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Neuroscience and Biobehavioral Reviews Jul 2019Depression is linked to deficits in cognitive control and a host of other cognitive impairments arise as a consequence of these deficits. Despite of their important role... (Review)
Review
Depression is linked to deficits in cognitive control and a host of other cognitive impairments arise as a consequence of these deficits. Despite of their important role in depression, there are no mechanistic models of cognitive control deficits in depression. In this paper we propose how these deficits can emerge from the interaction between motivational and cognitive processes. We review depression-related impairments in key components of motivation along with new cognitive neuroscience models that focus on the role of motivation in the decision-making about cognitive control allocation. Based on this review we propose a unifying framework which connects motivational and cognitive control deficits in depression. This framework is rooted in computational models of cognitive control and offers a mechanistic understanding of cognitive control deficits in depression.
Topics: Anhedonia; Cognitive Dysfunction; Decision Making; Depressive Disorder; Executive Function; Humans; Models, Biological; Motivation; Reward
PubMed: 31047891
DOI: 10.1016/j.neubiorev.2019.04.011 -
The American Journal of Psychiatry Aug 2020Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that... (Review)
Review
Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis-based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis-based treatments of thyroid hormones (T and T), and the HPG axis-based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.
Topics: Depressive Disorder, Major; Endocrine Glands; Hormones; Humans; Neurosecretory Systems; Treatment Outcome
PubMed: 32456504
DOI: 10.1176/appi.ajp.2020.19080848 -
Current Neuropharmacology 2020Depression is a frequent non-motor symptom of Parkinson's disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence... (Review)
Review
Depression is a frequent non-motor symptom of Parkinson's disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood, depression in PD is frequently associated with other neuropsychiatric symptoms and with late-stage complications such as dementia. Despite its profound impact on the quality of life and cognitive functioning in PD, depression in PD is often under-recognized and poorly treated. Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction of interactions between discrete brain areas rather than focal structural or functional abnormalities, and that it is sustained by pathological changes of several neurotransmitter/receptor complexes. In general, all traditional antidepressants and some dopamine agonists have been found to be safe and well-tolerated to treat depressive symptoms in PD, despite initial warning on worsening of parkinsonism. Available data suggest that the time-course of response differs among antidepressants. Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain, although pooled analysis suggests a moderate benefit. Several issues may critically impact the results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the overlap of symptoms between depression and PD, and the selection of appropriate end-points and rating scales.
Topics: Antidepressive Agents; Depressive Disorder; Disease Management; Humans; Parkinson Disease; Quality of Life; Treatment Outcome
PubMed: 31622207
DOI: 10.2174/1570159X17666191016094857 -
Anaesthesia Apr 2021Perinatal mental illness is common, affecting up to 20% of women, but remains under-recognised and under-diagnosed. It may have adverse effects on pregnancy and neonatal... (Review)
Review
Perinatal mental illness is common, affecting up to 20% of women, but remains under-recognised and under-diagnosed. It may have adverse effects on pregnancy and neonatal outcomes, and mental disorder remains one of the leading causes of maternal death in the UK. Women with mental ill health face difficult decisions in balancing risks and benefits of treatment. Stigma related to mental disorder may lead to non-engagement with maternity care. Some disorders bring specific challenges for anaesthetists working in maternity settings and it is vital that anaesthetists have knowledge of these disorders so they may offer care which is sensitive and appropriate.
Topics: Antidepressive Agents; Anxiety Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Mental Disorders; Postpartum Period; Pregnancy; Pregnancy Complications
PubMed: 33682099
DOI: 10.1111/anae.15424 -
The Journal of Clinical Psychiatry Mar 2021Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the...
OBJECTIVE
Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach.
METHODS
Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States.
RESULTS
The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD.
CONCLUSIONS
TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.
Topics: Absenteeism; Adult; Antidepressive Agents; Cost of Illness; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Health Care Costs; Humans; Prevalence; United States
PubMed: 33989464
DOI: 10.4088/JCP.20m13699 -
Journal of Neural Transmission (Vienna,... Nov 2019Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to... (Review)
Review
Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to poor response to antidepressant therapy. Progress in this area requires valid animal models. Current models are based either on manipulating the environment to which rodents are exposed (during the developmental period or adulthood) or biological underpinnings (i.e. gene deletion or overexpression of candidate genes, targeted lesions of brain areas, optogenetic control of specific neuronal populations, etc.). These manipulations can alter specific behavioural and biological outcomes that can be related to different symptomatic and pathophysiological dimensions of major depression. However, animal models of major depression display substantial shortcomings that contribute to the lack of innovative pharmacological approaches in recent decades and which hamper our capabilities to investigate treatment-resistant depression. Here, we discuss the validity of these models, review putative models of treatment-resistant depression, major depression subtypes and recurrent depression. Furthermore, we identify future challenges regarding new paradigms such as those proposing dimensional rather than categorical approaches to depression.
Topics: Animals; Behavior, Animal; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Disease Models, Animal
PubMed: 31584111
DOI: 10.1007/s00702-019-02084-y -
Journal of Child Psychology and... Mar 2020Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk... (Review)
Review
BACKGROUND
Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard-of-care treatments (psychotherapy and medication), roughly one third will not.
METHODS
Here, we have reviewed the literature in order to discuss the concept of treatment-resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials.
RESULTS
We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first- and second-line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence-based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted.
CONCLUSIONS
As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.
Topics: Adolescent; Antidepressive Agents; Combined Modality Therapy; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Humans; Psychotherapy; Selective Serotonin Reuptake Inhibitors
PubMed: 32020643
DOI: 10.1111/jcpp.13202 -
Psychiatry Research Sep 2023Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line... (Review)
Review
BACKGROUND
Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line pharmacological and psychotherapeutic antidepressive treatments is substantial, with treatment-resistant depression [TRD] affecting approximately one third of depressed patients. There is an urgent need for rapid acting and effective treatments in this population. Repetitive Transcranial Magnetic Stimulation [rTMS] is an non-invasive treatment option for patients with MDD or TRD. Recent studies have proposed new paradigms of TMS, one paradigm is accelerated intermittent Theta Burst Stimulation [aiTBS].
OBJECTIVE
This systematic review assesses the efficacy, safety and tolerability of aiTBS in patients with MDD.
METHODS
This review was registered with PROSPERO [ID number: 366556]. A systematic literature review was performed using Pubmed, Web of Science and PsycINFO. Case reports/series, open-label and randomized controlled trials [RCTs] were eligible for inclusion if they met the following criteria; full text publication available in English describing a form of aiTBS for MDD or TRD. aiTBS was defined as at least three iTBS treatments sessions per day, during at least four days for one week.
RESULTS
32 studies were identified describing aiTBS in MDD, 13 studies described overlapping samples. Six articles from five unique studies met eligibility criteria; two open-label studies and three RCTs [two double blind and one quadruple blind]. Response rates directly after treatment ranged from 20.0% to 86.4% and remission rates ranged from 10.0 to 86.4%. Four weeks after treatment response rates ranged from 0.0% to 66.7% and remission rates ranged from 0.0% to 57.1%. Three articles described a significant reduction in suicidality scores. aiTBS was well tolerated and safe, with no serious adverse events reported.
CONCLUSIONS
aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in MDD. Additionally, aiTBS was well tolerated and safe. However, the included studies had small samples sizes and differed in frequency, intersession interval, neuro localization and stimulation intensity. Replication studies and larger RCTs are warranted to establish efficacy, safety and long term effects.
Topics: Humans; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant; Stereotaxic Techniques; Randomized Controlled Trials as Topic
PubMed: 37625365
DOI: 10.1016/j.psychres.2023.115429 -
International Journal of Molecular... Mar 2020The acute treatment duration for major depressive disorder (MDD) is 8 weeks or more. Treatment of patients with MDD without predictors of treatment response and future... (Review)
Review
The acute treatment duration for major depressive disorder (MDD) is 8 weeks or more. Treatment of patients with MDD without predictors of treatment response and future recurrence presents challenges and clinical problems to patients and physicians. Recently, many neuroimaging studies have been published on biomarkers for treatment response and recurrence of MDD using various methods such as brain volumetric magnetic resonance imaging (MRI), functional MRI (resting-state and affective tasks), diffusion tensor imaging, magnetic resonance spectroscopy, near-infrared spectroscopy, and molecular imaging (i.e., positron emission tomography and single photon emission computed tomography). The results have been inconsistent, and we hypothesize that this could be due to small sample size; different study design, including eligibility criteria; and differences in the imaging and analysis techniques. In the future, we suggest a more sophisticated research design, larger sample size, and a more comprehensive integration including genetics to establish biomarkers for the prediction of treatment response and recurrence of MDD.
Topics: Biomarkers; Depressive Disorder, Major; Humans; Machine Learning; Neuroimaging; Recurrence
PubMed: 32245086
DOI: 10.3390/ijms21062148 -
Molecular Psychiatry Feb 2020Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is... (Meta-Analysis)
Meta-Analysis
Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is prospective evidence for biomarkers derived from leading theories. We focus on neuroimaging, gastrointestinal factors, immunology, neurotrophic factors, neurotransmitters, hormones, and oxidative stress. Searches were performed in Pubmed, Embase and PsychInfo for articles published up to 06/2019. References and citations of included articles were screened to identify additional articles. Inclusion criteria were having an MDD diagnosis as outcome, a biomarker as predictor, and prospective design search terms were formulated accordingly. PRISMA guidelines were applied. Meta-analyses were performed using a random effect model when three or more comparable studies were identified, using a random effect model. Our search resulted in 67,464 articles, of which 75 prospective articles were identified on: Neuroimaging (N = 24), Gastrointestinal factors (N = 1), Immunology (N = 8), Neurotrophic (N = 2), Neurotransmitters (N = 1), Hormones (N = 39), Oxidative stress (N = 1). Meta-analyses on brain volumes and immunology markers were not significant. Only cortisol (N = 19, OR = 1.294, p = 0.024) showed a predictive effect on onset/relapse/recurrence of MDD, but not on time until MDD onset/relapse/recurrence. However, this effect disappeared when studies including participants with a baseline clinical diagnosis were removed from the analyses. Other studies were too heterogeneous to compare. Thus, there is a lack of evidence for leading biological theories for onset and maintenance of depression. Only cortisol was identified as potential predictor for MDD, but results are influenced by the disease state. High-quality (prospective) studies on MDD are needed to disentangle the etiology and maintenance of MDD.
Topics: Biomarkers; Depressive Disorder, Major; Humans; Hydrocortisone; Prospective Studies
PubMed: 31745238
DOI: 10.1038/s41380-019-0585-z