviate positive symptoms but do not improve cognitive performance. We previously demonstrated that Toll-like receptors (TLRs), involved in cytokine production, can predict cognitive deficits in SZ patients. In this study, we aim to investigate the potential moderating effects of antipsychotic drugs on the associations between cytokines, TLRs, and cognition.

Methods: In total, 280 participants (201 controls and 79 cases of SZ) were recruited in Ireland. Venous blood from the participants was stimulated with TLR ligands. Levels of cytokines were measured from plasma and post-blood stimulation. The participants were administered a battery of cognitive tasks using the Cambridge Neuropsychological Test Automated Battery and Wechsler Adult Intelligence Scale-IIIR. Olanzapine equivalents were calculated using the defined daily dose method.

Results: The results indicate that antipsychotic drug dose does not predict TLR activity or cognition, indicating that antipsychotic drug dose does not have a direct effect on cognition or TLR activity. However, the relationship between TLR4 activity and visual learning and memory is moderated by the antipsychotic drug dose (B = -0.065; p < 0.001), where increasing doses have a decreasing impact on their relationship.

Conclusions: Our data indicate that the dose of antipsychotic drugs alone cannot predict changes in cognitive performance and TLR4-activity. It also suggests that antipsychotic drug doses significantly affect TLR activity and its relationship with cognition. These effects are more pronounced on some domains than others. These findings open up new avenues for understanding the complex interplay between antipsychotic drugs, TLRs, and cognitive deficits in SZ.

Background: Adolescent mental health has worsened, and prevention efforts have become increasingly important. The purpose of this study was to examine longitudinal symptom trajectories of depression and anxiety throughout adolescence, in a contemporary sample. The stress-diathesis model was used to inform potential vulnerability factors and stressors associated with these trajectories.

Methods: Symptoms of depression and generalized anxiety were assessed in a school-based population sample of N = 6102 adolescents (aged 13-14 at baseline). Growth mixture models across four time points were used to model longitudinal trajectories of symptoms. Multinomial regression was used to examine factors associated with each trajectory class.

Results: Of the full sample, 49.5% were female, 45.9% were male, and 4.6% were gender diverse. Four discrete classes for both depression and anxiety trajectories were identified, which comprised consistently low symptoms ('low'; 72.5% depression; 66.9% anxiety), consistently high symptoms ('high'; 11.5% depression; 18.4% anxiety), elevated symptoms that reduced over time ('decreasing'; 8.3% depression; 6.9% anxiety), and low-moderate symptoms that increased over time ('increasing'; 7.7% depression; 7.8% anxiety). Factors associated with poorer trajectories were being female or gender diverse, lower socioeconomic status, higher levels of neuroticism and lower levels of conscientiousness, greater adverse childhood experiences, higher levels of peer problems, bullying victimization, and negative family interactions.

Conclusions: A range of background vulnerabilities and specific stressors were associated with poorer depression and anxiety trajectories over a 3-year period. Prevention approaches may require policy and practice changes that promote more supportive family, school, and societal environments from childhood to adolescence.

Background: Anhedonia is defined as a reduced interest in or inability to experience pleasure from reward-related activities. Recent studies have demonstrated deficient effort-based motivation in anhedonia, but the neural dynamics underlying the interface between effort and reward remain unclear.

Methods: To address this issue, we recruited an anhedonia (ANH) group (N = 40) and a control (CNT) group (N = 40) to complete two tasks: (1) an effort-reward task where participants earned varying rewards by exerting different levels of physical effort and (2) an effort-based decision-making task where they chose between a no-effort option for a smaller reward and a high-effort option for a larger reward. We recorded EEG during both tasks and analyzed the resulting neural responses.

Results: As expected, the ANH group showed reduced reward responses in both self-reported ratings and event-related potential (ERP) data in response to cue stimuli (indexed by the cue-P3) and reward feedback (indexed by the reward positivity). Importantly, the ANH group exhibited inefficient integration between effort and reward, showing an absent effort-discounting effect on the feedback-P3 during reward evaluation and a lack of reward-related theta modulation during effort-based decision-making.

Conclusions: Our findings suggest a neurodynamic motivation model in anhedonia that informs precise interventions for relevant neuropsychiatric disorders.

Background: Although there are several evidence-based treatments for post-traumatic stress disorder (PTSD), up to half of patients do not experience significant symptom relief. Executive functioning (EF) impairment is believed to impede PTSD recovery and diminish treatment response, but is not directly targeted by traditional treatments. Cognitive training for EF has emerged as a promising treatment alternative for PTSD, but may only benefit certain patients. The present study aimed to identify, validate, and characterize the subgroup of patients with PTSD who respond to an EF training program.

Methods: Veterans with PTSD (N = 79) completed neuropsychological tests and a working memory task during functional magnetic resonance imaging scanning, followed by 16 sessions of an EF training program (working memory training [WMT]). Growth mixture modeling identified subgroups based on session-by-session working memory changes. Mixed-effects models then evaluated differences in spatial working memory and PTSD symptom improvement among these subgroups. Finally, the subgroups were compared on baseline neuropsychological performance and neural activity.

Results: Three subgroups were extracted, with one subgroup (labeled low-WM/steep improvement subgroup) exhibiting steeper working memory improvement across training and greater spatial working memory and PTSD symptom improvement following training. The low-WM/steep improvement subgroup was uniquely characterized by a combination of lower EF task performance and lower working memory-related neural activity at baseline.

Conclusions: WMT may be a promising alternative PTSD treatment for Veterans with EF impairments. Patients likely to benefit from WMT could be identified using a combination of neuropsychological and neuroimaging assessments, but further research is needed to confirm these indicators.

Background: Poverty is associated with the severity of common mental health disorders and increased physical comorbidities. However, its effects on severe mental illness (SMI), beyond increasing their incidence, are less understood, especially in low- and middle-income countries. We here examined the relationship between baseline household income and subsequent mental and physical health outcomes in a large cohort of individuals diagnosed with schizophrenia or bipolar disorder in Colombia.

Methods: Retrospective cohort and case-control study using electronic health records from over 5 million Colombians. We identified individuals diagnosed with schizophrenia or bipolar disorder and their baseline household income. Mental health outcomes included third-line antipsychotic treatments (clozapine or antipsychotic polypharmacy) and psychiatric hospitalizations. Physical outcomes included diagnoses of hypertension, type 2 diabetes, and HbA1c levels, compared with rates in individuals without SMI.

Results: We included 12,216 (6,485 women) participants newly diagnosed with bipolar disorder or schizophrenia between 2019 and 2023. Compared to middle-income participants (between $700-1,750USD/month), patients on a low income (less than $700USD/month) were more likely to require third-line antipsychotic treatment (OR 1.84 [1.64, 2.08]) and psychiatric hospitalization (incidence rate ratio 1.30 [1.21, 1.41]). Low-income participants with SMI had hypertension and diabetes rates like middle-income participants without SMI who were 20 years older. However, the combined effect of SMI and low income together posed a less-than-additive risk. Lower income was associated with higher HbA1c levels in diabetes, while a diagnosis of SMI was associated with lower levels.

Conclusions: Low income at SMI onset is associated with worse mental and physical health outcomes.