The Effect of Ibuprofen on Cytokine Production by Mononuclear Cells from Schizophrenic Patients.

The existence of a restrained inflammatory state in schizophrenic individuals posed the question whether anti-inflammatory drugs may exert antipsychotic effects. Therefore, the effect of ibuprofen (IB) on cytokine production by human peripheral blood mononuclear cells (PBMC) from schizophrenic patients was examined and compared to that of healthy subjects. PBMC from 25 schizophrenic patients and 24 healthy volunteers were incubated for 24 h with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IB. The levels of IL-1ß, IL-6, TNF-α, IL-10 and IL-1ra in the supernatants were tested applying ELISA kits. The secretion of TNF-α by cells from schizophrenic patients was significantly lower compared with controls. IB caused stimulation of TNF-α and IL-6 production by cells of the two groups and enhanced IL-1ß secretion by cells from schizophrenic patients. IB inhibited IL-1ra and IL-10 generation by cells from the two groups. Without IB, IL-1ra secretion was negatively correlated with the disease severity, while 200 µg/ml of IB positively correlated with the PANSS total score. IL-10 production was positively correlated with the PANSS positive subscale score both in the absence or presence of IB. The findings suggest that the effect of IB on the production of inflammatory cytokines may benefit the health of schizophrenic patients.

Difference in inflammatory cytokine production by mononuclear cells from obese and non-obese schizophrenic patients.

OBJECTIVE: Schizophrenic patients have an increased risk for obesity compared with the general population. Evidence suggests the existence of an inflammatory process in the etiology of both obesity and schizophrenia. Our study compares in vitro secretion of inflammatory cytokines by peripheral blood mononuclear cells (PBMC) obtained from obese and non-obese schizophrenic patients. METHOD: Mononuclear cells were isolated from 20 obese (BMI >27) and 20 non-obese (BMI <24) schizophrenic in-patients. The levels of TNF-α, IL-1ß, IL-6, IL-1ra, IL-10 or IL-2 and IFN-γ in the supernatants of stimulated PBMC, as well as leptin and adiponectin serum values were evaluated. RESULTS: Peripheral blood mononuclear cells from patients in the obese group showed a significantly increased TNF-α and IL-1ß production, whereas the release of IL-1ra was decreased as compared with the non-obese group. In the obese group, the serum concentration of leptin was significantly higher and that of adiponectin was significantly lower. The results of the remaining cytokines did not differ between the two groups. CONCLUSION: Our study indicates the existence of a difference between obese and non-obese schizophrenic subjects as for inflammatory cytokine production and serum leptin and adiponectin levels, suggesting a 'subclinical inflammatory state' in obese schizophrenic patients that may contribute to a predisposition to inflammation and infections.

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.

Werner's syndrome (adult progeria): an affected mother and son presenting with resistant psychosis.

Age-related psychotic conditions may be studied by focusing on the unique group of progeroid syndromes. This report will focus on Werner's syndrome, one of the better defined and studied progeroid syndromes. We applied clinical and histophysiological evaluations to two patients, a mother and son, suffering from Werner's syndrome. Both patients presented with resistant psychosis and evidence of impaired cellular repair mechanisms. Psychiatric morbidity in Werner's syndrome is rarely reported. This syndrome can serve as a possible model for aging-associated development of psychosis.

Clinical characteristics of neuroleptic-induced parkinsonism.

In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.

Higher natural killer cell activity in schizophrenic patients: the impact of serum factors, medication, and smoking.

Schizophrenia has been associated with altered immunity and reduced occurrence of autoimmune diseases and malignancies. A few studies in schizophrenic patients have assessed natural killer cell activity (NKA), but no consistent findings have emerged. However, NKA was assessed using standard procedures and in the absence of autologous serum and the various cytokines that modulate NKA and appear to be abnormal in schizophrenic patients. In the current study, therefore, the number of NK cells and the activity of the individual NK cell were assessed in whole blood shortly after blood withdrawal, in both the presence and the absence of autologous serum. Twenty-nine schizophrenic patients (11 nonmedicated), 8 nonschizophrenic control patients (bipolar and personality disorders), and 31 age-matched healthy controls were studied. Schizophrenic patients showed higher NKA per NK cell than controls and nonschizophrenic patients. This difference remained significant even when the nonmedicated schizophrenics, who showed the highest levels of NKA, were excluded. However, the increase in NKA was more pronounced in the presence of serum and was reduced to an insignificant level when serum was removed from the same samples. In both schizophrenic patients and controls, smokers and women showed lower NKA. Numbers of NK cells did not differ among groups, although medication affected blood concentration of other leukocytes. These findings indicate that the effects of serum factors, psychiatric medication, gender, and smoking should be considered when assessing NKA in schizophrenic patients. The observed higher NKA may help explain the surprising reports of low incidence of lung cancer and other malignancies in schizophrenic patients, despite their higher rate of smoking.

Obsessive and compulsive symptoms in schizophrenia: a randomized controlled trial with fluvoxamine and neuroleptics.

Obsessive-compulsive-related disorders are frequently comorbid with schizophrenia. The existence of obsessive and compulsive symptoms in patients with schizophrenia represents one of the most severe types of psychotic disorders and may predict a poor prognosis in most cases. Previous pilot studies and case reports have shown that the condition of some patients with schizophrenia did not exacerbate and even improved when serotonin reuptake inhibitors (SSRIs) were added to their standard neuroleptic regimen. The aim of this study was to evaluate the efficacy of a combination treatment of an SSRI (fluvoxamine) and standard neuroleptics for the treatment of obsessive-compulsive (OC) symptomatology in patients with schizophrenia compared with administration of neuroleptics only. Thirty inpatients who met DSM-IV criteria for schizophrenia and also had prominent OC symptoms were randomly divided into two groups. Fourteen patients were treated with conventional neuroleptics and fluvoxamine in doses of 100 to 200 mg/day for 8 weeks. Sixteen patients comprised a control group and received only their previous therapeutic neuroleptic therapy. The patients were assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Scale (CGI) at baseline and endpoint. Side effects were assessed weekly. The data were analyzed using an analysis of variance. A considerable reduction in PANSS (34.3%) and Y-BOCS (29.4%) scores was noted, and CGI scores decreased moderately in both groups. None of the patients showed an acute exacerbation at the end of the study. Side effects were mild and easily tolerated in most patients. This open, randomized, controlled study reveals that coadministration of fluvoxamine, an SSRI, and neuroleptics in patients with schizophrenia and OC symptoms was associated with specific improvements of these symptoms. Thus, the use of an SSRI in treating a patient with schizophrenia and OC symptomatology may be warranted and safe. Other implications of the findings, including general safety of the combined pharmacotherapy and the use of new antipsychotic medications, are also discussed.

An open study of fluvoxamine augmentation of neuroleptics in schizophrenia with obsessive and compulsive symptoms.

Patients whose schizophrenia is characterized by marked obsessive-compulsive features can be difficult to treat successfully and often require a combination treatment. The aim of this open-label study was to evaluate the efficacy and tolerability of an addition of fluvoxamine--a selective serotonin reuptake inhibitor (SSRI)--to standard neuroleptics in treatment of obsessive-compulsive (OC) symptomatology in patients with schizophrenia. Sixteen patients with schizophrenia were treated with conventional neuroleptics and fluvoxamine in doses of 100-200 mg/d for 8 weeks. The patients were assessed with use of the Brief Psychiatric Rating Scale (BPRS) and the Yale Brown Obsessive-Compulsive Scale (YBOCS) at baseline and endpoint. Results included considerable reduction in BPRS (39.4%) and Y-BOCS (32.9%) scores. None of the patients showed an acute exacerbation during the whole study period. Side effects were clinically insignificant. This open-label trial supports previous suggestions that coadministration of SSRIs and neuroleptics in patients with schizophrenia with OC symptoms is associated with robust improvements of these symptoms. Therefore, the use of SSRIs in patients with schizophrenia with OC symptomatology may be warranted and safe.

The relationship between subjective sleep estimation and objective sleep variables in depressed patients.

INTRODUCTION: To our knowledge there is no evidence in the literature about the relationship between subjective sleep estimation and objective sleep variables in depression. It is not known whether the subjective estimation of sleep quality and sleep duration is directly related to any objective sleep variable in depressed patients. METHODS: Thirty patients with major depression and 10 healthy subjects have been investigated in our sleep laboratory during 1 or 2 consecutive nights after 1 night for adaptation. Every subject, after final awakening in the laboratory, answered questions concerning the subjective feelings about sleep duration, number of awakenings and sleep depth. We compared the sleep estimation in both groups and calculated the correlation between objective and subjective sleep variables in depressed patients. RESULTS: The degree of a wrong sleep estimation in depressed patients is larger than in healthy subjects. Slow wave sleep (SWS) in depressed patients correlates positively with the subjective estimation of sleep duration. Eye movement density in REM sleep correlates with the subjective estimation of the number of awakenings. CONCLUSION: SWS in depression has a positive influence on the subjective feeling of sleep duration while phasic REM sleep activity has a negative influence.

Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia.

OBJECTIVE: The authors examined the efficacy, tolerability, and safety of ondansetron, a selective serotonin 3 receptor antagonist, in patients with tardive dyskinesia. METHOD: Twenty patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 12 mg/day of ondansetron for 12 weeks in an open-label study. RESULTS: Administration of ondansetron resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. CONCLUSIONS: Ondansetron may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia.

Priapism associated with risperidone treatment.

Priapism is the occurrence of sustained and painful erection that does not result from sexual desire and fails to subside despite orgasm. It is often accompanied by pain and tenderness. The aetiologies are idiopathic, alcohol abuse, drug therapy, perinatal trauma and sickle-cell anaemia. It is a very rare adverse effect of psychotropic medications, due to alphaadrenergic receptor blockade. Priapism is reported in a 19-year-old physically healthy mental patient after 4 days of risperidone treatment 2 mg/day. ( Int J Psych Clin Pract 2000; 4: 237 - 239).

Increased olfactory sensitivity in first episode psychosis and the effect of neuroleptic treatment on olfactory sensitivity in schizophrenia.

Olfactory sensitivity to two odorants, isoamyl acetate and androstenone, was assessed in 19 male schizophrenic patients and 10 control subjects. Tests were performed during a drug-free period and 2-3 weeks after initiation of neuroleptic drug therapy. Olfactory sensitivity in schizophrenic patients was significantly impaired during the drug-free period and neuroleptic treatment further reduced olfactory sensitivity in these patients. The same olfactory tests were administered to 22 first-episode-psychosis patients, 12 first-episode-schizophrenia and 10 brief-psychotic-disorder patients, as well as to 20 age-matched control subjects. The first-episode-psychosis patients had significantly higher sensitivity to isoamyl acetate and to androstenone, but the incidence of anosmia to androstenone was not higher in the first episode patient group as compared to the control group. We conclude that olfactory dysfunction in schizophrenic patients, and possibly other forms of psychosis, is mainly due to long-term effects of commonly used neuroleptic drugs.

Cancer morbidity in psychiatric patients: influence of lithium carbonate treatment.

The relationship between mental diseases and cancer development has been examined in a number of studies but the findings are still inconclusive and suffer from methodological problems. Studies conducted to examine the effect of lithium on malignant cells yielded inconsistent results. The study group included 609 patients treated by lithium carbonate and 2396 controls. A lower but non significant risk (RR = 0.79; CI = 0.17-3.60) to develop non-epithelial tumors was found among lithium carbonate treated psychiatric patients as compared to controls. A significantly (P = 0.05) inverse trend of cancer with lithium dose was observed. The risk of cancer development among each group of psychiatric patients was significantly lower than in the general population (RR = 0.68 for the lithium treated group versus 0.78 for controls). Mental patients have a lower cancer prevalence than the general population and lithium may have a protective effect.

Antibodies to neuroblastoma cell line proteins in patients with schizophrenia.

The presence of antibodies against neural antigens was investigated in the serum of patients with schizophrenia, major depression and normal controls. Different immunological abnormalities, humoral and cellular, were reported in schizophrenia and major depression. The pathogenesis of schizophrenia is multifactorial. An autoimmune mechanism was suggested as a possible factor. We tested the serum of 26 patients with schizophrenia, eight patients with major depression and 22 normal controls. The serum samples were tested for antibody binding to protein extracts of IMR-32 neuroblastma cell line using Western blot analysis. Immunoglobulins of eight patients with schizophrenia (30.71%) reacted with a protein of 80-85 kDa. Serum samples from subjects of other groups did not react with this protein. Sera of all patients with major depression but one, and all normal controls reacted with HSP 60 kDa to different extent. This is an apparent discrepancy with the findings of Kilidireas et al. [Kilidireas, K., Latov, N., Strauss, D.H., Gorig, A.D., Hashim, G.A., Gorman, J.M., Sadig, S.A., 1992. Antibodies to the human 60 kDa heat shock protein in patients with schizophrenia. Lancet 340, 569-572.] who demonstrated the presence of antibodies against HSP 60 kDa in 44% of patients with schizophrenia tested and 8% of normal subjects. HSP 60 kDa is an antigen of many pathogens and antibodies against it might be a result of an infection and cannot be a good indicator for an autoimmune process. The presence of antibodies against a protein of 80-85 kDa should be investigated as a possible specific indicator.

Increased number of peripheral blood CD34+ cells in lithium-treated patients.

Eight adult patients with bipolar disorder were prospectively examined to find whether lithium carbonate increased their peripheral blood CD34+ haemopoietic stem cells. Following lithium therapy for 3-4 weeks their neutrophil counts increased by a mean of 88% (from 4625 +/- 1350 x 10(9)/l, mean +/- SD pretreatment, to a peak of 8300 +/- 3910 x 10(9)/l). Concommitantly, there was a significant increment in their CD34+ cells (from 0.11 +/- 0.01% to a peak of 0.18 +/- 0.08%). There was a significant correlation between the rise in neutrophil count and that of the CD34+ cells (r = 0.795, P = 0.019). Lithium therapy may be used to mobilize peripheral blood CD34+ cells for marrow transplantation.