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Psychotherapy and Psychosomatics 2021Psychotic depression was initially considered to be at one end of a continuum of severity of major depression. Subsequent experience demonstrated that psychosis is an... (Review)
Review
Psychotic depression was initially considered to be at one end of a continuum of severity of major depression. Subsequent experience demonstrated that psychosis is an independent trait that may accompany mood disorders of varying severity. While much has been learned about the impact of severe mood congruent delusions and hallucinations on the course and treatment response of depression, less is known about fleeting or mild psychosis, mood incongruent features, or psychotic symptoms that reflect traumatic experiences. Acute treatment of psychotic unipolar depression generally involves the combination of an antidepressant and an antipsychotic drug or electroconvulsive therapy. There is inadequate information about maintenance treatment of unipolar psychotic depression and acute and chronic treatment of psychotic bipolar disorder. Decision-making therefore still must rely in part on clinical experience.
Topics: Bipolar Disorder; Depression; Depressive Disorder, Major; Diagnosis, Differential; Humans; Psychotic Disorders
PubMed: 33166960
DOI: 10.1159/000511348 -
The American Journal of Psychiatry May 2021Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based... (Review)
Review
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.
Topics: Antidepressive Agents; Delivery of Health Care; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dissociative Disorders; Excitatory Amino Acid Antagonists; Humans; Hypertension; Implementation Science; Ketamine; Lower Urinary Tract Symptoms; Monitoring, Physiologic; Patient Selection; Personnel Staffing and Scheduling; Psychoses, Substance-Induced; Substance-Related Disorders; Suicidal Ideation
PubMed: 33726522
DOI: 10.1176/appi.ajp.2020.20081251 -
Medicina (Kaunas, Lithuania) Nov 2021Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use... (Review)
Review
Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.
Topics: Alcoholism; Bipolar Disorder; Comorbidity; Humans; Psychotropic Drugs; Substance-Related Disorders
PubMed: 34833474
DOI: 10.3390/medicina57111256 -
Cell Apr 2024This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal...
This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
Topics: Child; Female; Humans; Infant; Pregnancy; Autism Spectrum Disorder; Biomarkers; Longitudinal Studies; Neurodevelopmental Disorders; Prospective Studies; Feces; Gastrointestinal Microbiome; Mood Disorders
PubMed: 38574728
DOI: 10.1016/j.cell.2024.02.035 -
JAMA Psychiatry Jan 2024Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.
IMPORTANCE
Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.
OBJECTIVE
To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023.
MAIN OUTCOMES AND MEASURES
Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview.
RESULTS
Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001).
CONCLUSIONS AND RELEVANCE
This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.
Topics: Humans; Female; Adult; Male; Bipolar Disorder; Depressive Disorder, Major; Mood Disorders; Diagnosis, Differential; Biomarkers
PubMed: 37878349
DOI: 10.1001/jamapsychiatry.2023.4096 -
Thyroid : Official Journal of the... Aug 2021Observational studies suggest that even minor variations in thyroid function are associated with the risk of mood disorders, including major depressive disorder (MDD)...
Observational studies suggest that even minor variations in thyroid function are associated with the risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). However, it is unknown whether these associations are causal or not. We used a Mendelian randomization (MR) approach to investigate causal effects of minor variations in thyrotropin (TSH) and free thyroxine (fT4) levels on MDD and BD risk. We performed two-sample MR analyses using data from the largest publicly available genome-wide association studies on normal-range TSH ( = 54,288) and fT4 ( = 49,269) levels, MDD (170,756 cases, 329,443 controls) and BD (20,352 cases, 31,358 controls). Secondary MR analyses investigated the effects of TSH and fT4 levels on specific MDD and BD subtypes. Reverse MR was also performed to assess the effects of MDD and BD on TSH and fT4 levels. There were no associations between genetically predicted TSH and fT4 levels and MDD risk, nor MDD subtypes and minor depressive symptoms. A one standard deviation increase in fT4 levels was nominally associated with an 11% decrease in the overall BD risk (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.80-0.98, = 0.022) and a 13% decrease in the BD type 1 risk (OR = 0.87, CI = 0.75-1.00, = 0.047). In the reverse direction, genetic predisposition to MDD and BD was not associated with TSH nor fT4 levels. Variations in normal-range TSH and fT4 levels have no effects on the risk of MDD and its subtypes, and neither on minor depressive symptoms. This indicates that depressive symptoms should not be attributed to minor variations in thyroid function. Borderline associations with BD and BD type 1 risks suggest that further clinical studies should investigate the effect of thyroid hormone treatment in BD.
Topics: Adult; Bipolar Disorder; Depressive Disorder, Major; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Mood Disorders; Risk; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine
PubMed: 33899528
DOI: 10.1089/thy.2020.0884 -
Canadian Journal of Psychiatry. Revue... May 2023Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on... (Review)
Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.
BACKGROUND
Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders.
OBJECTIVE
The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder.
METHODS
We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations.
RESULTS
Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results.
CONCLUSION
The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Cannabis; Marijuana Abuse; Canada; Anxiety; Substance-Related Disorders
PubMed: 35711159
DOI: 10.1177/07067437221099769 -
Nutrients Feb 2021This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant... (Review)
Review
This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies.
Topics: Adult; Antidepressive Agents; Combined Modality Therapy; Depressive Disorder, Major; Dietary Supplements; Female; Humans; Male; Mood Disorders; Nutrition Therapy; Randomized Controlled Trials as Topic; Trace Elements; Vitamins
PubMed: 33652997
DOI: 10.3390/nu13030767 -
Nutrients Aug 2020Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for... (Review)
Review
Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Brain; Brain Diseases; Child; Dietary Supplements; Docosahexaenoic Acids; Humans; Mental Disorders; Mood Disorders; Neurodevelopmental Disorders; Seafood
PubMed: 32759851
DOI: 10.3390/nu12082333 -
Journal of Affective Disorders Apr 2023Cognitive impairment experienced by people with bipolar disorders (BD) or major depressive disorder (MDD) is associated with impaired psychosocial function and poorer... (Review)
Review
BACKGROUND
Cognitive impairment experienced by people with bipolar disorders (BD) or major depressive disorder (MDD) is associated with impaired psychosocial function and poorer quality of life. Sleep disturbance is another core symptom of mood disorders which may be associated with, and perhaps worsen, cognitive impairments. The aim of this systematic review was to critically assess the relationship between sleep disturbance and cognitive impairment in mood disorders.
METHODS
In this systematic review, relevant studies were identified using electronic database searches of PsychINFO, MEDLINE, Embase and Web of Science.
FINDINGS
Fourteen studies were included; eight investigated people with BD, five investigated people with MDD, and one included both people with MDD and people with BD. One study was an intervention for sleep disturbance and the remaining thirteen studies used either a longitudinal or cross-sectional observational design. Ten studies reported a significant association between subjectively measured sleep disturbance and cognitive impairment in people with MDD or BD after adjusting for demographic and clinical covariates, whereas no such association was found in healthy participants. Two studies reported a significant association between objectively measured (actigraphy or polysomnography) sleep abnormalities and cognitive impairment in mood disorders. One study of cognitive behavioural therapy for insomnia modified for BD (CBTI-BD) found an association between improvements in sleep and cognitive performance in BD.
INTERPRETATION
There is preliminary evidence to suggest a significant association between sleep disturbance and cognitive impairment in mood disorders. These findings highlight the need for further research of sleep disturbances and cognitive impairment in people with mood disorders.
Topics: Humans; Mood Disorders; Depressive Disorder, Major; Cross-Sectional Studies; Quality of Life; Cognitive Dysfunction; Sleep; Sleep Wake Disorders
PubMed: 36739007
DOI: 10.1016/j.jad.2023.01.114