926
Brief Reports
BIOL PSYCHIATRY 1990;27:923-926
and homovanillic acid in cerebrospinal fluid with Rokaeus A~ Melander T, Hokfelt T, et al (1~84): A high performance liquid chromatography using galanin-like peptide in the central nervous system electrodermal detection. Annals of Biochemistry and intestine of the rat. Neuroscience Letters 131:246-253. 47:161-166. Roy A, Adinoff B, Roehrich L, et al (1988) Patho- Skofitsch G, Jacobowitz D (1985): lmmunohistological gambling: A psychobiological study. Arch chemical mapping of galanin-like neurons in the Gen Psychiatry 45:369-37? rat central nervous system. Peptides 6:509-546. Roy A, Pickar D, Paul S, Doran A, Gold P (1987): Skofitsch G, Jacobowitz D (1986): Quantitative disCerebrospinal fluid corticotropin-releasing factor tribution of galanin-like immunoreactivity in the in depressed patients and normal controls. Am J rat central nervous system. Peptides 7:609-613. Psychiatry 144:641-645. Seppala T, ScheilfinM, Capone A, LinnoilaM (1984): Spitzer R, Endicott J, Robbins E (1978): Research diagnostic criteria: Rationale and reliability. Arch Liquid chromatographic assay for CSF catecholGen Psychiatry 35:773-782. amines using electrochemical detection. Acta Pharmacol Toxicologica 55:81-87. Tatemoto K, Rokaeus A, Jornvall H, McDonald T, Mutt V (1983): Galanin--A novel biologically Scheinin M, Chang W, Kink K, Linnoila M (1983): active peptide from porcine intestine. FEBS Left Simultaneous determination of 3-methoxy-4-hy164:124-128. droxyphenylglycol, 5-hydroxyindoleacetic acid,
CSF 5-Hydroxyindoleacetic Acid Levels and Suicide Attempts in Schizophrenia Carmen Z. Lemus, Jeffrey A. Lieberman, Celeste A. Johns, Simcha Pollack, Peter Bookstein, and Thomas B. Cooper
Introduction The relationship between serotonergic function and suicidality has been extensively investigated. Asberg et al. (1976) were the first to report decreased levels of CSF 5-hydroxyin-
From Hillside Hospital, a division of Long Island Jewish Medical Center, Glen Oaks, New York (C.Z.L., J.A.L., C.A.J., S.P., P.B.); Albert Einstein College of Medicine, Bronx, New York (J.A.L.); Department of Quantitative Analysis, St. John's University, Queens, New York (S.P.); and New York State Psychi. attic Institute, New York, New York (T.B.C.). Address reprint requests to Carmen Z. Lemus, M.D., Hillside Hospital, Research Department, 75-59 263rd Street, Glen Oaks, NY 11004. Received July 31, 1989; revised November 13, 1989.
© 1990 Society of Biological Psychiatry
doleacetic acid (5-HIAA), the principal metabolite of serotonin (5-HT), in depressed suicidal patients. Subjects who had attempted suicide by violent methods had the lowest levels. This finding has been replicated (Agren 1980; Oreland et al. 1981) and extended to other diagnostic categories, including personality disorders (Brown et al. 1982), alcoholism (Banki et al. 1984), and adjustment disorders (Banki et al. 1984). In schizophrenia, however, the association between low CSF 5-HIAA and suicidal behavior is less clear, with both positive (van Praag 1983; Ninan et al. 1984) and negative (Roy et al. 1985; Pickar et al. 1986) findings reported. 0006-3223/90/$03.50
Brief Reports
We examined the lifetime history of suicide attempts and CSF 5-HIAA levels in a group of chronic schizophrenic and schizoaffective patients who participated in an antipsychotic drug treatment study which included a pretreatment lumbar puncture. Methods The sample consisted of 22 subjects who were admitted to an inpatient unit for evaluation and ultimately entered the treatment study. Each subject met DSM-III-R criteria for the diagnosis of schizophrenia or schizoaffective disorder. All gave written informed consent to participate in the study. Actively suicidal or violent patients were excluded because of the required sustained drug washout period. Demographic and clinical characteristics are shown in Table 1. Life history of suicide attempts was determined by detailed review of the patients' clinical records; this review was carded out by an investigator blind to the CSF 5-HIAA data. Of the 22 subjects, 6 had a positive lifetime history of suicide attempts (5 subjects by overdose, 1 by stab wound) and 16 had no lifetime history of suicide attempts. All patients were kept medication free for a minimum of ~4 days (range 14-39 days) before the lumbar puncture (LP) was performed. The subjects received a low monoamine meal for dinner and fasted for 14 hr prior to the procedure. The
BIOL PSYCHIATRY 1990;27:926-929
927
LPs were performed between 9:00 and 9:30 AM with the subject in the lateral decubitus position. Fifteen milliliters of CSF were collected as a pool and separated into 1 cc aliquots which were placed in dry ice at the bedside and subsequently stored at -70°C until assayed. CSF levels of 5-HIAA were determined using gas chromatography linked to a mass spectrometer according to the method described by Fri et al. (1974). Psychopathology was assessed within 24 hr of the LP with the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962).
Statistical Analysis The groups with and without suicide attempt histories were compared by t-test and analysis of variance (ANOVA) on a variety of demographic and clinical variables. Chi-square test was used to compare the groups by diagnostic subtype ofschizop,hrenia. A two-way ANOVA was done to determine the interaction of gender and suicide attempt history on CSF 5-HIAA. All probability values reported are two-tailed. Results
There were no significant differences (mean ± st)) between the groups with respect to gender (3 women in each group), age of onset of illness (18.6 ± 3.0 versus 20.8 ± 4.9), number of previous hospital admissions (7.6 ± 3.4 versus 6.4 ± 3.4), and duration of illness (6.0 ± 2.6 versus 9.8 ± 5.0). At the time of the LP, the Table 1. Characteristics of Suicide-Positive and Suicide-Negative Patients patients with a positive history of suicide attempts were slightly younger than the comparPositive Negative suicide history suicidehistory ison group (24.6 ± 2.5 versus 30.6 ± 6.2, (N--- 6) (N-- 16) F = 5.09, df = l, p = 0.03). Otherwise, the groups were comparable with respect to the duAge: Mean 24 30 ration of their medication-free period (25.5 ± Range 21-27 21-40 6.7 versus 23.3 ± 8.4 days, p = NS) and their Sex: Male (%) 50% 80% Diagnosis overall level of severity as reflected by the mean Schizophrenia (%) BPRS scores (2.07 ± 0.73 versus 3.03 ± l . l , Paranoid 50% 62% p = NS). In addition, there were no significant Undifferentiated m 25% differences in their level of depression, meaResidual 17% sured by the BPRS factor anxiety-depression Schizoaffective 33% 13% Duration of illness (2.6 versus 3.1, p = NS). (in years)--mean 6.0 9.8 The mean concentration of CSF 5-HIAA
928
Brief Reports
BIOL PSYCHIATRY 1990;27:926-929
60
55
MALE
, ~ 50
0 FEMALE 45 c 40 MEAN - 0
Brief Reports
BIOL PSYCHIATRY 1990;27:923-926
and homovanillic acid in cerebrospinal fluid with Rokaeus A~ Melander T, Hokfelt T, et al (1~84): A high performance liquid chromatography using galanin-like peptide in the central nervous system electrodermal detection. Annals of Biochemistry and intestine of the rat. Neuroscience Letters 131:246-253. 47:161-166. Roy A, Adinoff B, Roehrich L, et al (1988) Patho- Skofitsch G, Jacobowitz D (1985): lmmunohistological gambling: A psychobiological study. Arch chemical mapping of galanin-like neurons in the Gen Psychiatry 45:369-37? rat central nervous system. Peptides 6:509-546. Roy A, Pickar D, Paul S, Doran A, Gold P (1987): Skofitsch G, Jacobowitz D (1986): Quantitative disCerebrospinal fluid corticotropin-releasing factor tribution of galanin-like immunoreactivity in the in depressed patients and normal controls. Am J rat central nervous system. Peptides 7:609-613. Psychiatry 144:641-645. Seppala T, ScheilfinM, Capone A, LinnoilaM (1984): Spitzer R, Endicott J, Robbins E (1978): Research diagnostic criteria: Rationale and reliability. Arch Liquid chromatographic assay for CSF catecholGen Psychiatry 35:773-782. amines using electrochemical detection. Acta Pharmacol Toxicologica 55:81-87. Tatemoto K, Rokaeus A, Jornvall H, McDonald T, Mutt V (1983): Galanin--A novel biologically Scheinin M, Chang W, Kink K, Linnoila M (1983): active peptide from porcine intestine. FEBS Left Simultaneous determination of 3-methoxy-4-hy164:124-128. droxyphenylglycol, 5-hydroxyindoleacetic acid,
CSF 5-Hydroxyindoleacetic Acid Levels and Suicide Attempts in Schizophrenia Carmen Z. Lemus, Jeffrey A. Lieberman, Celeste A. Johns, Simcha Pollack, Peter Bookstein, and Thomas B. Cooper
Introduction The relationship between serotonergic function and suicidality has been extensively investigated. Asberg et al. (1976) were the first to report decreased levels of CSF 5-hydroxyin-
From Hillside Hospital, a division of Long Island Jewish Medical Center, Glen Oaks, New York (C.Z.L., J.A.L., C.A.J., S.P., P.B.); Albert Einstein College of Medicine, Bronx, New York (J.A.L.); Department of Quantitative Analysis, St. John's University, Queens, New York (S.P.); and New York State Psychi. attic Institute, New York, New York (T.B.C.). Address reprint requests to Carmen Z. Lemus, M.D., Hillside Hospital, Research Department, 75-59 263rd Street, Glen Oaks, NY 11004. Received July 31, 1989; revised November 13, 1989.
© 1990 Society of Biological Psychiatry
doleacetic acid (5-HIAA), the principal metabolite of serotonin (5-HT), in depressed suicidal patients. Subjects who had attempted suicide by violent methods had the lowest levels. This finding has been replicated (Agren 1980; Oreland et al. 1981) and extended to other diagnostic categories, including personality disorders (Brown et al. 1982), alcoholism (Banki et al. 1984), and adjustment disorders (Banki et al. 1984). In schizophrenia, however, the association between low CSF 5-HIAA and suicidal behavior is less clear, with both positive (van Praag 1983; Ninan et al. 1984) and negative (Roy et al. 1985; Pickar et al. 1986) findings reported. 0006-3223/90/$03.50
Brief Reports
We examined the lifetime history of suicide attempts and CSF 5-HIAA levels in a group of chronic schizophrenic and schizoaffective patients who participated in an antipsychotic drug treatment study which included a pretreatment lumbar puncture. Methods The sample consisted of 22 subjects who were admitted to an inpatient unit for evaluation and ultimately entered the treatment study. Each subject met DSM-III-R criteria for the diagnosis of schizophrenia or schizoaffective disorder. All gave written informed consent to participate in the study. Actively suicidal or violent patients were excluded because of the required sustained drug washout period. Demographic and clinical characteristics are shown in Table 1. Life history of suicide attempts was determined by detailed review of the patients' clinical records; this review was carded out by an investigator blind to the CSF 5-HIAA data. Of the 22 subjects, 6 had a positive lifetime history of suicide attempts (5 subjects by overdose, 1 by stab wound) and 16 had no lifetime history of suicide attempts. All patients were kept medication free for a minimum of ~4 days (range 14-39 days) before the lumbar puncture (LP) was performed. The subjects received a low monoamine meal for dinner and fasted for 14 hr prior to the procedure. The
BIOL PSYCHIATRY 1990;27:926-929
927
LPs were performed between 9:00 and 9:30 AM with the subject in the lateral decubitus position. Fifteen milliliters of CSF were collected as a pool and separated into 1 cc aliquots which were placed in dry ice at the bedside and subsequently stored at -70°C until assayed. CSF levels of 5-HIAA were determined using gas chromatography linked to a mass spectrometer according to the method described by Fri et al. (1974). Psychopathology was assessed within 24 hr of the LP with the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962).
Statistical Analysis The groups with and without suicide attempt histories were compared by t-test and analysis of variance (ANOVA) on a variety of demographic and clinical variables. Chi-square test was used to compare the groups by diagnostic subtype ofschizop,hrenia. A two-way ANOVA was done to determine the interaction of gender and suicide attempt history on CSF 5-HIAA. All probability values reported are two-tailed. Results
There were no significant differences (mean ± st)) between the groups with respect to gender (3 women in each group), age of onset of illness (18.6 ± 3.0 versus 20.8 ± 4.9), number of previous hospital admissions (7.6 ± 3.4 versus 6.4 ± 3.4), and duration of illness (6.0 ± 2.6 versus 9.8 ± 5.0). At the time of the LP, the Table 1. Characteristics of Suicide-Positive and Suicide-Negative Patients patients with a positive history of suicide attempts were slightly younger than the comparPositive Negative suicide history suicidehistory ison group (24.6 ± 2.5 versus 30.6 ± 6.2, (N--- 6) (N-- 16) F = 5.09, df = l, p = 0.03). Otherwise, the groups were comparable with respect to the duAge: Mean 24 30 ration of their medication-free period (25.5 ± Range 21-27 21-40 6.7 versus 23.3 ± 8.4 days, p = NS) and their Sex: Male (%) 50% 80% Diagnosis overall level of severity as reflected by the mean Schizophrenia (%) BPRS scores (2.07 ± 0.73 versus 3.03 ± l . l , Paranoid 50% 62% p = NS). In addition, there were no significant Undifferentiated m 25% differences in their level of depression, meaResidual 17% sured by the BPRS factor anxiety-depression Schizoaffective 33% 13% Duration of illness (2.6 versus 3.1, p = NS). (in years)--mean 6.0 9.8 The mean concentration of CSF 5-HIAA
928
Brief Reports
BIOL PSYCHIATRY 1990;27:926-929
60
55
MALE
, ~ 50
0 FEMALE 45 c 40 MEAN - 0
