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development of child and adolescent psychiatry in Europe were memorialized in the American Journal of Psychiatry in 1962 (Harms 1962). Kahlbaum was a pioneer in his recognition of the catatonic state as a syndrome rather than a specific disease process, although his view was not influential in Germany where catatonia later came to be linked to a subtype of schizophrenia. His approach to psychiatry as delineated in the title and subtitle of his 1863 monograph (Kahlbaum 1863) sounds familiar to modem psychiatrists and is reminiscent of some opening remarks in DSM-III-R: "The grouping of psychic diseases and the classification of mental disorders. A critical historical review of prior classifications and an effort to prepare an empirical scientific foundation of psychiatry as a clinical discipline" (author's translation). Michael Weller

Department of Psychiatry University of Wiirzburg Fiichsleinstr 15 8700 WOrzburg, Germany

Phospholipase A2 in Schizophrenia To the Editor: Bennett et al (1991) found no differences in the activity of phospholipase A, (PLAD in Epstein Barr virus-transformed lymphoblasts of schizophrenic patients as compared with healthy controls. These results prompted the authors to the conclusion that our finding of increased plasma PLA, activity in schizophrenia (Gattaz et al 1987) is a "state" characteristic and not a "trait" related to the etiology of the illness. They also considered it "highly unlikely that if a genetic defect is present in PLA2 activity in schizophrenic subjects, the methods used in their report would fail to detect such a defect." I think that these conclusions are premature, as they cannot be drawn from their experimental evidence. Firstly, I would like to ask the authors to clarify a methodological aspect of their experiments. As they stated in their paper the lymphoblast cultures were

References Abrams R, Taylor MA (1976): Catatonia: A prospective clinical study. Arch Gen Psychiatry 33:579-581. Barnes MP, Saunders M, Walls TJ, Saunders !. Kirk CA (1986): The syndrome of Karl Ludwig Kahlbaum. J Neurol Neurosurg Psychiatry 49:99!-996. Ferro FM, Janiri L, De Bonis C, Del Carmine R. Tempesta E (1991): Clinicaloutcome and psych~ndocrinological findings in a case of lethal catatonia. Bioi Psychiatr)" 3:197-200. Harms E (1962) Karl Kahlbaum's ideas on pedagogical treatment of mentally ill children. Am J Psychiatry 119:477-478. Kahlbaum KL (1863): Die Gruppirung der psychischen Krankheiten und die Eintheilung der SeelenstOrungen. Entwurf einer historisch-kritischen Darstellung tier bi~herigen Eintnei&msen und Versuch zur Anbahnung einer empirisch-wissenschaftlichen Grundlage tier PSYchiatrie als klinischer Disziplin. Danzig: A. W. Kafemann Verlag. Kahlbaum KL (1874): Die Katatonie oder das SpannungsIrresein. Eine klinische Form psychischerKrankheit. In Klini$che Abhandlungen fiber psychische Krankheitin. !. Heft. Berlin: August Hirschwald Verlag.

done in a medium with antibiotics. Several antibiotics are known to inhibit PLA., activity (Chang et al 1987). Did the authors investigate the possibility that an inhibition of PLA: activity by antibiotics in the cell culture reduced the difference between schizophrenics and controls? Moreover, schizophrenics were found to show a slower growth rate of fibroblasts in culture than healthy controls (Mehadik et al 1991). What were the growth rates of lymphoblasts in schizophrenics and controls in their culture? If lymphoblasts from schizophrenics took longer to grow in the culture (which would be an interesting finding), then they may have been exposed for a longer time to antibiotics; this could explain the increased inhibition of PLA2 activity in these patients' cells and thus the lack of a difference as compared with controls. These methodological aspects should be clarified before the data are further discussed. In the report of our replication study (Gattaz et al 1990), we suggested a possible mechanism to explain


the increment of PLA2 activity in schizophrenia. It seems to us unlikely that a genetic defect in the structure of the enzyme itself would cause an increment in its activity. The activity of the enzyme is modulated by a class of endogenous PLA2-inhibiting proteins (PLIPs) that are under genetic control (reviewed in Chang et al 1987). Accordingly we proposed, as a working hypothesis, that a genetically determined deficit in the synthesis or release of PLIPs could result in disinhibition of PLA2 and consequently in increased enzyme activity in schizophrenia. We are presently making an attempt to clarify this relation3hip b~tween PLIPs and PLA2 activity in schizophrenic patients. Such a mechanism cannot be ruled out by the data of Bennett et al, because as these authors stressed, the technique of cell growth in culture in their study neutralizes the influence of other biological factors on PLA2 activity. Thus, contrary to their suggestion, it is thoroughly possible that their approach in vitro would fall to detect a genetic defect in vivo, such as a deficit in PLIPs that results in increased PLA2 activity in schizophrenia. Their results suggest only that a defect in PLA2 per se (e.g., in the molecular structure of the enzyme) is not responsible for increased activity in schizophrenia, which is in fact a finding of interest. In the same way, their results do not support the conclusion that increased PLA2 activity is a "state" characteristic in schizophrenia. In addition to our findings of ;ncreased PLA2 activity in plasma and serum from two independent samples of drug-free schizophrenics (Gattaz et al 1987, 1990), we have recently concluded an investigation of the membrane bound enzyme activity in platelets (Gattaz et al 1990, manuscript in preparation). Platelets are frequently used as peripheric models for neurons, as both have been shown to share similar membrane and receptor characteristics (Pletscher 1986). In agreement with our published results in plasma and serum, we found a significant increment of platelet PLA2 activity in drug-free schizophrenics compared with healthy conu~ls and to nonschizophrenic psychiatric patients, suggesting further a specificity of this finding for schizophrenia. In our studies we did not find a consistent correlation between PLA2 activity and BRPS scores, which does not support the assumption that increased enzyme activity is a result of the "state" of increased psychopathology (e.g., activation, anxiety/depression, stress, etc). Moreover, if this were true, we should also expect increased PLA2 activity in the nonschi-

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zophrenic psychiatric patients investigated in our studies. Increased enzyme activity was also observed in first-onset, drag-naive schizophrenics, thus excluding the bias of a "chug state." Actually, neuroleptics were consistently found to reduce PLA2 activity (Gattaz et al 1990). In conclusion, we also found in schizophrenic patients an increased content of platelet lysophosphatidylcholine, the breakdown product of membrane phospholipids metabolism by PLA2 (Pangerl et al in press). Taken together, our data strongly suggest an accelerated breakdown of membrane phospholipids by PL,Az in schizophrenia. This h~s recently been supported by the results from a 3rapnuclear magnetic resonance (NMR) spectroscopy inw,~igation in the brain of schizophrenic patients (Pettegrew et al 1991). In the face of the crucial role of membrane phospholipid metabolism for neuronal function, I think it is an important task to clarify further the possible participation of PLA2 and of the factors modulating its activity in the etiology of at least a subgroup of schizophrenic psychoses. Wagaer F. Gattaz Central Institute of Mental Health P. O. Box 12 21 20 D-68000 Mannheim 1 Germany

References Bennett ER, Yedgar S, Lerer B, Ebstein RP (1991): Phospholipase A2 Activityin Epstein-Ban'vires-transformed lymphoblastcells from schizophrenicpatients. Biol Psy. chiatry 29:1058-1062. Chang J, Musser JH, McGregor H (1987): Phospholipase A2: Function and pharmacologicalregulation. Biochem Pharmaco136:2429-2436. Gattaz WF, K611ischM, Thuren T, Virtanen JA, Kinnunen PKJ (1987): Increased plasma PLA2 activity in schizophrenic patients: Reduction after neuroleptic therapy. Biol Psychiatry 22:421-426. Gattaz WF, Hiibner CK, Nevalainen TJ, Thuren T, Kinnunen PKJ (1990): Increased serum phospholipase A2 activity in schizophrenia: A replication study. Biol Psychiatry 28:495-501. Mehadik SP, Mukherjee S, Laev H, Ravinder R, Schnur DB (1991): Abnormal growth of skin fibroblasts from schizophrenic patients. Psychiatry Res 37:309-320. Pangerl A, Steudle A, Jaroni HW', Rfifer R, Gattaz WF: Increased platelet membranelysophosphatidylcholinein schizophrenia. Biol Psychiatry (in press). PettegrewJW, KeshavanMS, PanchalingamK, et al (1991):



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Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drugnaive schizophrenics. Arch Gen Psychiatry 48:563-568. Pletscher A (1986): Blood platelets as neuronal models: Use and limitations. Clin Neuropharmacol 9 (suppl 4):344-346.

Response To the Editor: We agree with Dr. Gattaz that strictly interpreted our results can only rule out a defect in the structural enzyme PLA2. If the increased PLA2 activity claimed by Dr. Gattaz in plasma and platelets is in fact due to changes in "endogenous PLA2-inhibiting proteins that are under genetic control" then it cannot be excluded that such differences would not have been detected using transformed cells. However, we must point out that our inability to see such differences with cultured cells hinges on the

presumed absence of such "endogenous factors" in EBV-transformed cells. Unfortunately, we have not examined transformed lymphoblasts for the presence of such endogenous factors and we are therefore unable to comment on this possibility. We are in agreement with Dr. Gattaz that further studies of PLA2 in schizophrenia are warranted. It might be best to concentrate such future studies to postmortem brain tissue or in vivo measurements, because studies of peripheral markers in schizophrenia have an unhappy history of sometimes producing spurious findings.

Richard P. Ebstein Sarah Herzog Memorial Hospital P. O. Box 140 Jerusalem 91001 Israel

Phospholipase A2 in schizophrenia.

214 Correspondence BIOL PSYCHIATRY 1992;31:209-216 development of child and adolescent psychiatry in Europe were memorialized in the American Journ...
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