Cognitive dysfunction in major depressive disorder Knight, Matthew J; Baune, Bernhard T
Current opinion in psychiatry,
2018-January, 2018-Jan, 2018-01-00, 20180101, Letnik:
31, Številka:
1
Journal Article
Recenzirano
PURPOSE OF REVIEWThe principal aim of this review is to highlight recent advances in our understanding of cognitive dysfunction in major depressive disorder (MDD). We review new assessment and ...treatment approaches, in which cognition and associated psychosocial dysfunction are considered primary outcomes.
RECENT FINDINGSCurrent work suggests that cognitive dysfunction reduces occupational productivity, and interferes broadly with domains of day-to-day and social functioning. These findings imply that cognitive dysfunction interacts with emotional and social factors relevant to MDD. Recent advances in screening instruments enable standardized detection of cognitive symptoms in MDD. Clinical trials suggest that cognitive symptoms are suitable targets and primary outcomes of psychological and pharmacological treatments.
SUMMARYA growing interest in cognitive dysfunction in MDD has improved our ability to assess and treat MDD. Future research will be strengthened by the use of consistent terminology, standardized cognitive screening, and treatments that target cognitive dysfunction in MDD. Integration of emotional and social treatment strategies may further advance clinical efficacy.
Major depressive disorder (MDD) is the most common psychiatric disorder and responds for important psychosocial consequences. Stressful life events, especially early life stress (ELS), contribute to ...an increased probability to develop MDD, leading in particular to severe and chronic manifestation and unfavorable treatment outcome. The association between ELS and MDD seems to have biological bases, consisting in dysregulations occurring at different levels. The aim of this narrative review is to propose an overview of the literature ranging from genetic, epigenetic, expression and protein to neuroimaging correlates underlying this relationship. A search on Pubmed of studies assessing biological correlates of ELS in MDD development, focusing on human studies conducted in both peripheral and brain tissues, was performed. Evidence indicated that the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic, dopaminergic, neurotrophin and oxytocin systems might play a role in the mediation between ELS and MDD. The most consistent results were found for genetic and epigenetic studies and indicated a joint involvement of the systems mentioned. Expression studies are less numerous and point to an involvement of stress-related systems. Concerning protein studies, the main mediators are markers related to the inflammatory and immune systems. Neuroimaging studies aiming at evaluating brain alterations connecting ELS and MDD in relation to biomarkers indicated the hippocampus, the amygdala and the frontal cortex as important anatomical mediators. These findings can build the bases for future research and clinical interventions; indeed, the clarification of biological mechanisms mediating the relationship between ELS and MDD can lead to new and individualized preventive and therapeutic possibilities.
•ELS strongly contributes to the vulnerability to develop MDD.•Several biomarkers underlie the relationship between ELS and MDD.•Imbalances in various biological pathways may mediate the relation between ELS and MDD.•Main mediators are markers related to the inflammatory and immune systems.•ELS biomarkers can lead to individualized therapeutic strategies in MDD.
Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available.
The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled ...trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2-3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores.
One hundred adults with MCI 70.1 (6.7) years; 68% women were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; relative effect size (95% confidence interval) -0.33 (-0.73, 0.06); P < .05 at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48). Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (-0.60, 0.28) combined and 48% higher (P < .04) for Global Domain z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined.
Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.
Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the ...relative effect of antidepressants on cognitive dysfunction in major depressive disorder.
MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model.
The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes.
This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder.
Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of ...psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus-pituitary-adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer's disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and/or therapeutic targets in psychiatric disorders.
There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have ...tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice. We also outline the investigations required and the appropriate therapeutic approaches, both psychiatric and immunological, for probable and definite cases of autoimmune psychoses, and discuss the ethical issues posed by this challenging diagnostic category.
Objectives: We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression.
Methods: Adults with self-reported ...depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis.
Results: n = 152 eligible adults aged 18-65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = −2.10, P = 0.04) and red meat/chicken (t = −2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = −2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = −0.298, P = 0.01), nuts (r = −0.264, P = 0.01), and vegetable diversity (r = −0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health.
Discussion: This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Patients with Major Depressive Disorder experience significantly reduced subjective Quality of Life (QOL), including impaired social and emotional functioning and greater fatigue and physical pain. ...Mounting evidence suggests that cognitive dysfunction (e.g., deficits in memory, executive function) contributes independently to the onset of reduced QOL, however the domain-specific nature of this relationship has not been investigated. The present study examined the relationship between specific cognitive domains (e.g., attention, spatial cognition) and specific deficits in mental and physical QOL in subjects with lifetime MDD, as well as acutely depressed, remitted and healthy participants.
Data were obtained (N = 387) from the Cognitive Function and Mood Study (COFAMS), a cross-sectional study of emotional, functional and cognitive status in individuals with mood disorders. Participants' (acutely depressed n = 93, remitted n = 170, and healthy control n = 124) QOL was assessed with the 36-Item Short Form Health Survey (SF-36) and cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Colorado Assessment Tests (CATs) and the Psychology Experiment Building Language (PEBL).
Analyses revealed that poor immediate and delayed memory were associated with reduced mental QOL in individuals with lifetime MDD, acutely depressed, and healthy controls. In contrast, cognitive functioning was not associated with mental QOL in remitted patients. No cognitive domains were significantly related to physical QOL in any participant group.
The result suggests that deficits in immediate and delayed memory may contribute to reduced mental QOL in acute MDD, whereas cognition does not appear to play a role in physical QOL. Memory should be considered important cognitive treatment targets for MDD patients suffering specifically from reduced mental QOL.
•Cognitive deficits in MDD are associated with mental, but not physical, quality of life.•There is an altered role of cognitive dysfunction in mental QOL across the course of illness in MDD•Executive function is related to mental QOL in depressed participants•Immediate and delayed memory are associated with mental QOL in healthy individuals and individuals with lifetime MDD
Highlights • Arterial stiffness is associated with markers of cerebral small vessel disease. • Arterial stiffness is also associated with decreased cognitive function. • The clinical usefulness of ...arterial stiffness measurement should now be evaluated.
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