Eli Robins

Function of the male sex organs in heroin and methadone users.

The function of the secondary sex organs was found to be markedly impaired in 29 participants in a methadone maintenance program. The ejaculate volume and seminal vesicular and prostatic secretions were reduced by over 50 per cent in methadone clients, as compared to 16 heroin addicts and 43 narcotic-free controls. Serum testosterone levels were also approximately 43 per cent lower in methadone clients than in controls or heroin users. Although the sperm count of methadone clients was more than twice the control levels, reflecting a lack of sperm dilution by secondary-sex-organ secretions, the sperm motility of these subjects was markedly lower than normal. On all measures of secondary-sex-organ and testicular function, heroin addicts appeared to fall between the methadone and control subjects, but, with the exception of sperm motility, the deviation from control values did not reach statisitcal significance.

A study of selected catecholamine metabolizing enzymes: a comparison of depressive suicides and alcoholic suicides with controls.

—The regional distributions of monamine oxidase (MAO) (EC 1.4.3.4), catechol‐O‐methyltransferase (COMT) (EC 2.1.1.6), tyrosine hydroxylase (TH) (EC 1.14.3.2), and dopamine‐β‐hydroxylase (DBH) (EC 1.14.2.1) have been examined in human brains obtained at autopsy from persons who died of natural causes (controls), and from persons who committed suicide and were further categorized as suffering from affective disorder (depression) or from alcoholism. Post mortem animal studies showed no changes in MAO or COMT activities in rabbit brain or in DBH activity in rat brain when the intact bodies were left at room temperature up to 24 h. TH activity in rabbit brains, however, began to decline immediately after death and after 24 h at room temperature it was approximately 48 per cent of the fresh brain level. There was no significant variation in activity of COMT, TH and DBH in human brain attributable to age or sex. MAO activities in the 60–70 yr decade were 34 per cent higher than in the 30–40 yr decade. MAO activities were highest in the hypothalamus and substantia nigra, TH activities were highest in substantia nigra, putamen and head of caudate, and DBH activities were greatest in tegmentum of pons and hypothalamus. Only minimal regional differences in COMT activities were observed. No significant differences were found between enzyme activities in brain areas of controls and suicides with the possible exception of TH in the substantia nigra, where the depressive suicides (but not the alcoholics) showed greater activity (P < 0·02). These findings appear not to support the catecholamine hypothesis of affective disorder.

QUANTITATIVE BIOCHEMICAL STUDIES OF WALLERIAN DEGENERATION IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEMS—I

SINCE the pioneer studies of NOLL (1 899) and MOTT and HALLIBURTON (1 901) on the chemical changes in degenerating nerve, many refinements in the methods of fraction.sting and determining the chemical constituents of nervous tissue have been made. BJMNTE (1949) was one of the first to study the changes of various lipid fractions in degenerating peripheral nerve using methods which determine the lipids as they are known today. These results have been greatly extended by ROSSITER and co-workers who have studied, in addition to the changes in the lipids, the changes in various phosphorus fractions and enzymic activities in degenerating sciatic nerve of the cat (JOHNSON, MCNABB and ROSSITER, 1949; LOGAN, MANNELL and ROSSITER, 19526; HOLLINGER, OSSITER and UPMALIS, 1952; HOLLINGER and ROSSITER, 1952). However, there has apparently been no report on the quantitative chemical changes during Wallerian degeneration in a central white tract. The study of chemical changes in degenerating central tracts as well as in peripheral nerve has been greatly facilitated in the present study by utilizing recent modifications and extensions of the original Linderstrom-Lang and Holter quantitative histochemical method (LOWRY, 1953; ROBINS, 1957). The advantages of this method, as compared with the classical technique of gross dissection and homogenization of the nerve tissue, include: (a) the use of highly sensitive microchemical methods which permits the chemical analysis of a great many different chemical constituents of small central tracts or of a single peripheral nerve trunk; (b) chemical constituents and enzymes are stable in frozen-dried material for years; thus one can return to the same material repeatedly; (c) close visual control of dissection eliminates the variability introduced by epineural connective tissue, meninges, major blood vessels, and adjacent nervous tissue. Unless the quantitative histochemical method was used, serious technical difficulties would arise both in getting enough control tissue for analysis and in dissecting an anatomically defined central tract. In this report, the changes in the concentrations of total lipids, 6 lipid fractions, phosphorus and amino-nitrogen fractions, and protein of a peripheral nerve (tibia1

DISTRIBUTION OF γ-AMINOBUTYRIC ACID IN THE LAYERS OF THE CEREBRAL AND CEREBELLAR CORTEX. IMPLICATIONS FOR ITS PHYSIOLOGICAL ROLE*

INTEREST in y-aminobutyric acid (yAB)t has been stimulated by its possible roles as an inhibitory substance in the mammalian nervous system, and as a compound involved in oxidative metabolism of the nervous system. The development of a sensitive and specific enzymic assay for yAB has made possible its measurement in the individual layers and sublayers of the cerebral and cerebellar cortex. These results will be presented and discussed with regard to the possible physiological role(s) of yAB.

Lithium treatment of mania: Clinical characteristics, specify of symptom change, and outcome

The effects of lithium treatment and prediction of response in 18 manic patients were studied as part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression. Patients were rated using the Mania Diagnostic and Severity Scale (MADS) and an additional battery of behavioral constructs developed for measurement of state and drug response in depressed patients. About 67% of the patients had good treatment outcome after 26 days of lithium treatment. Responders did not differ from nonresponders before treatment with respect to delusions, hallucinations, or irritable-paranoid symptoms. Nonresponders were rated as more anxious than responders before treatment and had higher scores on the Hamilton Rating Scale for Depression. Improvement on the MADS, however, did not correlate with pretreatment behavioral ratings. Patients with relatively high ratings for aspects of behavior not specific to mania tended to improve in these regardless of change in MADS score. Manic patients who were also depressed (44%) had higher mania ratings than manic patients who were not depressed. Patients with concomitant depression and mania had significantly worse overall treatment outcome, although their depression ratings improved during lithium treatment.

Obsessive-compulsive neurosis: Record, follow-up, and family studies. I. Inpatient record study

Abstract This study consisted of 150 inpatients in whom obsessions and compulsions were major or predominant symptoms. Twenty-one per cent of the patients were included in subgroup I. The clinical picture and course of illness in this subgroup consisted only of obsessions and compulsions, and the cause for hospitalization was incapacitation by these symptoms. Patients in this subgroup were distinguished from all other patients by the absence of decline in their occupational status. Subgroup II, the largest in the study, consisted of 38% of the patients in whom depression followed many years of severe obsessions and compulsions. Depression is recognized as “probably the most common complication of obsessional neurosis,”16 and it would appear that it is the largest single cause of hospitalization for patients with obsessive-compulsive neurosis. Eleven per cent of the patients had primary depressive illness with obsessions and compulsions and were included in subgroup IV which, despite its small size, was readily distinguishable from the previously mentioned subgroup II. The important question of the association between obsessive-compulsive illness and schizophrenia was raised by the 14 patients (9%) in subgroup V who are presented in detail in Table 5. The effective, paranoid, and sometimes remitting types of psychosis that appear to be associated with some cases of obsessive-compulsive illness do not meet the diagnostic criteria for schizophrenia that we have used, and the divergence of opinions in the literature may reflect the impressionistic, rather than systematic, way that the diagnosis of schizophrenia is made. A blind personal follow-up of the patients and the study of psychopathology in their families will provide us with more data that are essential to answer some of the questions and confirm (or reject) findings presented in this study.

Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment

Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.

Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: I. Background and theoretical considerations.

There are many reports which suggest that patients with effective illness (mania and/or depression) have abnormalities in the functioning of one or more neurobiological systems. At a conference convened by the Clinical Research Branch, Division of Extramural Research Programs, National Institute of Mental Health, these findings were reviewed and some of the factors impeding movement towards a more complete and integrated view of the functioning of neurobiological systems in patients with mania or depression were identified. As a result, a multi-research centre, collaborative approach to the study of the psychobiology of affective disorders was developed. In this collaborative programme, which has now been underway for several years, the focus has been upon: (a) the assessment of the functioning of several different types of biological systems in the same patient, both before and during treatment; (b) obtaining a reasonably large number of patients and comparison subjects; and (c) the use within and across centres of standardized diagnostic categories and behavioural rating methodologies. In this paper the history, background, and rationale for this collaborative effort are reviewed. Those biological systems chosen for study are noted, and issues such as reliability and validity of diagnoses, measurement of state variables, assessment of change with treatment, and logistical and coordinating problems are discussed.

The low level of 5-hydroxytryptophan decarboxylase in human brain☆

Abstract A modified fluorometric method using ninhydrin as a fluorescence reagent for measuring 5-hydroxytryptophan decarboxylase is described. The very low levels of this enzyme in human brain are demonstrated. Although there is no complete proof that the enzyme may be entirely absent, the weight of evidence suggests it is present at low levels. It is speculated that in human brain 5-hydroxytryptophan decarboxylase rather than tryptophan hydroxylase may be the rate-limiting step in serotonin synthesis, or that there is an as yet unknown pathway for serotonin synthesis in human brain.

QUANTITATIVE HISTOCHEMICAL STUDIES OF THE MORPHOGENESIS OF THE CEREBELLUM I—TOTAL LIPID AND FOUR ENZYMES*

THE HISTOLOGICAL appearance of the layers of the developing cerebellar cortex in the albino rat has been described in detail by ADDISON (191 1). In the foetal rat, as late as the nineteenth day, only the presumptive cerebellar layers--ependymal, mantle, and marginal-can be readily distinguished. At birth, or just before, relatively defined layers appear. These are the external granular layer, the molecular layer (including the Purkinje cells at its inner margin), the internal granular layer, and the subjacent white matter. Once these 4 layers have appeared (the white matter immediately subjacent to the internal granular layer will be referred to as a layer in this report), it is possible to follow discretely each into adult life or until disappearance (external granular layer). The early segregation of the layers of the cerebellar cortex offered, therefore, an unusual opportunity to study the development in the central nervous system of relatively homogeneous histological regions. To understand the chemistry of the developing nervous system in detail, it will be necessary ultimately to study it in terms of its individual histological elements. While this observation may be true for any tissue, it is particularly applicable to the nervous system because of its extreme architectural complexity. Because of the minute size of these individual cerebellar layers, their quantitative chemical study required the use of sensitive microchemical procedures and their isolation, under direct histological control, in a chemically intact state (LOWRY, 1953; ROBINS, 1957). The use of the rat offered an advantage, since almost the entire development of the cerebellum occurs postnatally. In this report, we will describe changes i n total lipid, lactic dehydrogenase (LDH)S, malic dehydrogenase (MDH), isocitric dehydrogenase (ICDH), and dipeptidase (PEPT) in the individual cerebellar layers of the @day (newborn), 9-day, 14-day, and adult rat. These quantitative histochemical data will be supplemented with data from