Impairment In Major Depression Research Articles

Remission of symptoms is not equal to functional recovery: Psychosocial functioning impairment in major depression.

The ultimate goal of depression treatment is to achieve functional recovery. Psychosocial functioning is the main component of functional impairment in depressed patients. The concept of psychosocial functioning has an early origin; however, its concept and connotation are still ambiguous, which is the basic and key problem faced by the relevant research and clinical application. In this study, we start from the paradox of symptoms remission and functional recovery, describe the concept, connotation, and characteristics of psychosocial functioning impairment in depressed patients, and re-emphasize its importance in depression treatment to promote research and clinical applications related to psychosocial functioning impairment in depressed patients to achieve functional recovery.

Prevalence of cognitive impairment in major depression and bipolar disorder.

The current study examines prevalence of cognitive impairment in four mood disorder samples, using four definitions of impairment. The impact of premorbid IQ on prevalence was examined, and the influence of treatment response. Samples were: (i) 58 inpatients in a current severe depressive episode (unipolar or bipolar), (ii) 69 unmedicated outpatients in a mild to moderate depressive episode (unipolar or bipolar), (iii) 56 outpatients with bipolar disorder, in a depressive episode, and (iv) 63 outpatients with bipolar disorder, currently euthymic. Cognitive assessment was conducted after treatment in Studies 1 (6weeks of antidepressant treatment commenced on admission) and 2 (16-week course of cognitive behaviour therapy or schema therapy), allowing the impact of treatment response to be assessed. All mood disorder samples were compared with healthy control groups. The prevalence of cognitive impairment was highest for the inpatient depression sample (Study 1), and lowest for the outpatient depression sample (Study 2). Substantial variability in rates was observed depending on the definition of impairment used. Correcting cognitive performance for premorbid IQ had a significant impact on the prevalence of cognitive impairment in the inpatient depression sample. There was minimal evidence that treatment response impacted on prevalence of cognitive impairment, except in the domain of psychomotor speed in inpatients. As interventions aiming to improve cognitive outcomes in mood disorders receive increasing research focus, the issue of setting a cut-off level of cognitive impairment for screening purposes becomes a priority. This analysis demonstrates important differences in samples likely to be recruited depending on the definition of cognitive impairment and begins to examine the importance of premorbid IQ in determining who is impaired.

The Effect of Emotion and Reward Contingencies on Relational Memory in Major Depression: An Eye-Movement Study with Follow-Up.

Background: Episodic memory disturbances were found to constitute a potential trait marker for major depression (MD). The recall of positive or rewarding information in a relational context is specifically impaired. Eye-movement recording constitutes a novel, direct approach to examine implicit memory performance. Here we aimed to assess the effect of emotional context and implicit virtual monetary reward or loss on viewing patterns in association with relational memory in a 6-months follow-up study in MD.Materials and Methods: Twenty-eight patients with MD and 30 healthy participants were trained to associate a face (happy/sad/neutral) with a background scene. After each pair a virtual monetary reward or loss appeared briefly. During testing, scenes were presented as a cue and then overlaid with three previously studied faces. Participants were asked to recall the matching face if present (Match trials), with eye-movements and subsequent forced-choice recognition being recorded.Results: Explicit recognition of the matching face was impaired in the MD group as compared to controls. In correlation with this, viewing of the matching face was significantly reduced in the MD group. We found a significant interaction of group (MD vs HC) with the relational memory condition (Match and Non-match), facial emotion and monetary reward and loss. MD patients attended longer to previously rewarded stimuli, but significantly less to sad faces in the Match condition. The relational memory impairment persisted at follow-up and correlated with symptom severity both at baseline and follow-up. Viewing patterns associated with previous virtual reward were associated with clinical symptoms at follow-up.Conclusion: Our current results provide novel evidence for a specific relational memory impairment in MD as supported by abnormal eye-movement behavior and a deficit in explicit recognition. MD patients showed an attentional bias to rewarded stimuli and decreased viewing of sad faces when relational memory information was present.

Incidental and intentional memory performance in depression and amnestic mild cognitive impairment

Incidental and intentional memory performance in depression and amnestic mild cognitive impairment

Mental state decoding impairment in major depression and borderline personality disorder: meta-analysis.

Patients with major depression and borderline personality disorder are characterised by a distorted perception of other people's intentions. Deficits in mental state decoding are thought to be the underlying cause of this clinical feature. To examine, using meta-analysis, whether mental state decoding abilities in patients with major depression and borderline personality disorder differ from those of healthy controls. A systematic review of 13 cross-sectional studies comparing Reading in the Mind of the Eyes Test (RMET) accuracy performance of patients with major depression or borderline personality disorder and healthy age-matched controls (n = 976). Valence scores, where reported, were also assessed. Large significant deficits were seen for global RMET performance in patients with major depression (d = -0.751). The positive RMET valence scores of patients with depression were significantly worse; patients with borderline personality disorder had worse neutral scores. Both groups were worse than controls. Moderator analysis revealed that individuals with comorbid borderline personality disorder and major depression did better than those with borderline personality disorder alone on accuracy. Those with comorbid borderline personality disorder and any cluster B or C personality disorder did worse than borderline personality disorder alone. Individuals with both borderline personality disorder and major depression performed better then those with borderline personality disorder without major depression for positive valence. These findings highlight the relevance of RMET performance in patients with borderline personality disorder and major depression, and the importance of considering comorbidity in future analysis.

Deficits in cue detection underlie event-based prospective memory impairment in major depression: an eye tracking study

This study examined the cue detection in the non-focal event-based prospective memory (PM) of individuals with and without a major depressive disorder using behavioural and eye tracking assessments. The participants were instructed to search on each trial for a different target stimulus that could be present or absent and to make prospective responses to the cue object. PM tasks included cue only and target plus cue, whereas ongoing tasks included target only and distracter only. The results showed that a) participants with depression performed more poorly than those without depression in PM; b) participants with depression showed more fixations and longer total and average fixation durations in both ongoing and PM conditions; c) participants with depression had lower scores on accuracy in target-plus-cue trials than in cue-only trials and had a higher gaze rate of targets on hits and misses in target-plus-cue trials than did those without depression. The results indicate that the state of depression may impair top-down cognitive control function, which in turn results in particular deficits in the engagement of monitoring for PM cues.

Bifrontal tDCS prevents implicit learning acquisition in antidepressant-free patients with major depressive disorder

The findings for implicit (procedural) learning impairment in major depression are mixed. We investigated this issue using transcranial direct current stimulation (tDCS), a method that non-invasively increases/decreases cortical activity. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS. We used a bifrontal setup - anode and cathode over the left and the right dorsolateral prefrontal cortex (DLPFC), respectively. The probabilistic classification-learning (PCL) task was administered before and during tDCS. The percentage of correct responses improved during sham; although not during active tDCS. Procedural or implicit learning acquisition between tasks also occurred only for sham. We discuss whether DLPFC activation decreased activity in subcortical structures due to the depressive state. The deactivation of the right DLPFC by cathodal tDCS can also account for our results. To conclude, active bifrontal tDCS prevented implicit learning in depressive patients. Further studies with different tDCS montages and in other samples are necessary.

Cortisol awakening response is associated with hippocampus-dependent cognitive impairment in major depression

Cortisol awakening response is associated with hippocampus-dependent cognitive impairment in major depression

Treatment response and cognitive impairment in major depression: Association with C-reactive protein

Levels of inflammatory markers have been found to be significantly associated with major depressive disorder (MDD) and cognitive impairment. The aim of this study was to investigate whether the level of C-reactive protein (CRP) is correlated with depressive mood and cognitive impairment in MDD patients. In 149 subjects with MDD, the 21-item Hamilton Rating Scale for Depression (HAM-D), Continuous Performance Test (CPT), Finger-Tapping Test (FTT), and Wisconsin Card-Sorting Test (WCST) were administered before and after antidepressant treatment. Besides, the level of CRP was measured. After 6weeks of treatment, the total HAM-D scores decreased significantly. In addition, the subjects' performance in the masked CPT and the WCST with completed categories significantly improved (p<0.001 and p=0.027, respectively) after the reliable change indices were corrected for practice effects. The CRP levels had increased significantly after six weeks of treatment after adjustment for age and gender (p<0.001). In addition, the CRP levels remained significantly high after six weeks of treatment in patients with a higher baseline level (r=0.657, p<0.001). Although the association between baseline CRP level and HAM-D score was not significant, the baseline CRP level was significantly correlated with treatment response at week 2 (r=0.327, p=0.020). The baseline CRP level was also negatively correlated with performance in the FTT before treatment (r=-0.580, p=0.006). Moreover, the baseline CRP level was significantly correlated with performance in the FTT (r=-0.501, p=0.021) and WCST with completed categories (r=-0.521, p=0.015) at week 6. The cognitive function of patients with high baseline CRP levels might remain impaired even if their mood symptoms improve after antidepressant treatment. Whether adjunctive anti-inflammatory medication may help to preserve cognitive function merits further investigation.

Testing the cognitive effort hypothesis of cognitive impairment in major depression

Background: It is widely accepted that depression is associated with deficits in a range of cognitive domains. However, there is no consensus regarding the neuropsychological profile in depression. Aim: The aim of the present report is to test the cognitive effort hypothesis as a possible framework for understanding the observed cognitive impairment in major depressive disorder (MDD), using the Delis Kaplan Executive Function system (D-KEFS). Method: Twenty-four patients with recurrent MDD, in the acute phase of illness, were compared with a healthy control group. We expected that the patient group would show impairment on tests that measure higher-level effortful cognitive processing, whereas basic cognitive skills would be equal to the control group. Results: There were no differences between the two groups on measures of basic cognitive skills, except for Colour Naming. Furthermore, MDD patients performed significantly worse than the control group on three out of seven of the cognitively effortful measures; namely Inhibition, Inhibition/Switching and Category Fluency. Conclusions: We could not find consistent support for the cognitive effort hypothesis in the present study. However, the results indicate that depressed patients have a specific impairment within the Executive Function domain affecting Inhibition, Inhibition/Switching and Category Fluency.

Cognitive impairment in major depression: Association with circadian salivary cortisol

Cognitive deficits and elevated cortisol are hallmarks of depression. Cortisol acts via mineralo- and glucocorticoid receptors, which have their highest density in the hippocampus, a brain area closely related to cognitive function. Several studies have separately investigated cortisol secretion and cognitive deficits in depression. However, only few studies have assessed their association and have come to inconclusive results. We examined 52 medication-free patients with major depression (37 women, 15 men, mean age 35 years±11, Hamilton Depression Scale mean score 27±5) and 50 healthy control subjects, matched for age, gender and years of education. We applied several neuropsychological tests. Salivary cortisol levels were measured on the same day at 8:00, 12:00, 16:00 and 22:00 hours. Compared to healthy subjects, patients had significantly higher cortisol levels and were impaired in verbal memory, visuospatial memory, working memory, and selective attention. In depressed patients, but not in healthy controls, we found a negative correlation between salivary cortisol levels (area under the curve) and hippocampus-related neuropsychological domains (verbal memory, visuospatial memory) and executive function. Cognitive deficits appear to be related to cortisol secretion in depressed patients. Elevated cortisol may downregulate minerolo- and glucocorticoid receptors in the hippocampus, which might in part be responsible for cognitive deficits in depressed patients.

Cognitive Impairment in Major Depression: Association with Salivary Cortisol

Cognitive deficits and elevated cortisol are hallmarks of depression. Cortisol acts via mineralocorticoid and glucocorticoid receptors, which have their highest density in the hippocampus, a brain area closely related to cognitive function. Several studies have separately examined cortisol secretion and cognitive deficits in depression. However, only few studies have assessed their association in the same patients producing inconclusive results. We examined 52 medication-free patients with major depression (37 women, 15 men; mean age 35 +/- 11 years; Hamilton Depression Scale mean score 27 +/- 5) and 50 healthy control subjects, matched for age, gender, and years of education. We applied several neuropsychological tests. Salivary cortisol levels were measured on the same day at 08:00, 12:00, 16:00, and 22:00 hours. Compared with healthy subjects, patients had significantly higher cortisol levels and were impaired in verbal memory, visuospatial memory, working memory, and selective attention. In depressed patients, but not in healthy control subjects, we found a negative correlation between salivary cortisol levels (area under the curve) and hippocampus-related neuropsychological domains (verbal memory, visuospatial memory) and executive function. Cognitive deficits, especially those closely related to hippocampus function, appear to be related to cortisol secretion in depressed patients. Elevated cortisol may downregulate mineralocorticoid and glucocorticoid receptors in the hippocampus, which could, in part, be responsible for cognitive deficits in depressed patients.

Low Plasma Brain-Derived Neurotrophic Factor and Childhood Physical Neglect Are Associated with Verbal Memory Impairment in Major Depression—A Preliminary Report

Early life stress has been suggested to mediate vulnerability to affective disorders. Animal models of repeated maternal separation have shown reduced brain-derived neurotrophic factor (BDNF) levels in specific brain regions implicated with hypothalamic-pituitary-adrenal axis and memory formation. In addition, BDNF levels are also reduced in major depressive disorder (MDD) and bipolar disorder. The aim of this study was to investigate whether childhood physical neglect (CPN) and plasma BDNF levels would impact on memory performance in adult female subjects with recurrent major depression. Recurrent female MDD outpatients with CPN (MDD + CPN, n = 17) and without CPN (MDD, n = 17) and healthy control subjects (n = 15) were assessed for plasma BDNF content and verbal memory performance. Memory was assessed through the logical memory component of the Weschler Memory Scale-Revised for immediate and delayed recall. Brain-derived neurotrophic factor was assessed with enzyme-linked immunosorbent assays (ELISAs). Major depressive disorder patients showed lower plasma BDNF concentrations than healthy control subjects (p < .001). Major depressive disorder + CPN had even lower BDNF levels compared with control subjects and MDD (p < .05). Brain-derived neurotrophic factor levels were negatively related to psychological morbidity and positively correlated to memory performance. Regression models showed that severity of self-reported CPN and low plasma BDNF predicted impairment on immediate verbal recall. Delayed recall impairment was predicted by severity of CPN and depression and memory retention by posttraumatic stress disorder (PTSD) severity symptoms. Our data suggest that CPN and plasma BDNF are important factors associated with depression and verbal memory performance, particularly with encoding processes.

Experimental evidence for a motivational origin of cognitive impairment in major depression

Diagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance. Goal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg Word Fluency Test (RWT), and the Number Combination Test (Zahlen-Verbindungs-Test, ZVT)] using either goal-setting or standard test instructions. Depressed patients showed lower baseline performance and lower generalized self-efficacy (p<0.0005) than controls. However, goal-setting instructions significantly improved patients' memory performance by 10% [AVLT: F(5, 54)=3.611, p=0.007] and psychomotor performance by 13% [ZVT: F(3, 56)=3.667, p=0.017]. Consequently, patients and control subjects demonstrated similar results when goal-setting instructions were applied. Goal-setting instructions showed a statistical trend, increasing patients' performance in the DST by 12% [F(1, 58)=2.990, p=0.089], although their verbal fluency measured by the RWT did not increase. No significant correlations of increased performance with generalized self-efficacy were found. Cognitive deficits in depressed patients are influenced by motivational shortcomings. Because generalized self-efficacy failed to correlate to increased test performance, future research needs to disentangle the effective components of goal-setting instructions. Task-specific self-efficacy as well as enhancement of task-focused attention might underlie the significant goal-setting effect in depressed patients.

Neuropsychological Impairment in Major Depression: Its Nature, Origin and Clinical Significance

Neuropsychological impairment is well established as a feature of major depressive disorder (MDD) but studies have shown a variable pattern of impairment. This paper seeks first to clarify this by examining methodological and clinical factors that give rise to variability in study findings. Second, it examines theories of the origin of these neuropsychological abnormalities. Third, it reviews evidence regarding the clinical significance of different patterns of deficit. A selective review was undertaken of the literature with a particular emphasis on methodological factors, the influence of clinical subtypes and prevalent theories of neuropsychological abnormality. Methodological issues and the heterogeneity of MDD account for considerable variability in results. Specific investigation of the subtypes of psychotic MDD, melancholic MDD and bipolar depression reduces this heterogeneity and results are more consistent in the elderly. Hypothalamic-pituitary-adrenal axis dysfunction is associated with neuropsychological dysfunction in MDD although evidence of direct causation is not definitive at present. Impairment of executive and psychomotor function is a consistent finding, particularly in the elderly, and may reflect frontostriatal-limbic dysfunction. There is growing evidence that this may have clinical significance. It is suggested that future research take very careful account of the exact phenotype of MDD. Classification based on neuropsychological profile may, in fact, be useful. Further research should examine further the clinical importance of patterns of neuropsychological impairment.

Neurocognitive deficits in major depression and a new theory of ADHD: A model of impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine depleted individuals

The study builds on the propositions introduced in a companion paper on the neuropharmacology of cognition and its relation to key findings in psychiatry. Cognitive inhibition is often invoked to explain performance in psychiatric illness. Yet it remains only a general conceptual model of executive dysfunction. Premotor theory proposes both neuroanatomical and neuropharmacological equivalents of conscious and unconscious processes. The interaction between monoaminergic and cholinergic neurotransmission is stated to have an inverse effect on these two fundamental psychological processes. If one conceives of cognitive inhibition as a failure to voluntarily suppress unconscious prepotent responses, then a deficit in monoaminergic antagonism of cholinergic facilitated prepotent responses accounts for the observed behavioural phenotypes. The plasticity of behaviour is further hypothesized to have an equivalent in intracellular signalling leading to plastic changes in neural networks. Apart from inhibition of prepotent responses it permits the formulation of new behavioural phenotypes. At the receptor level Gi-Gq/11 transduction coupling is proposed to mediate this effect. A hypofunctioning monoaminergic system is thought to underlie the clinical pictures of major depression and ADHD. The neurocognitive deficits of depression include memory loss, poor concentration and rumination. ADHD is characterized by inattention, impulsivity and hyperactivity. Both these syndromes effectively respond to raising serotonin and dopamine levels, respectively. The core symptoms can usefully be attributed to an imbalance between the neuromodulatory effects of monoamines and ACh. Taking the model of monoaminergic-muscarinic receptor interactions presented previously and extended here, a new hypothesis is proposed for the core symptoms of ADHD. Accordingly, impulsivity and hyperactivity result from impaired dopaminergic inhibition and remodelling of muscarinic mediated prepotent responses. The model also predicts memory impairment in major depression by proposing that low serotonin levels in the neocortex is linked to focal hippocampal dysfunction. Hippocampal theta is proposed to trigger phasic monoaminergic activation involved in encoding of cortical traces and plasticity of propotent networks. It proposes a hypothesis for the enhancement of mood and behaviour induced by antidepressants is partly a response to plasticity of neural networks, that is, remodelling of cholinergic-mediated negative habitual behaviours.

Long-lasting cognitive impairment in unipolar major depression: a 6-month follow-up study

The aim of the study was to investigate cognitive impairment in major depression both acutely and after 6 months. All patients were investigated within a neurocognitive experimental setting at two testing sessions: at inclusion and after 6 months. Automatic and effortful information processing was investigated with a visual search paradigm. Twenty-one patients with recurrent major depression according to DSM-IV and a Hamilton Depression Rating Scale score >18 were included in the study. Healthy subjects, matched for age and gender, were used as a control group. The results showed that the depressed patients performed equal to the control group on trials requiring automatic information processing at both sessions. However, the patients were impaired compared to the control group on trials requiring effortful information processing, also at both sessions. The depressed patients showed no improvement in cognitive performance from test 1 to test 2. The results indicate that the depressed patients had an impaired performance for effortful, but not automatic, visual search performance, and that the impairment remained after 6 months, despite significant improvement in their depression scores.

Brain-derived neurotrophic factor: a bridge between major depression and Alzheimer’s disease?

Cognitive impairment is common in major depression (MD) patients, with these individuals incurring increased risk for development of Alzheimer’s disease (AD). Further, depressive symptoms are common in AD patients. This apparent convergence suggests pathogenic factors common to AD and MD. Since decreased brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is related to both AD and MD, the author suggests that BDNF could be a bridge between AD and MD, explaining both the depressive symptoms in AD, and, cognitive impairment in MD. Evidence supporting this hypothesis suggests that early antidepressants treatment for aged MD patients may decrease the risk of AD, and agents that increase central BDNF may offer an alternative treatment for MD patients with cognitive impairment and/or for AD sufferers with depressive symptoms.

Residual symptoms and impairment in major depression in the community.

Studies of patients with major depression in treatment settings have found significant residual symptoms and impairment after resolution of the depressive episode. However, only a small proportion of individuals with major depression seek treatment, and little is known about the residual symptoms and impairment associated with major depression in the community. This study used data from the National Comorbidity Survey, which included a nationally representative household sample of respondents in the United States, to assess the course of residual symptoms and impairment after resolution of major depressive episodes in the community. National Comorbidity Survey respondents with lifetime major depression who were currently experiencing a major depressive episode and respondents whose last episode had ended more than 1 to 6 months, more than 6 to 12 months, or more than 12 months ago were compared with those without a history of major depression with regard to depressive symptoms and days of impairment in work functioning or other activities in the past 30 days. Respondents whose last episode of major depression had resolved even more than a year ago were still more symptomatic than those without a history of major depression, whereas the number of days of impairment returned to a level indistinguishable from that of respondents without a history of major depression after >6 to 12 months of resolution of the last episode. Major depression in the community, as in treatment settings, is associated with residual symptoms and impairment. In the community, however, residual impairment may resolve more quickly than residual symptoms.

38. Motor programming deficits in depression: support for a dopaminergic mechanism

Several investigators have reported parallels between motor and cognitive slowing in patients with major depression (MD). Such a relationship between depression and motor function suggests the possibility of a shared neuropathologic mechanism. This mechanism has remained elusive largely because depression may involve any of several neurotransmitters. While others have shown that MD and parkinsonism share a number of features, especially in the motor domain, previous technologies have not delineated the cognitive from neuromotor aspects of the motor impairment in MD. The aim of the present study was to examine motor programming in MD patients using a measure adopted from studies of parkinsonian bradykinesia. There is a general consensus that parkinsonian bradykinesia stems from an inability to modify, or scale, velocity during movement. In the present study, we hypothesized that a substantial proportion of MD patients would exhibit deficits in velocity scaling. Our measure of velocity scaling quantifies the extent to which a subject programs or scales movement velocity in anticipation of increasing target distance. We studied 54 patients who met DSM-IV criteria for major depression and 26 age and gender comparable healthy comparison subjects. All MD patients were unmedicated at the time of testing. An instrumental measure of wrist movement was developed to quantify several aspects of movement including reaction time (RT), peak velocity (PV), and velocity scaling (VS). Subjects were instructed to flex their wrist when a target box appeared on the computer screen and to reach the target as quickly and as accurately as possible. Results indicated that MD patients exhibited significantly (p < 0.001) longer mean RT (477 ms) than comparison subjects (391 ms). There was a trend (p = 0.07) for MD patients to have lower scores on the VS measure (2.68 deg/sec/deg) compared with comparison subjects (3.33 d/s/d). 53.7% of the MD patients had VS scores lower than the 95th percentile of the comparison subjects. These findings suggest that MD patients as a group exhibit delayed reaction times. Nevertheless, a significant proportion of MD patients also exhibit disturbances in the programming of movement velocity reflective of a putative dopaminergic disturbance, similar to that seen in parkinsonism.