-
JAMA Psychiatry Jun 2024Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is...
IMPORTANCE
Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown.
OBJECTIVE
To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features.
DESIGN, SETTING, AND PARTICIPANTS
This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population. Data were analyzed from January 2021 to August 2023.
EXPOSURES
Carrier status of deletions and duplications at 27 autosomal rCNV loci was determined from neonatal blood samples genotyped on single-nucleotide variant microarrays.
MAIN OUTCOMES AND MEASURES
Population-based rCNV prevalence was estimated with a survey model using finite population correction to account for oversampling of cases. Hazard ratio (HR) estimates and 95% CIs for psychiatric disorders were derived using weighted Cox proportional hazard models. Risks were compared across outcomes, dosage type, and locus features using generalized estimating equation models.
RESULTS
A total of 3547 rCNVs were identified in 64 735 individuals assigned male at birth (53.8%) and 55 512 individuals assigned female at birth (46.2%) whose age at the end of follow-up ranged from 7.0 to 34.7 years (mean, 21.8 years). Most observed increases in rCNV-associated risk for ADHD, ASD, or SSD were moderate, and risk estimates were highly correlated across these disorders. Notable exceptions included high ASD-associated risk observed for Prader-Willi/Angelman syndrome duplications (HR, 20.8; 95% CI, 7.9-55). No rCNV was associated with increased MDD risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint but not with dosage type. Comparison with published case-control and community-based studies revealed a higher prevalence of deletions and lower associated increase in risk for several rCNVs in iPSYCH2015.
CONCLUSIONS AND RELEVANCE
This study found that several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously. Most case-control studies overestimate rCNV-associated risk of psychiatric disorders, likely because of selection bias. In an era where genetics is increasingly being clinically applied, these results highlight the importance of population-based risk estimates for genetics-based predictions.
PubMed: 38922630
DOI: 10.1001/jamapsychiatry.2024.1453 -
JAMA Network Open Jun 2024There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization.
IMPORTANCE
There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization.
OBJECTIVE
To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024.
EXPOSURES
Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations.
MAIN OUTCOMES AND MEASURES
Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted.
RESULTS
A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.
Topics: Humans; Male; Female; Patient Discharge; Middle Aged; Self-Injurious Behavior; Adult; Retrospective Studies; Spain; Suicide; Mortality, Premature; Aged; Adolescent; Mental Disorders; Young Adult; Hospitals, Psychiatric
PubMed: 38922620
DOI: 10.1001/jamanetworkopen.2024.17131 -
Healthcare (Basel, Switzerland) Jun 2024On 25 May 2023, the Portuguese parliament approved the decriminalisation of euthanasia for incurable illnesses. As the experiences of other countries show us, it will be...
On 25 May 2023, the Portuguese parliament approved the decriminalisation of euthanasia for incurable illnesses. As the experiences of other countries show us, it will be a matter of time before mental disorders are addressed. Studying the phenomenon, particularly in vulnerable groups, in advance is essential for proper law drafting. Therefore, instruments that allow an objective assessment and comparison between groups must be available. This study aims to explore the validation of Faria's attitude about euthanasia scale in Portuguese older adults with mixed anxiety-depressive disorder. A sample of 114 older adults with mixed anxiety-depressive disorder collected by convenience in the Psychiatry Department of Senhora da Oliveira Hospital in Portugal was included. The pre-final version of the scale was tested in a small group with good results. The validity of the internal structure was analysed using exploratory factorial analysis. The internal consistency study verified reliability. For construct validity, we assessed the correlation with other validated scales measuring attitudes toward euthanasia, cognitive performance, personality and empathy. The attitude about euthanasia scale showed good internal consistency. One factor was retained in the principal component analysis. Significant correlations verified construct validity. The results support the scale's usefulness and validity. This study makes available a unique instrument to assess the overall tendency of the attitudes towards euthanasia from the European-Portuguese perspective, which can be used, for example, to compare Portuguese with Brazilian older adults suffering from the same disorder. Furthermore, the adapted scale paves the way for other cross-cultural translations, adaptations, validations, and comparative analyses.
PubMed: 38921334
DOI: 10.3390/healthcare12121221 -
European Journal of Investigation in... Jun 2024Previous studies have shown that the transition from the University environment to remote learning impacted student mental health. Our study aimed to investigate the...
Previous studies have shown that the transition from the University environment to remote learning impacted student mental health. Our study aimed to investigate the effects of university environment on anxiety and depressive symptoms in health sciences students. Students at the Technical University of Manabí, Ecuador, with 6-10 in-person semesters, who shifted to remote learning and then returned to face-to-face learning were selected. Students responded to the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). In addition, questions regarding social interaction, physical exercise, mood and sleep habits were also asked. This longitudinal study tracked 323 students during the return to in-person classes and term end. The results showed similar rates of anxiety (GAD-7, = 0.011- = 0.002) and depression (PHQ-9 = 0.001- = 0.032) among students at week 1 and week 15. Previous diagnosis of depression (OR, 0.171; CI 0.050-0.579, < 0.005) was shown to correlate with depression levels in week 1, with no changes seen at follow-up. Anxiety levels were shown to be associated with a previous diagnosis of the disorder at week 1, but not at follow-up (OR 0.233; CI 0.085-0.643, < 0.005). The return to in-person learning among university students maintained levels of anxiety and depressive symptoms, underscoring ongoing vulnerabilities to mental health disorders in this group.
PubMed: 38921084
DOI: 10.3390/ejihpe14060118 -
Behavioral Sciences (Basel, Switzerland) May 2024Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of...
Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD.
PubMed: 38920799
DOI: 10.3390/bs14060467 -
Diseases (Basel, Switzerland) Jun 2024Multiple sclerosis (MS) is a chronic, progressive neurological disorder that significantly impacts quality of life and functionality. Ocrelizumab, a monoclonal antibody...
Impact of Ocrelizumab on Disease Progression, Memory Improvement, and Quality of Life in Patients with Relapsing-Remitting Multiple Sclerosis: A Longitudinal MRI and Clinical Criteria Analysis.
Multiple sclerosis (MS) is a chronic, progressive neurological disorder that significantly impacts quality of life and functionality. Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, has emerged as a treatment for relapsing-remitting MS (RRMS). This study aimed to assess the impact of ocrelizumab on disease progression and quality of life over a longitudinal course, utilizing clinical criteria and magnetic resonance imaging (MRI) analyses. Conducted at the Neurology Department of Pius Brinzeu Clinical Emergency Hospital in Western Romania from 2020 to 2023, this observational study enrolled 93 patients with RRMS who commenced ocrelizumab therapy. The study employed the Expanded Disability Status Scale (EDSS) and MRI to evaluate disease progression, while quality of life was assessed using the World Health Organisation Quality of Life (WHOQOL) questionnaire, Beck Depression Index (BDI), and MOCA scales. Significant improvements were observed post-treatment. EDSS scores decreased from 4.61 to 4.08 ( = 0.038), indicating reduced disability. MRI analyses showed a substantial decrease in expansive lesions (from 67.74% to 26.88%, < 0.001) and an increase in stationary lesions (from 32.26% to 73.12%, < 0.001). Quality of life improvements were notable in the physical (from 58.42 to 64.84, = 0.005) and environmental domains (from 63.21 to 68.44, = 0.033). Cognitive functions, assessed via Montreal Cognitive Assessment (MOCA), showed a significant total score increase from 20.38 to 22.30 ( < 0.001). Subgroup analysis revealed more pronounced effects in females and younger patients, with a significant reduction in depressive symptoms measured by BDI scores (from 14.35 to 11.62, = 0.003). Ocrelizumab significantly reduced disease activity and disability in RRMS patients, as demonstrated by improvements in EDSS scores and MRI findings. Quality of life and cognitive functions also showed considerable enhancements. These findings support ocrelizumab's efficacy in not only managing MS symptoms but also improving overall patient well-being.
PubMed: 38920559
DOI: 10.3390/diseases12060127 -
Annali Dell'Istituto Superiore Di Sanita 2024Maternal antenatal depression affects 21-28% of expectants globally and negatively impacts both maternal and child health in the short and long term. (Comparative Study)
Comparative Study
BACKGROUND
Maternal antenatal depression affects 21-28% of expectants globally and negatively impacts both maternal and child health in the short and long term.
OBJECTIVE
To compare the psychometric properties and clinical utility of the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ-9) in pregnant individuals.
METHODS
In this cross-sectional study, 953 third-trimester pregnant Italian individuals completed both the EPDS and the PHQ-9.
RESULTS
Both scales demonstrated good internal consistency (EPDS ω=0.83, PHQ-9 ω=0.80) and a moderate correlation between their scores (r=0.59). Concordance at recommended cut-off points (≥14 for both) was moderate (k=0.55). Factor analyses indicated a bifactor solution for the EPDS (dimensions: "depression" and "anxiety") and for the PHQ-9 (dimensions: "depression", "pregnancy symptoms", "somatic"). Benchmarks for clinical change were also established.
CONCLUSIONS
The EPDS and PHQ-9 capture distinct aspects of perinatal depressive symptomatology. Clinically, these findings recommend using both scales in obstetric and gynaecologic settings to minimize false positives and negatives.
Topics: Humans; Female; Pregnancy; Adult; Cross-Sectional Studies; Pregnancy Complications; Psychometrics; Depression; Patient Health Questionnaire; Psychiatric Status Rating Scales; Depression, Postpartum; Italy; Young Adult; Surveys and Questionnaires; Reproducibility of Results; Mass Screening
PubMed: 38920259
DOI: 10.4415/ANN_24_01_08 -
Annals of the Academy of Medicine,... May 2024Anxiety and depressive disorders are highly prevalent mental health conditions worldwide. However, little is known about their specific prevalence in primary care...
INTRODUCTION
Anxiety and depressive disorders are highly prevalent mental health conditions worldwide. However, little is known about their specific prevalence in primary care settings. This study aimed to determine the prevalence of depression and anxiety in the primary care population and identify associated patient characteristics.
METHOD
We conducted a cross-sectional study using stratified sampling by age with a self-administered questionnaire survey in Singapore's National Health-care Group Polyclinics from December 2021 to April 2022. A total score of Patient Health Questionnaire-9 (PHQ-9) ≥10 represents clinical depression, and a total score of Generalised Anxiety Disorder-7 (GAD-7) ≥10 indicates clinical anxiety. Multivariable logistic regression was used to identify the factors associated with depression and anxiety.
RESULTS
A total of 5694 patients were approached and 3505 consented to the study (response rate=61.6%). There was a higher prevalence of coexisting clinical depression and anxiety (DA) (prevalence=5.4%) compared to clinical depression only (3.3%) and clinical anxiety only (1.9%). The odds of having DA were higher among those aged 21-39 years (odds ratio [OR] 13.49; 95% confidence interval [CI] 5.41-33.64) and 40-64 years (OR 2.28; 95% CI 1.03-5.03) compared to those ≥65 years. Women had higher odds of having DA (OR 2.33; 95% CI 1.54-3.50) compared to men. Respondents with diabetes had higher odds of having DA (OR 1.78; 95% CI 1.07-2.94) compared to those without diabetes.
CONCLUSION
Coexisting clinical depression and anxiety are significantly present in the primary care setting, especially among younger individuals, patients with diabetes and women. Mental health screening programmes should include screening for both depression and anxiety, and target these at-risk groups.
Topics: Humans; Primary Health Care; Middle Aged; Prevalence; Adult; Cross-Sectional Studies; Female; Male; Singapore; Risk Factors; Young Adult; Depression; Aged; Anxiety; Anxiety Disorders; Adolescent; Age Factors; Patient Health Questionnaire; Logistic Models; Surveys and Questionnaires; Depressive Disorder
PubMed: 38920221
DOI: 10.47102/annals-acadmedsg.2023195 -
NPP--Digital Psychiatry and Neuroscience 2024Reductions in default mode (DMN) connectivity strength have been reported in posttraumatic stress disorder (PTSD). However, the specificity of DMN connectivity deficits...
Reductions in default mode (DMN) connectivity strength have been reported in posttraumatic stress disorder (PTSD). However, the specificity of DMN connectivity deficits in PTSD compared to major depressive disorder (MDD), and the sensitivity of these alterations to acute stressors are not yet known. 52 participants with a primary diagnosis of PTSD ( = 28) or MDD ( = 24) completed resting-state functional magnetic resonance imaging immediately before and after a mild affective stressor. A 2 × 2 design was conducted to determine the effects of group, stress, and group*stress on DMN connectivity strength. Exploratory analyses were completed to identify the brain region(s) underlying the DMN alterations. There was significant group*stress interaction ( = 0.03), reflecting stress-induced reduction in DMN strength in PTSD ( = 0.02), but not MDD ( = 0.50). Nodal exploration of connectivity strength in the DMN identified regions of the ventromedial prefrontal cortex and the precuneus potentially contributing to DMN connectivity deficits. The findings indicate the possibility of distinct, disease-specific, patterns of connectivity strength reduction in the DMN in PTSD, especially following an experimental stressor. The identified dynamic shift in functional connectivity, which was perhaps induced by the stressor task, underscores the potential utility of the DMN connectivity and raises the question whether these disruptions may be inversely affected by antidepressants known to treat both MDD and PTSD psychopathology.
PubMed: 38919723
DOI: 10.1038/s44277-024-00011-y -
Frontiers in Psychiatry 2024Insulin-like growth factor-1 (IGF-1) has a variety of neurotrophic effects, including neurogenesis, remyelination and synaptogenesis, and is an effective regulator of...
PURPOSE
Insulin-like growth factor-1 (IGF-1) has a variety of neurotrophic effects, including neurogenesis, remyelination and synaptogenesis, and is an effective regulator of neuronal plasticity. Although multiple studies have investigated IGF-1 in depression-related disorders, few studies have focused on patients with a first episode of clearly diagnosed depression who had never used antidepressants before. Therefore, this study investigated first-episode and drug-naïve patients with depression to supplement the current evidence around IGF-1 levels in depressive disorders.
PATIENTS AND METHODS
This study consisted of two parts. In the first part, 60 patients with first-episode and drug-naïve depression and 60 controls matched for age, sex, and BMI were recruited from the outpatient department of the Fourth Hospital of Wuhu City, and the community. The case-control method was used to compare differences in serum IGF-1 levels between the two groups. In the second part, 13 case-control studies were screened through the database for meta-analysis to verify the reliability of the results.
RESULTS
Results of the case-control study demonstrated that serum IGF-1 levels are significantly higher in patients with first-episode and drug-naïve depression compared to healthy controls (<0.05), although there was no significant difference between men and women with diagnosed MDD, there was no significant correlation between serum IGF-1 level and age in patients with depression and no significant correlation between IGF-1 level and the severity of depression. The meta-analysis corroborates these findings and demonstrated that IGF-1 levels are significantly higher in MDD patients than in healthy controls.
CONCLUSION
Patients with first-episode and drug-naïve depression have higher IGF-1 levels, but the exclusion of confounding factors in studies of IGF-1 as it relates to depressive disorders must be taken into consideration strictly, and additional research is needed to fully understand the critical role of IGF-1 in depression.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023482222.
PubMed: 38919642
DOI: 10.3389/fpsyt.2024.1396938