The enzymatic changes in the facial nucleus of the rat occurring after single nerve transection were compared with those after double lesion. In a first operation the left facial nerve was transected and 2 weeks later, both the left and the right facial nerves were axotomized. The double or “conditioning” lesion produced a complex pattern of changes that differed from those after a single lesion. Three enzymes were investigated both biochemically and histochemically. Acetylcholinesterase is representative of the group of transmitter-related enzymes which in general showed a decrease after a single lesion. The hexose monophosphate shunt enzymes, represented here by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, are known to increase in the perikaryon. 5′-Nucleotidase is a marker enzyme for the perineuronal satellite glia which also increase in number during chromatolysis. The following results were obtained: (i) In comparison with the single-lesion side the conditioning-lesion side exhibited less activity of the pentose phosphate shunt enzymes on days 7 and 12 after the second operation. On the conditioning-lesion side the amount of enzyme per perikaryon was higher on days 1 and 3, approximately the same on day 7, and less on day 12 compared with the single-lesion side. (ii) The conditioning-lesion side displayed a more pronounced decrease of acetylcholinesterase. (iii) 5′-Nucleotidase increased again after a second axotomy and reached the same level of activity as after a single lesion. These data suggest that a conditioning lesion does not simply amplify the ongoing axonal reaction of the cells in a linear fashion, but that it leads to a complex response. The data are in favor of a shorter initial delay prior to the axonal outgrowth which occurs after a conditioning lesion. However, our data could not explain an enhancement of axonal outgrowth velocity after the second operation.

WHO COLLABORATIVE ACTIVITIES IN BIOLOGICAL PSTCHIATRY AND PSYCHOPHARMACOLOGY: RESULTS AND NEW INITIATIVES: PDF Only

Blood was drawn from 14 normal volunteers twice before, immediately after a 1-minute immersion of the nondominant hand in ice water (cold pressor test), and twice during recovery. Serum levels of β-endorphin, cortisol, prolactin, growth hormone, and opioid activity were determined, and measures of subjective pain appraisal and coping styles were obtained. Cortisol was the only variable to show a significant increase as a function of noxious stimulation. Correlational analysis yielded relationships between neuroendocrine variables and subjective pain appraisal as well as coping styles, suggesting complex interactions between neuroendocrine and psychological processes in human pain.

Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was measured in the CSF of 30 schizophrenic patients and 27 normal controls. The CSF DBH activity in the patients was not significantly different from that in controls. Levels of CSF DBH activity in individual patients were highly constant over time and were not influenced by clinical state or neuroleptic treatment. Low levels of DBH in CSF did significantly relate to good social and sexual functioning, good prognosis, less symptoms between hospitalizations, and excellent clinical response to neuroleptic treatment. We speculate from these data that low brain DBH activity may produce a type of vulnerability to psychotic decompensation and thereby influence the clinical course, although it does not cause schizophrenia, in general. Low CSF DBH activity may delineate a "reactive" subgroup from the heterogenous population of patients with diagnoses of schizophrenia.

In an earlier, separate study, the authors found that human aggression and suicide (a specific aggression-related behavior) were associated with lower levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. That study focused on subjects with personality disorders without affective illness. In the present study they examine the life history of aggression and history of suicidal behavior in 12 subjects with borderline personality disorders without major affective disorder. Histories of aggressive behaviors and of suicide attempts were significantly associated with each other, and each was significantly associated with lower 5-HIAA levels. Altered serotonin metabolism may be a highly significant contributing factor to these behaviors in whatever diagnostic group they occur.

SummarySix of eleven drug-free schizophrenic patients who were depressed following remission of their illness showed a significant decrease in their depressive symptomatology during a double-blind, placebo substitution lithium trial. Traditional indicators of prognosis did not predict lithium response in this small sample; the schizophrenic patients tolerated the lithium well. Lithium should be studied further in a larger patient sample as an adjunct in the treatment of post-psychotic depression, which frequently is treatment resistant.

The relationship between serum calcium and magnesium levels and neuroleptic-induced extrapyramidal symptoms (EPS) was studied in schizophrenic patients. The 16 patients in whom EPS developed had a significantly lower mean drug-free calcium level than the six patients in whom EPS did not develop. In patients in whom EPS developed, drug-free serum calcium and magnesium levels together correlated significantly with the neuroleptic dosage at which EPS first developed; lower calcium and magnesium values predicted EPS at lower dosages. We have previously shown that both serum calcium and magnesium levels were significantly lower during neuroleptic treatment than in the drug-free state. In this study, a similar trend was observed, but the calcium value tended to be, and the magnesium value was significantly lower at the onset of neuroleptic-induced EPS than during the mean of an entire pimozide trial.

Amphetamine has been clearly documented to be an efficacious treatment for hyperactive children. The pharmacokinetics of amphetamine have been studied in adults, but not in children. Sixteen male children who scored >2 SD from norms on Factors I and IV of Conners's Teacher Rating Scale and who were not excluded for reasons to do with medical or psychiatric conditions, intelligence, or age, had a plasma d-amphetamine apparent elimination half-life of 6.8±0.5 h. Peak plasma level occurred between 3 and 4 h (62.7±3.8 and 65.9±3.6 ng/ml, respectively). Six of these children had a repeat study and there were no significant differences within subject in apparent elimination half-lives and attained peak blood levels. The variation in plasma levels was greater during absorption than during elimination. Both behavioral and motor activity resonses as analyzed by differences between amphetamine and placebo days (by paired t-tests) indicate significant responses between hours 1–4; however, these responses do not correlate with plasma amphetamine levels; they occur during the absorption phase. The decreased response to later similar plasma levels of d-amphetamine may be related to depletion of catecholamine stores, to replacement by a ‘false neurotransmitter’ metabolite of amphetamine, or to alteration in receptor sensitivity.

Summary Serum calcium and magnesium were studied in drug-free and neuroleptic-treated schizophrenic patients. Calcium and magnesium were not significantly different in 31 unmedicated schizophrenic patients compared with normal controls. Serum calcium was altered, however, in two subgroups: (1) Patients who remitted after neuroleptic withdrawal were significantly lower in calcium than those who did not remit; (2) catatonic schizophrenic patients appeared to have an increased calcium at the onset of catatonic stupor. Patients treated with pimozide were found to have a significant decrease in both calcium and magnesium compared with their drug-free values. These same patients showed a similar decrease in both electrolytes during treatment with fluphenazine, a structurally different neuroleptic drug.

An increase in circulating leukocytes accompanied lithium treatment in 28 consecutively studied manic-depressive patients. Acutely manic patients showed the most marked changes and maintained leukocyte counts of 10,000 to 14,000 during the first two to four weeks of lithium administration. Leukocyte counts returned to pre-lithium levels within one week after discontinuation of the drug. In 11 patients receiving lithium for longer periods the elevation in white cell count persisted throughout treatment.

THE PURPOSE of this paper is to present the clinical results of an intensive longitudinal double-blind study in 30 manic-depressive and depressed patients; preliminary aspects of this work have been presented elsewhere.1,2In addition, we have reported on some biochemical changes occurring at various stages in the course of the lithiumcarbonate treatment of these patients2; this aspect of our work is the subject of other recent communications3,4and will not be reviewed here. The therapeutic use of lithium-carbonate in affective disorders has recently been the focus of considerable interest, particularly in light of clinical evidence that it may have beneficial effects not only in mania but also in some cases of depression.5An additional and perhaps unique feature of this drug is its reported long-term mood-stabilizing properties when used prophylactically.6If the initial clinical studies can be further substantiated, then the theoretical implications for a

IN 1943 several groups of mentally ill adult patients in the Pontiac State Hospital, Pon- tiac, Mich., were inoculated with different com¬ binations of diphtheria and tetanus toxoids, pertussis and typhoid vaccines, and scarlet fever toxin, according to defined dosage schedules.The subjects' reactions were studied, and their specific immune responses were measured in terms of circulating antibodies.

IN 1943 several groups of mentally ill adult patients in the Pontiac State Hospital, Pontiac, Mich., were inoculated with different combina,tions of diphtheria and t,etanus toxoids, pertussis and typhoid vaccines, and scarlet fever toxin, according to defined dosage schedules. The subjects' reactions were studied, and their specific immune responses were measured in terms of circulating antibodies. The results forme,d the basis for a series of reports, which demonstrated that responses to each antigen were excellent in all combinations studied (14). In 1956 many of the subjects from this investigation were still in residence at the hospital and available for a study of their responses to a booster dose oif antigen. These institutionalized subjects represented a different population from the noninstitutionalized subjects reported earlier (5). Not only did they differ with respect to their age ancd environment, but owing to an institutional policy, they had received subsequent boosters of diphtheria and tetanus toxoids. Even before we gave them tlhe injections in 1943, the institutionalized subjects had received numerous Schick tests and booster injections of diphtheria toxoid at intervals throughout their hospitalization, exteniding back as far as 1932. The study reported here was designed primarily to measure the responses of 290 institutionalized subjects to a small dose of diphtheria and tetanus toxoids to determine whether their responses differed from those of the noninstitutionalized subjects, reportecl previously, who had not been given intervening booster injections (5). Secondarily, the investigation was concerned with the effect of a small dose of pertussis vaccine on production of agglutinins. Because pertussis may occur in older children and adults, even t,hough injected with pertiissis vacc.ine in infancy (personal communication fromI Dr. Harold J. Lambert, July 1963), thlere is a growing interest in the extension of pertussis boosters beyond preschool age. It seemed Dr. Volk is commissioner, Saginaw County Health Department, Saginaw, Mich. Dr. Gottshall is chief, antigens and antisera unit, biologic products section, and Dr. Anderson is chief, biologic products section, division of laboratories, Michigan Department of Health, Lansing. Dr. Top is head, department of hygiene and preventive medicine, State University of Iowa, Iowa City. Dr. Bunney is vice president and director of manufacturing operations, E. R. Squibb & Sons, New York City. Dr. Serfling is chief, Statistics Section, Epidemiological Branch, Communicable Disease Center, Public Health Service, Atlanta, Ga. Maud G. Gilbert, Saginaw County Health Department, and Frances Angela, Michigan Department of Health laboratories, gave technical assistance in this study. This study was made in cooperation with the technical committee on immunization, epidemiology section, American Public Health Association, and was supported in part by research grant E-1115 from the National Institute of Allergy and Infectious Diseases, Public Health Service.

DURING the past 20 years we have studied the response to single and multiple antigen preparations in both institutionalized and non¬ institutionalized subjects (1-lf).In 1943-44, individuals in several of the study institutions were inoculated with different antigens: diph¬ theria and tetanus toxoids, typhoid and per¬ tussis vaccines, and scarlet fever toxin, singly or in various combinations.Many of the subjects were still available in 1958 for a followup study to determine their response to a booster injec¬ tion of some of the antigens.Among the individuals were 19 from an in¬ stitution for the mentally retarded with a rec¬ ord of no previous injections of tetanus toxoid.

FROM 1943 to 1950, large groups of institu¬ tionalized mentally ill or retarded patients and noninstitutionalized young adults and children were inoculated with different combinations of diphtheria and tetanus toxoids, pertussis and typhoid vaccines, and scarlet fever toxin.Studies, reported by Volk and associates (1lp), were made to determine the antibody re¬ sponses and the reactions elicited by different dosages and combinations of these antigens.When a reinoculation study of certain of these groups was initiated in 1956, the first problem to be resolved was the efficacy of booster doses consistent with freedom from reactions.This report.deals with the studies which led to the selection of a 0.2-ml.booster dose, and