Cognitive deficits in euthymic patients with recurrent depression.
ABSTRACT Neurocognitive impairments are found in people recovered from major depression compared with never-depressed controls. A total of 20 patients in recovery from recurrent unipolar depression and 20 healthy controls were tested using a neuropsychological battery containing tasks of executive function (Wisconsin Card Sort Test), attention, visuomotor speed, and working memory. The recovered-depressed group performed poorly in comparison to healthy controls on the planning and problem solving aspects of the Wisconsin Card Sort Test, even after controlling for subclinical depressive symptoms. There was no significant difference between the 2 groups on set-shifting aspects of the task and the other tests. These specific deficits, even after controlling for subclinical depressive symptoms, were correlated with the number of previous episodes of depression. These findings support the hypothesis that impairments in executive function are present in recovery from unipolar depression, and so are not simply state markers. Further longitudinal research on samples free of history of depression is needed to determine whether these impairments are intermediate markers for recurrent unipolar depression, rather than "scars" caused by past episodes.
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ABSTRACT: The cumulative duration of depressive episodes, and their repetition, has a detrimental effect on depression recurrence rates and the chances of antidepressant response, and even increases the risk of dementia, raising the possibility that depressive episodes could be neurotoxic. Psychomotor retardation could constitute a marker of this negative burden of past depressive episodes, with conflicting findings according to the use of clinical versus cognitive assessments. We assessed the role of the Retardation Depressive Scale (filled in by the clinician) and the time required to perform the neurocognitive d2 attention test and the Trail Making Test (performed by patients) in a sample of 2048 depressed outpatients, before and after 6 to 8 weeks of treatment with agomelatine. From this sample, 1140 patients performed the TMT-A and –B, and 508 performed the d2 test, at baseline and after treatment. At baseline, we found that with more past depressive episodes patients had more severe clinical level of psychomotor retardation, and that they needed more time to perform both d2 and TMT. When the analyses were performed again after treatment, and especially when the analyses were restricted to patients with clinical remission, the cognitive tests were the only ones correlated with past depressive episodes. Psychomotor retardation tested at a cognitive level was therefore systematically revealing the burden of past depressive episodes, with an increased weight for patients with less remaining symptoms. If prospectively confirmed, interventions such as cognitive remediation therapy could benefit from a more specific focus on neurocognitive retardation.European Neuropsychopharmacology 10/2014; 24(10). DOI:10.1016/j.euroneuro.2014.07.013 · 5.40 Impact Factor
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ABSTRACT: Cross-sectional studies suggest that cognitive deficits contribute to psychosocial impairment among individuals with mood disorders. However, studies examining whether cognition prospectively predicts psychosocial outcome are few, have used short follow-up periods, and have not demonstrated incremental validity (i.e., that cognition predicts future functioning even when controlling for baseline functioning). In a sample of 51 individuals with unipolar depression or bipolar disorder, we investigated whether attention/processing speed (APS) performance predicted social functioning 18 years later. Baseline APS predicted 18-year social functioning even after controlling for baseline social functioning and depressive symptoms, demonstrating incremental validity. Individuals with high baseline APS had stable social functioning over 18 years, whereas functioning deteriorated among those with low APS. This finding helps clarify the temporal order of cognitive and psychosocial deficits associated with mood disorders and suggests the clinical utility of cognitive measures in identifying those at risk of deterioration in social functioning.Journal of Nervous & Mental Disease 09/2013; 201(9):824-7. DOI:10.1097/NMD.0b013e31829db5ed · 1.81 Impact Factor
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ABSTRACT: The serotonergic system plays an important role in cognitive functions via various 5-HT receptors. Vortioxetine (Lu AA21004) in development as a novel multimodal antidepressant is a 5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist, a 5-HT(1B) receptor partial agonist, a 5-HT(1A) receptor agonist and a 5-HT transporter (5-HTT) inhibitor in vitro. Preclinical studies suggest that 5-HT(3) and 5-HT(7) receptor antagonism as well as 5-HT(1A) receptor agonism may have a positive impact on cognitive functions including memory. Thus vortioxetine may potentially enhance memory. We investigated preclinical effects of vortioxetine (1-10mg/kg administered subcutaneously [s.c.]) on memory in behavioral tests, and on cortical neurotransmitter levels considered important in rat memory function. Contextual fear conditioning and novel object recognition tests were applied to assess memory in rats. Microdialysis studies were conducted to measure extracellular neurotransmitter levels in the rat medial prefrontal cortex. Vortioxetine administered 1h before or immediately after acquisition of contextual fear conditioning led to an increase in freezing time during the retention test. This mnemonic effect was not related to changes in pain sensitivity as measured in the hotplate test. Rats treated with vortioxetine 1h before training spent more time exploring the novel object in the novel object recognition test. In microdialysis studies of the rat medial prefrontal cortex, vortioxetine increased extracellular levels of acetylcholine and histamine. In conclusion, vortioxetine enhanced contextual and episodic memory in rat behavioral models. Further demonstration of its potential effect on memory functions in clinical settings is warranted.Pharmacology Biochemistry and Behavior 02/2013; 105. DOI:10.1016/j.pbb.2013.01.019 · 2.82 Impact Factor