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Clinical Psychopharmacology and... May 2024Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms... (Review)
Review
Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms such as melatonin and cortisol, clock genes, and circadian preference have shown the relationship between bipolar disorder and circadian rhythm. The results differed across different studies. In some studies, a delay in the circadian rhythm was observed in the depressive episode and advanced circadian rhythm was observed during the manic episode. In other studies, a delay in circadian rhythm was observed independent of mood episodes. Accordingly, circadian rhythm disorder was proposed as a trait marker for bipolar disorder. The altered circadian rhythm may represent a pathological mechanism that contributes to the mood episodes. However, a prospective cohort study is needed for further clarification.
PubMed: 38627069
DOI: 10.9758/cpn.23.1093 -
JAMA Psychiatry Aug 2023The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown.
IMPORTANCE
The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown.
OBJECTIVE
To assess regional associations between ASM and bipolar disorder diagnosis frequencies.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study investigated the association between annual regional ASM and bipolar disorder diagnosis rates in Swedish adolescents aged 15 to 19 years in January 1, 2008, through December 31, 2021. Aggregated data without exclusions reported at the regional level encompassed 585 suicide deaths, constituting 588 unique observations (ie, 21 regions, 14 years, 2 sexes).
EXPOSURES
Bipolar disorder diagnosis frequencies and lithium dispensation rates were designated as fixed-effects variables (interaction term in the case of males). An interaction term between psychiatric care affiliation rates and the proportion of psychiatric visits to inpatient and outpatient clinics constituted independent fixed-effects variables. Region and year comprised random intercept effect modifiers. Variables were population adjusted and corrected for heterogeneity in reporting standards.
MAIN OUTCOMES AND MEASURES
The main outcomes were sex-stratified, regional, and annual ASM rates in adolescents aged 15 to 19 years per 100 000 inhabitants as analyzed using generalized linear mixed-effects models.
RESULTS
Female adolescents were diagnosed with bipolar disorder almost 3 times more often than male adolescents (mean [SD], 149.0 [19.6] vs 55.3 [6.1] per 100 000 inhabitants, respectively). Median regional prevalence rates of bipolar disorder varied over the national median by a factor of 0.46 to 2.61 and 0.00 to 1.82 in females and males, respectively. Bipolar disorder diagnosis rates were inversely associated with male ASM (β = -0.00429; SE, 0.002; 95% CI, -0.0081 to -0.0004; P = .03) independent of lithium treatment and psychiatric care affiliation rates. This association was replicated by β-binomial models of a dichotomized quartile 4 ASM variable (odds ratio, 0.630; 95% CI, 0.457-0.869; P = .005), and both models were robust after adjusting for annual regional diagnosis rates of major depressive disorder and schizophrenia. No such association was observed in females.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, lower suicide death rates in adolescent males was robustly associated with regional diagnosis rates of bipolar disorder at an estimated magnitude of approximately 4.7% of the mean national suicide death rate. The associations could be due to treatment efficacy, early diagnosis and management, or other factors not accounted for.
Topics: Humans; Male; Adolescent; Female; Bipolar Disorder; Sweden; Depressive Disorder, Major; Cross-Sectional Studies; Suicide; Lithium
PubMed: 37223908
DOI: 10.1001/jamapsychiatry.2023.1390 -
CNS Neuroscience & Therapeutics Dec 2023Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy... (Review)
Review
AIMS
Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy dysregulation in mania and further discussed whether targeting autophagy could be a promising strategy for mania therapy.
DISCUSSIONS
Accumulating evidence indicated the involvement of autophagy in the pathology of mania. One of the most well-accepted mechanisms underlying mania, circadian dysregulation, showed mutual interaction with autophagy dysfunction. In addition, several first-line drugs for mania therapy were found to regulate neuronal autophagy. Besides, deficiencies in mitochondrial quality control, neurotransmission, and ion channel, which showed causal links to mania, were intimately associated with autophagy dysfunction.
CONCLUSIONS
Although more efforts should be made to either identify the key pathology of mania, the current evidence supported that autophagy dysregulation may act as a possible mechanism involved in the onset of mania-like symptoms. It is therefore a potential strategy to treat manic disorder by correting autophagy.
Topics: Humans; Mania; Bipolar Disorder
PubMed: 37438945
DOI: 10.1111/cns.14353 -
Psychiatry Research May 2024The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment... (Clinical Trial)
Clinical Trial
The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4-month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty-three participants were enrolled in a single-arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA-IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.
Topics: Humans; Bipolar Disorder; Diabetes Mellitus, Type 2; Diet, Ketogenic; Pilot Projects; Proof of Concept Study; Schizophrenia
PubMed: 38547601
DOI: 10.1016/j.psychres.2024.115866 -
JAMA Psychiatry Jul 2023Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to...
IMPORTANCE
Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders.
OBJECTIVE
To assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs).
DESIGN, SETTING, AND PARTICIPANTS
Women from the Norwegian Mother, Father and Child Cohort Study were included in this genetic association study. PRSs were used to determine whether genetic liability for major depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism spectrum disorder were associated with the symptoms of premenstrual disorders, using the PRS for height as a somatic comparator. The sample was recruited across Norway between June 1999 and December 2008, and analyses were performed from July 1 to October 14, 2022.
MAIN OUTCOMES AND MEASURES
The symptoms of premenstrual disorders were assessed at recruitment at week 15 of pregnancy with self-reported severity of depression and irritability before menstruation. Logistic regression was applied to test for the association between the presence of premenstrual disorder symptoms and the PRSs for major psychiatric disorders.
RESULTS
The mean (SD) age of 56 725 women included in the study was 29.0 (4.6) years. Premenstrual disorder symptoms were present in 12 316 of 56 725 participants (21.7%). The symptoms of premenstrual disorders were associated with the PRSs for major depression (β = 0.13; 95% CI, 0.11-0.15; P = 1.21 × 10-36), bipolar disorder (β = 0.07; 95% CI, 0.05-0.09; P = 1.74 × 10-11), attention deficit/hyperactivity disorder (β = 0.07; 95% CI, 0.04-0.09; P = 1.58 × 10-9), schizophrenia (β = 0.11; 95% CI, 0.09-0.13; P = 7.61 × 10-25), and autism spectrum disorder (β = 0.03; 95% CI, 0.01-0.05; P = .02) but not with the PRS for height. The findings were confirmed in a subsample of women without a history of psychiatric diagnosis.
CONCLUSIONS
The results of this genetic association study show that genetic liability for both affective spectrum disorder and major psychiatric disorders was associated with symptoms of premenstrual disorders, indicating that premenstrual disorders have overlapping genetic foundations with major psychiatric disorders.
Topics: Child; Humans; Female; Adult; Cohort Studies; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Risk Factors; Attention Deficit Disorder with Hyperactivity; Genetic Predisposition to Disease; Multifactorial Inheritance
PubMed: 37163253
DOI: 10.1001/jamapsychiatry.2023.1137 -
Biological Psychiatry Feb 2024Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely... (Review)
Review
Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely influences, the pathogenesis of mental disorders, including major depressive disorder and bipolar disorder. However, while substantial advances in the field of microbiome science have been made, we have likely only scratched the surface in our understanding of how these ecosystems might contribute to mental disorder pathophysiology. Beyond the gut bacteriome, research into lesser explored components of the gut microbiome, including the gut virome, mycobiome, archaeome, and parasitome, is increasingly suggesting relevance in psychiatry. The contribution of microbiomes beyond the gut, including the oral, lung, and small intestinal microbiomes, to human health and pathology should not be overlooked. Increasing both our awareness and understanding of these less traversed fields of research are critical to improving the therapeutic benefits of treatments targeting the gut microbiome, including fecal microbiome transplantation, postbiotics and biogenics, and dietary intervention. Interdisciplinary collaborations integrating systems biology approaches are required to fully elucidate how these different microbial components and distinct microbial niches interact with each other and their human hosts. Excitingly, we may be at the start of the next microbiome revolution and thus one step closer to informing the field of precision psychiatry to improve outcomes for those living with mental illness.
Topics: Humans; Mood Disorders; Depressive Disorder, Major; Ecosystem; Gastrointestinal Microbiome; Bipolar Disorder
PubMed: 37661007
DOI: 10.1016/j.biopsych.2023.08.020 -
Nutrients Nov 2023Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study...
Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH)D, were measured simultaneously with a validated liquid chromatography-tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH)D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)D ( = -0.154, = 0.040), as well as the Young Mania Rating Scale and the VMR ( = -0.238, = 0.015). Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.
Topics: Humans; Vitamin D; Bipolar Disorder; Cross-Sectional Studies; Mania; Vitamins
PubMed: 38004146
DOI: 10.3390/nu15224752 -
Progress in Neuro-psychopharmacology &... Dec 2023Facial emotion (or expression) recognition (FER) is a domain of affective cognition impaired across various psychiatric conditions, including bipolar disorder (BD). We... (Meta-Analysis)
Meta-Analysis
Facial emotion (or expression) recognition (FER) is a domain of affective cognition impaired across various psychiatric conditions, including bipolar disorder (BD). We conducted a systematic review and meta-analysis searching for eligible articles published from inception to April 26, 2023, in PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO to examine whether and to what extent FER would differ between people with BD and those with other mental disorders. Thirty-three studies comparing 1506 BD patients with 1973 clinical controls were included in the present systematic review, and twenty-six of them were analyzed in random-effects meta-analyses exploring the discrepancies in discriminating or identifying emotional stimuli at a general and specific level. Individuals with BD were more accurate in identifying each type of emotion during a FER task compared to individuals diagnosed with schizophrenia (SCZ) (SMD = 0.27; p-value = 0.006), with specific differences in the perception of anger (SMD = 0.46; p-value = 1.19e-06), fear (SMD = 0.38; p-value = 8.2e-04), and sadness (SMD = 0.33; p-value = 0.026). In contrast, BD patients were less accurate than individuals with major depressive disorder (MDD) in identifying each type of emotion (SMD = -0.24; p-value = 0.014), but these differences were more specific for sad emotional stimuli (SMD = -0.31; p-value = 0.009). No significant differences were observed when BD was compared with children and adolescents diagnosed with attention-deficit/hyperactivity disorder. FER emerges as a potential integrative instrument for guiding diagnosis by enabling discrimination between BD and SCZ or MDD. Enhancing the standardization of adopted tasks could further enhance the accuracy of this tool, leveraging FER potential as a therapeutic target.
Topics: Adolescent; Child; Humans; Bipolar Disorder; Depressive Disorder, Major; Facial Recognition; Emotions; Anger
PubMed: 37625644
DOI: 10.1016/j.pnpbp.2023.110847 -
Blood Advances Sep 2023Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous... (Meta-Analysis)
Meta-Analysis
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.
Topics: Male; Humans; Female; Depressive Disorder, Major; Venous Thromboembolism; Bipolar Disorder; Schizophrenia; Risk Factors
PubMed: 37399490
DOI: 10.1182/bloodadvances.2023010562 -
The Primary Care Companion For CNS... Aug 2023To examine the funding priorities of the National Institute of Mental Health (NIMH) since 2016 to assess whether NIMH was continuing to prioritize basic research at the...
To examine the funding priorities of the National Institute of Mental Health (NIMH) since 2016 to assess whether NIMH was continuing to prioritize basic research at the expense of clinical research. Six psychiatric disorders (schizophrenia, bipolar disorder, depression, anxiety disorders, eating disorders, autism) were assessed using 2 publicly available data sources (ClinicalTrials.gov and the National Institutes of Health Research, Condition, and Disease Categorization [RCDC]) to determine the degree of NIMH support for drug trials and research on these disorders in general since 2016. From 2017 through 2022, ClinicalTrials.gov lists just 1 drug trial each for schizophrenia and bipolar disorder. The RCDC database for 2016 through 2021 shows that NIMH support for research projects on schizophrenia and bipolar disorder decreased by 22% and 20%, respectively. During that time, Congress increased the budget of NIMH by 40%. NIMH has continued to prioritize basic research over clinical trials, resulting in a steep decline in funding for possible treatments for the most serious and costly psychiatric diseases. .
Topics: United States; Humans; National Institute of Mental Health (U.S.); Bipolar Disorder; Schizophrenia; Anxiety Disorders; Autistic Disorder
PubMed: 37549433
DOI: 10.4088/PCC.23m03486