Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.

Cognitive deficits are routinely evident in schizophrenia, and are of sufficient magnitude to influence functional outcomes in work, social functioning and illness management. Cognitive remediation is an evidenced-based non-pharmacological treatment for the neurocognitive deficits seen in schizophrenia. Narrowly defined, cognitive remediation is a set of cognitive drills or compensatory interventions designed to enhance cognitive functioning, but from the vantage of the psychiatric rehabilitation field, cognitive remediation is a therapy which engages the patient in learning activities that enhance the neurocognitive skills relevant to their chosen recovery goals. Cognitive remediation programs vary in the extent to which they reflect these narrow or broader perspectives but six meta-analytic studies report moderate range effect sizes on cognitive test performance, and daily functioning. Reciprocal interactions between baseline ability level, the type of instructional techniques used, and motivation provide some explanatory power for the heterogeneity in patient response to cognitive remediation.

Cognitive rehabilitation therapies for Alzheimer’s disease (AD) are becoming more readily available to the geriatric population in an attempt to curb the insidious decline in cognitive and functional performance. However, people with AD may have difficulty adhering to these cognitive treatments due to denial of memory deficits, compromised brain systems, cognitive incapacity for self-awareness, general difficulty following through on daily tasks, lack of motivation, hopelessness, and apathy, all of which may be either due to the illness or be secondary to depression. Cognitive rehabilitation training exercises are also labor intensive and, unfortunately, serve as a repeated reminder about the memory impairments and attendant functional consequences. In order for cognitive rehabilitation methods to be effective, patients must be adequately engaged and motivated to not only begin a rehabilitation program but also to remain involved in the intervention until a therapeutic dosage can be attained. We review approaches to cognitive rehabilitation in AD, neuropsychological as well as psychological obstacles to effective treatment in this population, and methods that target adherence to treatment and may therefore be applicable to cognitive rehabilitation therapies for AD. The goal is to stimulate discussion among researchers and clinicians alike on how treatment effects may be mediated by engagement in treatment, and what can be done to enhance patient adherence for cognitive rehabilitation therapies in order to obtain greater cognitive and functional benefits from the treatment itself.

This article describes the psychometric validation of a scale designed to measure intrinsic motivation (IM) in schizophrenia. Recent studies have highlighted the relationship between motivation and functional outcome in schizophrenia and identified IM as an important mediating factor between neurocognition and psychosocial outcome. It therefore becomes imperative to have validated measures of IM for empirical use. To that end, we validated a self-report IM scale that gauges the central motivational structures identified by Self-determinism Theory as pertinent to cognitive task engagement, skill acquisition, treatment compliance, and remediation outcome. Participants were schizophrenia outpatients involved in a cognitive remediation study (n = 58), a convenience subsample of clinically stable schizophrenia outpatients (n = 15), and a group of healthy normals (n = 22). The Intrinsic Motivation Inventory for Schizophrenia Research (IMI-SR) is a concise instrument, possessing good internal consistency (alpha = .92) and test-retest reliability (intraclass correlation = .77). Data were analyzed to abridge the original 54 items into a final 21-item questionnaire comprised of 3 domains relevant to motivation for treatments (interest/enjoyment, perceived choice, value/usefulness). The scale was highly associated with germane constructs of motivation for health-related behaviors, including perceived competency for attempting challenging tasks and autonomous treatment engagement. Importantly, the scale was able to distinguish improvers and nonimprovers on a cognitive task and actual learning exercises, delineate high vs low treatment attendance, and demonstrate sensitivity to motivational changes due to intervention variation. The IMI-SR is a viable instrument to measure IM in schizophrenia as part of a cognitive remediation protocol or psychosocial rehabilitation program.

Amotivation is a telling hallmark of negative symptomatology in schizophrenia, and it impacts nearly every facet of behavior, including inclination to attempt the difficult cognitive tasks involved in cognitive remediation therapy. Experiences of external reward, reinforcement, and hedonic anticipatory enjoyment are diminished in psychosis, so therapeutics which instead target intrinsic motivation for cognitive tasks may enhance task engagement, and subsequently, remediation outcome. We examined whether outpatients could attain benefits from an intrinsically motivating instructional approach which (a) presents learning materials in a meaningful game-like context, (b) personalizes elements of the learning materials into themes of high interest value, and (c) offers choices so patients can increase their control over the learning process. We directly compared one learning method that incorporated the motivational paradigm into an arithmetic learning program against another method that carefully manipulated out the motivational variables in the same learning program. Fifty-seven subjects with schizophrenia or schizoaffective disorder were randomly assigned to one of the two learning programs for 10 thirty-minute sessions while an intent-to-treat convenience subsample (n=15) was used to account for practice effect. Outcome measures were arithmetic learning, attention, motivation, self competency, and symptom severity. Results showed the motivational group (a) acquired more arithmetic skill, (b) possessed greater intrinsic motivation for the task, (c) reported greater feelings of self competency post-treatment, and (d) demonstrated better post-test attention. Interestingly, baseline perception of self competency was a significant predictor of post-test arithmetic scores. Results demonstrated that incorporating intrinsically motivating instructional techniques into a difficult cognitive task promoted greater learning of the material, higher levels of intrinsic motivation to attempt the demanding task, and greater feelings of self efficacy and achievement to learn.

Cognitive rehabilitation for mild cognitive impairment (MCI) and early Alzheimer's disease is readily available to the geriatric population. Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone. Seventy four adults with subclinical cognitive decline were randomly assigned to computerised cognitive training (CCT), Cognitive Vitality Training (CVT), or an Active Control Group (ACG), and underwent neuropsychological evaluations at baseline and four-month follow-up. Significant differences were found in changes in performance on the Modified Mini Mental State Examination (mMMSE) and measures of verbal learning and memory across treatment groups. Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group, the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory, and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory. There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory. It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone, although both appear superior to more generic forms of cognitive stimulation.

Adherence to treatment in psychiatric populations is notoriously low. In this randomized, controlled, proof-of-concept study, we sought to examine whether motivational interviewing (MI) could be used to enhance motivation for, adherence to, and benefit obtained from cognitive rehabilitation. Dual diagnosis MI, developed specifically for individuals with psychotic symptoms and disorganization, was further adapted to focus on cognitive impairments and their impact. Sixty-four outpatients diagnosed with schizophrenia spectrum disorders completed baseline assessments and were randomized to receive either the 2-session MI focused on cognitive functioning or a 2-session sham control interview focused on assessment and feedback about preferred learning styles. Next, all participants were given 4 weeks during which they could attend up to 10 sessions of a computer-based math training program, which served as a brief analog for a full course of cognitive rehabilitation. As hypothesized, MI condition was associated with greater increases in task-specific motivation along with greater training program session attendance. Moreover, postinterview motivation level predicted session attendance. There were no significant differences in improvement on a measure of cognitive training content, which may have been due to the abbreviated nature of the training. While the literature on the efficacy of MI for individuals with psychosis has been mixed, we speculate that our positive findings may have been influenced by the adaptations made to MI as well as the focus on a nonpharmacological intervention.

No abstract