Psychological Medicine最新文献

Background: Late-life depression (LLD) is characterized by medial temporal lobe (MTL) abnormalities. Although gray matter (GM) and white matter (WM) differences in LLD have been reported, few studies have investigated them concurrently. Moreover, the impact of aetiological factors, such as neurodegenerative and cerebrovascular burden, on tissue differences remains elusive.

Methods: This prospective cross-sectional study involved 72 participants, including 33 patients with LLD (mean age 72.2 years, 23 female) and 39 healthy controls (HCs) (mean age 70.6 years, 24 female), who underwent clinical and positron emission tomography (PET)-magnetic resonance imaging (MRI) assessments. High-resolution 3D T1-weighted and T2-weighted FLAIR images were used to assess MTL GM volumes and white matter hyperintensities (WMHs), a proxy for cerebrovascular burden. Diffusion kurtosis imaging metrics derived from multishell diffusion MRI data were analyzed to assess WM microstructure in the following MTL bundles reconstructed using constrained spherical deconvolution tractography: uncinate fasciculus, fornix, and cingulum. Standardized uptake value ratio of 18F-MK-6240 in the MTL was used to assess Alzheimer's disease (AD) type tau accumulation as a proxy for neurodegenerative burden.

Results: Compared to HCs, patients with LLD showed significantly lower bilateral MTL volumes and WM microstructural differences primarily in the uncinate fasciculi bilaterally and right fornix. In patients with LLD, higher vascular burden, but not tau, was associated with lower MTL volume and more pronounced WM differences.

Conclusions: LLD was associated with both GM and WM differences in the MTL. Cerebrovascular disease, rather than AD type tau-mediated neurodegenerative processes, may contribute to brain tissue differences in LLD.

Background: Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.

Methods: Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort-cost computation.

Results: k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.

Conclusions: Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.

Background: Relatively little is known about mental healthcare-related harm, with patient safety incidents (PSIs) in community-based services particularly poorly understood. We aimed to characterize PSIs, contributory factors, and reporter-identified solutions within community-based mental health services for working-age adults.

Methods: We obtained data on PSIs reported within English services from the National Reporting and Learning System. Of retrieved reports, we sampled all incidents reportedly involving 'Death', 'Severe harm', or 'Moderate harm', and random samples of a proportion of 'Low harm' or 'No harm' incidents. PSIs and contributory factors were classified through qualitative content analysis using existing frameworks. Frequencies and proportions of incident types were computed, and reporter-identified solutions were inductively categorized.

Results: Of 1825 sampled reports, 1443 were eligible and classified into nine categories. Harmful outcomes, wherein service influence was unclear, were widely observed, with self-harm the modal concern amongst 'No harm' (15.0%), 'Low harm' (62.8%), and 'Moderate harm' (37.6%) categories. Attempted suicides (51.7%) and suicides (52.1%) were the most frequently reported events under 'Severe harm' or 'Death' outcomes, respectively. Incidents common to most healthcare settings were identified (e.g. medication errors), alongside specialty-specific incidents (e.g. Mental Health Act administration errors). Contributory factors were wide-ranging, with situational failures (e.g. team function failures) and local working conditions (e.g. unmanageable workload) widely reported. Solution categories included service user-directed actions and policy introduction or reinforcement.

Conclusions: Study findings provide novel insights into incidents, contributory factors, and reported solutions within community-based mental healthcare. Targets for safety improvement are outlined, aimed at strengthening system-based prevention of incidents.

Background: Previous studies (various designs) present contradicting insights on the potential causal effects of diet/physical activity on depression/anxiety (and vice versa). To clarify this, we employed a triangulation framework including three methods with unique strengths/limitations/potential biases to examine possible bidirectional causal effects of diet/physical activity on depression/anxiety.

Methods: Study 1: 3-wave longitudinal study (n = 9,276 Dutch University students). Using random intercept cross-lagged panel models to study temporal associations. Study 2: cross-sectional study (n = 341 monozygotic and n = 415 dizygotic Australian adult twin pairs). Using a co-twin control design to separate genetic/environmental confounding. Study 3: Mendelian randomization utilizing data (European ancestry) from genome-wide association studies (n varied between 17,310 and 447,401). Using genetic variants as instrumental variables to study causal inference.

Results: Study 1 did not provide support for bidirectional causal effects between diet/physical activity and symptoms of depression/anxiety. Study 2 did provide support for causal effects between fruit/vegetable intake and symptoms of depression/anxiety, mixed support for causal effects between physical activity and symptoms of depression/anxiety, and no support for causal effects between sweet/savoury snack intake and symptoms of depression/anxiety. Study 3 provides support for a causal effect from increased fruit intake to the increased likelihood of anxiety. No support was found for other pathways. Adjusting the analyses including diet for physical activity (and vice versa) did not change the conclusions in any study.

Conclusions: Triangulating the evidence across the studies did not provide compelling support for causal effects of diet/physical activity on depression/anxiety or vice versa.

Background: An accumulating body of evidence indicates that peripheral physiological rhythms help regulate and organize large-scale brain activity. Given that schizophrenia (SZ) is characterized by marked abnormalities in oscillatory cortical activity as well as changes in autonomic function, the present study aimed to identify mechanisms by which central and autonomic nervous system deficits may be related. We evaluated phase-amplitude coupling (PAC) as a physiological mechanism through which autonomic nervous system (ANS) and central nervous system (CNS) activity are integrated and that may be disrupted in SZ.

Methods: PAC was measured between high-frequency heart rate variability (HF-HRV) as an index of parasympathetic activity and electroencephalography (EEG) oscillations in 36 individuals with first-episode SZ and 38 healthy comparison participants at rest.

Results: HRV-EEG coupling was lower in SZ in the alpha and theta bands, and HRV-EEG coupling uniquely predicted group membership, whereas HRV and EEG power alone did not. HRV-EEG coupling in the alpha band correlated with measures of sustained attention in SZ. Granger causality analyses indicated a stronger heart-to-brain effect than brain-to-heart effect, consistent across groups.

Conclusions: Lower HRV-EEG coupling provides evidence of deficient autonomic regulation of cortical activity in SZ, suggesting that patterns of dysconnectivity observed in brain networks extend to brain-body interactions. Deficient ANS-CNS integration in SZ may foster a breakdown in the spatiotemporal organization of cortical activity, which may contribute to core cognitive impairments in SZ such as dysregulated attention. These findings encourage pursuit of therapies targeting autonomic function for the treatment of SZ.

Background: The structure of psychopathology can be organized hierarchically into a set of transdiagnostic dimensional phenotypes. No studies have examined whether these phenotypes are associated with brain structure or dementia in older adults.

Methods: Data were drawn from a longitudinal study of older adults aged 70-90 years at baseline (N = 1072; 44.8% male). Confirmatory factor models were fit to baseline psychiatric symptoms, with model fit assessed via traditional fit indices, model-based reliability estimates, and evaluation of model parameters. Bayesian plausible values were generated from the best-fitting model for use in subsequent analyses. Linear mixed models examined intraindividual change in global and regional gray matter volume (GMV) and cortical thickness over 6 years. Logistic regression examined whether symptom dimensions predicted incident dementia over 12 years.

Results: A higher-order model showed a good fit to the data (BIC = 28,691.85; ssaBIC = 28,396.47; CFI = 0.926; TLI = 0.92; RMSEA = 0.047), including a general factor and lower-order dimensions of internalizing, disinhibited externalizing, and substance use. Baseline symptom dimensions did not predict change over time in total cortical and subcortical GMV or average cortical thickness; regional GMV or cortical thickness in the frontal, parietal, temporal, or occipital lobes; or regional GMV in the hippocampus and cerebellum (all p-values >0.5). Finally, baseline symptom dimensions did not predict incident dementia across follow-ups (all p-values >0.5).

Conclusions: We found no evidence that transdiagnostic dimensions are associated with gray matter structure or dementia in older adults. Future research should examine these relationships using psychiatric indicators capturing past history of chronic mental illness rather than current symptoms.

Background: The prevalence of youth anxiety and depression has increased globally, with limited causal explanations. Long-term physical health conditions (LTCs) affect 20-40% of youth, with rates also rising. LTCs are associated with higher rates of youth depression and anxiety; however, it is uncertain whether observed associations are causal or explained by unmeasured confounding or reverse causation.

Methods: Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and Norwegian National Patient Registry, we investigated phenotypic associations between childhood LTCs, and depression and anxiety diagnoses in youth (<19 years), defined using ICD-10 diagnoses and self-rated measures. We then conducted two-sample Mendelian Randomization (MR) analyses using SNPs associated with childhood LTCs from existing genome-wide association studies (GWAS) as instrumental variables. Outcomes were: (i) diagnoses of major depressive disorder (MDD) and anxiety disorders or elevated symptoms in MoBa, and (ii) youth-onset MDD using summary statistics from a GWAS in iPSYCH2015 cohort.

Results: Having any childhood LTC phenotype was associated with elevated youth MDD (OR = 1.48 [95% CIs 1.19, 1.85], p = 4.2×10^-4) and anxiety disorder risk (OR = 1.44 [1.20, 1.73], p = 7.9×10^-5). Observational and MR analyses in MoBa were consistent with a causal relationship between migraine and depression (IVW OR = 1.38 [1.19, 1.60], p_FDR = 1.8x10^-4). MR analyses using iPSYCH2015 did not support a causal link between LTC genetic liabilities and youth-onset depression or in the reverse direction.

Conclusions: Childhood LTCs are associated with depression and anxiety in youth, however, little evidence of causation between LTCs genetic liability and youth depression/anxiety was identified from MR analyses, except for migraine.

Background: Racial, ethnic, and socioeconomic disparities persist in posttraumatic stress disorder (PTSD), which are partly attributed to minoritized women being trauma-exposed, while also contending with harmful contextual stressors. However, few have used analytic strategies that capture the interplay of these experiences and their relation to PTSD. The current study used a person-centered statistical approach to examine heterogeneity in trauma and contextual stress exposure, and their associations with PTSD and underlying symptom dimensions, in a diverse sample of low-income postpartum women.

Methods: Using a community-based sample of Black, Hispanic/Latina, and White postpartum women recruited from five U.S. regions (n = 1577), a latent class analysis generated profiles of past-year exposure to traumatic events and contextual stress at one month postpartum. Regression analyses then examined associations between class membership and PTSD symptom severity at six months postpartum as a function of race/ethnicity.

Results: A four-class solution best fit the data, yielding High Contextual Stress, Injury/Illness, Violence Exposure, and Low Trauma/Contextual Stress classes. Compared to the Low Trauma/Contextual Stress class, membership in any of the other classes was associated with greater symptom severity across nearly all PTSD symptom dimensions (all ps < 0.05). Additionally, constellations of exposures were differentially linked to total PTSD symptom severity, reexperiencing, and numbing PTSD symptoms across racial/ethnic groups (ps < 0.05).

Conclusions: A person-centered approach to trauma and contextual stress exposure can capture heterogeneity of experiences in diverse, low-income women. Moreover, racially/ethnically patterned links between traumatic or stressful exposures and PTSD symptom dimensions have implications for screening and intervention in the perinatal period.