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In view of a reported association between schizophrenia and the 5-HT2 receptor gene locus, as well as an association with treatment refractoriness at this locus, a case-control association study was conducted using a biallelic polymorphism. The distribution of the polymorphism was investigated among patients with schizophrenia (DSM-III-R, n = 174) and unaffected controls (n = 239). No significant differences in genotype distributions or allele frequencies were noted between the two groups. In support of the earlier report, a significant excess of individuals homozygous for allele C2 was noted among patients who responded unsatisfactorily to antipsychotic medication in comparison with the controls (odds ratio 1.78; 95% confidence intervals 1.06, 2.97). However, this difference was not significant following multivariate analysis. This study does not support an association between the 5-HT2 receptor gene locus and schizophrenia or subgroups based on treatment response.

Serum interleukin-6 (IL-6) was measured in picograms/ml (pg/ml) using an immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%) non-dextral individuals had serum IL-6 levels above the lower limit of the assay sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There were no significant correlations between previously determined mitogen stimulated interleukin-2 production and autoantibodies in a subset of the same individuals. While this data does not provide casual information, it adds to the evidence of the asymmetric regulation of immune functions by the cerebral hemispheres.

Using an enzyme immunoassay (ELISA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.

For patients who gain a troublesome amount of weight on antipsychotics, switching to a less obesogenic agent is an option. Aripiprazole appears to cause less weight gain than many other antipsychotics. We report on changes in weight, and other risk factors for heart disease, in thirty-three schizophrenia patients who agreed to switch from other antipsychotics to aripiprazole in an open, flexible-dose, eight-week trial. All patients were successfully switched. There were no significant changes in PANSS symptom scores or in CGI. Weight (Wt), waist circumference (WC), and low-density lipoprotein (LDL) decreased significantly in the group as a whole. In patients switched from olanzapine to aripiprazole, Wt, WC, LDL, fasting glucose, and triglycerides were significantly decreased as compared to baseline. Substantial decreases in several risk factors were also seen in patients switched from quetiapine, but these changes did not reach statistical significance.

This project evaluated the attitudes of psychiatric patients towards receiving either olanzapine or the first-generation antipsychotic agents. Newly admitted patients to a state psychiatric hospital who were either prescribed olanzapine (n=35) or other first-generation antipsychotic agents (n=34) were compared on measure of their personal attitudes toward receiving medicines using the Drug Attitude Inventory (DAI). Subjects were evaluated prior to receiving olanzapine and 8 weeks later unless they were discharged or discontinued sooner. The olanzapine-treated group recorded significantly greater improvements on their positive attitude scores toward taking the medicine, and reduced negative attitude scores relative to the comparator group. These results remained statistically significant even after correction of baseline differences between the two groups for the positive attitudes and a statistical trend persisted for negative attitude scores too. During the subsequent 30 month follow-up, significantly fewer of the olanzapine treated subjects (5, 14.3%) were readmitted to the hospital compared with 13 (38.2%) of the comparator group. These data suggest switching patients to olanzapine may improve their attitudes towards taking medicines at least in the short-term. These preliminary data need affirmation or refutation in a controlled random-assignment longer-term clinical trial where specific measures of adherence are evaluated, and where the comparators are the other second generation antipsychotic agents.

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.

Background Low cardiorespiratory fitness is a prominent behavioral risk factor for cardiovascular disease (CVD) morbidity and mortality, as cardiorespiratory fitness is strongly associated with CVD outcomes. High rates of CVD have been observed in the schizophrenia population, translating into a markedly reduced life expectancy as compared to healthy controls. Surprisingly however, while cardiorespiratory fitness is an eminent indicator for overall cardiovascular health as well as eminently modifiable risk factor for CVD, no studies have systematically assessed cardiorespiratory fitness in schizophrenia. Methods Community-dwelling schizophrenia patients underwent graded-exercise tests, to ascertain maximal oxygen uptake (Max Vo2), considered to be the gold standard for the evaluation of cardiorespiratory fitness and physical functional capacity. The modified Bruce protocol was used to ascertain cardiorespiratory fitness and physical functional capacity; data was normalized and compared to population standards derived from the ACLS (Aerobics Center Longitudinal Study) and the National Health and Nutrition Examination Surveys (NHANES), Cycles III and IV. Results Data for n = 117 participants (41% male, 46% white) was analyzed. Mean age (y) was 43.2 ± 9.9, and mean BMI was 37.2 ± 7.3. Peak HR attained during exercise was 145.6 ± 19.6, after 8.05 ± 3.6 min, achieving 111.2 ± 44.2 W. Max Vo2 was 1.72 ± 6.6 l/min, MaxVCo2 1.85 ± 7.2 l/min, and minute ventilation (VE) was 55.6 ± 21.9 ml/s. PANSS Positive subscores (13.3 ± 4.4; r = −0.21, p = 0.024) were inversely correlated with Max Vo2 ml− 1min− 1kg− 1. Neither PANSS Total (56.3 ± 12.3; r = −0.105, p = 0.72), PANSS Negative (14 ± 5.1; r = −0.52, p = 0.57) nor PANSS General Psychopathology (28.4 ± 7.4; r = −0.28, p = 0.76) scores were correlated with Max Vo2 ml− 1min− 1kg− 1. Peak heart rate and duration of exercise were not correlated with PANSS scores. Compared to healthy controls derived from the ACLS and NHANES, respectively, 115 participants achieved ‘low levels’ of fitness only, as well as highly significantly reduced Max Vo2, across all age groups. Conclusion The test was generally well received and tolerated by those who elected to participate; and adherence to the protocol was good. Among participants with schizophrenia, most of whom were obese, and across all age groups, cardiorespiratory fitness was exceedingly poor. Only two participants in our entire sample fit the categorization of ‘moderate fitness level’; that is, a fitness level at or above the 20th percentile of ACLS-derived population comparisons. Conversely, this left 98.3% of participants with schizophrenia below population standards. Low cardiorespiratory fitness emerges as an eminent modifiable risk factor for CVD mortality and morbidity in schizophrenia complicated by obesity.

Sera from schizophrenic patients (n = 186) and healthy control subjects (n = 346) were tested for the presence of seven common autoantibodies by standard immunological methods. The association between handedness and autoantibodies was tested in a multiway contingency table using a log-linear model. For men, but not women, nondextrals (patients and controls) were twice as likely to test positive for autoantibodies than dextrals (p = 0.0002). Although more women (33%) than men (24%) tested positive for autoantibodies, handedness was not a distinguishing factor among women. These data suggest that sinistrality and gender are associated with autoantibodies in a subgroup of schizophrenic patients and healthy control subjects.

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never- medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.

Over a 5-year period, 77 patients in their first episode of psychosis were recruited into a study of autoimmune factors in the pathogenesis of schizophrenia. In this article their demographic and clinical characteristics are compared to those of chronic patients recruited into the same study as well as to the entire outpatient population of a schizophrenia clinic in a Pittsburgh community mental health center. There were no significant demographic differences between the first-episode patients and either of the other groups of schizophrenic patients. There was a significantly higher proportion of black subjects in the clinic population compared to the catchment area from which they were drawn. Clinically, first-episode patients differed from chronic patients in having fewer negative symptoms and more of certain positive symptoms. Age of onset was not significantly different in male and female first-episode cases, although there was a trend of females to be slightly older. We conclude that if diagnosis includes followup and reassessment, findings from research cohorts such as ours can be generalized to populations of outpatient schizophrenic subjects volunteering for treatment.

Objectives: This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT). Methods: A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100–400 mg/day) or placebo. Patients who had achieved a ≥20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values. Results: Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo-treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to ≥10% from baseline), and no significant differences between the treatments on worsening of total Montgomery–Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate]. Conclusions: This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI.

The combination of clozapine and other potentially leukopenic drugs may pose a greater risk for neutropenia. However, neutropenia may not always be due to clozapine. When adding potentially leukopenic drugs, clinicians should look for possible alternatives especially as clozapine is often a drug used as the last resort in treatment refractory schizophrenia.

A case-control association study was conducted among patients with schizophrenia (DSM-III-R, n = 141) and unaffected controls (n = 177) of Caucasain and African-American ethnicity. No significant differences in the distribution of a dinucleotide repeat polymorphism in the neurotrophin-3 (NT-3) gene were noted between the two groups. This study does not support an association between schizophrenia and the NT-3 gene locus in a United States cohort.

Objective : To examine the associations between sociodemographic variables, body weight and quality of life in schizophrenic outpatients. Methods : Assessments included an interview to obtain sociodemographic data, administration of a Quality of Life questionnaire (the MOS SF-36) and measurement of height and weight. Body mass index was calculated (kg/m 2 ). SF-36 subscores were examined for statistical differences based on BMI categories: healthy weight (BMI≤24.9), overweight (BMI 25–29.9) and obese (BMI≥30). Correlations with sociodemographic variables were also examined. Results : Body weight was inversely correlated (level p ≤0.005) to the SF-36 items: physical functioning (PF, −0.452), role limitations due to physical functioning (−0.279), role limitations due to emotional functioning (−0.256), vitality (−0.200), general health (GH, −0.367) and physical component score (PCS, −0.400). Mental component score (MCS) was not significantly correlated to body weight. When comparing quality of life across BMI categories, obese subjects had worse physical functioning ( p ≤0.0005) and general health ( p ≤0.005), reported more role limitations due to emotional functioning ( p ≤0.05) and a lower physical component score ( p ≤0.005). Mental component score was not significantly influenced by BMI. Conclusions : Quality of life in schizophrenic patients is related to body weight. The burden of obesity is primarily experienced as a physical problem.

Objective: To evaluate the efficacy and safety of administering quetiapine once vs twice daily. Method: Utilizing a double-blind design, 21 hospitalized adult men or women with DSM-IV schizophrenia or schizoaffective disorder, who had received unchanged doses (for 2 weeks) of either 400 or 600 mg daily of quetiapine administered in 2 doses, were randomly assigned to once- or twice-daily administration for 4 weeks and then crossed over to the opposite dosing regimen for an additional 4 weeks. Standard psychopathology and safety measures were used in the study. Results: Nearly 70% (15/21) of the subjects met the a priori efficacy responder criteria with no statistical differences in response between those assigned to once- or twice-daily quetiapine administration. Statistical analyses confirmed that most subjects maintained efficacy during the switch to once- or twice-daily administration with quetiapine. A minority (15%) did experience worsening of symptoms or orthostatic hypotension during the crossover. Quetiapine was generally well tolerated at either twice- or once-daily administration. Conclusions: These pilot data suggest that it is clinically feasible to switch most quetiapine-treated subjects receiving a therapeutic twice-daily dosing schedule to a once-daily regimen. A minority may experience worsening of symptoms or orthostatic hypotension during the switch. This strategy of administering quetiapine entirely at bedtime may promote improved adherence to treatment.

Subsets of psychiatric patients gain excess body weight while receiving mood-stabilizing agents such as lithium carbonate or valproate sodium. Patients who gain excess weight may discontinue therapy, with severe consequences. Among the newer anticonvulsant agents, topiramate is a candidate agent for bipolar disorder and is associated with weight loss when used as adjunctive treatment.This open-label, nonrandomized, chart-review study assessed changes in body weight and body mass index (BMI) in patients receiving topiramate, lithium, or valproate.Data were extracted from the medical charts of patients admitted in 1999 and 2000 to a state psychiatric hospital with either schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric diagnoses who were prescribed valproate, lithium, or topiramate and were reviewed for changes in body weight and BMI. The use of concomitant psychotropic medicines was recorded (eg, antipsychotic agents, antidepressant agents, other mood stabilizers such as gabapentin or carbamazepine). Continuous variables were analyzed using a factorial analysis of variance and the Student t test. Contingency statistics were used to analyze categorical variables.A total of 214 patients were included in the chart review (123 men, 91 women; mean age, 39.4 years). Significantly more women than men received topiramate (P = 0.004). Patients receiving either lithium or valproate gained a mean (SD) of 6.3 (9.0) kg and 6.4 (9.0) kg, respectively, whereas patients receiving topiramate lost a mean 1.2 (6.3) kg (F = 11.54, df = 2,198; P0.001). Lithium- or valproate-treated patients experienced an increase in BMI (mean, 2.1 [3.0] for both groups), whereas topiramate-treated patients experienced a reduction in BMI (mean, -0.5 [2.4]); this result was statistically significant (F = 11.40, df = 2,198; P0.001). Finally, lithium- or valproate-treated patients gained8% of their baseline body weight (8.2% [11.5%] for lithium-treated patients and 8.5% [11.9%] for valproate-treated patients), whereas topiramate-treated patients lost 0.7% (7.2%) of their body weight (F = 9.93, df= 2,198; P0.001).Controlled studies for the efficacy of topiramate therapy in various psychiatric conditions are awaited. These data indicate that patients receiving topiramate experience body weight loss and a reduction in BMI. This advantage of topiramate may promote long-term adherence to treatment among psychiatric patients and possibly decrease the medical risks associated with obesity.

Background: The reliability of telephone interviews for rating 25 selected individual items of the Diagnostic Interview for Genetic Studies (DIGS) was assessed among persons with remitted bipolar disorder I (BPD I, n=20). Methods: The Diagnostic Interview for Genetic Studies (DIGS) was administered directly (with two raters present) and by telephone in random order to 20 adults with bipolar disorder I. Results: Telephone interviews achieved reliability comparable to direct interviews for 16 items (64%), but were considered unsatisfactory for seven others (28%). Two other items, which evaluated the overlap between substance abuse and mood disorder, were considered unreliable for both methods of interview. Limitations: The presence of two interviewers for the in-person interview may have led to over-estimation of in-person reliability. Investigator bias in favor of phone interviews and a relatively small sample may have confounded the results. Conclusions: Telephone interviews may be used to evaluate individuals with BPD I in remission, provided the limitations of this method are recognized. They have limited reliability for dissecting overlap between mood abnormalities and psychotic phenomena or substance abuse.

Background . There is evidence that, even during remission, schizophrenia (SZ) patients are especially vulnerable to de-compensate under stress, and that they tend to have a high baseline serum cortisol levels. This study was undertaken to determine whether raising serum cortisol by the infusion of hydrocortisone, in the absence of additional psychological stress, would result in different cerebral activity changes in schizophrenic patients compared to normal controls (CON). We were especially interested in cerebral activity in regions such as the medial temporal lobe and hippocampus, since structural abnormalities in these brain regions were frequent in association with schizophrenia. Methods . Serum cortisol levels were raised, by infusing hydrocortisone, in 8 pairwise-matched SZ patients and 8 CONs. The associated regional cerebral activity changes were analyzed using statistical parametric mapping (SPM). Results . There was increased regional cerebral activity in response to elevated cortisol in the left hippocampal region in the SZ group, while the controls showed evidence of decreased regional cerebral activity in the same anatomical location. For the rest of the brain regions, cerebral activity increases and decreases, in response to raised serum cortisol, in the SZ followed the same regional pattern as in the control group, but with a smaller overall magnitude of change. The blunted response in SZ was most marked in the regions that showed greatest regional cerebral activity changes in normal subjects. Conclusion . Patients with schizophrenia showed an abnormal increased regional cerebral activity response to cortisol infusion in the left hippocampal region, and similar but attenuated regional cerebral activity response in other regions, when compared to matched controls.

Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine (n = 35) or another first-line antipsychotic agent (n = 34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and mood-stabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.

This is the first report of an individual with several congenital abnormalities, including those suggestive of Treacher Collins syndrome, and an atypical schizophrenic illness. Cytogenetic studies have failed to detect any recognizable chromosomal abnormality.

BACKGROUND Patients with depressive disorders smoke tobacco more often than the population at large and find quitting more difficult. Furthermore, when they quit smoking, they are more likely to suffer a relapse of depression. We evaluated the addition of bupropion sustained release (SR) for smoking cessation among patients with a history of depressive disorders being maintained in a euthymic state with selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD Twenty-five adults with DSM-IV major depressive disorder or depressive disorder NOS currently receiving SSRI maintenance treatment and smoking > or = 15 cigarettes per day participated in the 9-week study. Bupropion SR, 150 mg/day, was added to SSRI treatment and increased to 300 mg/day. Subjects were counseled on smoking cessation measures and chose a target quit date 2 or 4 weeks after the initiation of bupropion SR. Self-reported smoking status, expired carbon monoxide (CO) measurements, Hamilton Rating Scales for Depression and Anxiety scores, and weight were measured at each visit. Subjects were abstinent if they reported not smoking during the prior 7 days, confirmed with an expired-air CO value of < or = 10 ppm. RESULTS Eight (32%) of 25 subjects were abstinent after 9 weeks. At 3-month follow-up, 3 subjects remained abstinent, 3 relapsed, and 2 were lost to follow-up. Eleven subjects (44%) were nonresponders, and 6 (24%) dropped out prior to 3 weeks of treatment due to side effects (N = 3) or were lost to follow-up (N = 3). Mean weight gain was approximately 0.5 lb (0.2 kg) for those completing 9 weeks of bupropion SR treatment. During the 9-week study and the 3-month follow-up, there was no evidence of emergent depression in any subject. Four subjects (16%) spontaneously reported an improvement in SSRI-associated sexual dysfunction. CONCLUSION These open data suggest modest effectiveness for and the safety of bupropion SR as a smoking cessation agent in individuals with depression maintained on treatment with SSRIs. Minimal weight gain, lack of emergent depressive episodes, and improvement of SSRI-associated sexual dysfunction are added advantages.

Patients with schizophrenia perform worse than healthy controls on many neuro-psychological tests. However, previous studies of neuro-cognitive function have mostly been carried out on acutely ill or institutionalized patients. The objective of this study was to generate norms for performance of partially remitted community-dwelling patients with schizophrenia on the Mini-Mental State Examination (MMSE). Partially remitted outpatients attending a depot antipsychotic clinic or a clozapine clinic (n=272) were tested using the MMSE. Demographic and clinical characteristics associated with MMSE performance, as well as the performance of specific items, were examined. MMSE score was significantly associated with educational status and race. Patients in our sample performed approximately 2–3 points below the population norms at all ages, but the mean score for the group was not in the impaired range. There was no apparent widening of this gap with advancing age. Patients who did poorly most frequently had difficulty with memory, attention and construction tasks. The MMSE is easy to administer to outpatients with schizophrenia and most patients score in the un-impaired range. The MMSE may be used to identify a subgroup of patients who score in the impaired range, for further investigations.

The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross-referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin-2, and increased serum concentrations of interleukin-2 receptor and interleukin-6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug-naive patients.

SynopsisSerum concentrations of anti-hippocampal antibodies andin vitroproduction of the lymphokine interleukin-2 (IL-2) in response to phytohaemagglutinin (PHA) stimulation were determined using an enzyme immunoassay in 49 schizophrenic patients and 41 healthy controls. Decrease in IL-2 production, a finding frequently associated with many autoimmune diseases, was associated with an elevation in anti-hippocampal antibody optical density (AHA-OD) in schizophrenic patients. Although some control subjects had elevated antibody levels, this elevation was not associated with decreased IL-2 production. Low IL-2 production is well known to be a state marker associated with active autoimmune disease. We suggest that production of hippocampal antibody is a trait marker of vulnerability to autoimmune diseases. Thus, our finding of low IL-2 production in patients with high concentrations of hippocampal antibody is compatible with the possibility that such patients have an ongoing autoimmune process.

Using a laterality questionnaire, 138 normal healthy individuals were classified as right-sided and 25 as non-right side. Interleukin-2 (IL-2) was generated from whole blood obtained from these subjects using mitogen (PHA) stimulation. IL-2 was quantitated in picograms/ml using an enzyme immunoassay (ELISA). Additionally, sera from these subjects were tested for 7 autoantibodies by standard serological methods. As compared to right sided subjects, non-right sided individuals had significantly lower IL-2 production. Non-right sided individuals with autoantibodies had significantly lower IL-2 production than right sided subjects with or without autoantibodies, but did not differ significantly from their non-right sided counterparts without autoantibodies. These data support the increasing evidence for the differential and lateralized regulation of immune functions by the right and left cerebral regions.

Background In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. Methods In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. Results The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; p < 0.0001) and in PANSS positive (-3.0; p < 0.0001), negative (-0.9; p = 0.171) and anxiety/depression (-1.4; p = 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal. Conclusion When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated. Trial registration ClinicalTrials.gov NCT00378183

In a survey of nutritional habits of 146 community dwelling patients with schizophrenia, we examined the prevalence, severity and duration of smoking and its association with caffeine intake, caloric intake, socio-demographic factors and body weight. Caffeine and caloric intake were calculated from a 24-hour diet recall interview using commercially available software and Body Mass Index (BMI) was calculated from measurements of weight and height as per guidelines. Information regarding the severity and duration of smoking was obtained by using a smoking history questionnaire. The sample consisted of 78 male (42 Caucasian, 36 African-American (A-A)) and 68 female patients (37 Caucasian, 31 A-A). There were no differences between the proportion of smokers among male and female patients. However, in this sample, the prevalence of smokers among A-A patients (49 of 67, 73%) was significantly higher than the prevalence of smokers among Caucasian patients (38 of 79, 48%; P2 = 9.4, p = 0.002). Even though the representation of smokers among A-A patients was high, Caucasian patients smoked significantly more number of cigarettes per day as compared to A-A patients (Mean + SD number of cigarettes smoked daily, Caucasian patients (n=38): 31.1 + 16.6, A-A patients (n=49): 18.3 + 9.0, t = 4.6, p

Background: Decreased interleukin-2 (IL-2) production is characteristic of active autoimmune diseases and has previously been reported in patients with schizophrenia. We attempted to replicate this finding in never-medicated schizophrenic patients and examine the possible correlation between IL-2 production and clinical variables. Methods: The production of IL-2 was measured in equal numbers (N=33) ofDSM-III-R—diagnosed schizophrenic patients and controls who were matched for age, race, and gender. Patients were also assessed for positive, negative, and depressive symptoms. Results: The production of IL-2 was significantly lower in patients than in controls. There was a significant positive correlation between IL-2 production and age at onset, and significant negative correlation between IL-2 production and negative symptom scores. In multivariate analyses, the predictive power was stronger for age at onset than for negative symptoms. Positive or depressive symptoms were unrelated to IL-2 production. Conclusions: Our finding of low IL-2 production in neuroleptic-naive schizophrenic patients confirms that this finding is not confounded by medications. The correlation of low IL-2 production with younger age at onset suggests that this may be a marker for a subtype of the illness or for severity.

Weekly clinical assessments were performed for severity of psychopathology using the BPRS. Weekly measurements of mitogen-stimulated interieukin-2 (!!.,-2) production, and serum levels of igG and IgM to hippocampal antigen were carried out using ELISA techniques. A mutual clinical and laboratory blindness was maintained during the course of the study. The patient had three psychotic relapses during the course of the study. There was a strong inverse correlation between IL-2 production and psychotic symptomatology during these periods. There were also significant differences between the mean IL-2 production (pg/ml) during periods of psychotic episodes (688.2 + 303.7) and inter-episode periods of remission (462.6 + 185.5). The conditional probability of being in relapse was inversely proportional to 11.,-2 production levelf at the time. Thus, in this patient previously reported correlations between decreased IL-2 pro. duction and psychosis were ¢~onfirmed in a within subject design.