Psychological Medicine最新文献

Background: While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.

Methods: Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.

Results: There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation - lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation - higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.

Conclusions: Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

Background: Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the 'Imperial Psychedelic Predictor Scale' (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience.

Methods: Using four independent datasets in which the IPPS was completed prospectively - two online surveys of 'naturalistic' use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) - we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS.

Results: Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of 'mystical', 'challenging', and 'emotional breakthrough' experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance.

Conclusions: Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.

Posttraumatic stress disorder (PTSD) is one of the most serious and incapacitating mental diseases that can result from trauma exposure. The exact prevalence of this disorder is not known as the literature provides very different results, ranging from 2.5% to 74%. The aim of this umbrella review is to provide an estimation of PTSD prevalence and to clarify whether the prevalence depends on the assessment methods applied (structured interview v. self-report questionnaire) and on the nature of the traumatic event (interpersonal v. not-interpersonal). A systematic search of major databases and additional sources (Google Scholar, EBSCO, Web of Science, PubMed, Galileo Discovery) was conducted. Fifty-nine reviews met the criteria of this umbrella review. Overall PTSD prevalence was 23.95% (95% confidence interval 95% CI 20.74-27.15), with no publication bias or significant small-study effects, but a high level of heterogeneity between meta-analyses. Sensitivities analyses revealed that these results do not change after removing meta-analysis also including data from underage participants (23.03%, 95% CI 18.58-27.48), nor after excluding meta-analysis of low quality (24.26%, 95% CI 20.46-28.06). Regarding the impact of diagnostic instruments on PTSD prevalence, the results revealed a lack of significant differences in PTSD prevalence when structured v. self-report instruments were applied (p = 0.0835). Finally, PTSD prevalence did not differ following event of intentional (25.42%, 95% CI 19.76-31.09) or not intentional (22.48%, 95% CI 17.22-27.73) nature (p = 0.4598). The present umbrella review establishes a robust foundation for future research and provides valuable insights on PTSD prevalence.

Background: Preserved ratio impaired spirometry (PRISm) is a new lung function impairment phenotype and has been recognized as a risk factor for various adverse outcomes. We aimed to examine the associations of this new lung function impairment phenotype with depression and anxiety in longitudinal studies.

Methods: We included 369 597 participants from the UK Biobank cohort, and divided them into population 1 without depression or anxiety and population 2 with depression or anxiety at baseline. Cox proportional hazard models were performed to evaluate the associations of lung function impairment phenotype with adverse outcomes of depression and anxiety, as well as their subtypes.

Results: At baseline, 38 879 (10.5%) participants were diagnosed with PRISm. In population 1, the adjusted hazard ratios (HRs) for PRISm (v. normal spirometry) were 1.12 (95% CI 1.07-1.18) for incident depression, and 1.11 (95% CI 1.06-1.15) for incident anxiety, respectively. In population 2, PRISm was a risk factor for mortality in participants with depression (HR: 1.46; 95% CI 1.31-1.62) and anxiety (HR: 1.70; 95% CI 1.44-2.02), compared with normal spirometry. The magnitudes of these associations were similar in the phenotypes of lung function impairment and the subtypes of mental disorders. Trajectory analysis showed that the transition from normal spirometry to PRISm was associated with a higher risk of mortality in participants with depression and anxiety.

Conclusions: PRISm and airflow obstruction have similar risks of depression and anxiety. PRISm recognition may contribute to the prevention of depression and anxiety.

Background: Very late-onset psychosis (VLOP) is associated with higher rates of dementia but the proportion who develop dementia with Lewy bodies (DLB) is unknown. We aimed to identify individuals with VLOP who develop dementia and DLB and characterize the risk factors for progression.

Methods: Anonymized data were retrieved from electronic records for individuals with VLOP. Patients developing dementia after psychosis were identified, in addition to those with >2 core features of DLB at the time of dementia or DLB identified by a natural language processing application (NLP-DLB). Demographic factors, Health of the National Outcome Scale (HoNOS) and symptoms at index psychosis were explored as predictors of progression to dementia.

Results: In 1425 patients with VLOP over 4.29 years (mean) follow up, 197 (13.8%) received a subsequent diagnosis of dementia. Of these, 24.4% (n = 48) had >2 core features of DLB and 6% (n = 12) had NLP-DLB. In cox proportional hazard models, older age and cognitive impairment at the time of psychosis were associated with increased risk of incident dementia. Visual hallucinations and 2+ core features of DLB at index psychosis were associated with increased risk of dementia with 2+ symptoms of DLB but not all-cause dementia. Two or more core features of DLB at index psychosis were associated with 81% specificity and 67% sensitivity for incident NLP-DLB.

Conclusions: In patients with VLOP who develop dementia, core features of DLB are common. Visual hallucinations or two core features of DLB in VLOP should prompt clinicians to consider DLB and support further investigation.

Background: Exposure to adversity in childhood is a risk factor for lifetime mental health problems. Altered pace of biological aging, as measured through pubertal timing, is one potential explanatory pathway for this risk. This study examined whether pubertal timing mediated the association between adversity (threat and deprivation) and adolescent mental health problems (internalizing and externalizing), and whether this was moderated by sex.

Methods: Aims were examined using the Adolescent Brain and Cognitive Development study, a large community sample from the United States. Data were used from three timepoints across the ages of 9-14 years. Latent scores from confirmatory factor analysis operationalized exposure to threat and deprivation. Bayesian mixed-effects regression models tested whether pubertal timing in early adolescence mediated the relationship between adversity exposure and later internalizing and externalizing problems. Sex was examined as a potential moderator of this pathway.

Results: Both threat and deprivation were associated with later internalizing and externalizing symptoms. Threat, but not deprivation, was associated with earlier pubertal timing, which mediated the association of threat with internalizing and externalizing problems. Sex differences were only observed in the direct association between adversity and internalizing problems, but no such differences were present for mediating pathways.

Conclusions: Adversity exposure had similar associations with the pace of biological aging (as indexed by pubertal timing) and mental health problems in males and females. However, the association of adversity on pubertal timing appears to depend on the dimension of adversity experienced, with only threat conferring risk of earlier pubertal timing.

Background: Structural anomalies in the frontal lobe and basal ganglia have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, these findings have been not always consistent because of ADHD diversity. This study aimed to identify ADHD subtypes based on cognitive function and find their distinct brain structural characteristics.

Methods: Using the data of 656 children with ADHD from the Adolescent Brain Cognitive Development (ABCD) Study, we applied unsupervised machine learning to identify ADHD subtypes using the National Institutes of Health Toolbox Tasks. Moreover, we compared the regional brain volumes between each ADHD subtype and 6601 children without ADHD (non-ADHD).

Results: Hierarchical cluster analysis automatically classified ADHD into three distinct subtypes: ADHD-A (n = 212, characterized by high-order cognitive ability), ADHD-B (n = 190, characterized by low cognitive control, processing speed, and episodic memory), and ADHD-C (n = 254, characterized by strikingly low cognitive control, working memory, episodic memory, and language ability). Structural analyses revealed that the ADHD-C type had significantly smaller volumes of the left inferior temporal gyrus and right lateral orbitofrontal cortex than the non-ADHD group, and the right lateral orbitofrontal cortex volume was positively correlated with language performance in the ADHD-C type. However, the volumes of the ADHD-A and ADHD-B types were not significantly different from those of the non-ADHD group.

Conclusions: These results indicate the presence of anomalies in the lateral orbitofrontal cortex associated with language deficits in the ADHD-C type. Subtype specificity may explain previous inconsistencies in brain structural anomalies reported in ADHD.

Background: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

Methods: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

Results: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

Conclusions: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Background: Mood and anxiety disorders are heterogeneous conditions with variable course. Knowledge on latent classes and transitions between these classes over time based on longitudinal disorder status information provides insight into clustering of meaningful groups with different disease prognosis.

Methods: Data of all four waves of the Netherlands Mental Health Survey and Incidence Study-2 were used, a representative population-based study of adults (mean duration between two successive waves = 3 years; N at T0 = 6646; T1 = 5303; T2 = 4618; T3 = 4007; this results in a total number of data points: 20 574). Presence of eight mood and anxiety DSM-IV disorders was assessed with the Composite International Diagnostic Interview. Latent class analysis and latent Markov modelling were used.

Results: The best fitting model identified four classes: a healthy class (prevalence: 94.1%), depressed-worried class (3.6%; moderate-to-high proportions of mood disorders and generalized anxiety disorder (GAD)), fear class (1.8%; moderate-to-high proportions of panic and phobia disorders) and high comorbidity class (0.6%). In longitudinal analyses over a three-year period, the minority of those in the depressed-worried and high comorbidity class persisted in their class over time (36.5% and 38.4%, respectively), whereas the majority in the fear class did (67.3%). Suggestive of recovery is switching to the healthy class, this was 39.7% in the depressed-worried class, 12.5% in the fear class and 7.0% in the high comorbidity class.

Conclusions: People with panic or phobia disorders have a considerably more persistent and chronic disease course than those with depressive disorders including GAD. Consequently, they could especially benefit from longer-term monitoring and disease management.