Faculty Bibliography

CONTEXT: Loosening of associations has long been considered a core feature of schizophrenia, but its neural correlate remains poorly understood. OBJECTIVE: To test the hypothesis that, in comparison with healthy control subjects, patients with schizophrenia show increased neural activity within inferior prefrontal and temporal cortices in response to directly and indirectly semantically related (relative to unrelated) words. DESIGN: A functional neuroimaging study using a semantic priming paradigm. SETTING: Lindemann Mental Health Center, Boston, Mass. PARTICIPANTS: Seventeen right-handed medicated outpatients with chronic schizophrenia and 15 healthy volunteers, matched for age and parental socioeconomic status. INTERVENTIONS: Functional magnetic resonance imaging as participants viewed directly related, indirectly related, and unrelated word pairs and performed a lexical decision task. MAIN OUTCOME MEASURES: Event-related functional magnetic resonance imaging measures of blood oxygenation level-dependent activity (1) within a priori temporal and prefrontal anatomic regions of interest and (2) at all voxels across the cortex. RESULTS: Patients and controls showed no behavioral differences in priming but opposite patterns of hemodynamic modulation in response to directly related (relative to unrelated) word pairs primarily within inferior prefrontal cortices, and to indirectly related (relative to unrelated) word pairs primarily within temporal cortices. Whereas controls showed the expected decreases in activity in response to semantic relationships (hemodynamic response suppression), patients showed inappropriate increases in response to semantic relationships (hemodynamic response enhancement) in many of the same regions. Moreover, hemodynamic response enhancement within the temporal fusiform cortices to indirectly related (relative to unrelated) word pairs predicted positive thought disorder. CONCLUSION: Medicated patients with chronic schizophrenia, particularly those with positive thought disorder, show inappropriate increases in activity within inferior prefrontal and temporal cortices in response to semantic associations.

OBJECTIVE:: Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication. METHODS:: Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12. RESULTS:: Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo. CONCLUSIONS:: Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may merit further study

Patients who present with a first episode of psychosis pose many challenges to psychiatry. While some morbidity from schizophrenia is probably not modifiable once acute psychosis has occurred, the best management of this stage of illness nevertheless holds the promise of improving long-term outcomes. We review the clinical literature on first-episode psychosis to derive clinical guidance with regard to timely diagnosis and optimal pharmacological and nonpharmacological treatment. We describe the illness course and the prognosis for this acute phase of illness and the immediate, postpsychotic period

Hepatitis C virus (HCV) infection occurs in up to 20% of patients with chronic mental illnesses. To determine the prevalence of hepatitis C in a diagnostically well-defined sample, the authors screened all schizophrenia outpatients in a clozapine clinic (N=98) for HCV antibodies. Eight patients were positive for hepatitis C antibodies (antibody-positive prevalence: 8.2%); of those, 50% had detectable viral loads (viremia-positive prevalence: 4.1%). Screening for HCV infection should be considered for outpatients with schizophrenia. However, clinical experience treating HCV in schizophrenia patients is limited; in this cohort, 2 years after screening, no patient had received interferon/ribavirin treatment

Persons with serious mental illness represent a special at-risk population, with elevated medical comorbidity and mortality rates, mainly due to cardiovascular disease. For this reason, the treatment plan for patients with mental illness must include the assessment of medical risk factors, beginning at the time of the initial psychiatric evaluation. Follow-up assessments should proceed as recommended by the Expert Consensus Development Panel convened by the American Diabetes Association, the American Psychiatric Association, and other relevant specialty organizations. Because the various second-generation antipsychotics (SGAs) have unique side effect profiles with respect to cardiometabolic risk factors, such as weight gain and dyslipidemia, the selection of an SGA always should weigh efficacy versus potential risks. Prior to initiating antipsychotic therapy, the psychiatrist should not only explain to the patient the risks of the medication and alternative treatments, but also address preventive strategies and the importance of monitoring. To help evaluate the patient's response and manage SGA-related adverse effects, the psychiatrist should spend considerable time in contact with the patient, the patient's family and/or caregivers (as appropriate), and the patient's primary care physician. To enhance overall patient care, the psychiatrist in private practice should implement procedures to ensure adequate patient education and address overall health monitoring. Furthermore, the psychiatrist must serve as a patient advocate, actively working to foster communication with medical colleagues, especially primary care practitioners, and identify resources in the community that facilitate preventive health care

Patients with chronic mental illness have multiple health care needs. These patients, particularly those with schizophrenia, have higher incidences of heart disease and metabolic syndrome than the general population and show increased risks of infectious disease, pulmonary disease, and substance abuse. In order to effectively monitor and treat these patients, psychiatric and general health care should be integrated as much as possible. This presentation describes the role of the psychiatrist in helping to maintain the physical health of his or her patients, including monitoring for weight gain and other cardiac risk factors that may be increased by psychotropic medications, and explains the importance of communication between psychiatrists and primary care physicians

The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention

Previous research has demonstrated that prenatal infections with bacterial or viral agents during pregnancy are associated with an increased risk of schizophrenia in the offspring during adulthood. Furthermore, there has been evidence linking obstetric complications to schizophrenia. In parallel, there is a separate body of evidence relating subclinical chronic inflammation and schizophrenia in individuals, usually in their adulthood, who have already developed schizophrenia. On the other hand, unequivocal experimental, epidemiological and clinical evidence has emerged during the past decade linking inflammation to the development of insulin resistance and metabolic disturbances, which are common in the schizophrenic population. Inflammation might be an important common pathophysiological process related to both schizophrenia psychopathology and metabolic disturbances seen in patients with schizophrenia. Future studies targeting proinflammatory cytokines and their molecular signaling pathways may lead to novel pharmacological intervention strategies treating both psychopathology and medical comorbidity in patients with this devastating mental illness

BACKGROUND: Although people with schizophrenia display impaired abilities for consent, it is not known how much impairment constitutes incapacity. AIMS: To assess a method for determining the categorical capacity status of potential participants in schizophrenia research. METHOD: Expert-judgement validation of capacity thresholds on the sub-scales of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) was evaluated using receiver operating characteristic (ROC) analysis in 91 people with severe mental illness and 40 controls. RESULTS: The ROC areas under the curve for the understanding, appreciation and reasoning sub-scales of the MacCAT-CR were 0.94 (95% CI 0.88-0.99), 0.85 (95% CI 0.76-0.94) and 0.80 (95% CI 0.70-0.90). These findings yielded negative and positive predictive values of incapacity that can guide the practice of investigators and research ethics committees. CONCLUSIONS: By performing such validation studies for a few categories of research with varying risks and benefits, it might be possible to create evidence-based capacity determination guidelines for most schizophrenia research