Psychological Medicine最新文献

Background: Stressful life events (SLEs) increase the risk for subsequent major depression (MD) episodes. Most prior studies of SLEs utilized questionnaires or interview-based assessments. We sought to develop and evaluate an environmental risk score (ERS) for MD from multiple classes of SLEs obtained from national Swedish registries.

Methods: We assessed, in the entire adult population of Sweden (n = 7,105,712), the occurrence of 52 categories of SLEs derived from registry information for the 6 months prior to January 9, 2010 and the risk for MD registration over the subsequent 6 months. Weights for our ERS were obtained from a random half of our sample and ERS and its relationship to MD risk was evaluated in the second half.

Results: The ERS was robustly related to risk for subsequent MD episodes. Women were more sensitive to the depressogenic effect of the ERS than men. Those with prior episodes of MD had larger absolute increases in MD risk from our ERS than those without previous episodes. Genetic risk for MD was associated with a greater sensitivity to the depressogenic effects of the ERS. A co-sibling control analysis suggested that most, but not all, of the association between ERS and subsequent risk for MD was causal.

Conclusions: Valid measures of SLEs that predispose to risk for MD can be assessed from high-quality registry data. While not all event categories (e.g. interpersonal or romantic difficulties) can be assessed, this method avoids problems with accurate dating and recall bias and can be performed in very large samples.

Background: We seek to clarify how changes in the prevalence of drug use disorder (DUD) in Sweden in the 1950-1990 birth cohort impact the aggregation and co-aggregation in siblings of DUD and alcohol use disorder (AUD).

Methods: We examined risk for DUD and AUD in siblings of 102,624 DUD cases and matched control probands and 123,837 AUD case and matched control probands identified using Swedish registries. Flexible parametric survival models assessed the difference in disorder risk in siblings of case versus control probands.

Results: Over birthyears 1950-1990, rates of DUD increased substantially in the Swedish population. In siblings of DUD cases versus controls, the risk for DUD increased dramatically starting in birthyear 1965 while their risk for AUD fell moderately. A similar, but less pronounced pattern, was seen in the siblings of AUD versus control probands. These differences were much larger in male than in female siblings.

Conclusions: The factors that drove upward population rates of DUD in Sweden (e.g. increased availability, reduced stigma) produced much stronger effects in high-risk subjects (siblings of DUD and AUD probands) than in normal risk groups (siblings of controls), thereby increasing familial aggregation of DUD. However, parallel declines in AUD rates in high-risk versus normal-risk siblings were observed, likely due to 'competitive effects' reducing coaggregation of DUD and AUD. Results of genetic studies of substance use disorders can be substantially impacted by changes in availability and stigma of psychoactive substance use and indirectly by 'competition' as predicted by behavioral economic models, between abusable substances.

Background: Numerous studies have explored the relationship between brain aging and major depressive disorder (MDD) and attempted to explain the phenomenon of faster brain aging in patients with MDD from multiple perspectives. However, a major challenge in this field is elucidating the ontological basis of these changes. Here, we aimed to explore the relationship between brain structural changes in MDD-related brain aging and neurotransmitter expression levels and transcriptomics.

Methods: Imaging data from 670 Japanese participants (MDD: health controls = 233:437) and the support vector regression model were utilized to predict and compare brain age between MDD patients and healthy controls. A map of differences in cortical thickness was generated, furthermore, spatial correlation analysis with neurotransmitters and correlation analysis with gene expression were performed.

Results: The degree of brain aging was found to be significantly higher in patients with MDD. Moreover, significant cortical thinning was observed in the left ventral area, and premotor eye field in patients with MDD. A significant correlation was observed between MDD-related cortical thinning and neurotransmitter receptors/transporters, including dopaminergic, serotonergic, and glutamatergic systems. Enriched Gene Ontology terms, including protein binding, plasma membrane, and protein processing, contribute to MDD-related cortical thinning.

Conclusions: The findings of this study provide further evidence that patients with MDD experience more severe brain aging, deepening our understanding of the underlying neural mechanisms and genetic basis of the brain changes involved. Additionally, these findings hold promise for the development of interventions aimed at preventing further deterioration in MDD-related brain aging, thus offering potential therapeutic avenues.

Background: Suicidal thoughts and behaviors (STBs) are a major concern in people with psychotic disorders. There is a need to examine their prevalence over long-term follow-up after first-episode psychosis (FEP) and determine their early predictors.

Methods: Of 510 participants with FEP evaluated on 26 risk factors for later outcomes, 260 were reassessed after 21 years of follow-up for lifetime ratings of most severe suicidal ideation, number of suicide attempts, and lethality of the most severe attempt. Risk factors and STB outcomes were modeled using hierarchical linear regression analysis.

Results: Over the 21-year follow-up period, 62.7% of participants experienced suicidal thoughts, 40.8% attempted suicide, and 18 died of suicide (3.5% case fatality and 20.6% proportionate mortality). Suicidal ideation was independently predicted by parental socioeconomic status, familial load of major depression, neurodevelopmental delay, poor adolescence social networks, and suicidal thoughts/behavior at FEP. The number of suicide attempts was independently predicted by years of follow-up, familial load of major depression, obstetric complications, childhood adversity, and suicidal thoughts/behavior at FEP. Lethality was independently predicted by familial load of major depression, obstetric complications, neurodevelopmental delay, and poor adolescence social networks. The proportion of variance in suicidal ideation, attempts, and lethality explained by the independent predictors was 29.3%, 21.2%, and 18.1%, respectively.

Conclusions: STBs are highly prevalent in psychotic disorders and leads to substantial morbidity and mortality. They were predicted by a number of early risk factors, whose clinical recognition should contribute to improved prediction and prevention in people with psychotic disorders.

Background: Novel ultrasound neuromodulation techniques allow therapeutic brain stimulation with unmet precision and non-invasive targeting of deep brain areas. Transcranial pulse stimulation (TPS), a multifrequency sonication technique, is approved for the clinical treatment of Alzheimer's disease (AD). Here, we present the largest real-world retrospective analysis of ultrasound neuromodulation therapy in dementia (AD, vascular, mixed) and mild cognitive impairment (MCI).

Methods: The consecutive sample involved 58 patients already receiving state-of-the-art treatment in an open-label, uncontrolled, retrospective study. TPS therapy typically comprises 10 sessions (range 8-12) with individualized MRI-based target areas defined according to brain pathology and individual pathophysiology. We compared the CERAD-Plus neuropsychological test battery results before and after treatment, with the CERAD Corrected Total Score ( CTS) as the primary outcome. Furthermore, we analyzed side effects reported by patients during the treatment period.

Results: CERAD Corrected Total Score (CTS) significantly improved (p = .017, d = .32) after treatment (Baseline: M = 56.56, SD = 18.56; Post-treatment: M = 58.65, SD = 19.44). The group of top-responders (top quartile) improved even by 9.8 points. Fewer than one-third of all patients reported any sensation during treatment. Fatigue and transient headaches were the most common, with no severe adverse events.

Conclusions: The findings implicate TPS as a novel and safe add-on therapy for patients with dementia or MCI with the potential to further improve current state-of-the-art treatment results. Despite the individual benefits, further randomized, sham-controlled, longitudinal clinical trials are needed to differentiate the effects of verum and placebo.

Background: This study aimed to deepen the understanding of the psychological mechanisms underlying the formation and maintenance of clinical high-risk symptoms for psychosis (CHR-P) in real-life contexts. Specifically, it examined whether (i) momentary feelings of stress increase the frequency of CHR-P symptoms, or conversely, (ii) CHR-P symptoms increase the intensity of stress. Additionally, potential moderators of the relationship between stress and CHR-P symptoms were explored.

Methods: Using Ecological Momentary Assessment, 79 patients (age: 11-36; 50.6% female) recruited from an early detection center for psychosis, reported their momentary stress levels and the frequency of CHR-P symptoms eight times a day for seven days. Time series data were analyzed using residual dynamic structural equation modeling in a random intercept cross-lagged panel design, comparing differently modeled contemporaneous effects.

Results: There was no evidence of a contemporaneous or temporal link between stress on CHR-P symptoms. However, a contemporaneous effect of CHR-P symptoms on stress was found, while the corresponding temporal effect was not significant. The severity of interview-assessed CHR-P symptoms, age, and type of CHR-P symptoms (i.e., basic symptoms vs. [attenuated] positive symptoms) did not affect the contemporaneous effect of CHR-P symptoms on stress. However, nonperceptive symptoms had a greater contemporaneous effect on stress than perceptive symptoms.

Conclusions: The findings suggest a greater contemporaneous impact of CHR-P symptoms on stress than vice versa. The experience of nonperceptive symptoms, in particular, may alter the appraisal of stress in daily life and represent a target for early interventions in real-time daily life (i.e., ecological momentary interventions).

Background: Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.

Aim: To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.

Methods: A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.

Results: Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).

Conclusions: Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.

Background: Mentalizing-our ability to make inferences about the mental states of others-is impaired across psychiatric disorders and robustly associated with functional outcomes. Mentalizing deficits have been prominently linked to aberrant activity in cortical regions considered to be part of the "social brain network" (e.g., dorsomedial prefrontal cortex, temporoparietal junction), yet emerging evidence also suggests the importance of cerebellar dysfunction. In the present study-using a transdiagnostic, clinical psychiatric sample spanning the psychosis-autism-social anxiety spectrums-we examined the role of the cerebellum in mentalizing and its unique contributions to broader social functioning.

Methods: Sixty-two participants (38 with significant social dysfunction secondary to psychiatric illness and 24 nonclinical controls without social dysfunction) completed a mentalizing task during functional magnetic resonance imaging. General linear model analysis, latent variable modeling, and regression analyses were used to examine the contribution of cerebellum activation to the prediction of group status and social functioning.

Results: Mentalizing activated a broad set of social cognitive brain regions, including cerebral mentalizing network (MN) nodes and posterior cerebellum. Higher posterior cerebellum activation significantly predicted clinical status (i.e., individuals with psychiatric disorders versus nonclinical controls). Finally, cerebellar activation accounted for significant variance in social functioning independent of all other cerebral MN brain regions identified in a whole-brain analysis.

Conclusions: Findings add to an accumulating body of evidence establishing the unique role of the posterior cerebellum in mentalizing deficits and social dysfunction across psychiatric illnesses. Collectively, our results suggest that the posterior cerebellum should be considered - alongside established cerebral regions - as part of the mentalizing network.

To optimize the antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS), it is important to examine the impact of brain state during therapeutic rTMS. Evidence suggests that brain state can modulate the brain's response to stimulation, potentially diminishing antidepressant efficacy if left uncontrolled or enhancing it with inexpensive psychological or other non-pharmacological methods. Thus, we conducted a PRISMA-ScR-based scoping review to pool studies administering rTMS with psychological and other non-pharmacological methods. PubMed and Web of Science databases were searched from inception to 10 July 2024. Inclusion criteria: neuropsychiatric patients underwent rTMS; studies assessed depressive symptom severity; non-pharmacological tasks or interventions were administered during rTMS, or did not include a wash-out period. Of 8,442 studies, 20 combined rTMS with aerobic exercise, bright light therapy, cognitive training or reactivation, psychotherapy, sleep deprivation, or a psychophysical task. Meta-analyses using random effects models were conducted based on change scores on standardized scales. The effect size was large and therapeutic for uncontrolled pretest-posttest comparisons (17 studies, Hedges' g = -1.91, (standard error) SE = 0.45, 95% (confidence interval) CI = -2.80 to -1.03, p < 0.01); medium when studies compared active combinations with sham rTMS plus active non-pharmacological methods (8 studies, g = -0.55, SE = 0.14, 95% CI = -0.82 to -0.28, p < 0.01); and non-significant when active combinations were compared with active rTMS plus sham psychological methods (4 studies, p = 0.96). Attempts to administer rTMS with non-pharmacological methods show promise but have not yet outperformed rTMS alone.

Background: There is evidence that attachment, trauma, and voice appraisals individually impact voice hearing in psychosis, but their intersectional relationship has not been examined. The aim of this study was to identify subgroups of individuals from the intersectional relationship between these factors and examine differences between subgroups on clinical outcomes.

Methods: A latent profile analysis was conducted on baseline data from the AVATAR2 trial (n = 345), to identify statistically distinct subgroups of individuals with psychosis who hear distressing voices based on co-occurring patterns of trauma, fearful attachment, and voice appraisals. The association between profile membership and demographic characteristics, voice severity, posttraumatic stress disorder symptoms, emotional distress, and difficulties with motivation and pleasure was then examined. Experts by experience were consulted throughout the process.

Results: Four profiles were identified: 'adverse voices and relational trauma', 'low malevolent and omnipotent voices', 'adverse voices yet low relational trauma', and 'high benevolent voices'. Negative voice appraisals occurred in the presence of high and low trauma and attachment adversities. The first profile was associated with being female and/or other non-male genders and had worse voice severity and emotional distress. High adversities and worse emotional distress occurred in the presence of voice benevolence and engagement. Black and South Asian ethnicities were not associated with specific profiles.

Conclusions: The identified profiles had negative and positive voice appraisals associated with higher and lower occurrence of adversities, and different clinical outcomes. These profiles could inform detailed case formulations that could tailor interventions for voice hearers.