Neuroimaging studies have consistently reported similar brain structural abnormalities across different psychiatric disorders. Yet, the extent and regional distribution of shared morphometric ...abnormalities between disorders remains unknown.
Here, we conducted a cross-disorder analysis of brain structural abnormalities in 6 psychiatric disorders based on effect size estimates for cortical thickness and subcortical volume differences between healthy control subjects and psychiatric patients from 11 mega- and meta-analyses from the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) consortium. Correlational and exploratory factor analyses were used to quantify the relative overlap in brain structural effect sizes between disorders and to identify brain regions with disorder-specific abnormalities.
Brain structural abnormalities in major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder were highly correlated (r = .443 to r = .782), and one shared latent underlying factor explained between 42.3% and 88.7% of the brain structural variance of each disorder. The observed shared morphometric signature of these disorders showed little similarity with brain structural patterns related to physiological aging. In contrast, patterns of brain structural abnormalities independent of all other disorders were observed in both attention-deficit/hyperactivity disorder and autism spectrum disorder. Brain regions showing high proportions of independent variance were identified for each disorder to locate disorder-specific morphometric abnormalities.
Taken together, these results offer novel insights into transdiagnostic as well as disorder-specific brain structural abnormalities across 6 major psychiatric disorders. Limitations comprise the uncertain contribution of risk factors, comorbidities, and medication effects to the observed pattern of results that should be clarified by future research.
Objective: The aims of this review article are to present psychophysiological and behavioral pathways for the involvement of worry and generalized anxiety disorder (GAD) upon cardiovascular function. ...The review will focus on persons with and without coronary heart disease (CHD), and encompass etiological and prognostic studies. Methods: Articles (1975-2011) reporting on GAD or worry affecting CHD prognosis or cardiovascular function were found using MEDLINE, EMBASE, SCOPUS and PsychINFO database searches, and extracted to form a narrative review. Results: Available evidence in experimental and observational studies in CHD free samples consistently showed that worry was associated with diminished heart rate variability (HRV) and elevated heart rate. Worry and GAD were commonly associated with blood pressure and diagnosed hypertension or medication use in both disease-free and established CHD populations. No evidence was found to support worry being beneficial to cardiovascular function or conducive to health promoting behaviors. The literature indicated that measures of worry were associated with fatal and nonfatal CHD in seven etiological studies of initially disease-free individuals; however, females were underrepresented. Three studies reported that GAD was associated with poorer prognosis in establish CHD, independent of depression. The median GAD prevalence was 10.4% in 3266 patients across 15 studies, suggesting that GAD is marginally less common in CHD samples than is depression. Conclusions: A growing literature highlights the association between worry and development of CHD. The association between worry, GAD and CHD risk factors (e.g. blood pressure), and HRV are leading mechanisms of cardiopathogenesis that may affect cardiovascular function. Findings regarding worry and GAD in established CHD are less clear.
Abstract The association between cognitive performance and general functioning in depression is controversial. The present study evaluated the association between cognitive dysfunction and major ...depressive disorder (MDD, N = 70) as compared with age- and gender-matched healthy controls ( n = 206) and its relationship to general functioning (physical and mental health quality of life, activities of daily living, and employment status) in participants with current MDD ( n = 26) and those with previous MDD only ( n = 44). Participants were assessed clinically using the Mini International Neuropsychiatric Interview (M.I.N.I.) for the depression groups and the Diagnostic Interview for Psychoses (DIP-DM) for the control group. Measures to evaluate cognition and quality of lifes comprised the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Short Form-36 Health Survey Questionnaire, and the Activities/Instrumental Activities of Daily Living (ADL/IADL); employment status was also assessed in MDD. The results showed that a) while individuals with current depression had worse cognitive performance in all domains than healthy controls, those individuals with previous depression had lasting cognitive impairments in the domains of immediate memory and attention as compared with healthy controls; b) individuals with current depression had lower scores in the visuospatial/constructional and attention domains and the total score than individuals with previous depression; c) individuals in the depression group as a whole who were currently unemployed had significantly lower scores in all domains (except attention) of cognitive function; d) cognitive function was not related to either physical or mental quality of life or impairments of activities of daily living (ADL, IADL); e) that unemployment in previous depression was related to poor cognitive function similar to those with current depression. The results indicate that MDD may have detrimental and lasting effects on cognitive performance partly related to poorer general functioning.
Abstract While neuropsychological dysfunction is a contributor to major depressive disorder (MDD) in adult MDD, little is known about neuropsychological function in MDD during adolescence and early ...adulthood. The aim of this review is to evaluate literature on neuropsychological function in this young age group. A database search of Medline, the Cochrane database and PsycInfo was conducted. Inclusion/exclusion criteria yielded seven case-control studies on neuropsychological functioning in MDD (12–25 years of age) published since 1995. Effect sizes were calculated. Results show a broader range of statistically significant neuropsychological deficits in MDD compared to controls in the cognitive domains of executive function (EF), working memory (WM), psychomotor and processing speed (PPS), verbal fluency (VF) and visual (-spatial) memory (VM). Most convincingly, three out of four studies investigating WM and three out of four studies investigating PPS found statistically significant impairments in MDD with varying effect sizes. EF deficits were reported only in three out of seven studies with small, medium and large effect sizes. While some evidence was found for impaired VM and VF, no evidence was observed for attention and verbal learning and memory; however, these domains have been less extensively studied. Further research is required to broaden the study base.
About one third of depression patients do not respond to the first antidepressant trial. Difficult-to-treat depression was suggested to characterize the often chronic and severe course of disease. ...Previous data indicate that tranylcypromine is effective in case of treatment-refractory depression. Many antidepressants are contraindicated in combination with tranylcypromine and other monoamine-oxidase inhibitors because of the risk of serotonin syndrome. The combination of tranylcypromine and amitriptyline was reported to be efficacious and safe in patients with electroconvulsive therapy-resistant major depression.
In this retrospective chart review, we report a series of 3 cases, in which patients with electroconvulsive therapy-resistant depression were treated with the combination of tranylcypromine and mirtazapine. There are no published clinical data on this combination yet. Disease severity and treatment response were retrospectively assessed with the Clinical Global Impression-Severity and Improvement Scales.
All 3 patients had severe difficult-to-treat depression with chronic course of disease and several times of inpatient treatment without achieving remission. The combination treatment was tolerated well, although the patients had somatic comorbidities. One patient developed mild and self-limiting neuroleptic malignant syndrome in the long-term course after dose increase of concomitant aripiprazole. All 3 patients showed either much or very much improvement.
Under tight clinical controls in inpatient setting and after exhausting of alternatives, the combination of tranylcypromine and mirtazapine could be considered in patients, who do not achieve adequate improvement through common treatment options recommended in the guidelines. The combination has to be ceased, if symptoms of possible serotonin syndrome occur.
We currently observe a disconcerting phenomenon in machine learning studies in psychiatry: While we would expect larger samples to yield better results due to the availability of more data, larger ...machine learning studies consistently show much weaker performance than the numerous small-scale studies. Here, we systematically investigated this effect focusing on one of the most heavily studied questions in the field, namely the classification of patients suffering from Major Depressive Disorder (MDD) and healthy controls based on neuroimaging data. Drawing upon structural MRI data from a balanced sample of N = 1868 MDD patients and healthy controls from our recent international Predictive Analytics Competition (PAC), we first trained and tested a classification model on the full dataset which yielded an accuracy of 61%. Next, we mimicked the process by which researchers would draw samples of various sizes (N = 4 to N = 150) from the population and showed a strong risk of misestimation. Specifically, for small sample sizes (N = 20), we observe accuracies of up to 95%. For medium sample sizes (N = 100) accuracies up to 75% were found. Importantly, further investigation showed that sufficiently large test sets effectively protect against performance misestimation whereas larger datasets per se do not. While these results question the validity of a substantial part of the current literature, we outline the relatively low-cost remedy of larger test sets, which is readily available in most cases.
Deciding when and how to change treatment in patients with major depressive disorder who have inadequate response to initial antidepressant therapy is an important everyday clinical question. Here, ...we ask whether an early change of approach is superior to a delayed change. We consider the recommendations provided by recent guidelines, examine the evidence behind this guidance and suggest a decision tree to clarify treatment options and timing. Both the early and late-change strategies may have their place in clinical practice. However, we take the view that an earlier than currently usual change in antidepressant treatment should be considered more frequently in cases of non-response. Specific studies are needed to identify and to better understand predictors of early and late response.
Limited data exist on concordance between patients' and health care providers' (HCPs) perceptions regarding symptoms of major depressive disorder (MDD) and treatment priorities, particularly across ...disease phases. This study examined concordance during the acute, post-acute, and remission phases of MDD. In an online survey, 2,008 patients responded based on their experience with MDD, and 1,046 HCPs responded based on their clinical experience treating patients with MDD. Questions included symptom frequency and severity, treatment priorities, and impact on psychosocial functioning. Patients reported more frequently mood, physical, and cognitive symptoms than HCPs in the post-acute and remission phases and greater impact on psychosocial functioning. Patients reported that all these symptoms require high treatment priority across the phases of MDD, generally to a greater extent than HCPs. Patients also gave high emphasis to addressing impairment in psychosocial functioning early in the treatment course. A substantial difference in the effectiveness of treating symptoms of MDD between patients and HCPs was observed. This is the first study to quantify, broadly, differences in perceptions of MDD symptom prevalence, severity, and treatment priorities across MDD phases, and the study findings highlight a need for improved communication between patients and HCPs about symptoms, their impact on psychosocial functioning, and treatment priorities across phases.
PURPOSE OF REVIEWThis review aims to describe the current understanding of neuroinflammation in neurodegeneration and evaluate the value of various anti-inflammatory treatments.
RECENT ...FINDINGSInflammation plays important roles in common disease such as dementia and depression. Underlying mechanisms including the role of inflammasomes in these diseases have been recently described. Interventions using Ω-3 polyunsaturated fatty acids, NSAIDs and targeted antagonists (e.g., etanercept) show no convincing clinical efficacy in inflammation-associated depression, cognitive decline and dementia.
SUMMARYTherapeutic targeting of inflammation appears to be relevant in brain conditions characterized by neuroinflammation and neurodegeneration, although published anti-inflammatory interventions have shown no relevant clinical efficacy. Newly described pharmacological targets in the neuroinflammation pathways may not only offer a more profound understanding of the underlying pathophysiology but also raise hope for the development of novel pharmacological agents.
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