Summary Eighteen patients with manic‐depressive disease were grouped into pairs in a double blind study. The patients within each pair were treated either with lithium or with placebo in a random manner. When one of the patients within a pair relapsed, the trial was discontinued for that pair. All 9 patients who received placebo relapsed within 1‐31 weeks, 3 with depressive and 6 with manic episodes. Later, 3 of the patients who received lithium discontinued treatment on their own initiative, and also relapsed into manic states.

In a double-blind study on 22 patients with major depressive disorder the effects of lithium and clomipramine on signs and symptoms and on calcium and magnesium in plasma were compared. Ratings of antidepressant and side effects were performed by 2 psychiatrists at the end of a placebo period of 5-7 days and after treatment for 2 and 4 weeks. Psychopathology was rated by 15 reported and 4 observed items from the Comprehensive Psychopathological Rating Scale (CPRS). Eleven items present in 72-100% of the patients were used to evaluate the effect of the two drugs. After 2 weeks of treatment the rated scores dropped for more than half of the CPRS items. After 4 weeks the scores for all but one item were reduced in both groups. The sums of scores were significantly reduced after 2 weeks in both groups and after 4 weeks global scores were reduced as well. The drugs had notable and similar antidepressant effects. Lithium treatment was associated with fluctuations in calcium and magnesium levels in plasma not seen during clomipramine treatment. Serum prolactin increased during clomipramine treatment but was unaffected by lithium treatment. No correlations were found between the sum of rating scores and blood levels of drugs, prolactin, calcium or magnesium.

Abstract: The serotonin metabolite 5‐hydroxyiryptophol was studied in human cerebrospinal fluid. A minor fraction (∼13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing 3‐ glucuronidase activity. A concentration gradient of 5‐hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5‐Hydroxytryptophol and 5‐hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5‐Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml ± 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5‐hydroxytryptophol.

In 66 physically and mentally healthy human subjects the total concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), 5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and dihydroxyphenyl acetic acid (DOPAC) in urine collected between midnight and 8 AM were analyzed by mass fragmentography. In the volunteers reporting the occurrence of psychiatric morbidity among relatives an increased variance in their MOPEG levels was found as compared to the volunteers without such a family history. In the male subjects with no family history of psychiatric disease there was a positive correlation between urine and cerebrospinal fluid levels of MOPEG. The urine levels of 5-HIAA, HVA, and DOPAC did not demonstrate any changes that could be related to psychopathology within the family. Changes in urine secretion of MOPEG indicate an altered metabolism of norepinephrine/MOPEG in some subjects with the occurrence of severe psychiatric disease within the family. MOPEG levels in urine may be a predictor of a family vulnerability for psychiatric morbidity in healthy subjects.

In 60 physically and mentally healthy human subjects, lumbar cerebrospinal fluid was analysed by mass fragmentography for 5-HIAA, HVA and MOPEG. Individuals with a family history of psychiatric morbidity had significantly greater variation in monoamine metabolite concentrations than subjects without such a family history. In subjects with a family history of schizophrenic psychosis 5-HIAA and HVA concentrations were significantly higher than in subjects with depressive disorders within the family. For subjects with deviant 5-HIAA levels the probability of having a psychiatric family history was 2.7 times higher than in subjects with normal values. For HVA and MOPEG similar relationships, but of a lower significance level, were found. The results suggest that the cerebral monoaminergic transmitter amines play critical roles in the pathophysiology of psychotic and depressive disorders with a family disposition. They also indicate a value of monoamine metabolite determination in CSF for the prediction of family vulnerability for psychiatric morbidity in healthy subjects.

SummarySixty‐three alcohol‐discordant male twin pairs, aged 45–65 years, have been investigated with respect to psycho‐social conditions, psychiatric symptoms and use of psychotropic drugs. The low consumers were significantly more often found to be married and to remain married in their first marriage, to have children and to have a higher education than their high consuming co‐twins. No differences were obtained as regards employment, income, living standard or criminality. A significantly larger number of the high consumers had been convicted for being drunk. As far as political and social activities are concerned the high alcohol consumers showed less interest and activity than their low‐consuming co‐twins. No evident disparities were found with respect to psychiatric symptoms and use of psychotropic drugs but a significantly larger number of the high consumers had seen a physician because of nervousness. The results indicate different life styles and personality traits in the group of high consumers as compared to the low alcohol consumers but no differences as to serious social disturbances between the two groups.

The clinical effects of chlorpromazine (CPZ) administered in accordance with a double‐blind design in one of three doses (200, 400 or 600 mg) were examined in 44 psychotic patients. The relationships between the effects and the CPZ concentrations in plasma and cerebrospinal fluid (CSF) were analyzed. The antipsychotic and side effects were rated according to the CPRS and the Simpson and Angus scale. CPZ concentrations were measured by a mass fragmentographic method. Treatment with CPZ resulted in a significant reduction of morbidity scores, without any clear dose relation. The final outcome was more favourable in women than in men. Extrapyramidal side effects but not somnolence were positively dose related. The antipsychotic effects tended to be positively related to the dose of CPZ in mg/kg as well as the CPZ concentrations in plasma and CSF. The greatest number of significant correlations between the CPZ concentration in CSF and the morbidity scores were seen after 2 weeks of treatment. The results indicated marked clinical improvement with CPZ concentrations above 1 ng/ml in CSF and 40 ng/ml in plasma. After 4 weeks of treatment the correlations between the CPZ concentrations and the clinical improvement were still positive but the coefficients were lower than at 2 weeks and only occasionally significant. Extrapyramidal symptoms were significantly related to the CPZ concentrations in plasma and CSF. Somnolence was significantly related to the CPZ concentrations in CSF.

Levels of HVA, MOPEG and 5‐HIAA in cerebrospinal fluid (CSF) from psychotic men and women with a schizophrenic symptomatology were measured by mass fragmentography. Measurements were made before, 2 and 4 weeks after treatment with chlorpromazine (CPZ) which was given randomly in doses of 200, 400 or 600 mg per day. Before treatment there were positive correlations between the levels of HVA and 5‐HIAA in both sexes. During CPZ treatment HVA was significantly elevated, whereas MOPEG and 5‐HIAA were reduced. There was a tendency towards tolerance to CPZs effect on HVA during treatment but a significant effect persisted after 4 weeks. No indication of tolerance to the effects on MOPEG or 5‐HIAA was found. There were the same tendencies for the elevations of the HVA/MOPEG and HVN5‐HIAA ratios. The changes in HVA, MOPEG, 5‐HIAA, HVA/MOPEG and HVA/5‐HIAA were related to dose of CPZ in men but not in women. The bidirectional change of the different metabolites in CSF during CPZ treatment excludes a general and non‐specific mechanism for the metabolite changes. The HVA elevations is in accordance with previous results in animals and man, and is pesumably related to blockade of central dopamine receptors. Possible mechanisms for the effects on MOPEG and 5‐HIAA are discussed.

The present paper summarizes work carried out at the Karolinska Institute, Stockholm, Sweden, over the last few years. The studies deal with the possibility of finding chemical parameters useful for the selection of drugs and their dosage to treat psychotic patients.

In psychotic patients, levels of prolactin in cerebrospinal fluid (CSF) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine (CPZ). CPZ was given in one of three randomly selected fixed doses: 200, 400 or 600 mg per day. Before treatment, low levels of immunoreactive prolactin‐like material (PRL) were found in the CSF of most patients. The concentration in CSF was about 20 % of the plasma level. In CSF but not in plasma, the pre‐treatment level of PRL was significantly higher in women than in men. During CPZ treatment, the PRL levels in CSF as well as in plasma were significantly elevated in both sexes after 2 as well as 4 weeks. The elevation was significantly greater in women, and was similar at the two time intervals studied. There was a significantly positive relationship between the dose of CPZ and the PRL elevation in both body fluids in both men and women. Before treatment no significant correlation between the PRL levels in CSF and plasma in either sex could be observed. During treatment, there was a significant correlation between the change in PRL levels in CSF and plasma in both men and women. CPZ treatment did not increase the levels of total protein, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), thyroid‐stimulating hormone (TSH) or oestradiol‐(17‐β) in either the CSF or the plasma.

(1976). Klinisk behandlingseffekt av klorpromazin och nagra farmakokinetiska och farmakodynamiska parametrar. Nordisk Psykiatrisk Tidsskrift: Vol. 30, No. 7, pp. 500-506.

20 male, alcohol-discordant twin pairs, aged 45 to 65 yr. were compared for field-dependent cognitive style and general intelligence by means of one-sample t and multivariate Td2-tests. The high alcohol group was more field-dependent (p less than .01) than the low alcohol group, mainly because of poorer scores on the Embedded-figures Test. When general intelligence was controlled for, the amount of embedded-figures variance accounted for by consumption of alcohol dropped considerably.

Cerebral arterio-venous differences of homovanillic acid (HVA) and cerebral blood flow were measured in 24 patients, 6 adults and 18 children, anaesthetized by different techniques. A statistically significant release of HVA from the brain (p < 0.001) was demonstrated in five children anaesthetized by barbiturate, nitrous oxide and droperidol/fentanyl. The release rate was 509 pmoles HVA/100 g brain tissue/minute - corresponding to approximately 1.3 mg HVA/24 hours from the whole brain.

This chapter discusses mass fragmentometric determination of homovanillic acid (HVA) in lumbar cerebrospinal fluid (CSF) of schizophrenic patients during treatment with antipsychotic drugs. Dopamine is stored in specific neurons of the central nervous system, where it in all probability plays a role as a transmitter substance. Dopamine is formed from dietarytyrosine and it is metabolized to HVA, which appears to be the major metabolite leaving the central nervous system. From experiments in animals, there is evidence that antipsychotic drugs markedly accelerate brain dopamine synthesis. Thus, following administration of chlorpromazine and haloperidol, levels of the dopamine metabolites, 3-methoxy-tyramine and HVA, are markedly elevated. The mass fragmentometric technique involves the use of dideuterium labeled HVA as an internal standard.

A double‐blind cross‐over comparison of diazepam, haloperidol and placebo was carried out in 51 out‐patients with neurotic anxiety‐tension states. Each drug was given for 1 week: diazepam 15 mg and haloperidol 1 mg per day. Both drugs were significantly better than placebo.Thirty‐three of the patients had anxiety without obvious precipitating factors. In this group, diazepam was significantly better than haloperidol in eight of 15 items, but there was no difference with regard to subjective side effects. Eighteen patients had anxiety resulting from recognizable factors. In this group, no significant difference in therapeutic effect was seen, although haloperidol gave fewer side effects.

Acta Psychiatrica ScandinavicaVolume 49, Issue 3 p. 230-236 TIME COURSE FOR THE EFFECT OF LITHIUM ON THYROID FUNCTION IN MEN WOMEN B. Fyrö M. D., B. Fyrö M. D. Department of Psychiatry St. Goran's Hospital 11 2 81 Stockholm SwedenSearch for more papers by this authorU. Petterson M. D., U. Petterson M. D. Department of Pharmacology Karolinska Institutet 104 01 Stockholm SwedenSearch for more papers by this authorG. Sedvall M. D., G. Sedvall M. D. Department of Psychiatry St. Goran's Hospital 112 81 Stockholm SwedenSearch for more papers by this author B. Fyrö M. D., B. Fyrö M. D. Department of Psychiatry St. Goran's Hospital 11 2 81 Stockholm SwedenSearch for more papers by this authorU. Petterson M. D., U. Petterson M. D. Department of Pharmacology Karolinska Institutet 104 01 Stockholm SwedenSearch for more papers by this authorG. Sedvall M. D., G. Sedvall M. D. Department of Psychiatry St. Goran's Hospital 112 81 Stockholm SwedenSearch for more papers by this author First published: June 1973 https://doi.org/10.1111/j.1600-0447.1973.tb04416.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES Bellak, L. (1952): Manic-depressive psychosis and allied conditions. Grune & Stratton, New York . Web of Science®Google Scholar Bennie, E. H., & J. H. Lazarus (1972): Lithium-induced thyroid dysfunction. 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Acta Psychiatrica ScandinavicaVolume 49, Issue s243 p. 54-54 HOMOVANILLIC ACID IN CEREBROSPINAL FLUID OF SCHIZOPHRENIC PATIENTS BEFORE AND DURING CiHLORPROMAZINE TREATMENT BENGT FYRÖ, BENGT FYRÖSearch for more papers by this authorBIRGITTA WODE-HELGODT, BIRGITTA WODE-HELGODTSearch for more papers by this authorSTEFAN BORG, STEFAN BORGSearch for more papers by this authorGÖRAN SEDVALL, GÖRAN SEDVALLSearch for more papers by this author BENGT FYRÖ, BENGT FYRÖSearch for more papers by this authorBIRGITTA WODE-HELGODT, BIRGITTA WODE-HELGODTSearch for more papers by this authorSTEFAN BORG, STEFAN BORGSearch for more papers by this authorGÖRAN SEDVALL, GÖRAN SEDVALLSearch for more papers by this author First published: August 1973 https://doi.org/10.1111/j.1600-0447.1973.tb10479.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume49, Issues243August 1973Pages 54-54 RelatedInformation