Search

Deficits in episodic memory have been reported in various psychiatric conditions, including Major Depressive Disorder (MDD). Many widely used episodic memory tests do not have the ability to distinguish between impaired memory of separate components of a real-life event (e.g., what happened, where it happened and when), and impaired binding of such real-life features. To address this issue, a naturalistic, real-world What-Where-When memory task was employed to assess the nature of episodic memory impairments in MDD. A validation study established that the task is sensitive to age-related episodic memory changes, and that intentional encoding does not invalidate the task. The main study then compared the performance of patients with depression and control participants on the intentionally encoded WWW task. Patients with MDD presented an overall episodic memory impairment arising from deficits in object memory and the ability to bind objects to temporal context. Taken together, our study confirms the episodic memory impairment in MDD, by providing evidence of deficient object memory and reduced ability to bind temporal context to objects in patients. Our naturalistic WWW task presents a promising approach for thorough identification of the nature of episodic memory impairments, under a real-world environment, in various conditions, including MDD. [ABSTRACT FROM AUTHOR]

Background: The relationship between major depressive disorder (MDD) and personality disorders is complex, with implications for diagnosis and treatment. We sought to explore the relationship between these disorders quantitatively in an inpatient setting. Methods: We conducted a structured observational study exploring symptoms of depression and selected neurocognitive functions over the span of an inpatient admission in those with depression and personality disorders. Sixty inpatients presenting with symptoms of depression completed ratings of mood and neurocognitive function. Diagnosis was confirmed by structured clinical interview (SCID-5-RV) at discharge and used to allocate patients to one of the two groups for analysis: those with MDD-only and those with a personality disorder (with or without MDD). Results: On admission, observer-based ratings of depression were significantly higher in the MDD-only group while subjective ratings were higher in the personality disorder group. Depression rating scores lessened in both groups during the admission, but at discharge, the personality disorder group continued to report higher subjective ratings. The personality disorder group also rated themselves as more cognitively impaired than the MDD-only group and unlike the MDD-only group, they did not report subjective improvements in cognitive function over the course of admission. Objective assessment of cognitive function demonstrated improvements in both groups. Conclusions: In this study, the presence of a personality disorder was associated with greater subjective severity of depressive symptomatology and selected neurocognitive functioning, despite similar or lower objective severity in comparison with those with MDD. This finding has implications for understanding the patient journey through health care settings. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction. Methods: Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning. Results: Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning. Conclusions: Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD. [ABSTRACT FROM AUTHOR]

Objectives: To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction. Methods: Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV). Results: Cognitive performance in unselected CFS patients is in average range on most measures. However, 0–23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition. Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050). Conclusion: Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed. [ABSTRACT FROM AUTHOR]

Objective: Depression is known to negatively impact social functioning, with patients commonly reporting difficulties maintaining social relationships. Moreover, a large body of evidence suggests poor social functioning is not only present in depression but that social functioning is an important factor in illness course and outcome. In addition, good social relationships can play a protective role against the onset of depressive symptoms, particularly in late-life depression. However, the majority of research in this area has employed self-report measures of social function. This approach is problematic, as due to their reliance on memory, such measures are prone to error from the neurocognitive impairments of depression, as well as mood-congruent biases.Method: Narrative review based on searches of the Web of Science and PubMed database(s) from the start of the databases, until the end of 2015.Results: The present review provides an overview of the literature on social functioning in (late-life) depression and discusses the potential for new technologies to improve the measurement of social function in depressed older adults. In particular, the use of wearable technology to collect direct, objective measures of social activity, such as physical activity and speech, is considered.Conclusion: In order to develop a greater understanding of social functioning in late-life depression, future research should include the development and validation of more direct, objective measures in conjunction with subjective self-report measures. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents research which examined the occurrence of childhood trauma in children with bipolar disorder. Topics covered include the impact of stress on the treatment course for the children and the rate of childhood trauma in patients with the condition. Also mentioned is the use of the Childhood Trauma Questionnaire in the study.

Background: Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. Methods/design: Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Discussion: Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments. [ABSTRACT FROM AUTHOR]

Hypothalamic–pituitary–adrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants. Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile. Aspects of neuropsychological performance, notably working memory, are susceptible to corticosteroid modulation and are impaired in depression. Aspirin has been shown to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression. To examine the effect of sub-acute (300 mg daily for 7 days) aspirin pre-treatment on the cortisol awakening response and the effect of acute (600 mg) and sub-acute aspirin on the neuroendocrine and neuropsychological response to the arginine vasopressin analogue, desmopressin. We demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH response to desmopressin but, as hypothesised, significantly reduced the cortisol awakening response and improved working memory. Further studies to examine the impact of aspirin on neuropsychological performance and HPA axis function are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Neurocognitive deficits have been widely reported in patients with mood disorders. However, relatively little is known of the short-term trajectory of neurocognitive improvement once treatment has been initiated. Method: A neurocognitive test battery was administered to unipolar depressed (major depressive disorder, MDD) patients (aged 18-65 years) who had been medication-free for at least 6 weeks, and to healthy controls. Patients were then treated according to clinical need, predominantly with standard pharmacotherapy, and all participants were followed up within 6 months. Results: Of the 25 MDD patients who returned at follow up, 11 were defined as remitted and 14 as not remitted. Significantly less baseline psychomotor dysfunction was observed in patients who remitted compared to those who did not (effect size, d =0.78, 95% confidence interval (CI) =0.07-1.44). Analysis of the change scores between assessments revealed a significantly greater improvement in verbal memory in patients who remitted compared to those who did not (d =0.73, 95%CI =0.03-1.39). Conclusions: This preliminary report suggests that there may be distinct temporal trajectories of neurocognitive improvement following remission in MDD. Aspects of neurocognitive functioning should be examined further as a means of providing a useful objective marker of treatment response. [ABSTRACT FROM AUTHOR]

Reduced serotonin (5-HT) function and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the aetiology of major depression. We sought to examine this issue in the elderly by assessing the effects of lowering brain 5-HT on salivary and plasma cortisol in elderly patients who had recovered from at least one episode of major depression and in a healthy, age matched comparison group. A double-blind, cross-over design involving administration of two nutritionally balanced amino acid mixtures (with or without tryptophan) was used. Salivary cortisol was measured at intervals before and after the drink. There was no effect of acute tryptophan depletion (ATD) on salivary cortisol (ATD by time; F=0.97, df= 7,210, p=0.454) but a significant interaction between group and time (F=3.91, df=7,210, p=0.010). Healthy subjects showed a marked increase in cortisol levels 2-3 hours into the procedure regardless of drink composition while recovered depressed subjects did not. In elderly patients who had recovered from depression there was no evidence of greater vulnerability of hypothalamic 5-HT pathways to 5-HT depletion. However, they demonstrated reduced reactivity of the HPA axis compared to healthy subjects. [ABSTRACT FROM AUTHOR]

Rationale. It has been suggested that corticosteroid-serotonin interactions are central to the pathophysiology of depression. These interactions have been investigated in healthy and depressed humans, primarily using neuroendocrine techniques. Objectives. To review the evidence regarding the nature of these interactions in healthy and depressed humans. Methods. Electronic searches were performed for relevant papers, employing MEDLINE and Web of Science. To focus the review, we selected only those articles involving (i) assessment of serotonergic function following experimental manipulation of the HPA axis in healthy volunteers; and (ii) assessment of both serotonergic and HPA axis function in clinically depressed subjects. Results. Pre-treatment with hydrocortisone, both acutely and sub-acutely attenuates the GH response to GHRH in healthy subjects. This complicates the interpretation of 5-HT neuroendocrine studies employing GH output as a measure. In depression there is evidence that reduced availability of l-tryptophan impairs HPA axis feedback. There is also evidence that depressed and healthy subjects may adapt differently both to low tryptophan and hypercortisolaemic challenges. There is no consistent evidence of a simple relationship between HPA axis function and 5-HT function in depression. Conclusions. The putative reduction in central 5-HT function has not been shown to be a direct consequence of hypercortisolaemia. Rather, the 5-HT system and HPA axis have complex inter-relationships. Challenges to either system, such as stress or reduced dietary tryptophan, may perturb the other and subjects vulnerable to depression may fail to adapt to such challenges. [ABSTRACT FROM AUTHOR]

Background: Although neurocognitive impairment has been widely reported in major depressive disorder (MDD), confounding factors, such as the effects of psychotropic medication, have rarely been controlled for.Aims: To examine neurocognitive function in medication-free patients with MDD and healthy controls.Method: Forty-four patients meeting DSM-IV criteria for MDD, all psychotropic-medication-free for at least 6 weeks, and 44 demographically matched, healthy comparison subjects completed a comprehensive neurocognitive battery.Results: Patients with depression were impaired significantly in a range of cognitive domains, including attention and executive function and visuospatial learning and memory, compared with controls. Motor and psychomotor functions were intact. Severity of depression correlated with learning and memory performance, but not executive function.Conclusions: Pronounced neurocognitive impairment was found in this sample of young adult out-patients with MDD. This is not attributable to the confounding effects of psychotropic medication and could therefore provide an objective marker of brain dysfunction in depression. [ABSTRACT FROM AUTHOR]

Abstract: Background: An aspect of neuropsychological impairment which has been linked specifically to depression is an abnormal response to failure. That is, a rapid deterioration of performance after receiving feedback that an error was made on the previous task. We aimed to examine this phenomenon in unmedicated, depressed outpatients. Methods: Forty-four patients meeting DSM-IV criteria for major depression, all psychotropicmedication-free for at least six weeks, and 44 demographically matched, healthy control participants completed a computerised simultaneous/delayed matching-to-sample task (S/DMTS). Results: Patients with depression were significantly less accurate than controls on the S/DMTS task. Both groups augmented their performance after an error had been made. The probability of making an error following an error was significantly greater in depressed compared with control participants, even when total number of errors was controlled for. Response latencies reduced significantly after an error had been made for both groups. Limitations: Both groups made relatively few errors. This reduced the power of analysis particularly when examining the effect of delay. Conclusions: The abnormal response to negative feedback previously identified in depressed samples was replicated in the current unmedicated, less severely depressed group. The impairment shown in the depressed sample may be due to a reduction in the motivating effect of an error compared with healthy controls. This has possible relevance to both neurobiological and psychological theories of depression. [Copyright &y& Elsevier]