James F. M. Cornwell

Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder

OBJECTIVE Varenicline has been shown to be an effective anti-smoking treatment in smokers without identified psychiatric illness, and the drugs pharmacology suggests possibilities of pro-cognitive effects. However, recent reports suggest varenicline may have the potential for important psychiatric side-effects in some people. We present the first prospective quantitative data on the effects of varenicline on cognitive function, cigarette smoking, and psychopathology in a small sample of schizophrenic patients. METHOD Fourteen schizophrenic smokers were enrolled in an open-label study of varenicline with a pre-post design. Measures of cognitive function (RBANS, Virtual Water-Maze Task), cigarette smoking (cotinine levels, CO levels, self-reported smoking and smoking urges), and psychopathology (PANSS) were evaluated prior to and during treatment with varenicline. Data on psychopathology changes among schizophrenic smokers in another drug study, in which patients were not receiving varenicline, were used for comparison. RESULTS 12 patients completed the study, and 2 patients terminated in the first two weeks of active varenicline because of complaints of nausea or shaking. Varenicline produced significant improvements in some cognitive test scores, primarily associated with verbal learning and memory, but not in scores on visual-spatial learning or memory, or attention. Varenicline significantly decreased all indices of smoking, but did not produce complete smoking abstinence in most patients. During treatment with varenicline there were no significant increases in psychopathology scores and no patient developed signs of clinical depression or suicidal ideation. CONCLUSIONS Our small prospective study suggests that treatment with varenicline appears to have some beneficial cognitive effects which need to be confirmed in larger studies with additional neuropsychological tests. Varenicline appears to have some anti-smoking efficacy in schizophrenia but longer studies are needed to determine whether it will produce rates of smoking abstinence similar to those found in control smokers. Treatment with varenicline may not increase psychopathology or depression in most patients with schizophrenia, but we cannot accurately estimate the absolute risk of a potentially rare side-effect from this small sample.

Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study.

BACKGROUND Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative. METHOD Hospitalized patients with chronic schizophrenia (DSM-IV), most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting glucose, insulin, insulin-related metabolic measures, and prolactin were assessed, and an oral glucose tolerance test (OGTT) was performed during baseline and months 1, 2, and 5 of treatment. Weight was assessed monthly, and waist and hip measures were taken at baseline and month 5. Data were analyzed on 23 patients randomly assigned to risperidone and 23 patients randomly assigned to olanzapine. The study was conducted from February 2003 to August 2007. RESULTS Most patients were overweight or obese at baseline (mean body mass index [BMI] = 29.4), but there were no differential drug effects on weight change and no differences between drug groups at the 5-month time point. There were no overall drug treatment differences in fasting glucose or glycohemoglobin or 2-hour glucose levels in OGTT and no differences between the two drug groups at the 5-month time point. There were no consistent drug treatment differences in the number of patients who developed borderline or diabetic glucose levels. Olanzapine-treated patients showed a significantly greater increase than risperidone-treated patients in a fasting measure of insulin resistance (P = .041), and olanzapine patients showed greater decreases in insulin sensitivity during OGTT (P = .023) compared to risperidone-treated patients. Olanzapine-treated patients had a significantly greater increase in 1-hour glucose and insulin levels during OGTT in subsequent months compared to baseline and greater increase in glucose and insulin area under the curve over time than the risperdone-treated patients. Prolactin levels decreased in olanzapine patients and increased in risperidone patients (P values approximately .02). There were no significant drug treatment differences in C-peptide levels or 2 indices proposed as measures of insulin secretion or beta-cell function (homeostasis model assessment of beta-cell function [HOMA-B], BIGTT-acute insulin response surrogate measure [BIGTT-AIR]). Changes in insulin resistance over time were not strongly related to changes in BMI or waist circumference during study drug treatment. CONCLUSIONS The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of beta-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patients risk for conversion to type 2 diabetes. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT00287820.

Repeating the Past Prevention Focus Motivates Repetition, Even for Unethical Decisions

Prevention-focused individuals are motivated to maintain the status quo. Given this, we predicted that individuals with a strong prevention focus, either as a chronic predisposition or situationally induced, would treat their initial decision on how to behave on a first task as the status quo and would thus be motivated to repeat that decision on a subsequent task—even for decisions that were ethically questionable. Results from five studies supported this prediction in multiple ethical domains: whether or not to overstate performance (Studies 1, 2a, and 2b), whether or not to disclose disadvantageous facts (Study 3), and whether or not to pledge a donation (Study 4). The prevention-repetition effect was observed both when the initial and subsequent decisions were in the same domain (Studies 1–3) and when they were in different domains (Study 4). Alternative accounts for this effect, such as justification for the initial decision and preference for consistency, were ruled out (Study 2b).

Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: A randomized five month study

OBJECTIVE Metabolic syndrome and elevated lipids, related to cardiovascular risk factors, are more prevalent in schizophrenia and there has been much debate about the extent to which specific antipsychotics contribute more to the increased risk of developing hyperlipidemia and metabolic syndrome. Most studies have concentrated on fasting levels in patients recently started on medication. Randomized prospective studies of metabolic effects of 2nd generation antipsychotics using both fasting measures and provocative tests may provide results that are more informative. We present results of a randomized prospective study of lipid metabolism and metabolic syndrome in chronic schizophrenic patients using both fasting and post-prandial lipid measures. METHOD Hospitalized patients with chronic schizophrenia, most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting levels of lipids, free fatty acid (FFA) and leptin were assessed. At baseline and end of month 2 of treatment patients had a fatty meal test (FMT) in which postprandial lipids were measured at several time points before and after meal ingestion. Weight was assessed monthly and waist measures were taken at baseline and month 5. Data was analyzed on 23 patients randomized to risperidone and 23 patients randomized to olanzapine. RESULTS Overall, there were no differential drug effects on any fasting lipid measure and fasting triglycerides did not increase in olanzapine treated patients after 5 months of treatment. However, at 2 months of drug treatment the FMT revealed a significantly greater increase in triglycerides, and very low density (VLDL) cholesterol and triglycerides, in olanzapine compared to risperidone patients (Ps=.05-.01). There was no difference between treatments with olanzapine vs. risperidone on development of metabolic syndrome during the 5 month treatment period. CONCLUSIONS Chronic schizophrenic patients treated for years with first and second generation antipsychotics may have developed tolerance to the effects of olanzapine on increasing fasting triglycerides and other lipids, but some underlying metabolic abnormalities may be revealed in postprandial tests of lipid metabolism. These findings suggest that the development of standardized tests and criteria for measurement of postprandial triglycerides and related lipid levels, in addition to fasting levels, may be helpful in identifying metabolic effects of olanzapine and other second generation antipsychotics in chronically treated schizophrenics. In some reports postprandial increases in triglycerides have been identified as important risk factors for cardiovascular disease, but the actual differential consequences of these lipid metabolic differences for development of atherosclerosis and cardiovascular disease in patients treated with different antipsychotics need more objective outcome measures to determine and quantify cardiovascular risk outcomes.

Morality and Its Relation to Political Ideology The Role of Promotion and Prevention Concerns

Our research investigated whether promotion concerns with advancement and prevention concerns with security related to moral beliefs and political ideology. Study 1 found that chronic prevention and promotion focus had opposite relations to binding foundation endorsement (as measured by the Moral Foundations Questionnaire), that is, positive for prevention and negative for promotion, and opposite relations to political ideology, that is, more conservative for prevention and more liberal for promotion, and the relation between focus and political ideology was partially mediated by binding foundation endorsement. Study 2 showed that promotion and prevention, even as situationally induced states, can contribute to differences in binding foundation endorsement, with prevention producing stronger endorsement (compared with a control) and promotion producing weaker endorsement.

Truth, control, and value motivations: the "what," "how," and "why" of approach and avoidance

The hedonic principle—the desire to approach pleasure and avoid pain—is frequently presumed to be the fundamental principle upon which motivation is built. In the past few decades, researchers have enriched our understanding of how approaching pleasure and avoiding pain differ from each other. However, more recent empirical and theoretical work delineating the principles of motivation in humans and non-human animals has shown that not only can approach/avoidance motivations themselves be further distinguished into promotion approach/avoidance and prevention approach/avoidance, but that approaching pleasure and avoiding pain requires the functioning of additional distinct motivations—the motivation to establish what is real (truth) and the motivation to manage what happens (control). Considering these additional motivations in the context of moral psychology and animal welfare science suggests that these less-examined motives may themselves be fundamental to a comprehensive understanding of motivation, with major implications for the study of the “what,” “how,” and “why” of human and non-human approach and avoidance behavior.

Judging Political Hearts and Minds How Political Dynamics Drive Social Judgments

We investigated how judgments of political messengers depend upon what would benefit one’s preferred candidate. In Study 1a, participants were asked to evaluate the warmth and competence of the writer of a pro- or anti-Obama political message for the 2012 presidential election (Obama/warm; Romney/competent). When judging the messages, warmth was emphasized by Democrats and competence by Republicans. Study 1b replicated these effects for messages about Romney as well. Study 2 examined the 2004 presidential election where perceptions of the party candidates’ warmth and competence reversed (Bush/warm; Kerry/competent). There competence was emphasized by Democrats and warmth by Republicans. Study 3 showed that varying the warmth and competence of each party’s prospective candidates for the 2016 election influences whether warmth or competence is emphasized by Democrats or Republicans. Thus, differences between Republicans and Democrats in emphasizing warmth or competence reflect a dynamic motivated cognition that is tailored to benefit their preferred candidate.

Locomotion concerns with moral usefulness: When liberals endorse conservative binding moral foundations

Moral Foundations Theory has provided a framework for understanding the endorsement of different moral beliefs. Our research investigated whether there are other reasons to endorse moral foundations in addition to epistemic concerns; specifically, the perceived social usefulness of moral foundations. In Study 1, we demonstrate that those showing stronger locomotion concerns for controlling movement tend toward a higher endorsement of binding foundations, and that this effect is stronger among political liberals who otherwise do not typically endorse these foundations. In Study 2, we show that priming participants with assessment concerns (emphasizing truth) rather than locomotion concerns (emphasizing control) reduces the response variance among liberals and also removes the association between locomotion and the binding foundations. In Study 3, we directly ask participants to focus on moral truth versus moral usefulness, with moral truth replicating the Study 2 effect of assessment priming, and moral usefulness replicating the effect of locomotion priming.

Eager feelings and vigilant reasons: Regulatory focus differences in judging moral wrongs.

For over a decade, moral psychologists have been actively researching the processes underlying moral judgments that are made intuitively without reference to an actions concrete harms or injustice, such as the well-known case of nonprocreative, consensual incest. We suggest that the reason some judge such scenarios as wrong (using intuitive feelings) and others do not (using deliberative reasons) is due to an important motivational distinction. Consistent with this view, across 7 studies, we demonstrate that negative judgments of such moral scenarios are more intense when processed in the promotion focus compared to the prevention focus, and that this is due to differences in whether eager (intuitive feelings) versus vigilant (deliberative reasons) means are employed in judging these moral wrongs. By examining both boundary conditions and possible underlying mechanisms for regulatory focus differences in moral judgment intensity, we expand our understanding of the differences between promotion and prevention regarding how proscriptive judgments are processed, while integrating these differences with existing theories in moral psychology.

The "Ought" Premise of Moral Psychology and the Importance of the Ethical "Ideal"

Researchers’ interest in the psychology of ethics has increased dramatically in the last 20 years. Because of the influence of “modern” moral philosophy on psychology, what has received most attention, and has even been taken by some to be an essential characteristic of morality, are oughts (i.e., duties and obligations). Consistent with some more recent advances in the psychological literature (and contemporary philosophy), we propose that this is not the only approach to moral value. Using regulatory focus theory as a lens, we suggest that more attention should also be paid to an important motivational alternative—ethical ideals (i.e. advances and aspirations). We review evidence that we believe supports the conclusion that ethics consists of (at least) 2 evaluative systems—not only a system of oughts that is concerned with maintaining obligations, but also a system of ideals that is concerned with attaining virtues.