BackgroundCognitive deterioration is a core symptom of many neuropsychiatric disorders and target of increasing significance for novel treatment strategies. Hence, its reliable capture in long-term follow-up studies is prerequisite for recording the natural course of diseases and for estimating potential benefits of therapeutic interventions. Since repeated neuropsychological testing is required for respective longitudinal study designs, occurrence, time pattern and magnitude of practice effects on cognition have to be understood first under healthy good-performance conditions to enable design optimization and result interpretation in disease trials.MethodsHealthy adults (N = 36; 47.3 ± 12.0 years; mean IQ 127.0 ± 14.1; 58% males) completed 7 testing sessions, distributed asymmetrically from high to low frequency, over 1 year (baseline, weeks 2-3, 6, 9, months 3, 6, 12). The neuropsychological test battery covered 6 major cognitive domains by several well-established tests each.ResultsMost tests exhibited a similar pattern upon repetition: (1) Clinically relevant practice effects during high-frequency testing until month 3 (Cohen's d 0.36-1.19), most pronounced early on, and (2) a performance plateau thereafter upon low-frequency testing. Few tests were non-susceptible to practice or limited by ceiling effects. Influence of confounding variables (age, IQ, personality) was minor.ConclusionsPractice effects are prominent particularly in the early phase of high-frequency repetitive cognitive testing of healthy well-performing subjects. An optimal combination and timing of tests, as extractable from this study, will aid in controlling their impact. Moreover, normative data for serial testing may now be collected to assess normal learning curves as important comparative readout of pathological cognitive processes.
Molecular mechanisms underlying bipolar affective disorders are unknown. Difficulties arise from genetic and phenotypic heterogeneity of patients and the lack of animal models. Thus, we focused on only one patient (n = 1) with an extreme form of rapid cycling. Ribonucleic acid (RNA) from peripheral blood mononuclear cells (PBMC) was analyzed in a three-tiered approach under widely standardized conditions. Firstly, RNA was extracted from PBMC of eight blood samples, obtained on two consecutive days within one particular episode, including two different consecutive depressive and two different consecutive manic episodes, and submitted to (1) screening by microarray hybridizations, followed by (2) detailed bioinformatic analysis, and (3) confirmation of episode-specific regulation of genes by quantitative real-time polymerase chain reaction (qRT-PCR). Secondly, results were validated in additional blood samples obtained one to two years later. Among gene transcripts elevated in depressed episodes were prostaglandin D synthetase (PTGDS) and prostaglandin D2 11-ketoreductase (AKR1C3), both involved in hibernation. We hypothesized them to account for some of the rapid cycling symptoms. A subsequent treatment approach over 5 months applying the cyclooxygenase inhibitor celecoxib (2 × 200 mg daily) resulted in reduced severity rating of both depressed and manic episodes. This case suggests that rapid cycling is a systemic disease, resembling hibernation, with prostaglandins playing a mediator role.
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