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An amphetamine model of manic depressive illness.

Many features of manic-depressive illness can be mimicked in man by the use and withdrawal of amphetamines. In higher doses these drugs induce a syndrome virtually indistinguishable from paranoid schizophrenia. In this paper, some of the biochemical and physiological effects of the amphetamines are examined with the hope of clarifying the nature of the biological changes in these two major functional psychoses. The actions of the amphetamines are shown to reveal the operation of specific homeostatic or adaptive nervous mechanisms. These appear likely also to operate in adaptation to psychological stress. Evidence is presented that these mechanisms are malfunctioning in manic-depressive and acute schizophrenic states and that this accounts for many of the clinical features of these conditions.

Adaptation, Psychological↗

Manic depressive illness in adolescence and childhood: review and case report.

The literature on this topic from its inception by Kraepelin is reviewed. While Kraepelin and the French school always recognized juvenile mania, the Anglo-American school has no such unanimity of opinion. Less than 100 cases are described in the world literature. In Canada affective psychoses are rarely diagnosed under age 10 and of all affective psychoses admitted to institutions less than 5% are under age 20. The differences between child and adult mania are outlined. It is proposed that manic-depressive illness occurs in children but is not diagnosed more often because of its dissimilar presentation to the adult form and doubts about its existence in childhood. The case history of a 14 year old boy who presented in a hypomanic state is described. There was a strong family history of affective disorder. Both his parents and his half-sister were already on lithium for manic-depressive illness.

Adolescent↗

[Therapeutic pathomorphosis of affective psychoses during the process of long-term treatment with lithium salts].

The authors report of some results in a long-term (not less than 3 years) prophylactical administration of lithium preparations in 123 patients wiht manic-depressive psychosis and with favourable recurrent schizophrenia. The data contain some considerations in relation to variants of fractional, even and a partial reduction of the psychopathological phasic signs. In 28 patients in the interphasic period there was an anesthetic subdepression. The achieved results are analyzed by the authors from the point of view of a positive and negative therapeutical pathomorphosis.

Bipolar Disorder↗

Psychoses precipitated by psychotomimetic drugs. A follow-up study.

Fifteen patients who developed prolonged psychotic reactions following psychotomimetic drug use (probably primarily LSD) were followed up 1.9 to 5.8 years later. Two patients had committed suicide. Approximately half of the patients had a relatively good outcome and half did poorly. Aspects of the initial clinical picture that correlated with outcome measures are discussed. The possibility is considered that vulnerability to a prolonged psychotic reaction following psychotomimetic drug use may be related to a genetic vulnerability to illnesses in the manic-depressive/schizo-affective spectrum. In some instances this vulnerability may implicate central serotonergic neuronal systems.

Adolescent↗

Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness. Occurrence in the family of a lithium carbonate-responsive schizo-affective proband.

Studies with X-chromosome markers in mental illness have been limited to the diagnostic concept of primary affective disorders. The present study is the first to our knowledge to demonstrate statistically measurable linkage between color blindness and manic-depressive illness in a family identified by a schizo-affective proband. Linkage data and lithium carbonate response in the proband suggest that the schizophreniform-affective spectrum in members of the pedigree may reflect a genetically distinct disorder. The use of a genetic marker as a heuristic diagnostic criterion in a subgroup of heredofamilial psychoses with unclear diagnostic boundaries is proposed.

Adult↗

[Etiology and classification of mental disorders from viewpoint of "Universal genesis of psychoses"].

The concept of a "Universal genesis of psychoses" has been worked on by the author for about 12 years. It is mostly biologically orientated and deals with the development, classification and therapy of psychotic syndromes in an unconventional manner. Prejudices which would only interfere with research have been avoided as far as possible, and new results e.g. of biochemistry have been included. A more purposeful treatment with psycho-pharmacological agents is aimed at. Special emphasis is laid on the negation of real demarcations between manic-depressive, cycloid and schizophrenic syndromes which are assumed to be caused by many factors, and on the fact that psychopathological basic symptoms are "fundamental conditions" principally characteristic of all psychotic syndromes in different constellations.

Brain↗

[Cerebral embolism and psychosis with special reference to cardiac surgery (author's transl)].

Cerebral embolism can manifest itself in certain cases as pure psychosis. In the absence of neurological symptoms it might be mistaken for schizophrenia or manic-depressive psychosis. Cardiac disease and cardiac surgery involve a high risk of embolism. Microembolism plays a special role with extracorporal circulation. There is a significant increase of postoperative psychosis in cases with E.C.C. in comparison to closed heart surgery. Immediately post-operatively there occurs what has been described as the "catastrophic reaction" or "immobilization syndrome". This reaction is in fact an akinetic, parkinsonian-like state for which there is good evidence that it is due to transient microembolism of the basal ganglia ("striatum apoplexy"). After its disappearance around the 3rd--5th day "cardiac psychoses" (cardiac delirium) may manifest themselves. Patients who develop these "late" psychoses have a significantly higher correlation with endogenous psychoses in their family histories. On the psychopathological level--in the absence of disturbances of consciousness and orientation--it is not possible to differentiate between "exogenous" and "endogenous" psychosis. A special type of psychopathological reaction is dependent, as in neurological disease, on the severity of brain damage, its localization and on hereditary factors.

Basal Ganglia↗

Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels.

Plasma chlorpromazine (CPZ) levels of 50 psychotic inpatients were measured by gas liquid chromatography; the clinical progress of 29 of these patients with acute psychoses was also assessed. CPZ levels of 50-300 ng/ml were usually associated with clinical improvement; there was also a relationship between CPZ levels and increases in certain symptoms. The 50-300 ng/ml level was best attained by doses of 400-800 mg/day. Trihexyphenidyl decreased plasma CPZ by a mean of 44.7% in 12 of 15 patients. A single 400-800-mg dose of CPZ at bedtime produced steady states equal to or better than those achieved with multiple doses. Those patients who failed to attain CPZ levels of more than 70 ng/ml despite doses of 400-1000 mg/day were receiving lithium throughout the study and had discharge diagnoses of manic-depressive psychosis, manic type, and schizo-affective schizophrenia--a finding with implications for future research.

Acute Disease↗

Secondary mania: manic syndromes associated with antecedent physical illness or drugs.

While mania usually occurs as a phase of manic-depressive disease, it can occur in association with organic dysfunction--medical and pharmacological--in patients with no history of affective disorder. In reviewing the literature, we have found that mania occurs secondary to drugs, infection, neoplasm, epilepsy, and metabolic disturbances. These cases are best considered secondary manias. They suggest that mania--like, for example, hypertension--is a syndrome with multiple causes and that with further research many manic syndromes currently considered primary will be shifted into the secondary category. Furthermore, the concept of secondary mania casts doubt on any unitary or single-agent hypothesis of the etiology of mania and supports the notion of a continuum of psychopathologic syndromes. Clinicians are alerted to the existence of this syndrome and are urged to screen for it when conditions warrant.

Adrenal Cortex Hormones↗

The course of affective disorders. I. Change of diagnosis of monopolar, unipolar, and bipolar illness.

All patients suffering from affective psychoses (ICD 296) who were admitted to the Psychiatric University Clinic of Zurich between 1959 and 1963 were studied in a follow-up investigation until 1975. Of 254 affective psychoses, 95 were bipolar patients (37.4%) and 159 were monopolar (62.6%). The sample of bipolar patients was complemented with all patients who had been admitted in the period 1959--1963 because of manic or mixed manic-depressive syndromes. This paper describes the change of diagnosis in the two diagnostic groups. In 10% (N = 20) of monopolar depression cases there was a change of diagnosis to bipolar affective illness. An analysis shows that the diagnosis of patients with three or more depressive episodes (unipolar depressives) was especially prone to change. A mathematical correction of some diagnostic errors leads to the conclusion that the ratio of unipolar depression to bipolar illness may be about 1:1. A major source of diagnostic error lies in the change of affective to schizo-affective illness. Up to now, no clinical criterion exists that would exclude this error, which was found in 6% (n=12) of the monopolar but also in 7.5% (n = 3) of the bipolar index patients. It is recommended that studies of affective disorders should be based on truly representative samples of the illness, including patients with one or two episodes, and that the term 'unipolar depression' be used synonymously with the term 'monopolar depression,' originally created by Kleist (1947) and Leonhard (1957).

Affective Symptoms↗

A method for testing differences in morbidity risk for affective psychoses.

A modified method for testing differences between two proportions is described and its use for testing differences in the morbidity risk for affective psychoses is discussed. The method is based upon the u test for comparisonof two proportions. An example of the application of the method to study sex differences in morbidity risk for affective psychoses in parents of probands with unipolar depression and manic-depressive psychosis presented.

Bipolar Disorder↗

The common pathophysiology of monaminergic psychoses: a new hypothesis.

Several recent data indicate the blood-brain transport of amino acids as a critical factor in the synthesis of monoamines. The complex, peripheral and central regulation of TP transport plays an essential role sine TP-hydroxylase is not a saturated enzyme. The hydroxylated derivatives 5-HTP and dopa are probably transported into the brain by similar mechanisms as their precursors TP and tyrosine, respectively. The maic-depressive patients show an increased uptake of administered L-5-HTP in the depressive phase, whereas L-dopa uptake is enhanced in the manic phase. Heuristically, we propose a biochemical model of manic-depressive psychosis in which an increased TP uptake causes alternation in the balance of monoaminergic system activity. Depression is possibly characterized by a hyperserotonergic and a relative hypocatecholaminergic activity. In contrast, mania is possibly determined by a hypercatecholaminergic (NA and DA) and a relative hyposerotonergic activity. The data offered by the physiology of monoamines, the semeiology and the biological alterations of the manic-depressive psychosis, as well as the monoaminergic and the electrolyte theory of manic-depressive psychosis. A diminution of the transport of TP with consequent increase of that of tyrosine represents a possible biochemical model of schizophrenia which may be well explained by a hyposerotonergic-hyperdopaminergic activity, with or without noradrenergic insufficiency. This model is compatible with our knowledge on the monoamine physiology, the biological alterations of schizophrenia, the therapeutical results as well as with the classical clinical notions (typology, intermediate syndromes and crossed heritance).

5-Hydroxytryptophan↗

Serum dopamine-beta-hydroxylase in affective disorders.

Serum dopamine-beta-hydroxylase (DBH) activity was tested in 160 psychiatric patients suffering from affective disorders. The patients were divided into subgroups according to strict diagnostic criteria and clinical state at the time of the examination. Since no relationship was found between DBH activity and age or sex, these variables have been discarded from further analyses. Bipolar (manic-depressive) patients had lower (p less than 0.05) BDH mean values than patients suffering from unipolar, recurrent depressive psychoses. No other differences were found either among group or in relation to the clinical state. As such a wide range of DBH values was recorded in all the groups examined, measurements of DBH activity do not seem to be useful as a diagnostic acid, or as an indicator of the clinical state of patients suffering from affective disorders.

Adult↗

Cognitive and affective responses to lithium in patients with organic brain syndrome.

The authors describe a series of patients with organic brain syndrome who showed a dramatic clinical response to lithium carbonate therapy. None of the patients had been diagnosed as manic-depressive. Most had extensive psychiatric treatment experiences and had been given both affective and cognitive diagnoses. Six of the eight patients also qualified for the diagnosis of alcoholism. They had been treated with a wide variety of psychotherapeutic medications. Lithium was found to be rapidly and dramatically effective in patients with static lesions of the central nervous system who showed a combination of dementia and agitated depression.

Affect↗

Schneider-oriented versus Conrad-oriented psychiatric diagnosis in the same German clinic.

The Chair of the University Nervenklinik in Homburg/Saar was held by Klaus Conrad from 1949-58 and by H.-H. Meyer, a former pupil and colleague of Kurt Schneider, from 1962-72. As the catchment area and admission policy of the clinic remained substantially unchanged throughout, comparison of the relative proportions of all admissions allocated to different diagnostic categories in 1949-58 and 1962-72 can be used to elucidate the similarities and differences between Conrad's and Schneider's diagnostic criteria. The results of this comparison indicate that Schneider's concept of schizophrenia was broader than Conrad's, and his concept of manic-depressive depression more restricted. More detailed comparisons are complicated by differences in nomenclature and in the varieties of functional mental illness recognized in the two periods. However, it seems that Conrad's concept of mania was wider only when the atypical schizophrenia-like psychoses diagnosed during the Conrad era were added to the Conrad-oriented cases of mania; when this was not done, the Schneiderian concept of mania was broader.

Adjustment Disorders↗

Genetical analysis of unipolar and bipolar endogenous affective psychoses.

The mode of inheritance of affective psychoses was studied in 800 first degree and 582 second degree relatives of 122 probands. Morbidity risk for unipolar depression was 12.0+/-3.2 and 11.4+/-2.7 per cent respectively for parents and siblings of probands suffering from unipolar depression. Morbidity risk for manic-depressive psychosis for the respective groups of first degree relatives of manic-depressive probands was 15.1+/-3.2 and 16.9+/-3.2 per cent. In second degree relatives the morbidity risk was 3.4+/-1.0 and 5.3+/-1.4 per cent for unipolar depression and manic-depressive psychosis respectively. The results indicate the role of genetical factors in the etiology of both types of affective disorder and show that unipolar depression and manic-depressive psychosis are distinct entities. The hypothesis of X-linked dominant transmission was not confirmed in either of these affective disorders. By means of the computational model of Slater, no results compatible with a polygenic inheritance of unipolar depression or manic-depressive psychosis were found.

Adolescent↗

[Genetics of endogenous psychoses].

As the endogeneous psychoses do not show a Mendelian mode of inheritance, empirical risk figures have to be calculated. They are heterogeneous and nurture as well as nature have a share in the manifestation of illness. The genetic basis of the schizophrenias is demonstrated by twin and adoption studies. The concordance rate in monozygotic twins is four times the rate in dizygotic twins. Schizophrenia is to be found in the biological families of schizophrenic adoptees but not in the adoptive families. However, despite their genetic identity, monozygotic twins do not show 100% concordance but 60% only. Nongenetic factors must be considered. Obviously they are nonspecific and vary between individuals. The same principles apply to the affective psychoses. At present research is most interested in the problem of heterogeneity. Do pure depressive and manic-depressive disease form one genetic entity, or two different ones, or have they in common part of their genetic basis? Some remarks on genetic counselling are made.

Adoption↗

[Use of long-acting lithium carbonate--micalite--in the treatment of affective psychoses].

Micalite (microcapsulated lithium carbonate with a retarded action) was used for the treatment of manic states and the prevention of attacks of manic-depressive psychosis in 40 patients. The preparation was administered once daily. This provided the necessary concentration of lithium in the blood on a stable level. According to its therapeutical effectiveness and the frequency of side-effects micalite does not differ from other lithium preparations with a simgle daily administration of micalite there are much less distubrances in the treament regime.

Bipolar Disorder↗