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Clinician-rated symptom scales are the current standard for outcome measures in Schizophrenia Spectrum Disorders (SSD) research. There has been growing interest in the development of self-report measures for people with SSD to support measurement-based care and inclusive research. We developed the Inspire Self Report Scale (ISRS), which measures the current magnitude of well-being, mood symptoms, psychosis, negative symptoms and cognition using 10 questions on a Likert or Visual analogue scale (VAS). The main aim of this report was to investigate the correlation and concordance between patient self-report and clinician ratings on the ISRS during a clinical encounter. When ratings were discordant, we sought to identify whether the participant's or psychiatrist's rating was more accurate. The results indicated a moderately strong statistically significant correlation between participant and clinician ratings. There was a moderate concordance between participant and clinician ratings on the ISRS. When the results were discordant, the participant ratings were assessed to be more accurate than the clinician rating over 70% of the time. The ISRS has distinct utility compared to existing scales due to the measurement of present symptom severity, capturing multiple clinical domains, and time efficiency and ease of use. Thus, it may be useful in clinical and research settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Performance of endurance exercise is associated with a broad range of cognitive benefits, with notable improvements shown across a wide variety of populations including healthy populations as well as those with impaired cognition. By examining the effects of exercise in general populations, as well in populations where cognitive deficits are pronounced, and critical to self-care, we can learn more about using exercise to ameliorate cognitive issues and apply that knowledge to other patient populations, such as those eligible for cardiac rehabilitation (CR). Cognitive challenges are a concern within CR, as management of a chronic disease is cognitively taxing, and, as expected, deficits in cognition predict worse outcomes, including lower attendance at CR. Some subsets of patients within CR may be particularly at high risk for cognitive challenges including those with heart failure with low ejection fraction, recent coronary bypass surgery, multiple chronic conditions, and patients of lower socioeconomic status. Attendance at CR is associated with cognitive gains, likely through the progressive exercise component, with larger amounts of exercise over longer periods having greater benefits. Programs should identify at-risk patients, who could gain the most from completing CR, and provide additional support to keep those patients engaged. While engaged in CR, patients should be encouraged to exercise, at least at moderate intensity, and transitioned to a long-term exercise regimen. Overall, CR programs are well-positioned to support these patients and make significant contributions to their long-term well-being., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Structural variation in the complement 4 gene (C4) confers genetic risk for schizophrenia. The variation includes numbers of the increased C4A copy number, which predicts increased C4A mRNA expression. C4-anaphylatoxin (C4-ana) is a C4 protein fragment released upon C4 protein activation that has the potential to change the blood-brain barrier (BBB). We hypothesized that elevated plasma levels of C4-ana occur in individuals with schizophrenia (iSCZ). Blood was collected from 15 iSCZ with illness duration < 5 years and from 14 healthy controls (HC). Plasma C4-ana was measured by radioimmunoassay. Other complement activation products C3-ana, C5-ana, and terminal complement complex (TCC) were also measured. Digital-droplet PCR was used to determine C4 gene structural variation state. Recombinant C4-ana was added to primary brain endothelial cells (BEC) and permeability was measured in vitro. C4-ana concentration was elevated in plasma from iSCZ compared to HC (mean = 654 ± 16 ng/mL, 557 ± 94 respectively, p = 0.01). The patients also carried more copies of the C4AL gene and demonstrated a positive correlation between plasma C4-ana concentrations and C4A gene copy number. Furthermore, C4-ana increased the permeability of a monolayer of BEC in vitro. Our findings are consistent with a specific role for C4A protein in schizophrenia and raise the possibility that its activation product, C4-ana, increases BBB permeability. Exploratory analyses suggest the novel hypothesis that the relationship between C4-ana levels and C4A gene copy number could also be altered in iSCZ, suggesting an interaction with unknown genetic and/or environmental risk factors., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Schizophrenia is a debilitating psychiatric illness that remains poorly understood. While the bulk of symptomatology has classically been associated with disrupted brain functioning, accumulating evidence demonstrates that schizophrenia is characterized by systemic inflammation and disturbances in metabolism. Indeed, metabolic disease is a major determinant of the high mortality rate associated with schizophrenia. Antipsychotic drugs (APDs) have revolutionized management of psychosis, making it possible to rapidly control psychotic symptoms. This has ultimately reduced relapse rates of psychotic episodes and improved overall quality of life for people with schizophrenia. However, long-term APD use has also been associated with significant metabolic disturbances including weight gain, dysglycemia, and worsening of the underlying cardiometabolic disease intrinsic to schizophrenia. While the mechanisms for these intrinsic and medication-induced metabolic effects remain unclear, inflammation appears to play a key role. Here, we review the evidence for roles of inflammatory mechanisms in the disease features of schizophrenia and how these mechanisms interact with APD treatment. We also discuss the effects of common inflammatory mediators on metabolic disease. Then, we review the evidence of intrinsic and APD-mediated effects on systemic inflammation in schizophrenia. Finally, we speculate about possible treatment strategies. Developing an improved understanding of inflammatory processes in schizophrenia may therefore introduce new, more effective options for treating not only schizophrenia but also primary metabolic disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5-10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk., Methods: Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO 2 max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12 weeks of interventions., Discussion: It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens., Trial Registration: Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

Competing Interests: The authors report no financial relationships with commercial interests.

Individuals with schizophrenia (SZ) display cognitive deficits that have been identified as major determinants of poor functioning and disability, representing a serious public health concern and an important target for interventions. At present, available treatments offer only minimal to moderate benefits to ameliorate cognitive deficits. Thus, there remains an urgent need to identify novel interventions to improve cognition in people with SZ. Emerging evidence from animal and basic human research suggests aerobic exercise training (AE) has beneficial effects on cognition. Preliminary findings suggest that AE is efficacious in improving cognitive functioning in SZ, however the extant studies have been limited by small samples, a dearth of information on biologically-relevant covariates, and limited information on impact on daily functioning. Additionally, while AE-related cognitive benefits have been linked to Brain-Derived Neurotrophic Factor (BDNF) upregulation, this putative mechanism needs confirmation. The present report describes a study protocol designed to address these limitations-we review and summarize the current literature on treatment of cognitive deficits in SZ, state the rationale for employing AE to target these deficits, and describe the current protocol-a multi-site, single-blind, randomized clinical trial aiming to recruit 200 community-dwelling individuals with SZ. Participants are randomized to one of two 12-week interventions: AE using active-play video games ( i.e. , Xbox Kinect) and traditional cardiovascular exercise equipment or a stretching-and-toning (ST) control intervention. Participants undergo assessments of aerobic fitness, cognition, and daily functioning, as well as BDNF and other biomarkers of cognitive change, at baseline and after 6-and 12-weeks., Competing Interests: CONFLICTS OF INTEREST The authors declares that they have no conflicts of interest associated with this project.

New methods in genetics research, such as linkage disequilibrium score regression (LDSR), quantify overlap in the common genetic variants that influence diverse phenotypes. It is becoming clear that genetic effects often cut across traditional diagnostic boundaries. Here, we introduce genetic correlation analysis (using LDSR) to a nongeneticist audience and report transdisciplinary discoveries about schizophrenia. This analytical study design used publically available genome wide association study (GWAS) data from approximately 1.5 million individuals. Genetic correlations between schizophrenia and 172 medical, psychiatric, personality, and metabolomic phenotypes were calculated using LDSR, as implemented in LDHub in order to identify known and new genetic correlations. Consistent with previous research, the strongest genetic correlation was with bipolar disorder. Positive genetic correlations were also found between schizophrenia and all other psychiatric phenotypes tested, the personality traits of neuroticism and openness to experience, and cigarette smoking. Novel results were found with medical phenotypes: schizophrenia was negatively genetically correlated with serum citrate, positively correlated with inflammatory bowel disease, and negatively correlated with BMI, hip, and waist circumference. The serum citrate finding provides a potential link between rare cases of schizophrenia (strongly influenced by 22q11.2 deletions) and more typical cases of schizophrenia (with polygenic influences). Overall, these genetic correlation findings match epidemiological findings, suggesting that common variant genetic effects are part of the scaffolding underlying phenotypic comorbidity. The "genetic correlation profile" is a succinct report of shared genetic effects, is easily updated with new information (eg, from future GWAS), and should become part of basic disease knowledge about schizophrenia.

Background: The average age of onset of psychosis coincides with the age of college enrollment. Little is known about the impact of educational engagement on DUP in a college-aged population., Aims: To determine DUP, and the impact of educational engagement, for college-aged participants of the RAISE study (n = 404)., Method: We conducted secondary data analyses on the publicly available RAISE dataset. Subsamples were analyzed to determine the impact of age and educational engagement on DUP., Results: DUP was significantly shorter (p < 0.02) for participants who were college-aged (18-22 years, n = 44) and engaged in post-secondary education (median = 12 weeks, mean = 29 weeks) compared with participants who were college-aged and not engaged in higher education (n = 92, median = 29 weeks, mean = 44 weeks)., Conclusions: Educational engagement appears to be associated with a shorter DUP. This may be partially explained by the presence of on-site wellness centers in college settings. However, even among young people who engaged in post-secondary education DUP was still at, or beyond, the upper limit of WHO recommendations in this group. Future research exploring how colleges could improve their capacity to detect and refer at risk students for treatment at an earlier stage is recommended.

Purpose/background: The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis., Methods/procedures: We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine., Findings/results: People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis., Implications/conclusions: We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.

For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs) which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

Objective: Active-play video games have been used to enhance aerobic fitness in various clinical populations, but their use among individuals with schizophrenia has been limited., Methods: Feasibility, acceptability, safety, and adherence data were obtained for use of aerobic exercise (AE) equipment by 16 individuals with schizophrenia during a 12-week AE program consisting of three one-hour exercise sessions per week. Equipment included exercise video games for Xbox 360 with Kinect motion sensing devices and traditional exercise equipment., Results: Most participants (81%) completed the training, attending an average of 79% of sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on any other type of equipment. When using Xbox, participants played 2.24±1.59 games per session and reported high acceptability and enjoyment ratings, with no adverse events., Conclusions: Measures of feasibility, acceptability, adherence, and safety support the integration of active-play video games into AE training for people with schizophrenia.

Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; "treatment as usual"; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO2 peak ml/kg/min), neurocognition (MATRICS Consensus Cognitive Battery), and serum-BDNF before and after and 12-week period. Twenty-six participants (79%) completed the study. At follow-up, the AE participants improved their AF by 18.0% vs a -0.5% decline in the TAU group (P = .002) and improved their neurocognition by 15.1% vs -2.0% decline in the TAU group (P = .031). Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4% and 14.6% of the neurocognitive improvement variance, respectively. The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population. Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe, nonstigmatizing, and side-effect-free intervention., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-mass index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hierarchical regression analysis indicated that AF accounted for 22% of the neurocognition variance. Furthermore, AF was significantly correlated with overall daily-functioning (r=0.46). In contrast, BMI displayed significant inverse correlations with neurocognition, but no associations to daily-functioning. AF was significantly correlated physical activity. The authors discuss the potential use of AF-enhancing interventions to improve neurocognitive and daily-functioning in schizophrenia, along with putative neurobiological mechanisms underlying these links, including Brain-Derived Neurotrophic Factor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Previous research has shown that healthy individuals who fail to differentiate among emotional states (i.e., those with low emotional granularity; EG) have poorer social functioning (SF) than those with high EG. It is unknown, however, whether these associations extend to clinical disorders characterized by impaired SF, such as schizophrenia. In the present study, we compared SF and EG in individuals with schizophrenia and healthy controls, and then, within the schizophrenia group, we examined the links between EG and SF. Employing an Experience Sampling Method approach, 77 individuals with schizophrenia and 27 healthy controls rated their momentary emotions (sadness, anxiety, anger, and happiness) up to 10 times/day over a two-day period using mobile electronic devices. For each participant, we then calculated the within-subject average correlations among the momentary emotion ratings, producing two EG indices - EGIall for all emotions and EGIneg for negative ones. A subsample of participants with schizophrenia also completed self-report, interview, and ability-based measures of SF. Compared to healthy controls, individuals with schizophrenia displayed significantly poorer SF and lower EGIall, but comparable EGIneg. Within the schizophrenia group, hierarchical multiple regression analyses indicated that EGIall, but not EGIneg, significantly predicted social dysfunction after controlling for emotional awareness, symptoms, and emotional intensity and variability. Our findings indicate that individuals with schizophrenia have a relatively intact ability to differentiate among negative emotions in everyday life. However, they experience significant difficulties differentiating between positive and negative emotions, and this may contribute to their social difficulties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway., (2010 Elsevier Ltd. All rights reserved.)

Many factors have been associated with the development of schizophrenia, yet few studies have looked at these same factors in individuals considered at risk for schizophrenia, but who have not yet reached diagnostic threshold. The rate of obstetrical complications was assessed as part of a comprehensive battery in subjects at risk (N=52), or in the first episode of schizophrenia (N=18), and in normal comparison subjects (N=43). The rate of obstetrical complications was increased in the at risk (46%) and first episode (39%) samples compared to the normal comparison (19%) group, however, follow-up analyses were only significant between the at risk and normal comparison subjects. Obstetrical complications may be an important risk factor in identifying vulnerable subjects and ultimately may, along with other risk factors, be part of an algorithm for determining likelihood of developing schizophrenia.

Deficits in social functioning are potential risk factors for schizophrenia. Social functioning was assessed in 55 individuals "at risk" for schizophrenia, 16 first episode patients with schizophrenia and 45 normal comparison subjects. The Social Adjustment Inventory for Children and Adolescents (SAICA) was administered to adolescents <18 and the Social Adjustment Scale (SAS-SR) to young adults >17. The at risk and first episode groups significantly differed from the normal subjects on measures of social functioning in the domains of peer, family, work and school relationships. Individuals at risk for schizophrenia have significant functional deficits which may be potential indicators of increased vulnerability for psychosis.

Background: Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity for abuse and is frequently used for off-label indications. The objective of this study was to systematically review the available evidence supporting the clinical use of modafinil., Data Sources: The search term modafinil OR Provigil was searched on PubMed. Selected articles were mined for further potential sources of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil., Data Synthesis: There have been 33 double-blind, placebo-controlled trials of modafinil. Additionally, numerous smaller studies have been performed, and case reports of modafinil's use abound in the literature., Conclusions: Modafinil is a promising drug with a large potential for many uses in psychiatry and general medicine. Treating daytime sleepiness is complex, and determining the precise nature of the sleep disorder is vital. Modafinil may be an effective agent in many sleep conditions. To date, the strongest evidence among off-label uses exists for the use of modafinil in attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal and as an adjunct to antidepressants for depression.

Background: The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels., Method: The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses., Results: Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations., Conclusion: It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.