Psychological Medicine最新文献

Background: Low levels of vitamin D during pregnancy are associated with offspring behavioral problems but little is known about pre-pregnancy influences. Additionally, Black American individuals are underrepresented in studies, limiting translational impact. We tested independent and interactive effects of preconception and prenatal vitamin D in Black women in relation to positive behavioral and emotional outcomes in early childhood.

Methods: Black-identifying participants (N = 156) enrolled in the longitudinal Pittsburgh Girls Study (PGS) provided venous blood samples before and during pregnancy to measure 25-hydroxyvitamin D (25[OH]D) levels. Participants completed questionnaires assessing sociodemographic factors, depression severity and life stress, and later reported on child behavioral and emotional problems and prosocial behavior between 2 and 4 years.

Results: Mean serum 25(OH)D concentrations were 15.5 ng/ml (s.d. = 7.7) before pregnancy and 18.0 ng/ml (s.d. = 9.2) during pregnancy; below the sufficiency threshold according to commonly used dietary guidelines. After adjusting for covariates, prenatal 25(OH)D was negatively related to behavior problems and positively related to prosocial behavior in children, although the association attenuated for behavior problems after accounting for preconception 25(OH)D, which may reflect patterns of stability. Maternal 25(OH)D was unrelated to child emotional problems, and no synergistic effects of 25(OH)D timing were observed for any child outcome.

Conclusions: Findings have relevance for Black women living in the northeast U.S. Results suggest specific associations between maternal vitamin D and positive behaviors in early childhood, regardless of sufficiency levels and suggest potential opportunities for early interventions to support healthy child development.

Background: Pain resilience and regional gray matter volume (rGMV) are established correlates of adaptation to chronic pain within cross-sectional studies. Extending such work, this prospective cohort study tested the status of baseline pain resilience dimension scores and rGMV as risk factors for subsequent exacerbations in chronic pain disability and intensity.

Methods: 142 adults with chronic musculoskeletal pain completed an initial assessment comprising a structural magnetic resonance imaging scan and self-report measures of cognitive/affective positivity and behavioral perseverance pain resilience dimensions, disability, pain intensity, and demographics. Disability and pain intensity were outcomes re-assessed at a 6-month follow-up. The impact of pain resilience dimension scores and identified rGMV sites on follow-up outcomes was examined after controlling for other baseline correlates of outcomes. Mediating effects of identified rGMV sites on pain resilience dimension-follow-up outcome relations were also evaluated.

Results: Aside from the significant multivariate effect of lower behavioral perseverance and cognitive/affective positivity scores, augmented left precuneus, temporal pole, superior temporal gyrus (STG), and precentral gyrus rGMV combined to predict higher follow-up disability levels, independent of covariates. Higher left fusiform gyrus rGMV levels predicted follow-up exacerbations in pain intensity, but pain resilience dimension scores did not. Finally, left precuneus and left temporal pole STG rGMV partially mediated cognitive/affective positivity-follow-up disability relations.

Conclusions: Findings underscore deficits in pain resilience and increased rGMV as potential risk factors for poorer subsequent outcomes of chronic musculoskeletal pain and provide foundations for further prospective extensions as well as targeted intervention research.

Background: Research suggests that most mental health conditions have their onset in the critically social period of adolescence. Yet, we lack understanding of the potential social processes underlying early psychopathological development. We propose a conceptual model where daily-life social interactions and social skills form an intermediate link between known risk and protective factors (adverse childhood experiences, bullying, social support, maladaptive parenting) and psychopathology in adolescents - that is explored using cross-sectional data.

Methods: N = 1913 Flemish adolescent participants (Mean age = 13.8; 63% girls) were assessed as part of the SIGMA study, a large-scale, accelerated longitudinal study of adolescent mental health and development. Self-report questionnaires (on risk/protective factors, social skills, and psychopathology) were completed during class time; daily-life social interactions were measured during a subsequent six-day experience-sampling period.

Results: Registered uncorrected multilevel linear regression results revealed significant associations between all risk/protective factors and psychopathology, between all risk/protective factors and social processes, and between all social processes and psychopathology. Social processes (social skills, quantity/quality of daily social interactions) were uniquely predicted by each risk/protective factor and were uniquely associated with both general and specific types of psychopathology. For older participants, some relationships between social processes and psychopathology were stronger.

Conclusions: Unique associations between risk/protective factors and psychopathology signify the distinct relevance of these factors for youth mental health, whereas the broad associations with social processes support these processes as broad correlates. Results align with the idea of a social pathway toward early psychopathology, although follow-up longitudinal research is required to verify any mediation effect.

Background: This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10-20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Methods: Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Results: Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Conclusions: Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.

Background: This article presents the results of two studies investigating increased intra-individual variability (IIV) in the performance of individuals with attention deficit hyperactivity disorder (ADHD), in two cognitive domains: numerosity judgments and quantitative and verbal reasoning.

Methods: Study 1, a pre-registered experiment, involved approximately 200 participants (42.66% female; mean age: 36.86; standard deviation of age: 10.70) making numerical judgments at two time-points. ADHD-symptom severity was assessed on a continuous scale. In Study 2, we collected the data of approximately 3000 examinees who had taken a high-stakes admissions test for higher education (assessing quantitative and verbal reasoning). The sample comprised only people formally diagnosed with ADHD. The control group consisted of approximately 200 000 examinees, none of whom presented with ADHD.

Results: The results of Study 1 revealed a positive correlation between IIV (distance between judgments at the two time-points) and ADHD symptom severity. The results of Study 2 demonstrated that IIV (distance between the scores on two test chapters assessing the same type of reasoning) was greater among examinees diagnosed with ADHD. In both studies, the findings persisted even after controlling for performance level.

Conclusions: The results indicate that individuals with ADHD, v. those without, exhibit less consistent numerosity judgments and greater fluctuation in performance on verbal and quantitative reasoning. The measurement of the same psychological constructs appears to be less precise among individuals with ADHD compared to those without. We discuss the theoretical contributions and practical implications of our results for two fields: judgment and decision-making, and assessment.

Background: People with schizophrenia-spectrum and bipolar disorders (severe mental illnesses; 'SMI') experience excess mortality. Our aim was to explore longer-term trends in mortality, including the COVID-19 pandemic period, with a focus on additional vulnerabilities (psychiatric comorbidities and race/ ethnicity) in SMI.

Methods: Retrospective cohort study using electronic health records from secondary mental healthcare, covering a UK region of 1.3 million people. Mortality trends spanning fourteen years, including the COVID-19 pandemic, were assessed in adults with clinician-ascribed ICD-10 diagnoses for schizophrenia-spectrum and bipolar disorders.

Results: The sample comprised 22 361 people with SMI with median follow-up of 10.6 years. Standardized mortality ratios were more than double the population average pre-pandemic, increasing further during the pandemic, particularly in those with SMI and psychiatric comorbidities. Mortality risk increased steadily among people with SMI and comorbid depression, dementia, substance use disorders and anxiety over 13-years, increasing further during the pandemic. COVID-19 mortality was elevated in people with SMI and comorbid depression (sub-Hazard Ratio: 1.48 [95% CI 1.03-2.13]), dementia (sHR:1.96, 1.26-3.04) and learning disabilities (sHR:2.30, 1.30-4.06), compared to people with only SMI. COVID-19 mortality risk was similar for minority ethnic groups and White British people with SMI. Elevated all-cause mortality was evident in Black Caribbean (adjusted Rate Ratio: 1.40, 1.11-1.77) and Black African people with SMI (aRR: 1.59, 1.07-2.37) during the pandemic relative to earlier years.

Conclusions: Mortality has increased over time in people with SMI. The pandemic exacerbated pre-existing trends. Actionable solutions are needed which address wider social determinants and address disease silos.

Background: While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Methods: Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

Results: After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

Conclusions: We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Background: Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response.

Methods: Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia.

Results: Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10^-10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10^-10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10^-4 and p = 9 × 10^-3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10^-14).

Conclusions: Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

Background: The Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising framework to identify the neurobiological mechanisms of psychopathology. Many forms of psychopathology are characterized by dysfunctional emotional reactivity. The late positive potential (LPP) is an event-related potential component that provides an index of neurobiological emotional reactivity. Several categorical disorders have demonstrated a similar association with the emotion-modulated LPP. It is possible that higher-order dimensional representations of psychopathology might explain the comparable results. The present study examined the association between HiTOP-consistent pathological personality dimensions across multiple levels of the hierarchy and neurobiological emotional reactivity.

Methods: The sample included 215 18-35-year-old adults (86% female) who were oversampled for psychopathology. Participants completed the emotional interrupt task while electroencephalography was recorded to examine the LPP. Participants also completed the Comprehensive Assessment of Traits relevant to Personality Disorders to assess pathological personality.

Results: At the spectra level, higher negative emotionality was associated with a larger emotion-modulated LPP, while higher detachment was associated with a smaller emotion-modulated LPP. There were no associations between higher-order psychopathology levels and the emotion-modulated LPP. Compared to categorical diagnoses, spectra-level personality pathology dimensions significantly improved the prediction of the emotion-modulated LPP.

Conclusions: The present study indicates that HiTOP spectra levels of negative emotionality and detachment demonstrate unique associations with neurobiological emotional reactivity. The study highlights the utility of examining dimensional and hierarchical, rather than categorical, representations of psychopathology in the attempt to identify the neurobiological origins of psychopathology.

Background: Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD.

Method: Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT).

Results: MEMI was more efficacious than SM in improving pre-post inhibition (β = -2.075, 95% [-3.388, -0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = -2.916, 95% [-5.142, -0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre-post EF outcomes except attentional control. Only pre-post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = -0.605, 95% [-1.357, -0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = -0.024, 95% [-0.054, -0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations.

Conclusions: Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.