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Cell Jan 2022Psychiatric disease is one of the greatest health challenges of our time. The pipeline for conceptually novel therapeutics remains low, in part because uncovering the...
Psychiatric disease is one of the greatest health challenges of our time. The pipeline for conceptually novel therapeutics remains low, in part because uncovering the biological mechanisms of psychiatric disease has been difficult. We asked experts researching different aspects of psychiatric disease: what do you see as the major urgent questions that need to be addressed? Where are the next frontiers, and what are the current hurdles to understanding the biological basis of psychiatric disease?
Topics: Animals; Antidepressive Agents; Data Science; Depression; Depressive Disorder; Genomics; Humans; Neurons; Precision Medicine; Prefrontal Cortex; Translational Research, Biomedical; Treatment Outcome
PubMed: 34995512
DOI: 10.1016/j.cell.2021.12.010 -
Journal of Neurophysiology Jan 2022Adolescence is a developmental period associated with major neural reorganization and the onset of many psychological disorders. Depression in particular is prevalent... (Review)
Review
Adolescence is a developmental period associated with major neural reorganization and the onset of many psychological disorders. Depression in particular is prevalent and impairing in adolescents and rates have been rising in recent years. Recent advances in the neurobiology of adolescent depression contribute to a better understanding of functional connectivity among neural networks and represent a promising start for determining biomarkers of depression and potential areas of intervention.
Topics: Adolescent; Brain; Connectome; Depression; Depressive Disorder; Humans; Nerve Net
PubMed: 34879212
DOI: 10.1152/jn.00327.2021 -
Psychophysiology Jan 2018Unipolar depression has been characterized as involving diminished approach motivation and reward sensitivity. A psychophysiological indicator of approach motivation...
Unipolar depression has been characterized as involving diminished approach motivation and reward sensitivity. A psychophysiological indicator of approach motivation involves an asymmetry in frontal EEG activity, such that greater left relative to right frontal cortical activity indicates increased approach motivation. Consistent with the perspective of reduced approach motivation tendencies, depression has been associated with decreased relative left frontal cortical activity. To date, supporting research has primarily relied on categorical diagnoses or composite symptom counts. However, given the heterogeneity in depression, it is unclear what specific symptom dimensions relate to decreased relative left frontal cortical activity. The present study examined the association between multiple depression symptom dimensions and asymmetrical frontal cortical activity while anticipating reward in separate undergraduate (n = 75) and clinical samples (current major depressive disorder [n = 68] and never depressed controls [n = 67]). All participants completed the Inventory of Depression and Anxiety Symptoms, a self-report measure of factor-analytically derived symptom dimensions. Frontal cortical activity was assessed during a computerized slot machine task while participants anticipated potential monetary reward or no incentive. In undergraduates with low depression symptoms and never depressed controls, reward trials relative to no-incentive trials elicited greater relative left frontal cortical activity. Furthermore, in both samples across all participants, increased dysphoria and lassitude symptoms were associated with decreased relative left frontal cortical activity while anticipating reward. The present study suggests that depression symptoms consistent with motivational disengagement are associated with decreased relative left frontal cortical activity.
Topics: Anticipation, Psychological; Depression; Depressive Disorder, Major; Electroencephalography; Female; Frontal Lobe; Functional Laterality; Humans; Male; Reward; Young Adult
PubMed: 28555883
DOI: 10.1111/psyp.12892 -
Translational Psychiatry Feb 2019There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically...
There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically appraise the roles of major study characteristics in the accuracy of study findings. This systematic review aims to critically appraise the impact of study characteristics on the association between DNA methylation and depression, and summarize the overview of this association. Electronic databases and gray literatures until December 2017 were searched for English-language studies with standard diagnostic criteria of depression. A total of 67 studies were included in this review along with a summary of their study characteristics. We grouped the findings into etiological and treatment studies. Majority of these selected studies were recently published and from developed countries. Whole blood samples were the most studied common tissues. Bisulfite conversion, along with pyrosequencing, was widely used to test the DNA methylation level across all the studies. High heterogeneity existed among the studies in terms of experimental and statistical methodologies and study designs. As recommended by the Cochrane guideline, a systematic review without meta-analysis should be undertaken. This review has, in general, found that DNA methylation modifications were associated with depression. Subgroup analyses showed that most studies found BDNF and SLC6A4 hypermethylations to be associated with MDD or depression in general. In contrast, studies on NR3C1, OXTR, and other genes, which were tested by only few studies, reported mixed findings. More longitudinal studies using standardized experimental and laboratory methodologies are needed in future studies to enable more systematical comparisons and quantitative synthesis.
Topics: DNA Methylation; Depression; Depressive Disorder; Humans
PubMed: 30718449
DOI: 10.1038/s41398-019-0412-y -
Journal of the American Medical... May 2012Antidepressant medications are the most common psychopharmacologic therapy used to treat depressed nursing home (NH) residents. Despite a significant increase in the... (Review)
Review
BACKGROUND
Antidepressant medications are the most common psychopharmacologic therapy used to treat depressed nursing home (NH) residents. Despite a significant increase in the rate of antidepressant prescribing over the past several decades, little is known about the effectiveness of these agents in the NH population.
OBJECTIVE
To conduct a systematic review of the literature to examine and compare the effectiveness of antidepressant medications for treating major depressive symptoms in elderly NH residents.
METHODS
The following databases were searched with searches completed prior to January 2011 and no language restriction: MEDLINE, Embase, PsycINFO, CINHAL, CENTRAL, LILACS, ClinicalTrials.gov, International Standard Randomized Controlled Trial Number Register, and the WHO International Clinical Trial Registry Platform. Additional studies were identified from citations in evidence-based guidelines and reviews as well as book chapters on geriatric depression and pharmacotherapy from several clinical references. Studies were included if they described a clinical trial that assessed the effectiveness of any currently-marketed antidepressant for adults aged 65 years or older, who resided in the NH, and were diagnosed by DSM criteria and/or standardized validated screening instruments with Major Depressive Disorder, minor depression, dysthymic disorder, or Depression in Alzheimer's disease.
RESULTS
A total of eleven studies, including four randomized and seven non-randomized open-label trials, met all inclusion and exclusion criteria. It was not feasible to conduct a meta-analysis because the studies were heterogeneous in terms of study design, operational definitions of depression, participant characteristics, pharmacologic interventions, and outcome measures. Of the four randomized trials, two had a control group and did not demonstrate a statistically-significant benefit for antidepressant pharmacotherapy over placebo. While six of the seven non-randomized studies identified a response to an antidepressant, their results must be interpreted with caution as they lacked a comparison group.
CONCLUSIONS
The limited amount of evidence from randomized and non-randomized open-label trials suggests that depressed NH residents have a modest response to antidepressant medications. Further research using rigorous study designs are needed to examine the effectiveness and safety of antidepressants in depressed NH residents, and to determine the various facility, provider, and patient factors associated with response to treatment.
Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depression; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Geriatric Assessment; Homes for the Aged; Humans; Male; Nursing Homes; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 22019084
DOI: 10.1016/j.jamda.2011.08.009 -
The American Journal of Geriatric... Dec 2019The study examines the relationship of negative emotions with: 1) non-emotional symptoms (e.g., vegetative and physical symptoms) and 2) the course of depression in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study examines the relationship of negative emotions with: 1) non-emotional symptoms (e.g., vegetative and physical symptoms) and 2) the course of depression in suicidal older adults with Major Depressive Disorder (MDD) and cognitive impairment treated with psychotherapy.
DESIGN
The authors identified a subgroup of participants (N = 26) who expressed suicidal ideation at Baseline or Week 12 from a randomized controlled trial (RCT) of two psychosocial interventions, Problem Adaptation Therapy (PATH) and Supportive Therapy for Cognitively Impaired. The authors assessed negative emotions, non-emotional symptoms of depression, depression severity, and suicidal ideation at entry, week 4, week 8, and week 12.
PARTICIPANTS
Participants were 65 years and older and had a diagnosis of unipolar depression, varying degrees of cognitive impairment (up to moderate dementia) and suicidal ideation.
SETTING
The study was conducted in the Outpatient Department of New York Presbyterian/Weill Cornell Medicine in Westchester, NY.
MEASUREMENTS
Negative emotions and non-emotional items were identified with the 24-item Hamilton Depression Rating Scale (Ham-D).
RESULTS
Among participants with suicidal ideation, the reduction in negative emotions from baseline to week 4, week 4 to week 8, and week 8 to week 12 was significantly associated with the reduction in non-emotional symptoms of depression at weeks 4, 8, and 12 (F = 6.20, p = 0.02) and with the reduction in overall depression severity at weeks 4, 8, and 12 (F = 26.63, p <0.0001) after controlling for depression severity at baseline (HAM-D total score) and time trends.
CONCLUSION
Our findings may guide the treatment of older patients with depression and suicidal ideation to help reduce depression and suicide risk.
Topics: Aged; Aged, 80 and over; Cognitive Dysfunction; Depression; Depressive Disorder, Major; Emotions; Female; Humans; Male; Psychotherapy; Severity of Illness Index; Suicidal Ideation
PubMed: 31582195
DOI: 10.1016/j.jagp.2019.08.018 -
Comprehensive Psychiatry Jan 2021Clinical audit is a sustained cyclical quality improvement process seeking to improve patient care and outcomes by evaluating services against explicit standards and...
Quality of English inpatient mental health services for people with anxiety or depressive disorders: Findings and recommendations from the core audit of the National Clinical Audit of Anxiety and Depression.
BACKGROUND
Clinical audit is a sustained cyclical quality improvement process seeking to improve patient care and outcomes by evaluating services against explicit standards and implementing necessary changes. National audits aim to improve population-level clinical care by identifying unwarranted variations and making recommendations for clinicians, managers and service commissioners. The National Clinical Audit of Anxiety and Depression aimed to improve clinical care for people admitted to English hospitals for treatment of anxiety and depression, to provide comparative data on quality of care, and to support local quality improvement initiatives by identifying and sharing examples of best practice.
PROCEDURES
Thirteen standards were developed based on NICE guidelines, literature review and feedback from a steering committee and reference group of service users and carers. All providers of NHS inpatient mental health services in England were asked to submit details of between 20 and 100 eligible service users/patients admitted between April 2017 and September 2018. To ascertain data reliability, participating services re-audited 5 sets of case-notes with a second auditor, and the coordinating team checked 10 randomly-selected sets of case-notes from 3 services, also selected at random. The reference group and steering committee identified key findings and developed a series of recommendations, which were discussed in regional quality improvement workshops and on-line webinars.
FINDINGS
Data from 3795 case notes were analysed. A sizeable proportion of records indicated that at least one important aspect of initial assessment was not documented. Many service users/patients who could have benefited from an intervention targeted at optimising physical health did not receive it. Only a minority (39%) were referred for psychological therapy. Use of outcome measures varied considerably but no single outcome measure was being used routinely. Most individuals had a care plan recorded in the notes, but a review date was documented in only two-thirds, and almost half of individuals had not received a copy.
CONCLUSIONS
There was considerable variation between English mental health services across many variables, and much scope for improvement. Clinicians should ensure that care plans are developed collaboratively with service users/patients and identified carers should be provided with information about support services. Health services should investigate the reasons for low referral rates for psychological therapies. Clinicians should ensure all service users have jointly developed crisis plans in place at discharge. Service managers should agree outcome measures to evaluate the treatment provided and clinicians should use these measures at initial assessment and review appointments. The implementation of such changes provides an opportunity for collaborative research into mental health service delivery and quality.
Topics: Anxiety; Clinical Audit; Depression; Depressive Disorder; Humans; Inpatients; Mental Health Services; Reproducibility of Results
PubMed: 33160123
DOI: 10.1016/j.comppsych.2020.152212 -
Scientific Reports Nov 2021Current criteria for depression are imprecise and do not accurately characterize its distinct clinical presentations. As a result, its diagnosis lacks clinical utility...
Current criteria for depression are imprecise and do not accurately characterize its distinct clinical presentations. As a result, its diagnosis lacks clinical utility in both treatment and research settings. Data-driven efforts to refine criteria have typically focused on a limited set of symptoms that do not reflect the disorder's heterogeneity. By contrast, clinicians often write about patients in depth, creating descriptions that may better characterize depression. However, clinical text is not commonly used to this end. Here we show that clinically relevant depressive subtypes can be derived from unstructured electronic health records. Five subtypes were identified amongst 18,314 patients with depression treated at a large mental healthcare provider by using unsupervised machine learning: severe-typical, psychotic, mild-typical, agitated, and anergic-apathetic. Subtypes were used to place patients in groups for validation; groups were found to be associated with future outcomes and characteristics that were consistent with the subtypes. These associations suggest that these categorizations are actionable due to their validity with respect to disease prognosis. Moreover, they were derived with automated techniques that might theoretically be widely implemented, allowing for future analyses in more varied populations and settings. Additional research, especially with respect to treatment response, may prove useful in further evaluation.
Topics: Adolescent; Adult; Aged; Bipolar Disorder; Depression; Depressive Disorder; Electronic Health Records; Female; Humans; Male; Middle Aged; Psychotic Disorders; Retrospective Studies; Unsupervised Machine Learning; Young Adult
PubMed: 34789827
DOI: 10.1038/s41598-021-01954-4 -
Medical Science Monitor : International... Nov 2015In addition to irregularities relating to the emotional sphere, the cognitive impairment in depression is a part of the clinical picture of this affective disorder. Some... (Review)
Review
In addition to irregularities relating to the emotional sphere, the cognitive impairment in depression is a part of the clinical picture of this affective disorder. Some of the cognitive deficits may be associated with the severity of psychopathological symptoms of depression, while others are more established and can also occur during periods of remission. The participation in cognitive functioning of people with depression have a number of factors: the severity of symptoms, concurrent anxiety disorders, gender, age, education, duration of the disease, and number of previous episodes, as well as general somatic health or medication used. The pharmacological treatment may have varying impact on the different areas of cognition. Research on pharmacotherapy for depression and its impact on cognitive functioning continue and are very popular among clinicians and researchers. The relationship between antidepressants and cognitive abilities is always modulated by the type of depressive disorder, neurobiological factors, and demographic variables. This article presents a review of the studies relating to assessment of the effects of various antidepressants on cognitive abilities among patients with depression.
Topics: Antidepressive Agents; Cognition; Depression; Depressive Disorder; Drug Therapy; Humans; Randomized Controlled Trials as Topic
PubMed: 26599597
DOI: 10.12659/msm.895156 -
The Psychiatric Quarterly Mar 2018Depression treatment has been proven to relieve depressive symptoms and pain and may therefore improve the health-related quality of life (HRQoL) among adults with...
Depression treatment has been proven to relieve depressive symptoms and pain and may therefore improve the health-related quality of life (HRQoL) among adults with arthritis. The objective of the current study was to examine the HRQoL associated with depression treatment among adults with arthritis and depression. A retrospective longitudinal cohort study design using data from the Medical Expenditure Panel Survey (2009-2012) was adopted. The study sample consisted of adults (≥ 21 years) with co-existing arthritis and depression (N = 1692). Depression treatment was categorized into: antidepressants only, psychotherapy with or without antidepressants, and neither antidepressants nor psychotherapy. Multivariable Ordinary Least Square (OLS) regressions, which controlled for observed selection bias with inverse probability treatment weights (IPTW) were built to examine the association between depression treatment categories and the HRQoL scores. The OLS regression controlled for factors in the biological, psychological and social domains that may affect HRQoL. A majority of individuals reported taking antidepressants only (52%), 24.4% reported receiving psychotherapy with or without antidepressants and 23% did not receive either antidepressants or psychotherapy. In multivariable OLS regression with IPTWs, adults using only antidepressants had marginally higher physical component summary scores (beta = 0.96, p value = 0.096) compared to no depression treatment. There were no significant associations between depression categories and mental component summary scores. HRQoL was not affected by depression treatment in adults with coexisting arthritis and depression. Improvement in HRQoL may require a collaborative care approach and such intense care may not be replicated in real-world practice settings.
Topics: Adult; Aged; Antidepressive Agents; Arthritis; Combined Modality Therapy; Comorbidity; Depression; Depressive Disorder; Female; Humans; Longitudinal Studies; Male; Middle Aged; Psychotherapy; Quality of Life; Retrospective Studies; Treatment Outcome; United States; Young Adult
PubMed: 28612178
DOI: 10.1007/s11126-017-9520-0