Psychological Medicine最新文献

Background: Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.

Methods: We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 ¹H-MRS studies and further divided the sample based on Axis I disorders.

Results: Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.

Conclusions: Altered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.

Background: Epidemiological samples provide opportunity to understand the development of mental health trajectories to better understand whether such epidemiological data can help to plan and modify service delivery for youth mental health. Variation between countries is not well understood and thus applying evidence from other countries to national strategies limits support service policy and planning. We therefore examine developmental patterns of youth mental health across different countries using the Growing Up in Ireland (GUI) Cohorts, with comparison to existing UK longitudinal cohort data (Millennium Cohort Study, MCS; Growing up in Scotland, GUS).

Methods: Youth mental health problems within each cohort across development (5-17/18 years) were assessed using parent reported Strengths and Difficulties Questionnaire (SDQ) scores. Using latent growth curve analyses, we examined trajectories of emotional, conduct, and hyperactivity problems for boys and girls, separately for each cohort.

Results: Across cohorts, we observed similar developmental patterns for emotional, conduct, and hyperactivity problems. However, the GUI emotional problems in Ireland emerged earlier than in the UK. By adolescence, GUI emotional scores were similar to the UK, suggesting that the differences in emotional problems between the ROI and UK had narrowed by adolescence. Covariates also had different associations with youth mental health trajectories across cohorts.

Conclusions: Utilizing multiple nationally representative cohort longitudinal datasets can help inform clinically meaningful conclusions and potential recommendations on population level multi-tiered service needs and development in the area of child and adolescent mental health support and future provision.

Background: Psychedelic drugs are a focus of interest in the treatment of depression and other disorders but there are longstanding concerns about possible adverse psychiatric consequences. Because the relevant literature is largely informal, the seriousness of these risks is difficult to evaluate.

Methods: Searches were made for case reports of schizophrenia-spectrum, affective or other psychiatric disorders after use of psychedelic drugs. Case reports of flashbacks were also searched for. Individuals with recent use of other drugs (apart from cannabis and alcohol) and/or a previous history of major psychiatric disorder were excluded. Symptoms were tabulated using the Syndrome Check List of the Present State Examination (PSE-9).

Results: We found 17 case reports of schizophrenia spectrum disorder, 17 of affective disorder (depression, mania, or both), 3 cases of anxiety, 1 of depersonalization, and 1 of unclassifiable illness. The states could develop after a single use of the drug (5/17 schizophrenia; 6/17 affective disorder), and duration was highly variable. Recovery was the rule in cases of affective disorder but not in schizophrenia spectrum disorder. Twelve of 29 cases of flashbacks showed psychiatric symptomatology definitely outlasting the attacks, mainly anxiety (5 cases) and depression (8 cases). Flashback symptoms resolved within twelve months in approximately half of the cases but in a few persisted for years.

Conclusions: Reliable descriptions of schizophrenia spectrum disorder and major affective disorder after psychedelic drug use disorder exist but are relatively uncommon. Flashbacks are sometimes but not always associated with psychiatric symptomatology, mainly anxiety or depression.

Background: Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders.

Methods: We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles.

Results: SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE.

Conclusions: SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.

Background: The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications.

Methods: The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes.

Results: Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [-0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus.

Conclusions: Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.

Background: Mental disorders and physical-health conditions frequently co-occur, impacting treatment outcomes. While most prior research has focused on single pairs of mental disorders and physical-health conditions, this study explores broader associations between multiple mental disorders and physical-health conditions.

Methods: Using the Norwegian primary-care register, this population-based cohort study encompassed all 2 203 553 patients born in Norway from January 1945 through December 1984, who were full-time residents from January 2006 until December 2019 (14 years; 363 million person-months). Associations between seven mental disorders (sleep disturbance, anxiety, depression, acute stress reaction, substance-use disorders, phobia/compulsive disorder, psychosis) and 16 physical-health conditions were examined, diagnosed according to the International Classification of Primary Care.

Results: Of 112 mental-disorder/physical-health condition pairs, 96% of associations yielded positive and significant ORs, averaging 1.41 and ranging from 1.05 (99.99% CI 1.00-1.09) to 2.38 (99.99% CI 2.30-2.46). Across 14 years, every mental disorder was associated with multiple different physical-health conditions. Across 363 million person-months, having any mental disorder was associated with increased subsequent risk of all physical-health conditions (HRs:1.40 [99.99% CI 1.35-1.45] to 2.85 [99.99% CI 2.81-2.89]) and vice versa (HRs:1.56 [99.99% CI 1.54-1.59] to 3.56 [99.99% CI 3.54-3.58]). Associations were observed in both sexes, across age groups, and among patients with and without university education.

Conclusions: The breadth of associations between virtually every mental disorder and physical-health condition among patients treated in primary care underscores a need for integrated mental and physical healthcare policy and practice. This remarkable breadth also calls for research into etiological factors and underlying mechanisms that can explain it.

Background: Borderline personality disorder (BPD) is a debilitating condition characterized by pervasive instability across multiple major domains of functioning. The majority of persons with BPD engage in self-injury and up to 10% die by suicide - rendering persons with this condition at exceptionally elevated risk of comorbidity and premature mortality. Better characterization of clinical risk factors among persons with BPD who die by suicide is urgently needed.

Methods: We examined patterns of medical and psychiatric diagnoses (1580 to 1700 Phecodes) among persons with BPD who died by suicide (n = 379) via a large suicide death data resource and biobank. In phenotype-based phenome-wide association tests, we compared these individuals to three other groups: (1) persons who died by suicide without a history of BPD (n = 9468), (2) persons still living with a history of BPD diagnosis (n = 280), and (3) persons who died by suicide with a different personality disorder (other PD n = 589).

Results: Multivariable logistic regression models revealed that persons with BPD who died by suicide were more likely to present with co-occurring psychiatric diagnoses, and have a documented history of self-harm in the medical system prior to death, relative to suicides without BPD. Posttraumatic stress disorder was more elevated among those with BPD who died by suicide relative to the other PD group.

Conclusions: We found significant differences among persons with BPD who died by suicide and all other comparison groups. Such differences may be clinically informative for identifying high-risk subtypes and providing targeted intervention approaches.

Background: Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression.

Methods: Data from three assessments of the Australian Genetics of Depression Study (N = 4405; 52.2 years ± 14.9; 76.2% females) were analyzed. Outcomes included COVID-19 clinical outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and long COVID, noting the low incidence of COVID-19 cases in Australia at that time) and COVID-19 psychological outcomes (COVID-related stress and COVID-19 burnout). Predictors included PRS for depression, bipolar disorder, schizophrenia, and anxiety. The associations between these PRSs and the outcomes were assessed with adjusted linear/logistic/multinomial regressions. Mediation (N = 4338) and moderation (N = 3326) analyses were performed to explore the potential influence of anxiety symptoms and resilience on the identified associations between the PRSs and COVID-19 psychological outcomes.

Results: None of the selected PRS predicted SARS-CoV-2 infection or long COVID. In contrast, the depression PRS predicted higher levels of COVID-19 burnout. Anxiety symptoms fully mediated the association between the depression PRS and COVID-19 burnout. Resilience did not moderate this association.

Conclusions: A higher genetic risk for depression predicted higher COVID-19 burnout and this association was fully mediated by anxiety symptoms. Interventions targeting anxiety symptoms may be effective in mitigating the psychological effects of a pandemic among people with depression.

Background: Involuntary admissions to psychiatric hospitals are on the rise. If patients at elevated risk of involuntary admission could be identified, prevention may be possible. Our aim was to develop and validate a prediction model for involuntary admission of patients receiving care within a psychiatric service system using machine learning trained on routine clinical data from electronic health records (EHRs).

Methods: EHR data from all adult patients who had been in contact with the Psychiatric Services of the Central Denmark Region between 2013 and 2021 were retrieved. We derived 694 patient predictors (covering e.g. diagnoses, medication, and coercive measures) and 1134 predictors from free text using term frequency-inverse document frequency and sentence transformers. At every voluntary inpatient discharge (prediction time), without an involuntary admission in the 2 years prior, we predicted involuntary admission 180 days ahead. XGBoost and elastic net models were trained on 85% of the dataset. The models with the highest area under the receiver operating characteristic curve (AUROC) were tested on the remaining 15% of the data.

Results: The model was trained on 50 634 voluntary inpatient discharges among 17 968 patients. The cohort comprised of 1672 voluntary inpatient discharges followed by an involuntary admission. The best XGBoost and elastic net model from the training phase obtained an AUROC of 0.84 and 0.83, respectively, in the test phase.

Conclusion: A machine learning model using routine clinical EHR data can accurately predict involuntary admission. If implemented as a clinical decision support tool, this model may guide interventions aimed at reducing the risk of involuntary admission.

The impact of vitamin D supplementation on depressive symptoms remains uncertain. This study aimed to investigate the dose-dependent effects of vitamin D supplementation on depressive and anxiety symptoms in adults. We systematically searched PubMed, Scopus, and Web of Science up to December 2022 to identify randomized controlled trials evaluating the effects of vitamin D₃ supplementation on depression and anxiety symptoms in adults. Using a random-effects model, we calculated the standardized mean difference (SMD) for each 1000 IU/day vitamin D₃ supplementation. The GRADE tool assessed the certainty of evidence. Our analysis included 31 trials with 24189 participants. Each 1000 IU/day vitamin D₃ supplementation slightly reduced depressive symptoms in individuals with and without depression (SMD: -0.32, 95% CI -0.43 to -0.22; GEADE = moderate). The effect was more pronounced in those with depressive symptoms (SMD: -0.57, 95% CI -0.69 to -0.44; n = 15). The greatest reduction occurred at 8000 IU/day (SMD: -2.04, 95% CI -3.77 to -0.31). Trials with follow-up ⩽8 weeks (SMD: -0.45, 95% CI -0.70 to -0.20; n = 8) and 8 to ⩽24 weeks (SMD: -0.47, 95% CI -0.70 to -0.24; n = 15) showed stronger effects compared to those lasting 24 to ⩽52 weeks (SMD: -0.13, 95% CI -0.28 to 0.02; n = 5) or longer than 52 weeks (SMD: 0.14, 95% CI -0.16 to 0.44; n = 3) (p group difference <0.001). Vitamin D₃ supplementation had no significant effects on anxiety symptoms. In summary, this study suggests that vitamin D₃ supplementation may effectively reduce depressive symptoms in short term. Further high-quality trials are warranted for a conclusive assessment of its impact on anxiety.