Escitalopram reduces attentional performance in anxious older adults with high-expression genetic variants at serotonin 2A and 1B receptors

Older adults are among the most vulnerable to adverse cognitive effects of psychotropic medications and, therefore, the personalization of psychotropic treatment based on adverse drug reactions in this demographic is of great importance. We examined changes on neuropsychological tests of attention attributable to selective serotonin reuptake inhibitor (SSRI) treatment in anxious older adults. We also examined whether variation in serotonin receptor genes was associated with reduced attentional performance with SSRIs. We examined change from pre- to post-treatment in two attention measures – digit span and coding – in 133 adults aged ≥60 yr with generalized anxiety disorder in a 12-wk trial of escitalopram vs. placebo. We also examined attentional change in relation to genetic variability in four central serotonin receptors: the serotonin transporter and serotonin 1A, 2A and 1B receptors. Digit span scores were significantly lowered in patients receiving escitalopram relative to placebo, indicating reduced attentional performance attributable to the SSRI. Individuals with high-transcription variants in the receptors 5-HTR(2A) rs6311 and 5-HTR(1B) rs11568817 had greater reductions in attention with SSRI treatment compared to placebo. We conclude that SSRIs reduce attention in older adults, particularly in those with high-expression genetic variants at the serotonin 2A and 1B receptors. Analysing neuropsychological changes with SSRIs in relation to genetic variation in the serotonin system may be a useful strategy for detecting subgroups of older adults who are more susceptible to side-effects of SSRIs. These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects

Decreased delta sleep ratio and elevated alpha power predict vulnerability to depression during interferon-alpha treatment

ObjectiveAlthough poor sleep accompanies depression, it is unknown which specific sleep abnormalities precede depression. This is similarly the case for depression developing during interferon-α (IFN-α) therapy. Because vulnerability becomes evident in those who slept poorly before IFN-α, we prospectively determined which specific aspect of sleep could predict subsequent depression.MethodsTwo nights of polysomnography with quantitative electroencephalogram (EEG) were obtained in 24 adult, euthymic subjects – all subsequently treated with IFN-α for hepatitis C. Every 2 weeks, a Beck Depression Inventory-II (BDI-II) score was obtained, and the maximal increase in BDI-II from pre-treatment baseline – excluding the sleep question – was determined.ResultsThe delta sleep ratio (DSR; an index of early-night restorative delta power) was inversely associated with BDI-II increases (p&lt;0.01), as was elevated alpha power (8–12 Hz; p&lt;0.001). Both delta (0.5–4 Hz) and alpha power exhibited high between-night correlations (r=0.83 and 0.92, respectively). In mixed-effect repeated-measure analyses, there was an interaction between alpha power and DSR (p&lt;0.001) – subjects with low alpha power and elevated DSR were resilient to developing depression. Most other sleep parameters – including total sleep time and percentage of time in slow wave sleep – were not associated with subsequent changes in depression.ConclusionsBoth high DSR and low alpha power may be specific indices of resilience. As most other aspects of sleep were not associated with resilience or vulnerability, sleep interventions to prevent depression may need to specifically target these specific sleep parameters.</jats:sec