Gregory W. Dalack

Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia

Frontal lobe dysfunction in individuals with schizophrenia has frequently been detected using both neuroimaging and neuropsychological testing. Results from previous studies vary in the findings of regional specificity vs. generalized frontal cortical dysfunction. We sought to examine potential regional differences in frontal cortical functioning among patients with schizophrenia vs. a comparison group using two different neurocognitive tasks: the Gambling Task (GT) and the Wisconsin Card Sorting Test (WCST). In general, the GT is thought to reflect function of the ventromedial prefrontal cortex (VMPFC), while the WCST reflects function of the dorsolateral prefrontal cortex (DLPFC). Twenty individuals with schizophrenia or schizoaffective disorder and 15 nonpsychiatrically ill comparison subjects underwent an assessment battery consisting of the GT, WCST, and positive and negative symptom ratings. Patients with schizophrenia performed worse on the GT with respect to total monetary gain (p=0.05) and total monetary loss (p<0.05). They also preferred disadvantaged vs. advantaged cards (p<0.04). Surprisingly, WCST performance was poor in both groups and was not significantly different between groups. These findings are at some variance with those in the previously reported literature, but nonetheless support the idea that prefrontal cortical areas mediating different cognitive tasks may be distinguished by specific neurocognitive assessments.

Differential prevalence of cigarette smoking in patients with schizophrenic vs mood disorders

Rates of substance-use disorders among psychiatric patients are consistently higher than in the general population, yet there is no clear specificity to the relationship between types of substance use and psychiatric diagnoses. Cigarette smoking may represent a substance-use behavior which has greater specificity for major psychiatric diagnoses. We examined the self-reported history of cigarette smoking vs marijuana, alcohol and cocaine use among 83 male veteran psychiatric patients with primary mood (major depression or bipolar disorder; n = 20) or schizophrenic (schizophrenia or schizoaffective; n = 63) disorders. Those in the SCZ group compared to those in the AFF group were more likely to be ever-smokers (OR 8.5, 95% CI [2.2, 32.3]), and current smokers (OR 12.0%, 95% CI [3.6, 40]), independent of age differences between the groups. There were no significant differences in marijuana, alcohol or cocaine use between the two groups when age differences were controlled. Generalizability of the findings is limited by small number of subjects, male gender and veteran status; however, the significantly higher prevalence of smoking among individuals with schizophrenic disorders may support the growing evidence of linkages between the effects of nicotine and the neurobiology of schizophrenia.

Excess heart-disease-related mortality in a national study of patients with mental disorders: identifying modifiable risk factors.

OBJECTIVE People with mental disorders are estimated to die 25 years younger than the general population, and heart disease (HD) is a major contributor to their mortality. We assessed whether Veterans Affairs (VA) health system patients with mental disorders were more likely to die from HD than patients without these disorders, and whether modifiable factors may explain differential mortality risks. METHODS Subjects included VA patients who completed the 1999 Large Health Survey of Veteran Enrollees (LHSV) and were either diagnosed with schizophrenia, bipolar disorder, other psychotic disorders, major depressive disorder or other depression diagnosis or diagnosed with none of these disorders. LHSV data on patient sociodemographic, clinical and behavioral factors (e.g., physical activity, smoking) were linked to mortality data from the National Death Index of the Centers for Disease Control and Prevention. Hierarchical multivariable Cox proportional hazards models were used to assess 8-year HD-related mortality risk by diagnosis, adding patient sociodemographic, clinical and behavioral factors. RESULTS Of 147,193 respondents, 11,809 (8%) died from HD. After controlling for sociodemographic and clinical factors, we found that those with schizophrenia [hazard ratio (HR)=1.25; 95% confidence interval (95% CI): 1.15-1.36; P<.001] or other psychotic disorders (HR=1.41; 95% CI: 1.27-1.55; P<.001) were more likely to die from HD than those without mental disorders. Controlling for behavioral factors diminished, but did not eliminate, the impact of psychosis on mortality. Smoking (HR=1.32; 95% CI: 1.26-1.39; P<.001) and inadequate physical activity (HR=1.66; 95% CI: 1.59-1.74; P<.001) were also associated with HD-related mortality. CONCLUSIONS Patients with psychosis were more likely to die from HD. For reduction of HD-related mortality, early interventions that promote smoking cessation and physical activity among veterans with psychotic disorders are warranted.

Nicotine Withdrawal and Psychiatric Symptoms in Cigarette Smokers with Schizophrenia

The prevalence of smoking is markedly elevated in schizophrenia. Low smoking cessation rates and reports that some smokers with schizophrenia experience an acute increase in symptoms during attempts to quit smoking, suggest a self-medication model. Alternatively, smoking may modulate medication side effects. The effects of treated and untreated smoking abstinence on psychotic symptoms and medication side effects were examined in this study. Nineteen outpatients with schizophrenia or schizoaffective disorder participated in a randomized, double-blind, balanced crossover study: 1 day of ad libitum smoking followed by 3 days of acute smoking abstinence while wearing 22 mg/day active or placebo transdermal nicotine patches, with a return to 3 days of smoking between patch conditions. Daily symptom and side-effect ratings, nicotine and cotinine blood levels were collected. Twelve subjects completed the study. Neither positive symptoms nor mood symptoms changed. An increase in negative symptoms during the first abstinent day occurred in both placebo and active patch conditions, but was not sustained over subsequent abstinent days. Despite physiological signs of withdrawal, completers did not endorse increased nicotine withdrawal symptoms. Dropouts reported higher withdrawal symptoms, but also had no increase in psychiatric symptoms in either phase of the study. Of note, dyskinesias decreased during abstinence and placebo patch treatment, but increased during abstinence and the active patch conditions. Acute exacerbation of psychiatric symptoms is an unlikely explanation for any difficulty smokers with schizophrenia have in early abstinence.

Smoking smoking withdrawal and schizophrenia : case reports and a review of the literature

Our efforts to study and understand the complex clinical, behavioral, neurochemical and neuroanatomical manifestations of the schizophrenias are plagued by the heterogeneity of findings, and lack of ability to define subtypes within the syndrome. Theoretically, a behavior associated with schizophrenia among a majority of those affected might provide more broadly applicable information about the illness. Cigarette smoking represents such a behavior. Herein we present an overview of evidence linking cigarette smoking and schizophrenia, and describe three cases suggesting that nicotine withdrawal leads to an exacerbation of schizophrenic symptoms.

Effects of the 2011 Duty Hour Reforms on Interns and Their Patients: A Prospective Longitudinal Cohort Study

IMPORTANCE In 2003, the first phase of duty hour requirements for US residency programs recommended by the Accreditation Council for Graduate Medical Education (ACGME) was implemented. Evidence suggests that this first phase of duty hour requirements resulted in a modest improvement in resident well-being and patient safety. To build on these initial changes, the ACGME recommended a new set of duty hour requirements that took effect in July 2011. OBJECTIVE To determine the effects of the 2011 duty hour reforms on first-year residents (interns) and their patients. DESIGN As part of the Intern Health Study, we conducted a longitudinal cohort study comparing interns serving before (2009 and 2010) and interns serving after (2011) the implementation of the new duty hour requirements. SETTING Fifty-one residency programs at 14 university and community-based GME institutions. PARTICIPANTS A total of 2323 medical interns. MAIN OUTCOME MEASURES Self-reported duty hours, hours of sleep, depressive symptoms, well-being, and medical errors at 3, 6, 9, and 12 months of the internship year. RESULTS Fifty-eight percent of invited interns chose to participate in the study. Reported duty hours decreased from an average of 67.0 hours per week before the new rules to 64.3 hours per week after the new rules were instituted (P < .001). Despite the decrease in duty hours, there were no significant changes in hours slept (6.8 → 7.0; P = .17), depressive symptoms (5.8 → 5.7; P = .55) or well-being score (48.5 → 48.4; P = .86) reported by interns. With the new duty hour rules, the percentage of interns who reported concern about making a serious medical error increased from 19.9% to 23.3% (P = .007). CONCLUSIONS AND RELEVANCE Although interns report working fewer hours under the new duty hour restrictions, this decrease has not been accompanied by an increase in hours of sleep or an improvement in depressive symptoms or well-being but has been accompanied by an unanticipated increase in self-reported medical errors.

Risk factors associated with metabolic syndrome in bipolar and schizophrenia subjects treated with antipsychotics: the role of folate pharmacogenetics.

Abstract Folate has been implicated in cardiovascular disease with atypical antipsychotic (AAPs) use, and individuals with methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) variants are at greater risk. This study examined the relationship between the MTHFR 677C/T, MTHFR 1298A/C, and COMT Val158Met variants; metabolic syndrome; and lifestyle measures in schizophrenia and bipolar subjects. A total of 237 subjects with bipolar or schizophrenia receiving an antipsychotic for at least 6 months were included in this cross-sectional analysis. Subjects were screened for the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and MTHFR 677C/T, MTHFR 1298A/C, and Val158Met genotypes. In addition, serum folate and homocysteine were measured along with lifestyle factors. The subject’s mean age was 44.7 (SD, 11.7) years; 72% were white, and 51% male; 61% were receiving an AAP; the mean body mass index was 32.6 (SD, 8.2) kg/m2, and 48% were current smokers. Overall, 41% met metabolic syndrome criteria (n = 98). There were no differences in age, sex, AAP exposure, or body mass index between genotype groups. Metabolic syndrome was related to age, smoking, and the MTHFR 677T and COMT 158Val alleles (&khgr;2 = 34.4, P < 0.0001). In addition, AAP use showed a trend association with metabolic syndrome (&khgr;2 = 3.21, P = 0.07). These data support our previous reports and add more data pointing to folate’s role in mediating a link between mental illness and cardiovascular disease. Use of this information clinically may help to reduce the risk for AAP metabolic complications in those whose clinical care necessitates the use of AAPs.

Buddy-to-Buddy, a citizen soldier peer support program to counteract stigma, PTSD, depression, and suicide.

Citizen soldiers (National Guard and Reserves) represent approximately 40% of the two million armed forces deployed to Afghanistan and Iraq. Twenty‐five to forty percent of them develop PTSD, clinical depression, sleep disturbances, or suicidal thoughts. Upon returning home, many encounter additional stresses and hurdles to obtaining care: specifically, many civilian communities lack military medical/psychiatric facilities; financial, job, home, and relationship stresses have evolved or have been exacerbated during deployment; uncertainty has increased related to future deployment; there is loss of contact with military peers; and there is reluctance to recognize and acknowledge mental health needs that interfere with treatment entry and adherence. Approximately half of those needing help are not receiving it. To address this constellation of issues, a private–public partnership was formed under the auspices of the Welcome Back Veterans Initiative. In Michigan, the Army National Guard teamed with the University of Michigan and Michigan State University to develop innovative peer‐to‐peer programs for soldiers (Buddy‐to‐Buddy) and augmented programs for military families. Goals are to improve treatment entry, adherence, clinical outcomes, and to reduce suicides. This manuscript describes training approaches, preliminary results, and explores future national dissemination.

Using A Pharmacy-Based Intervention To Improve Antipsychotic Adherence Among Patients With Serious Mental Illness

Background: Similar to patients with other chronic disorders, patients with serious mental illness (SMI) are often poorly adherent with prescribed medications. Objective: We conducted a randomized controlled trial examining the effectiveness of a pharmacy-based intervention (Meds-Help) in increasing antipsychotic medication adherence among Department of Veterans Affairs (VA) patients with SMI. We also examined the impact of Meds-Help on psychiatric symptoms, quality of life, and satisfaction with care. Methods: We enrolled 118 patients from 4 VA facilities with schizophrenia, schizoaffective, or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios (MPRs) <0.8 in the prior year. Patients were randomized to usual care (UC; n = 60) or the pharmacy-based intervention (Meds-Help; n = 58). We reassessed adherence at 6 and 12 months, at which time patients completed Positive and Negative Symptom Scales (PANSS), Quality of Well-being Scales (QWB), and Client Satisfaction Questionnaires (CSQ-8). Results: Prior to enrollment, Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55, respectively. At 6 months, mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients; at 12 months, they were 0.86 for Meds-Help and 0.62 for UC patients. In multivariate analyses adjusting for patient factors, Meds-Help patients had significantly higher MPRs at 6 and 12 months (P < .0001). There were no significant differences between groups in PANSS, QWB, or CSQ-8 scores, but power to detect small effects was limited. Conclusions: Congruent with prior studies of patients with other disorders, a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI. However, SMI patients may require additional care management components to improve outcomes.

The role of life events in onset and recurrent episodes of schizophrenia and schizoaffective disorder

The experience of both positive and negative recent life events has long been recognized as a possible precipitant of episodes of psychiatric illness. Among individuals with recurrent mood disorders, investigators have found that recent life events are more likely to be associated with initial and early episodes of illness, with later episodes less likely to be temporally associated with life events. This study investigated the relationship between recent life events and episodes of illness in schizophrenia (defined as the number of acute episodes of schizophrenia requiring hospitalization). Among 32 male U.S. Military veteran inpatients, those with three or fewer episodes of illness reported significantly more recent life events than those patients with more than three episodes of illness (P = 0.01). Overall, recent life events were negatively correlated with number of episodes (P < 0.05). These data suggest that initial or early episodes of schizophrenic illness are more likely to be associated with recent life events than are later episodes.