Correspondence
BIOL PSYCHIATRY 1992;32:207-213
2i 1
and her osmolality by 5.7% to 298 mos/kg. After 1 hr the desipramine level had declined to 81 ng/ml and the osmolality to 289 mos/kg. Ms. B was a 22-year-old female with a diagnosis of dysthymia and non-purging bulimia nervosa who had been taking amitriptyline 150 mg a day at bedtime. The combined serum levels of amitriptyline and nortriptyline increased from 101 ng/ml to 116 ng/ml after running (14.9%), and fell again to 94 ng/ml I hr after the exercise was stopped. All of these total tricyclie levels consisted of approximately equal parts of amitdptyline and nortriptyline. Serum osmolality remained almost stable with 285 mos/kg pre-running, 298 mos/kg immediately after (increase of 2.1%), and 286 mos/kg i nr after running. In both patients a moderate increase of antidepressant serum levels occurred after running : 10% and 14.9%, respectively. This is outside the withinday coefficients of variation, which are 4%-6% for these drugs using GCMS. One hour after exercise was stopped, and after the patients were allowed to eat and drink, the increase had disappeared. It is possible that exercise may reduce the volume of distribution of the drugs through changes in blood flow, plasma protein and tissue binding, temperatuce, and pH changes (Van Baak, 1990). The slight increase of serum osmolality (5.7% and 2.1%, respectively) due to loss of sweat during exercising might
in part explain this phenomenon, because this leads to increased protein binding of drugs. However, only "free" (unbound) drug is in equilibrium with tissue and therefore biologically active. The exact mechanism of the change in volume distribution after exercising remains unclarified. Whereas our results emphasize the importance of controlling physical activity in pharmacokinetic studies, the practical consequences are far less clear. The results seem to suggest that short-term strenuous exercise does not ir,crease tricyclic serum levels to a degree that is clinically significant. Further studies are warranted to investigate the effect of long-term exercise on antidepressant serum levels.
Herpes Simplex Mimicking Functional Psychosis
echolalia and perseveration. On admission her blood pressure (BP)was 160/100. Erythrocyte sedimentation rate (ESR) was 21 with a normal white count. All other blood tests, including cultures, were unremarkable. Pregnancy test was negative. CxR was normal. Brain computed tomography (CT) was normal. An electroencephalogram (EEG) was inconclusive due to her physical agitation. A complicating factor on admission was the presence of a large abdominal mass. An abdominal ultrasound 3 months earlier had suggested that this was an ovarian cyst. A recommended laparotomy was never done. On admission, clinical examination showed the mass to have grown somewhat. A repeat ultrasound had to be abandoned again due to her extreme agitation despite 30 mg of haloperidol QDS.
To the Editor: It is unusual for a case of encephalitis to present to a psychiatric service. Nonetheless, it does occur, and Lishman, in his classic text Organic Psychiatry, says, "Special interest attaches to the occasional cases which present with psychiatric disorder." A 31-year-old Ghanaian woman was admitted to an acute psychiatric ward in a London teaching hospital following referral by her general practitioner. She was accompanied by her husband, an educated man, who provided mush of the history. She presen:ed with visual hallucinations, paranoia, and a 3week history of headaches. She exhibited marked
Martina de Zwaan Dept. of Psychiatry University of Vienna Wahringer Gtirtel, 8-20 1090 Vienna, Austria
References Van Baak (1990): Influence of exercise on the pharmacokinetic of drugs. Clin Ph~wmacokinet19:3243.
212
BIOL PSYCHIATIIY
Correspondence
1992;32:207-213
A week after admission, her BP became increasingly labile, ranging between 160/90 and 190/130. She became pyrexial (38.5 axilla). Repeat blood cultures were negative and she was started on intramuscular Cephalospodn. Her white count rose to 16.0 and ESR to 40. A malarial parasite screen was neg,_.t!,te. She developed clouding of consciousness and had difficulty breathing due to stiffness of the neck and chest muscles. Pulse was 120/min and she was incontinent of urine. Neuroleptic malignant syndrome was diagnosed (creatinine phosphokinase was not measured), haloperidol was stopped, and efforts were made to control her excitement on large doses of diazepam, which proved to be most difficult (60 mg daily, intravenously). A lumbar puncture was attempted but not completed due to her agitation. Ten days after admission, right-sided rhythmic movements developed. Phenytoin was commenced to no effect. The patient became mute and did not respond to commands, At this point, she was transferred to an acute medical ward. Another EEG had to be abandoned due to movement. The lumbar puncture was repeated, this time successfully, showing possible cryptosporidium. Immediate transfer was arranged to a regional neurological center. Here, cryptosporidium was in fact ruled out. Tests for HIV 1 and 2 were negative. The white count had normalized, but the ESR had risen to 70. Three separate blood films showed neither malarial parasites nor trypanosomes. Protein electrophoresis and auto.antibody and immune complex screenings were unremarkable as were serum and cerebrospinal
fluid virology. Mantoux test was negative. An EEG, done successfully this time, showed three fits during the recording, each beginning from different foci in the left hemisphere. Three CT scans were normal. Herpes simplex encephalitis wu~ t,.~ ~nosr. ~ and IV acyclovir and chloramphenicol were commenced. The fits continued and proved extremely difficult to control despite combination treatment with five antiepileptic drugs--phenytoin, sodium valproate, clorazepam, phenobarbitone, and vigabatrinmall given intravenously. ESR remained high and touched i 10. Blood cultures remained negative througheut. After 2 weeks of little progress, high doses of steroids were commenced. This had a dramatic effect and over the next 3 weeks her level of consciousness improved to the point where she could walk with the physical support of the nursing staff. After 5 weeks she was transfered back to the initial referring teaching hospital. A gynecological examination showed that the abdominal mass was resolving and laparotomy was not done. The patient could now recognize her relatives. She could speak a meaningful sentence but only to her husband. She was able to walk slowly, unsupported. She remained afebrile. Two weeks after her return to the initial hospital she was discharged. She had asked to return to Ghana and her husband did in fact return there with her soon after her discharge, where she has remained, being cared for by her brother and sisters. Philip Steadman St George's Teaching Hospital London SWl7
Neurodevelopmental Model of Schizophrenia
prising because they cited and compared their imaging results with those of Jernigan et al (199 !), who cited our 1982 model in some d:~ail. i should like to remind those interested in our neurodevelopmental hypothesis that there were wree arguments advanced in 1982. The ~irst was that there is strong evidence that the braia undergoes profound changes in the second decade of life: this evidence includes a marked decline in cerebral metabolic rate as measured by the Kety-Schmidt method (evidence greatly strengthened and ex-
To the Editor: Dr. Swayze et al develop the view that schizophrenia might result from a developmental disorder of synaptic pruning during the second decade of life, but neglect to state that I put forward this notion in 1982 (Feinberg 1982/83). With my associates, we further extended our hypothesis to affective illness in 1990 (Feinberg et al 1990). This oversight is sur-
BIOL PSYCHIATRY 1992;32:207-213
2i 1
and her osmolality by 5.7% to 298 mos/kg. After 1 hr the desipramine level had declined to 81 ng/ml and the osmolality to 289 mos/kg. Ms. B was a 22-year-old female with a diagnosis of dysthymia and non-purging bulimia nervosa who had been taking amitriptyline 150 mg a day at bedtime. The combined serum levels of amitriptyline and nortriptyline increased from 101 ng/ml to 116 ng/ml after running (14.9%), and fell again to 94 ng/ml I hr after the exercise was stopped. All of these total tricyclie levels consisted of approximately equal parts of amitdptyline and nortriptyline. Serum osmolality remained almost stable with 285 mos/kg pre-running, 298 mos/kg immediately after (increase of 2.1%), and 286 mos/kg i nr after running. In both patients a moderate increase of antidepressant serum levels occurred after running : 10% and 14.9%, respectively. This is outside the withinday coefficients of variation, which are 4%-6% for these drugs using GCMS. One hour after exercise was stopped, and after the patients were allowed to eat and drink, the increase had disappeared. It is possible that exercise may reduce the volume of distribution of the drugs through changes in blood flow, plasma protein and tissue binding, temperatuce, and pH changes (Van Baak, 1990). The slight increase of serum osmolality (5.7% and 2.1%, respectively) due to loss of sweat during exercising might
in part explain this phenomenon, because this leads to increased protein binding of drugs. However, only "free" (unbound) drug is in equilibrium with tissue and therefore biologically active. The exact mechanism of the change in volume distribution after exercising remains unclarified. Whereas our results emphasize the importance of controlling physical activity in pharmacokinetic studies, the practical consequences are far less clear. The results seem to suggest that short-term strenuous exercise does not ir,crease tricyclic serum levels to a degree that is clinically significant. Further studies are warranted to investigate the effect of long-term exercise on antidepressant serum levels.
Herpes Simplex Mimicking Functional Psychosis
echolalia and perseveration. On admission her blood pressure (BP)was 160/100. Erythrocyte sedimentation rate (ESR) was 21 with a normal white count. All other blood tests, including cultures, were unremarkable. Pregnancy test was negative. CxR was normal. Brain computed tomography (CT) was normal. An electroencephalogram (EEG) was inconclusive due to her physical agitation. A complicating factor on admission was the presence of a large abdominal mass. An abdominal ultrasound 3 months earlier had suggested that this was an ovarian cyst. A recommended laparotomy was never done. On admission, clinical examination showed the mass to have grown somewhat. A repeat ultrasound had to be abandoned again due to her extreme agitation despite 30 mg of haloperidol QDS.
To the Editor: It is unusual for a case of encephalitis to present to a psychiatric service. Nonetheless, it does occur, and Lishman, in his classic text Organic Psychiatry, says, "Special interest attaches to the occasional cases which present with psychiatric disorder." A 31-year-old Ghanaian woman was admitted to an acute psychiatric ward in a London teaching hospital following referral by her general practitioner. She was accompanied by her husband, an educated man, who provided mush of the history. She presen:ed with visual hallucinations, paranoia, and a 3week history of headaches. She exhibited marked
Martina de Zwaan Dept. of Psychiatry University of Vienna Wahringer Gtirtel, 8-20 1090 Vienna, Austria
References Van Baak (1990): Influence of exercise on the pharmacokinetic of drugs. Clin Ph~wmacokinet19:3243.
212
BIOL PSYCHIATIIY
Correspondence
1992;32:207-213
A week after admission, her BP became increasingly labile, ranging between 160/90 and 190/130. She became pyrexial (38.5 axilla). Repeat blood cultures were negative and she was started on intramuscular Cephalospodn. Her white count rose to 16.0 and ESR to 40. A malarial parasite screen was neg,_.t!,te. She developed clouding of consciousness and had difficulty breathing due to stiffness of the neck and chest muscles. Pulse was 120/min and she was incontinent of urine. Neuroleptic malignant syndrome was diagnosed (creatinine phosphokinase was not measured), haloperidol was stopped, and efforts were made to control her excitement on large doses of diazepam, which proved to be most difficult (60 mg daily, intravenously). A lumbar puncture was attempted but not completed due to her agitation. Ten days after admission, right-sided rhythmic movements developed. Phenytoin was commenced to no effect. The patient became mute and did not respond to commands, At this point, she was transferred to an acute medical ward. Another EEG had to be abandoned due to movement. The lumbar puncture was repeated, this time successfully, showing possible cryptosporidium. Immediate transfer was arranged to a regional neurological center. Here, cryptosporidium was in fact ruled out. Tests for HIV 1 and 2 were negative. The white count had normalized, but the ESR had risen to 70. Three separate blood films showed neither malarial parasites nor trypanosomes. Protein electrophoresis and auto.antibody and immune complex screenings were unremarkable as were serum and cerebrospinal
fluid virology. Mantoux test was negative. An EEG, done successfully this time, showed three fits during the recording, each beginning from different foci in the left hemisphere. Three CT scans were normal. Herpes simplex encephalitis wu~ t,.~ ~nosr. ~ and IV acyclovir and chloramphenicol were commenced. The fits continued and proved extremely difficult to control despite combination treatment with five antiepileptic drugs--phenytoin, sodium valproate, clorazepam, phenobarbitone, and vigabatrinmall given intravenously. ESR remained high and touched i 10. Blood cultures remained negative througheut. After 2 weeks of little progress, high doses of steroids were commenced. This had a dramatic effect and over the next 3 weeks her level of consciousness improved to the point where she could walk with the physical support of the nursing staff. After 5 weeks she was transfered back to the initial referring teaching hospital. A gynecological examination showed that the abdominal mass was resolving and laparotomy was not done. The patient could now recognize her relatives. She could speak a meaningful sentence but only to her husband. She was able to walk slowly, unsupported. She remained afebrile. Two weeks after her return to the initial hospital she was discharged. She had asked to return to Ghana and her husband did in fact return there with her soon after her discharge, where she has remained, being cared for by her brother and sisters. Philip Steadman St George's Teaching Hospital London SWl7
Neurodevelopmental Model of Schizophrenia
prising because they cited and compared their imaging results with those of Jernigan et al (199 !), who cited our 1982 model in some d:~ail. i should like to remind those interested in our neurodevelopmental hypothesis that there were wree arguments advanced in 1982. The ~irst was that there is strong evidence that the braia undergoes profound changes in the second decade of life: this evidence includes a marked decline in cerebral metabolic rate as measured by the Kety-Schmidt method (evidence greatly strengthened and ex-
To the Editor: Dr. Swayze et al develop the view that schizophrenia might result from a developmental disorder of synaptic pruning during the second decade of life, but neglect to state that I put forward this notion in 1982 (Feinberg 1982/83). With my associates, we further extended our hypothesis to affective illness in 1990 (Feinberg et al 1990). This oversight is sur-
