J.‐O. Ottosson

CAN SELF‐RATING REPLACE DOCTOR'S RATING IN EVALUATING ANTI‐DEPRESSIVE TREATMENT?

Sixteen depressive out‐patients with endogenous or mixed endogenous‐psychogenic depression were rated before and during antidepressive drug treatment using the Zung self‐rating scale, the Cronholm‐Ottosson depression scale and a global rating. The scores displayed a parallel course, but the correlations between them were only moderate, and between the score differences were still lower. When levels of significance of score differences and global ratings were used as measures of treatment effects, the self‐ratings were least sensitive. The study gives no support for a replacement of the doctors rating scale with self‐rating according to Zung.

PERINATAL CONDITIONS OF UNWANTED CHILDREN

1. In their study of children who were born after their mothers had been denied a legal abortion Forssman & Thuwe (1966) showed that the children’s mental health, social adjustment and educational level were more unfavourable than in appropriate controls. The authors interpretation of their findings is that the mothers transmit their mental vulnerability to the children either through genes or via lack of stability and security in the home environment. The latter hypothesis was supported by a comparison of those unwanted children and their controls who were living with both their real parents until they were 15; these reduced groups did not differ significantly with the criteria used (although there still was a similar tendency). We wanted to extend this analysis by examining whether, in addition to a genetic and social handicap, there was also a physical handicap, i.e. whether the new-borii children displayed any deviations in the regularly registered features weight, length, head circumference, intrauterine growth rate, prematurity, perinatal mortality and malformations, all of which might reflect an adverse prenatal influence on the foetus.

CEREBRAL ARTERIAL DEFORMITIES IN RELATION TO SENILE DETERIORATION

Three types of cerebral arterial changes, ”Gefassknauelbildungen” (glomerular loop formations), ”Gefassgeflechte” (vascular wickerworks) and ”Gefassbundel” (vascular bundles) were described by Cerletti (1 91 0) mostly in patients with ”malaria perniciosa” but also in some cases of senile dementia. Glomerular loop formations were also seen in ordinary routine-stained sections by Alzheimer (1904) in general paralysis, by Sarteschi (1909) in senile dementia, and by Gelferstedt (1933) in normal senescence, but these authors only mentioned the changes en passant. With the aid of stereo-microangiography Hassler (1 965) demonstrated an abundant occurrence of the changes in a comparatively small material, mainly brains from patients with senile dementia. In a continued study Hassler (1967) investigated the occurrence of these deformities in a file of 231 consecutive autopsies of subjects aged 1 year or more from the Department of Pathology, Ume% University Hospital. The changes were rarely observed in subjects under the age of 60, but were common after the age of 70, almost equally distributed in the two sexes. They were not notably related to heart weight, degree of cerebral arteriosclerosis, density of senile plaques or brain weight. Vascular wickerworks were more common in subjects with vascular bundles than in those without. The glomerular loops occurred as a rule together with marked spiralling and may be looked upon as products of excessive spiralling. The author calculated that the deformities reduced the total cerebral blood flow by about 10 O/o. A pertinent question is whether these cerebral pathological changes have any clinical significance. Since they were first identified in patients with senile dementia and since they increase with age, it is conceivable that they have an association with senile deterioration. Their significance

A COMPARISON BETWEEN DIAZEPAM, DIXYRAZINE, OPRIPRAMOL AND PLACEBO IN ANXIETY STATES

Anti-anxiety drugs form a fairly large proportion of all psychotropic drugs prescribed by psychiatrists and, to a still higher degree, in general practice. At the time when this investigation started, there were three drugs: diazepam (Valium, Roche), dixyrazine (Esucos, UCB) and opipramol (Ensidon, Geigy) all then quite new, that were claimed by manufacturers to have a favourable effect on states characterized by anxiety, muscular tension, vegetative symptoms, sleep disturbances and other symptoms belonging to or secondary to the anxiety syndrome. Moreover, it was maintained that this anxiolytic effect was quite specific, i.e. not being part of a general sedative-hypnotic action. The basis of the present use of these three drugs is partly several casuistic reports and uncontrolled studies, partly some controlled studies. In controlled studies in non-psychotic anxiety states, which are the only ones to be considered here, diazepam, which is a benzodiazepine derivate was not more effective than placebo in one study (NesseEhof et al. 1965) wheras in others it was superior to placebo (Di Francesco 1963, GeertJorgensen 1963, Lingjaerde 1964). In comparison with other drugs diazepam was reported to be better than chlordiazepoxide (Kerry & jenner 1962, Darling 1963, Daneman 1964), amylobarbital (Capstick et al. 1965, McDowall et al. 1966), pentobarbital (Brandt & Oakes 1965), hydroxyzine (Marrubini G Tretola 1965) and phenothiazines (Hare 1963, Smith & Chassan 1964). Dixyrazine, a phenothiazine with piperazine chain, has shown better results than placebo (Bensch & Rundberg 1964, Fokstuen 1965, Hakola & Hakola 1967) and chlordiazepoxide (Paguay et al. 1961). Opipramol, an iminostilben derivate with piperazine chain which was originally introduced as an antidepressant but later claimed to belong to the anxiolytics, has proved superior to placebo (Splitter 1963) and equal to chlordiazepoxide (Grosser & Ryan 1965).

SERUM LEVELS OF PHENYLALANINE AND TYROSINE IN HUNTINGTON'S CHOREA

Attempts to identify a metabolic abnormality in Huntington’s chorea and carrier states have so far been unsuccessful (review see Myrianthopoulus 1966, Ctrrzon 1967, Hornykiewicz 1968). The biochemical correlates of Parkinsonian symptoms have directed interest to the metabolism of biogenic amines, especially dopamine, but no deviation has been demonstrated up till now in choreatics. Screenings for abnormal levels of aminoacids in serum and urine have also been negative on the whole, and it has been concluded that a primary aminoacidopathy in Huntington’s chorea is unlikely (Oliphant, Evans & Forrest 1960, Oepen & Oepen 1964, Oepen & Bickel 1964, Bruyn 1966). However, some investigations report deviations, such as increased excretions in the urine of indole (Forrest 1957) and raised serum level of alanine (Cowie & Seakins 1962). The investigations mentioned do not seem to give much promise for further research into aminoacids in Huntington’s chorea. Howevcr, even i f the studies so far have indicated that gross abnormalities do not exist, they cannot exclude minor quantitative but still relevant deviations. The studies are made on small patient series using rather crude electrophoretic methods and without controls, e.g. of the food factor. In view of the evidence of the role of amines for other basal ganglia symptoms it seems premature to abandon this line of research with all the steps from aminoacids, the precursors, to the final acid metabolites. The present study concerns the serum levels of phcnylalaniiic and tyrosine which are precursors of dopamine and noradrenaline.

SCREENING FOR VITAMIN B12 DEFICIENCY IN PSYCHIATRIC PATIENTS

During recent years a great deal of interest has been devoted to the role of Biz-hypovitaminosis for mental disorders, and screening investigations have been performed on various samples of psychiatric patients (see Table 1). There is fairly great variation in the frequencies in different investigations and also in the interpretation of the pathogenesis and clinical significance of Biz-hypovitaminosis. Whereas it is sometimes taken for granted that a low serum level of Bi2 is an important etiological factor for mental disorders, the possibility of the reverse condition, i.e. low level as a consequence of the mental disorders via nutritional difficulties for example, has also been suggested (Shulman 1967 b) . It is also possible, as suggested by Rafaelsen (1967), that the mental disorder and the low level of Biz are coincidental phenomena, and that in old age, for example, there is a physiological decrease of the serum level without definite pathogenic importance. Finally, it has been suggested that the low Biz-level is an artefact due to influence on the test organism Euglena gracilis from chlorpromazine (Herberts et al. 1965). This has been disputed from several quarters (eg. Edwin et al. 1966). (i) to ascertain the frequency of vitamin Biz hypovitaminosis in a Swedish mental hospital, (ii) to anal yse the pathogenesis and clinical significance of the deficiency, (iii) to study the effects of treatment with vitamin Biz in deficiency states. The present investigation had three purposes:

LITHIUM CARBONATE IN HYPOKALAEMIC PERIODIC PARALYSIS—THERAPEUTIC TRIAL WITH NEGATIVE RESULT

Mypokalaemic periodic paralysis is a disease in which disturbances in the distribution of electrolytes and body-water are prominent, as shown in a study with multiple isotope technique which demonstrated an entry of potassium and water into cells during attacks (Coppen G Reynolds 1966). A therapeutic trial with lithium salts in this disease seems justified for the following reasons: ( i ) In affective disorders it has been maintained to be a changed distribution of water and electrolytes with increased intracellular sodium and water and dccrcased intracellular potassium, both in depressive a:td still more pronounced in manic states (Shaw & Coppen 1966, review by Coppen 1967). Lithium salts have an anti-manic effect (Schou et al. 1954, Maggs 1963) as well as probably a prophylactic action in periodic affective disorders (Baartrrrp & Schort 1967). I t may be hypothesized that this effect is a consequence of an influence on the transport of electrolytes across biological membranes; this has been demonstrated in several animal preparations (review by Giacobini 1969). The observations on patients under lithium treatment are still contradictory but an increase of intracellul~.r water seems to occur (Coppen, Malleson & Shaw 1965, Coppen C Shaw 1967). (ii) Lithium salts have a favourable effect on the premenstrual tension syndrome, which is another periodic putative disturbance of the distrihution o f electrolytes and water (Sletten & Gershon 1966). One reason why lithium may not have a favourable influence in hypokalaemic periodic paralysis is a recently reported case with paroxysmal muscular weakness during lithium treatment (Helmchen, H o f f m a n & Kanowks i 1969). Much still remains to be elucidated concerning the pattern, cause and importance of a changed distribution of electrolytes and water, both in the above states and in other disorders with assumed deficiencies in electrolyte transport mechanisms across cell membranes. However, positive

Pregnancy and delivery of unwanted children.

There is some evidence that the course of pregnancy and delivery may be influenced by emotional factors of the mothers and modern antenatal care aims, among other things, a t alleviating tension and anxiety and creating trust and security a t the delivery. Two prospective American studies found a correlation between anxiety as measured by various psychological methods and duration of labour (Grimm 1961, McDonald et al. 1963) and a Swedish, also prospective, study reported correlations between negative emotional attitudes and reactions during pregnancy and uterine inertia and foetal asphyxia (Engs tro tn et al. 1964). While some of the anxiety measured in the former studies gives the impression of being related to the act of delivery, the distress in the Swedish women seems to have been more deeply rooted in disturbed psycho-social conditions. A pertinent question is whether a negative attitude to pregnancy may cause disturbances of pregnancy and delivery. I t may be imagined that such a negative attitude may act both directly, via nervous and endocrine influence, or indirectly via inappropriate way of living and deficient antenatal care. Women who have applied for legal abortion have manifested a strong negative attitude to their pregnancy, in any case during the initial part, and if their application is refused a possibility is offered of studying the influence of this attitude on the further course of the pregnancy. In connection with a study of such unwanted children (Hultin & Ottosson 1971) we have examined the frequency of abnormalities of pregnancy, delivery and puerperium.

Hereditary goitrous cretinism. Report of a family.

Goitrous cretinism is a condition with goitre and gross retardation in physical and mental development due to failure in the formation of thyroid hormones in foetal life or during early postnatal growth. It is known from areas with iodine deficiency and may also be genetically determined. In recent years the complex series of reactions leading to the formation of thyroid hormones has been elucidated, and it has also been possible in several cases to identify the site of the lesion in the metabolic sequence. Hereditary goitrous cretinism can therefore be ranged among Garrod’s inborn errors of metabolism where genetically determined deficiency of specific enzymes gives plausible explanations of the pathogenesis of the disease. Up till now at least 5 metabolic errors have been described: (i) inability to concentrate iodide selectively into the thyroid gland; (ii) defect in building iodide organically into the iodotyrosines. Two steps in this process may be affected: conversion of iodide into iodine, and organification of iodine into monoand diiodotyrosines; (iii) impaired coupling of iodotyrosines into iodothyronines; (iv) impaired release of iodine from iodotyrosines (dehalogenase defect); (v) decreased proteolytic activity possibly due to abnormal iodoproteins. Reviews on this subject are given by Stanbury (1960 ,1961), von Harnack (1962), Lamberg (1962), Lehmann (1964) and others. We have encountered a sibship where four sibs obviously had hereditary goitrous cretinism, two of which were studied in some detail. Since such cases contribute to the relatively scanty casuistry, this report is presented.

SCREENING FOR PORPHYRIA AMONG PSYCHIATRIC PATIENTS

In his classical investigation Wuldenstrom (1 937) showed that acute intermittent porphyria (AIP) in Sweden had its origin in the northern part of the country, and Wetterberg (1967) estimated the prevalence of AIP in the two northern counties to 1: 1500 inhabitants above the age of 15. Since AIP is often associated with mental disorders, primary as well as secondary, and since (ab)use of alcohol and barbiturates may elicit attacks of AIP it would be reasonable to expect a number of patients with AIP to pass through the department of psychiatry at UmeS university hospital, which is county hospital in the second most northern county in Sweden. The fact, that no more than 8 patients (4 belonging to one family), out of an estimated 100 AIP-cases in the whole county, received the diagnosis AIP between 1960 and 1965 may indicate that some cases were overlooked. The polymorphic symptomatology and diagnostical difficulties in AIP are well-known. The diagnosis of AIP is established by the demonstration of increased excretion of porphyrins or presence of the porphyrin precursors d-aminolaevulinic acid (ALA) and porphobilinogen (PBG) in the urine. In 1941 Watson & Schwartz (W & S ) described a simple, inexpensive and largescale method for qualitative examination of PBG in urine, which was developed from Ehrlich’s aldehyde reaction for urobilinogen. Later Watson et al. (1961) modified the method (extraction with n-butanol after extraction with chloroform) in order to increase the specificity (cf. Townsend 1964). Large-scale investigations with the W & S screening method have been reported from several quarters, with various outcomes. Hammond G Welcher (1948) and Townsend (1964) examined 1000 patients each from general hospitals without finding a single positive reaction. Markowitz (1957) found 47 positive cases among 91 epileptics, whereas Scott (1965) reported negative reactions throughout in 93 epileptics. Jancar G Philpot