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PloS One 2022Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues,...
Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5-0.03), and neuroticism score (p-value range = 2.9x10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Mood Disorders; PCSK9 Inhibitors; Polymorphism, Single Nucleotide; Proprotein Convertase 9; Ubiquitin Thiolesterase; Quantitative Trait Loci
PubMed: 36580462
DOI: 10.1371/journal.pone.0279381 -
Lithium and suicide prevention in mood disorders and in the general population: A systematic review.Neuroscience and Biobehavioral Reviews Sep 2020Suicide contributes to 1-4 % of deaths worldwide every year. We conducted a systematic review aimed at summarizing evidence on the use of lithium for the prevention of... (Review)
Review
Suicide contributes to 1-4 % of deaths worldwide every year. We conducted a systematic review aimed at summarizing evidence on the use of lithium for the prevention of suicide risk both in mood disorders and in the general population. We followed the PRISMA methodology (keywords: "lithium", "suicide" AND "suicidal" on Pubmed, Cochrane CENTRAL, Clinicaltrial.gov, other databases). Inclusion criteria: lithium therapy in mood disorder or found in drinking water or scalp in the general population. Exclusion criteria: no lithium administration. From 918 screened references, 18 prospective (number of participants: 153786), 10 retrospective (number of participants: 61088) and 16 ecological studies (total sample: 2062) were included. Most of the observational studies reported a reduction in suicide in patients with mood disorders. All studies about lithium treatment's duration reported that long-term lithium give more benefits than short-term lithium in suicide risk The evidence seems to attribute an intrinsic anti-suicidal property of lithium, independent of its proven efficacy as a mood stabilizer.
Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium; Mood Disorders; Prospective Studies; Retrospective Studies; Suicide Prevention
PubMed: 32561344
DOI: 10.1016/j.neubiorev.2020.06.017 -
Progress in Neuro-psychopharmacology &... Jan 2021Numerous pharmacological treatments for mood disorders are currently available; however, rates of treatment resistance, relapse and recurrence remain high. Therefore,... (Review)
Review
Numerous pharmacological treatments for mood disorders are currently available; however, rates of treatment resistance, relapse and recurrence remain high. Therefore, novel treatments acting outside of the conventionally targeted monoamine system are urgently needed to improve patient outcomes. Emerging and converging evidence suggests that immune dysfunction, oxidative stress, impaired cerebral blood flow (CBF) and decreased neurotrophic factors all contribute to mood disorder pathophysiology and are therefore treatment targets of interest. Pentoxifylline (PTX) is a phosphodiesterase inhibitor with potent anti-inflammatory and antioxidant effects, with additional pleiotropic effects that lead to improved CBF and increases in brain derived neurotrophic factor (BDNF) levels. The direct effect of non-specific phosphodiesterase inhibition may also improve alertness and cognitive function through enhancing second messenger systems. Replicated preclinical studies have demonstrated antidepressant-like effects in animal models. Small preliminary clinical trials have demonstrated promising results for antidepressant and procognitive effects, however, have yet to be replicated in larger mood disorder samples. Only one randomized clinical trial (RCT) specifically assessed the effects of adjunctive PTX in major depressive disorder (MDD), showing clinically and statistically significant antidepressant effects compared to placebo. No studies have assessed PTX in bipolar disorder (BD), where inflammation and altered CBF have also been strongly implicated. Taken together, PTX presents as a promising pleiotropic agent with several potential novel mechanisms of action meriting further evaluation in clinical trials to evaluate target engagement, antidepressant, procognitive and mood stabilizing effects.
Topics: Animals; Antidepressive Agents; Antimanic Agents; Drug Delivery Systems; Free Radical Scavengers; Humans; Mood Disorders; Pentoxifylline; Phosphodiesterase Inhibitors; Treatment Outcome
PubMed: 32634540
DOI: 10.1016/j.pnpbp.2020.110032 -
Journal of Affective Disorders Jul 2022Understanding how symptoms of mood disorders vary over time in relation to each other is potentially valuable for diagnosis and predicting episodes of illness. In this...
BACKGROUND
Understanding how symptoms of mood disorders vary over time in relation to each other is potentially valuable for diagnosis and predicting episodes of illness. In this paper, we characterize the degree of similarity of time series of different mood disorder symptoms.
METHODS
We collected 32,215 mood disorder symptom questionnaires, administered twice-daily over 18 months to (n = 19) subjects with rapidly cycling bipolar disorder and (n = 20) healthy control subjects, using visual analog scales to rate 11 sets of symptom severity ratings plus a control item. We used Dynamic Time Warping to calculate similarity ratings between all within-subject pairs of severity ratings followed by Exploratory Factor Analysis (EFA) to identify latent factors of symptom time series across all subjects.
RESULTS
Two latent factors were identified: one with depression and anxiety; and a second, with concentration, energy, irritability, fatigue, appetite, euphoria/elation and overall mood. Restlessness, racing thoughts, and the control item (daily hours of daylight) did not cluster with any of the others.
LIMITATIONS
Limited sample size dictated that we pool bipolar and healthy patients and use an iterative EFA procedure.
CONCLUSION
This analysis suggests that, in a pooled sample of individuals with bipolar disorder and in healthy controls, severity ratings of overall depression and overall anxiety vary jointly as one dynamic factor, while some but not all other DSM mood symptoms vary jointly along with overall mood rating as a second dynamic factor. Further investigation may determine if these findings can simplify subjective symptom reporting in mood-monitoring studies.
Topics: Affect; Bipolar Disorder; Humans; Irritable Mood; Mood Disorders; Psychiatric Status Rating Scales; Time Factors
PubMed: 35461820
DOI: 10.1016/j.jad.2022.04.117 -
BMC Psychiatry Mar 2022The early detection of patients at risk of developing schizophrenia and bipolar disorder, and more broadly mood spectrum disorder, is a public health concern. The...
BACKGROUND
The early detection of patients at risk of developing schizophrenia and bipolar disorder, and more broadly mood spectrum disorder, is a public health concern. The phenotypical overlap between the prodromes in these disorders calls for a simultaneous investigation into both illness trajectories.
METHOD
This is an epidemiological, retrospective, multicentre, descriptive study conducted in the Grand-Est region of France in order to describe and compare early symptoms in 205 patients: 123 of which were diagnosed with schizophrenia and 82 with bipolar disorder or mood spectrum disorder. Data corresponding to the pre-morbid and prodromal phases, including a timeline of their onset, were studied in child and adolescent psychiatric records via a data grid based on the literature review conducted from birth to 17 years of age.
RESULTS
Two distinct trajectories were highlighted. Patients with schizophrenia tended to present more difficulties at each developmental stage, with the emergence of negative and positive behavioural symptoms during adolescence. Patients with mood spectrum disorder, however, were more likely to exhibit anxiety and then mood-related symptoms. Overall, our results corroborate current literature findings and are consistent with the neurodevelopmental process. We succeeded in extracting a decision tree with good predictability based on variables relating to one diagnosis: 77.6% of patients received a well-indexed diagnosis. An atypical profile was observed in future mood spectrum disorder patients as some exhibited numerous positive symptoms alongside more conventional mood-related symptoms.
CONCLUSION
The combination of all these data could help promote the early identification of high-risk patients thereby facilitating early prevention and appropriate intervention in order to improve outcomes.
Topics: Adolescent; Bipolar Disorder; Child; Decision Trees; Humans; Mood Disorders; Retrospective Studies; Schizophrenia
PubMed: 35300648
DOI: 10.1186/s12888-022-03835-0 -
CJEM Jan 2022Frequent emergency department (ED) use is a growing problem that is associated with poor patient outcomes and increased health care costs. Our objective was to analyze...
OBJECTIVES
Frequent emergency department (ED) use is a growing problem that is associated with poor patient outcomes and increased health care costs. Our objective was to analyze the association between mood disorders and the incidence of frequent ED use.
METHODS
We used the Canadian Community Health Survey conducted by Statistics Canada, 2015-2016. Mood disorder was defined as depression, bipolar disorder, mania, or dysthymia. Frequent ED use was defined as 4 or more visits in the year preceding the interview. Multivariable log-binomial regression models were used to determine the associations between mood disorders and frequent ED use.
RESULTS
Among the 99,009 participants, 8.4% had mood disorders, 80.3% were younger than 65, and 2.2% were frequent ED users. Mood disorders were significantly associated with the 1-year cumulative incidence of frequent ED use (RR = 2.5, 95% CI 2.2-2.7), after adjusting for several potential confounders.
CONCLUSIONS
This national survey showed that people with a mood disorder had a three-fold risk of frequent ED use, compared to people without mood disorder. These results can inform the development of policies and targeted interventions aimed at identifying and supporting ED patients with mood disorder.
Topics: Canada; Cross-Sectional Studies; Emergency Service, Hospital; Humans; Mood Disorders; Surveys and Questionnaires
PubMed: 34669174
DOI: 10.1007/s43678-021-00204-w -
Canadian Journal of Public Health =... Oct 2020The inflammatory biomarker C-reactive protein (CRP) measures systemic inflammation and has been shown to be increased in patients with mood disorders such as depression....
OBJECTIVES
The inflammatory biomarker C-reactive protein (CRP) measures systemic inflammation and has been shown to be increased in patients with mood disorders such as depression. The objective of this study was to determine the association between self-reported mood disorders with CRP levels in a representative sample of the Canadian population using the Canadian Health Measures Survey (CHMS) data 2013-2014.
METHODS
The CHMS is an ongoing national cross-sectional survey of Canadians about their general health. The current study used the data collected from Cycle 3 (2012/13) and was limited to adults aged 18 and older. Survey weights were assigned to adjust for non-response and non-random sample selection of the responding sample.
RESULTS
Data were analyzed from 5782 respondents (400 (6.9%) self-reported mood disorders and 5382 (93.1%) reported no mood disorders). The CRP level was significantly higher among those with mood disorders than among those without (3.22 (0.17) vs. 2.34 (0.04) mg/L, p = 0.003). Respondents with CRP levels > 10.00 mg/L had 2.69 greater odds of reporting a mood disorder compared with those with CRP levels ≤ 1.00 mg/L (p = 0.02). Higher proportions of respondents with mood disorders were older, had lower BMI, had secondary education, had weak sense of community, had higher proportion of asthma or arthritis, were current/past smokers, had daily consumption of 3+ drinks of alcohol, and used prescription drugs, cannabis/hashish, or other drugs compared with those without mood disorders (all p's < 0.05).
CONCLUSION
This study supported the association of CRP and mood disorder, specifically in a representative sample of the Canadian population. Targeting inflammation in depression and mood disorder warrants further study.
Topics: Adult; C-Reactive Protein; Canada; Cross-Sectional Studies; Female; Health Surveys; Humans; Male; Middle Aged; Mood Disorders
PubMed: 32130717
DOI: 10.17269/s41997-020-00297-3 -
Journal of Affective Disorders Jan 2022As it is not clear how body-mass index (BMI) may relate to diagnosis, symptom-severity, illness-course, and treatment-response among psychiatric patients, we related BMI...
OBJECTIVE
As it is not clear how body-mass index (BMI) may relate to diagnosis, symptom-severity, illness-course, and treatment-response among psychiatric patients, we related BMI to psychiatric diagnosis and to selected clinical and demographic factors in major affective disorder subjects.
METHODS
We analyzed mean BMI levels vs. diagnosis, and evaluated selected risk factors for association with overweight and obesity among subjects with DSM-5 major affective disorders.
RESULTS
In 1884 subjects, BMI ranged from 23.4 kg/m with anxiety disorders to 27.6 with psychotic disorders, and averaged 24.1 among 1469 affective disorder subjects. Mood-disorder subjects with BMI ≥ 25 (overweight/obese) were more likely: men, older, married, with more children and siblings, less education, lower socioeconomic status, engaged less in physical exercise, smoked more, and lived in less densely populated areas. They also were more likely to have: BD than MDD, familial mood disorders, no co-occurring ADHD, higher serum triglyceride levels, more time depressed and less improvement in depression ratings with treatment.
CONCLUSIONS
Risk of being overweight or obese was greatest with psychoses, least with anxiety, personality, and minor depressive disorders, and intermediate with major mood disorders. Several plausible risk factors for high BMI were identified in mood disorder subjects, including male sex and with BD > MDD. Striking were selectively greater prospective morbidity and decreased treatment-response for depression vs. mania with BMI ≥ 25.
Topics: Child; Depressive Disorder, Major; Humans; Male; Mood Disorders; Morbidity; Overweight; Prospective Studies
PubMed: 34699849
DOI: 10.1016/j.jad.2021.10.032 -
Current Psychiatry Reports Sep 2016Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments,... (Review)
Review
Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions.
Topics: Behavioral Symptoms; Drug Therapy; Humans; Mood Disorders; Psychotropic Drugs; Risk Adjustment; Suicidal Ideation; Suicide; Treatment Outcome; Suicide Prevention
PubMed: 27542851
DOI: 10.1007/s11920-016-0715-0 -
Depression and Anxiety Jul 2015We conducted a meta-analysis to review the diagnostic accuracy of the Mood Disorder Questionnaire (MDQ) among patients with mood disorders. We used a bivariate random... (Meta-Analysis)
Meta-Analysis Review
We conducted a meta-analysis to review the diagnostic accuracy of the Mood Disorder Questionnaire (MDQ) among patients with mood disorders. We used a bivariate random effects model to calculate summary sensitivity and specificity. Twenty-one studies were included. At the standard or modified cutoff value of 7, summary sensitivity was .62 and summary specificity was .85. When we pooled 11 studies including both patients with bipolar disorder (BD) and those with unipolar depression, the summary sensitivity was .76 and summary specificity was .81. However, among the six studies that excluded patients with known BD, the summary sensitivity was significantly reduced to .37 and summary specificity was .88. There were no significant differences on the diagnostic accuracy of the MDQ between studies from Eastern and Western countries after adjusting for various clinical correlates. The overall diagnostic accuracy of the MDQ was relatively good. However, when the MDQ is applied among patients with depression without previous diagnoses of BD, its sensitivity was significantly reduced. This suggests that when the MDQ is applied among this population, its optimal cutoff value should be adjusted to enhance its sensitivity.
Topics: Bipolar Disorder; Depressive Disorder, Major; Humans; Mood Disorders; Psychiatric Status Rating Scales; Psychometrics; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires
PubMed: 26010478
DOI: 10.1002/da.22374