BIOL PSYCHIATRY 1992132:735-738
735
Antinuclear and Gastric Parietal Cell Autoantibodies in Schizophrenic Patients Rohan Ganguli, Bruce S. Rabin, and Jaspreet S. Brar
Introduction
Methods
There are two approaches to determine whether a disease has an autoimmune pathology (Rose 1991). The direct approach, as exemplified by myasthenia gravis and Graves' disease, is the detection of antigen-specific autoantibodies with pathophysiological significance (Roitt et al 1989). However, in most diseases such as systemic lur:~ ythematosus (SLE), rheumatoid artiwitis, and multiple sclerosis there is only indirect evidence of autoimmunity. This indirect evidence is provided by (1), the occurrence of other autoimmune disorders in other family members, (2), non-organ specific autoantibodies such as antinuclear antibody (ANA) which may covary with exacerbations and remissions of illness, and (3) altered lymphokine production (Kroe. mer et al 1991). If some schizophrenics have an autoimmune disease as suggested by us (Ganguli et al 1987, 1989) and others, then an increased prevalence of autoantibodies in association with the disorder would be predicted. In this study, we report our findings on the prevalence of seven common circulating autoantibodies in schizophrenic patients (including first-episode, neuroleptic-naive patients) and healthy control subjects.
Clinical Patients (n = 225; 125 men, 100 women) who met the Research Diagnostic Criteria (Spitzer et al 1978a) for Schizophrenia or Schizo-Affective disorder (mainly schizophrenic), based on a modified Schedule for Affective Disorder and Schizophrenia (Spitzer et al 1978b) interview were recruited from the Western Psychiatric Institute and Clinic, Pittsburgh, PA. The diagnosis in first-episode patients (n = 53) was reconfirmed 9-12 months later as described elsewhere (Ganguli and Brat 1992). Positive and negative symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) and the Manchester Scale (Kraweicka 1977). Depression was rated using the Montgomery-Asberg scale (Montgomery and Asberg 1979). Control subjects (n = 327; 141 men, 186 women) from the Pittsburgh metropolitan area were recruited for this study, and excluded if they had any mental disorder, immune disorder, current drug or alcohol abuse, or addiction. Fifty-three age-, race-, and gendermatched controls were selected from this sample for comparison with the first-episode patients.
Immunologic From the Departments of Psychiatry and Pathology, Immunopsychiatry Programme and Immunopathology Division, University of Pittsburgh School of Medicine and Brain Behaviour and Immunity Center, Pittsburgh, PA. Address reprint requests to Rohan Ganguli, M.D.. Western Psychiatric Institute & Clinic, 3811 O'Hara Street, Pittsburgh, PA ! 5213-2593. Received March 11, 1992; revised July 8, 1992.
© 1992 Society of Biological Psychiatry
Sera was tested for seven common autoantibodies using standard serological methods: thyroglobulin and thyroid microsomal agent by indirect hemagglutination; immunofluorescence for antinuclear antibody (HEp-2 cell line), smooth 0006-3223/92/$05.00
736
BIOLPSYCHIATRY
Brief Reports
1992;32:735-738
muscle, mitochondria, and gastric parietal cell (mouse stomach and kidney); rheumatoid factor by fluorescence immunoassay. Subjects were considered positive if the titer of any one or more of the autoantibodies exceeded the threshold established by the clinical serology laboratory of this university hospital.
cated and previously medicated), lower BPRS and negative symptoms scores were found in the ANA-positive group (see Table 2). Discussion
Our findings confirm an increased prevalence of autoantibodies in schizophrenic patients (Fessel 1961; DeLisi and Wyatt 1982; Canoso et al 1990); Results however, this increase does not appear to be a The prevalence of autoantibodies in these two generalized increase in all common autoantipopulations was compared using Pearson's X2 bodies as we first hypothesized but to be specific and Fisher's exact tests (Table 1). Notable were to ANA and to a lesser extent gastric parietal the differences in the prevalence of ANA (Bon- cell antibody. Based on the earlier work with ferroni corrected p ffi 0.047) between the two chlorpromazine (Berglund et al 1970; Quispopulations. Furthermore, ANA was twice as morio et al 1975; Alarcon-Segovia et al 1973; frequent in female patients than in males (X2 = Zarrabi et al 1979; Gammon et al 1980; Yannitsi 5.92, p = 0.012). Although gastric parietal cell et al 1990), the increase in ANA in schizoantibodies were also twice as frequent among phrenics might be suspected to be due to medpatients compared with controls, the diffi:rence ications, and this can still not be ruled out. By failed to reach statistical significance. Eight of including the largest sample of never-medicated the 10 patients that were positive for gastric patients so far studied, we had hoped to deterparietal cell antibodies were African-American mine if increased ANA was related to medications. There was no statistically significant dif(Fisher's exact, 2-tailed p -- 0.046). ANA was positive in 9.43% of never-med- ference between never-medicated patients and icated patients compared with 5.66% in age-, age-, race-, and gender-matched controls. Howrace-, and gender-matched controls, but the dif- ever, this may be an issue of statistical power as it would take 593 never-medicated patients ferences were not statistically significant. There was a significant linear association be- and an equal number of controls for the observed tween ANA positivity and age in patients (exact difference to reach statistical signficance (power p - 0,0001; Armitage 1955). A similar trend = 0.80; I tailed ¢t set at 0.05). Earlier studies was also found with duration of illness. of never-medicated patients have reported an Among all acutely ill patients (never-medi- increase in ANA (DeLisi and Wyatt 1982) and
Table I. Prevalenceof Autoantibodies in SchizophrenicPatients and Healthy Controls Autoantibody
Patient" (225) (%)
Controls (327) (%)
ANA Smooth muscle Gastric parietal cell Mitochondrial Thyroglc~n Thyroid n,crosomal" Rheumatoid factor Sum 7
30 (13.33) 23 (10.22) 10 (4.44) I (0.44) 7 (3,11) 15 (6,67) 7 (3. I I) 69 (29.78)
20 30 7 2 13 25 10 ~
°Includes53 first episode, drug-naivepatients.
(6,12) (9,17) (2,14) (0,61) (3,98) (7,65) (3,06) (27.5)
X2
p (
735
Antinuclear and Gastric Parietal Cell Autoantibodies in Schizophrenic Patients Rohan Ganguli, Bruce S. Rabin, and Jaspreet S. Brar
Introduction
Methods
There are two approaches to determine whether a disease has an autoimmune pathology (Rose 1991). The direct approach, as exemplified by myasthenia gravis and Graves' disease, is the detection of antigen-specific autoantibodies with pathophysiological significance (Roitt et al 1989). However, in most diseases such as systemic lur:~ ythematosus (SLE), rheumatoid artiwitis, and multiple sclerosis there is only indirect evidence of autoimmunity. This indirect evidence is provided by (1), the occurrence of other autoimmune disorders in other family members, (2), non-organ specific autoantibodies such as antinuclear antibody (ANA) which may covary with exacerbations and remissions of illness, and (3) altered lymphokine production (Kroe. mer et al 1991). If some schizophrenics have an autoimmune disease as suggested by us (Ganguli et al 1987, 1989) and others, then an increased prevalence of autoantibodies in association with the disorder would be predicted. In this study, we report our findings on the prevalence of seven common circulating autoantibodies in schizophrenic patients (including first-episode, neuroleptic-naive patients) and healthy control subjects.
Clinical Patients (n = 225; 125 men, 100 women) who met the Research Diagnostic Criteria (Spitzer et al 1978a) for Schizophrenia or Schizo-Affective disorder (mainly schizophrenic), based on a modified Schedule for Affective Disorder and Schizophrenia (Spitzer et al 1978b) interview were recruited from the Western Psychiatric Institute and Clinic, Pittsburgh, PA. The diagnosis in first-episode patients (n = 53) was reconfirmed 9-12 months later as described elsewhere (Ganguli and Brat 1992). Positive and negative symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) and the Manchester Scale (Kraweicka 1977). Depression was rated using the Montgomery-Asberg scale (Montgomery and Asberg 1979). Control subjects (n = 327; 141 men, 186 women) from the Pittsburgh metropolitan area were recruited for this study, and excluded if they had any mental disorder, immune disorder, current drug or alcohol abuse, or addiction. Fifty-three age-, race-, and gendermatched controls were selected from this sample for comparison with the first-episode patients.
Immunologic From the Departments of Psychiatry and Pathology, Immunopsychiatry Programme and Immunopathology Division, University of Pittsburgh School of Medicine and Brain Behaviour and Immunity Center, Pittsburgh, PA. Address reprint requests to Rohan Ganguli, M.D.. Western Psychiatric Institute & Clinic, 3811 O'Hara Street, Pittsburgh, PA ! 5213-2593. Received March 11, 1992; revised July 8, 1992.
© 1992 Society of Biological Psychiatry
Sera was tested for seven common autoantibodies using standard serological methods: thyroglobulin and thyroid microsomal agent by indirect hemagglutination; immunofluorescence for antinuclear antibody (HEp-2 cell line), smooth 0006-3223/92/$05.00
736
BIOLPSYCHIATRY
Brief Reports
1992;32:735-738
muscle, mitochondria, and gastric parietal cell (mouse stomach and kidney); rheumatoid factor by fluorescence immunoassay. Subjects were considered positive if the titer of any one or more of the autoantibodies exceeded the threshold established by the clinical serology laboratory of this university hospital.
cated and previously medicated), lower BPRS and negative symptoms scores were found in the ANA-positive group (see Table 2). Discussion
Our findings confirm an increased prevalence of autoantibodies in schizophrenic patients (Fessel 1961; DeLisi and Wyatt 1982; Canoso et al 1990); Results however, this increase does not appear to be a The prevalence of autoantibodies in these two generalized increase in all common autoantipopulations was compared using Pearson's X2 bodies as we first hypothesized but to be specific and Fisher's exact tests (Table 1). Notable were to ANA and to a lesser extent gastric parietal the differences in the prevalence of ANA (Bon- cell antibody. Based on the earlier work with ferroni corrected p ffi 0.047) between the two chlorpromazine (Berglund et al 1970; Quispopulations. Furthermore, ANA was twice as morio et al 1975; Alarcon-Segovia et al 1973; frequent in female patients than in males (X2 = Zarrabi et al 1979; Gammon et al 1980; Yannitsi 5.92, p = 0.012). Although gastric parietal cell et al 1990), the increase in ANA in schizoantibodies were also twice as frequent among phrenics might be suspected to be due to medpatients compared with controls, the diffi:rence ications, and this can still not be ruled out. By failed to reach statistical significance. Eight of including the largest sample of never-medicated the 10 patients that were positive for gastric patients so far studied, we had hoped to deterparietal cell antibodies were African-American mine if increased ANA was related to medications. There was no statistically significant dif(Fisher's exact, 2-tailed p -- 0.046). ANA was positive in 9.43% of never-med- ference between never-medicated patients and icated patients compared with 5.66% in age-, age-, race-, and gender-matched controls. Howrace-, and gender-matched controls, but the dif- ever, this may be an issue of statistical power as it would take 593 never-medicated patients ferences were not statistically significant. There was a significant linear association be- and an equal number of controls for the observed tween ANA positivity and age in patients (exact difference to reach statistical signficance (power p - 0,0001; Armitage 1955). A similar trend = 0.80; I tailed ¢t set at 0.05). Earlier studies was also found with duration of illness. of never-medicated patients have reported an Among all acutely ill patients (never-medi- increase in ANA (DeLisi and Wyatt 1982) and
Table I. Prevalenceof Autoantibodies in SchizophrenicPatients and Healthy Controls Autoantibody
Patient" (225) (%)
Controls (327) (%)
ANA Smooth muscle Gastric parietal cell Mitochondrial Thyroglc~n Thyroid n,crosomal" Rheumatoid factor Sum 7
30 (13.33) 23 (10.22) 10 (4.44) I (0.44) 7 (3,11) 15 (6,67) 7 (3. I I) 69 (29.78)
20 30 7 2 13 25 10 ~
°Includes53 first episode, drug-naivepatients.
(6,12) (9,17) (2,14) (0,61) (3,98) (7,65) (3,06) (27.5)
X2
p (
