Executive dysfunction and treatment response in late-life depression
ABSTRACT Executive dysfunction in geriatric depression has been shown to predict poor response to antidepressant medication. The purpose of this review is to clarify which aspects of executive functioning predict poor antidepressant treatment response.
From our review, the aspects of executive functioning that appear to be associated with antidepressant response rates are verbal fluency and response inhibition. There is some indication that the semantic strategy component may account for the effects of verbal fluency, although evidence comes from one study and needs replication. Processing speed has been proposed as a substrate that may underlie the effects of executive dysfunction on treatment response. Although processing speed does not appear to account for the relationship between response inhibition and treatment outcome, this issue has yet to be assessed with respect to verbal fluency.
Verbal fluency and response inhibition are specific aspects of executive dysfunction that appear to impact antidepressant response rates. Disruption of the frontostriatal limbic circuit (particularly the anterior cingulate and dorsolateral prefrontal cortex) may explain the relation between these two mechanisms.
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ABSTRACT: The ability to cognitively regulate emotional responses to aversive events is important for mental and physical health. Little is known, however, about neural bases of the cognitive control of emotion. The present study employed functional magnetic resonance imaging to examine the neural systems used to reappraise highly negative scenes in unemotional terms. Reappraisal of highly negative scenes reduced subjective experience of negative affect. Neural correlates of reappraisal were increased activation of the lateral and medial prefrontal regions and decreased activation of the amygdala and medial orbito-frontal cortex. These findings support the hypothesis that prefrontal cortex is involved in constructing reappraisal strategies that can modulate activity in multiple emotion-processing systems.Journal of Cognitive Neuroscience 12/2002; 14(8):1215-29. DOI:10.1162/089892902760807212 · 4.69 Impact Factor
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ABSTRACT: BACKGROUND: Depression is common in the elderly and in the last few years this led to a significant increase in antidepressant prescription rates. However, little is known about antidepressant efficacy profile in relation with socio-demographic and clinical features in this population. The aim of the present study was to define the most suitable socio-demographic and clinical profile for the use of antidepressant treatments in late-life depression. METHODS: MEDLINE, EMBASE and PsycINFO were searched for randomized controlled trials (RCTs) focused on efficacy of antidepressants of all classes in major depressed elderly subjects (>60 years old). Reviews and meta-analyses focusing on this topic have been considered as well. Thirty-four RCTs were included and socio-demographic and clinical features were investigated via meta-regression analysis as moderators of efficacy measures (standardized mean difference based on Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale). RESULTS: A lower rate of response to antidepressants of all classes was found in patients of male gender, of older age, and with a longer mean duration of the current episode. On the contrary, a higher rate of response was found in patients with a higher baseline severity and at their first episode of illness. Subsamples treated with selective serotonin reuptake inhibitors alone yielded similar results. LIMITATIONS: RCTs only have been included. CONCLUSIONS: A number of socio-demographic and clinical features have been found to moderate antidepressant efficacy in elderly population. Those variables could help clinicians for a more individualized treatment.Journal of Affective Disorders 12/2012; 147(1-3). DOI:10.1016/j.jad.2012.11.053 · 3.71 Impact Factor
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ABSTRACT: We present a comprehensive overview of the neurobiology of unipolar major depression and antidepressant drug action, integrating data from affective neuroscience, neuro- and psychopharmacology, neuroendocrinology, neuroanatomy, and molecular biology. We suggest that the problem of depression comprises three sub-problems: first episodes in people with low vulnerability ('simple' depressions), which are strongly stress-dependent; an increase in vulnerability and autonomy from stress that develops over episodes of depression (kindling); and factors that confer vulnerability to a first episode (a depressive diathesis). We describe key processes in the onset of a 'simple' depression and show that kindling and depressive diatheses reproduce many of the neurobiological features of depression. We also review the neurobiological mechanisms of antidepressant drug action, and show that resistance to antidepressant treatment is associated with genetic and other factors that are largely similar to those implicated in vulnerability to depression. We discuss the implications of these conclusions for the understanding and treatment of depression, and make some strategic recommendations for future research.Neuroscience & Biobehavioral Reviews 12/2012; 37(10). DOI:10.1016/j.neubiorev.2012.12.007 · 10.28 Impact Factor