Pinkhas Sirota

Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients

1. The interleukins play an important role in the development and maintenance of the immune system 2. Decreased cell mediated immunity measures were found in schizophrenic patients. 3. The purpose of the present study was to study the spontaneous production of interleukin-1 (IL-1) and interleukin-3 like activity (IL-3-LA) by human mononuclear cells from schizophrenic patients in comparison to healthy individuals. 4. Interleukin-1 was increased significant by schizophrenic patients as compared to controls. 5. Interleukin-3 like activity was slightly elevated in schizophrenic patients as compared to controls. 6. These findings support the hypothesis of an autoimmune dysfunction in some schizophrenic patients.

Autoantibodies to DNA in multicase families with schizophrenia

In an attempt to define the autoimmune status of members of multicase families with schizophrenia, sera of both patients and healthy relatives from 28 such cases were tested for antinuclear antibodies, anti-double-stranded DNA, and anti-single-stranded DNA autoantibodies. These autoantibodies were significantly more frequent in both schizophrenic patients and healthy relatives than in normal subjects. Immunoglobulin (Ig) M anti-DNA antibodies were more common in patients, whereas in healthy relatives, IgG anti-DNA antibodies were more common. No significant differences were found between schizophrenic patients and their healthy relatives. The data indicate that an autoimmune process may be involved in the etiology of a subset of patients with schizophrenia.

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.

Overproduction of neutrophil radical oxygen species correlates with negative symptoms in schizophrenic patients: parallel studies on neutrophil chemotaxis, superoxide production and bactericidal activity

Defective neutrophil function in schizophrenic patients has recently been reported. There are several lines of evidence to support the contribution of oxygen free radicals in schizophrenia, including increased lipid peroxidation, fatty acids and alterations in blood levels of anti-oxidant enzymes. Eighteen schizophrenic patients (DSM-IV) and 15 healthy controls were studied. Neutrophil chemotaxis, superoxide production and bactericidal activity were investigated. A statistically significant increase of superoxide anion release was found in schizophrenic patients compared with controls (mean+/-S.E.M., patients: 6.89+/-0.30 nmol O2-/10(6) cells/min, controls: 5.13+/-0.55 nmol O2-/10(6) cells/min). Moreover, a significant positive correlation between superoxide production and negative symptoms as assessed by the Positive and Negative Syndrome Scale was demonstrated. No differences were detected in chemotaxis and phagocytosis between schizophrenic patients and healthy controls. The present findings of a positive correlation between superoxide generation and negative symptoms in schizophrenic patients support the hypothesis that superoxide anion may participate in the pathogenesis of schizophrenia, as an excess of free radicals could contribute to the deterioration phase of the disease. Further studies are required to establish the role of oxidative stress in the ethiopathogenesis of schizophrenia.

Anticardiolipin antibodies are elevated in drug-free, multiply affected families with schizophrenia

The objective of this study was to measure anticardiolipin antibodies in patients and healthy relatives in multicase families with schizophrenia. Twenty-eight (28) multicase families with schizophrenia were examined. One hundred three drug-free patients and 66 first-degree relatives consented to evaluation by DSM-III-R criteria. Criteria for patient definition included the following: age ≥16, a confirmed hospital diagnosis of schizophrenia, knowledge of biological parents, and consent to participate. Additional data were drawn from family history and medical records. Serum samples were tested separately for IgG and IgM anticardiolipin by enzyme-linked immunosorbent assay (ELISA) and designated positive/negative by comparison to the reactivity of an age-matched control group. IgG anticardiolipin antibodies were significantly more common in both patients and relatives compared to controls. IgM anticardiolipin antibodies were significantly more common in patients. In 75% of families at least one member was anticardiolipin positive and this positivity correlated with patient positivity. The relevance of anticardiolipin antibodies in both patients and healthy relatives of some multicase families to the pathogenesis of schizophrenia is discussed.

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 × 109/l, mean ± SD pretreatment, to a peak of 8300 ± 3910 × 109/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.

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.

Perseveration and over-switching in schizophrenia

Perseveration and switching in positive and negative schizophrenic patients are usually seen as manifestations of attention disorders. They may be closely related to each other, but have not been investigated in an integrated fashion. Such integrated investigation could contribute to the neurophysiological understanding of the relationship between the regional and the pharmacological deficit in schizophrenia. This study has developed a new tool-the Combined Attention Test (CAT)-for the simultaneous measuring of perseveration and switching. Forty-one unmedicated schizophrenic patients were tested. Using the Positive and Negative Sorting Scale (PANSS), subjects were classified into the two experimental groups: positive and negative schizophrenics. The control group consisted of 24 healthy subjects. Schizophrenic patients with positive symptoms tended to switch more than schizophrenic patients with negative symptoms and normal subjects; schizophrenic patients with negative symptoms tended to perseverate more than schizophrenic patients with positive symptoms and normal subjects. Over-switching is discussed as a specific symptom related to positive schizophrenia.

Increased anti-Sm antibodies in schizophrenic patients and their families

1. Autoantibodies in the Sm complex have become a useful serologic aid in the diagnosis of systemic lupus erythematosus (SLE) and have rarely been observed in other diseases. 2. A subset of SLE patients have a variety of psychiatric abnormalities, including schizophrenia. 3. The authors have recently observed that schizophrenic patients have a high incidence of autoantibodies suggesting that autoimmune phenomena may play a role in the pathogenesis of this disease. 4. In the present study the authors investigated multicase families with schizophrenia for the presence of anti-Sm antibodies and showed that these autoantibodies are elevated both in patients and in their healthy relatives. 5. An autoimmune process may be involved in the pathology of schizophrenia.

Superoxide anion production by neutrophils derived from peripheral blood of schizophrenic patients

Evidence indicates that excess free radicals formation may occur in patients with schizophrenia. A study comparing the production of superoxide anion by peripheral blood neutrophils of 29 schizophrenic patients with that of 17 healthy volunteers detected a significant statistical increase in superoxide anion production in schizophrenic patients compared to the healthy control group. Despite the fact that oxidative mechanisms may play a role in schizophrenia, further studies are needed to define their involvement. Such studies would shed light on the etiology and pathogenesis of schizophrenia and may lead to new therapeutic approaches using antioxidants, which might partially alleviate or prevent the symptoms of schizophrenia.