Eleven patients in remission from manic-depressive illness were studied by means of metabolic balances before and after the administration of lithium carbonate. Lithium caused a sharp diuresis of isotonic saline and a smaller excretion of potassium over the course of two days. During the subsequent two days there occurred a compensatory retention of Na, K and water. These short-term changes were not associated with any significant alteration in the patients' mood. There was no significant and systematic retention of Na, K or water over the 14 days of Li administration. The recovery of Li was measured simultaneously. During the first week only a proportion of the administered Li was recovered in the urine and faeces, suggesting that a gradual distribution of Li throughout its body space was occurring. After the first week, nearly all the administered Li was recovered, indicating an equilibrium with an even distribution of the ion throughout its body space. This equilibrium was more complete at this early stage in those patients who had been given a smaller dose of lithium carbonate.

The ‘General Health Questionnaire’ was used to assess the psychiatric morbidity among 365 consecutive attenders at a general practice and to compare this with a systematic random sample of 213 patients drawn from the lists of the same practice. Those attending a general practitioner are shown to be more psychiatrically disturbed than a random sample of the practice population, and this difference remains when those attending for psychological symptoms are discounted. Various social and demographic characteristics which distinguish between those who do and those who do not attend a doctor with a given set of psychological symptoms are described.

It has been proposed that p-hydroxynorephedrine, a metabolite of amphetamine, is responsible for the tolerance that occurs to this drug. To test this idea, the development of tolerance to amphetamine has been examined in two species, the rat and the guinea pig, the former of which produces p-hydroxynorephedrine from amphetamine while the latter does not. In both species, tolerance develops to the anorectic and hyperthermic actions of amphetamine, and similar changes in the pattern of behavioural stimulation are seen.

The hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the pathophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as.postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-striatal sites.

A slow, continuous infusion of 1000 μg TRH (thyrotropin releasing hormone) over a period of 4 h had a very faint and diffuse short-lasting beneficial effect on a group of 10 depressive patients. This was assessed in a double blind cross-over trial with placebo. The effect was of no therapeutic value. No difference was found between the depressive patients and a control group of normal subjects in TSH response, T3 resin uptake, T4 or free thyroxine index values as a consequence of the TRH infusion.

Cerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excessive CNS exposure to glucocorticoids.

A sample of individuals who had carried out acts of self-poisoning or self-injury were interviewed and information was also obtained from their general practitioners. More of both the men and the women had visited their general practitioners in the year before the acts than would have been predicted from national statistics, although this was not found to the same extent for persons aged 16–24. Thirty-six per cent of the sample had contacted their general practitioners during the week before the act and over 60% in the month beforehand. Sixty-three per cent had visited them for a variety of psychiatric and social reasons during the preceding year and had nearly all been prescribed psychotropic drugs, usually tranquillizers or sedatives. These were commonly the drugs taken in acts of self-poisoning. Methods of prevention are discussed.

Urinary free Cortisol (UFC) excretion was determined in 60 depressed inpatients and in 35 psychiatric inpatients with other disorders. The depressed patients had high daily UFC values, while the other patients excreted normal amounts. Over 40% of the depressed patients had UFC excretions in the range seen in Cushing's disease, while only 6% of the other patients excreted such high amounts of Cortisol. Age and sex differences did not account for the results. Among the depressed patients those with depressive neuroses excreted less than unipolar or bipolar depressives. Following treatment, more normal UFC excretion was found in depressed patients. The estimation of UFC and its clinical utility are discussed in detail. UFC determination is a simple and informative indicator of adrenal cortical activation and its application to psychoendocrine studies is recommended.

An interview assessment of marriage relationships is described. It is shown to have good inter-rater reliability, high consistency across the accounts of both marriage partners and to be resistant to methodologic bias. A four-year follow-up study demonstrated high predictive validity to later marriage breakdown. The marriage measure also showed a strong association with behavioural deviance in the children. The intercorrelations between individual measures of various aspects of the marriage and the summary measure are given. A shortened version of the interview is described and preliminary findings are given on its validity.

Nurses rated schizophrenics, subclassified upon the basis of the presence or absence of electrodermal orienting responses, with Wittenborn scales. Amongst non-institutionalized patients responders, who are more highly aroused psychophysiologically than non-responders, were more manic, anxious, assaultive and attention-demanding. Amongst institutionalized patients skin conductance levels and spontaneous fluctuations were associated with behaviour of a schizophrenic character.

The plasma lithium levels of 18 subjects receiving one standard and two slow-release preparations of lithium carbonate were measured at frequent intervals during the 24 hours following oral ingestion of a single dose of the drug. Although the slow-release tablets showed slow-release in vitro, this was not so in vivo. One slow-release preparation, in particular, was ineffectively absorbed by some subjects. There was no difference in the rate of absorption and excretion between the other slow-release product and the standard BP preparation. The implications of the results are discussed.

Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptaminę) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.

Seventeen acute psychotic patients were studied in the course of chlorpromazine (CPZ) treatment. Blood samples were taken weekly both before and two hours after the morning CPZ dose. Plasma levels of CPZ, CPZ sulphoxide (CPZSO) monodesmethylated CPZ (NOR1CPZ) and 7-hydroxy CPZ (7OH CPZ) were estimated by gas chromatography. Plasma prolactin, luteinizing hormone, testosterone and oestrogens were measured by radioimmunoassay. Six of the seven patients who showed no clinical improvement had plasma CPZ levels equal to or higher than those of patients who improved. ‘Non-responders’ had a greater proportion of CPZ SO in pre-dosage samples. The occurrence of parkinsonian side effects was associated with a mean plasma CPZ of > 50 ng/ml and a mean plasma prolactin of > 30 ng/ml two hours after dosage. The elevation of prolactin preceded the onset of parkinsonian symptoms by 1–2 weeks. There was a significant positive correlation between mean plasma prolactin and mean plasma CPZ levels. The prolactin response may prove a useful index of the central antidopaminergic effect of neuroleptic drugs.

Increases in plasma noradrenaline were found in a group of 12 subjects smoking cigarettes. The associated rises in pulse rate, blood pressure and plasma free fatty acids could be prevented by β-blockade with oxprenolol. This inhibition of the peripheral effects of catecholamines did not affect subjective satisfaction, indicating that central effects or other rewards are more important reinforcers. It is suggested that noradrenaline release in the hypothalamus is the final common pathway to pleasure in many situations, including smoking.

An inverse factor analysis of 880 depressed inpatients on 33 endogenous–neurotic variables yielded four patient types. Type 3 resembled the endogenous depressions and Type 2 the neurotic depressions. Type 3 patients responded well to both imipramine and chlorpromazine and did poorly on a placebo. Type 2 patients showed the greatest overall improvement at three weeks irrespective of treatment received, including a placebo.

An investigation into observer variation and depressive phenomenology is described. A group of 6 clinicians independently completed a 43-item sheet for 20 depressed patients at the same clinical interview. The coefficient of agreements on the items are given. Patient variables and observer variables did not have any influence on the degree of agreement. There was also an agreement in the subtyping of depression.

A study has been made of cases coming before the Brighton coroner in the period 1970–2. Fifty cases in which a suicide verdict was recorded were specially studied, and relatives and acquaintances of the deceased were interviewed. The information thus obtained was compared with information available to the coroner in considering his verdict in 83 further cases in which he made a verdict of ‘suicide’. The reliability of thewhich the coroner's decision is based was largely validated. A study was made of variables which differentiated ‘suicide’ from 25 ‘open’ and 33 ‘accident’ cases considered by the same coroner. The prevalence of depression did not differentiate ‘suicide’ and ‘open’ cases, and this finding contradicts suggestions that the association of depression and suicide might be an artefact of the method of arriving at a suicide verdict. A number of other demographic and clinical factors did however significantly vary between ‘suicide’, ‘open’ and ‘accident’ cases.

Fifty-seven chronic agoraphobic outpatients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure, group versus individual exposure, and high versus medium anxiety arousal during individual exposure. The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up. Assessment was blind with respect to drug and psychological treatment. Patients in all treatment conditions improved significantly in phobias and in related life areas.

Outcome to group exposure on phobias and other measures was similar in all three drug conditions (placebo, waning diazepam, peak diazepam) with no significant differences between them. Diazepam patients had significantly less discomfort than placebo patients during group exposure treatment. Group exposure patients improved slightly but significantly more than individual exposure patients on non-phobic measures, though group exposure was accompanied by more panics during treatment yet was easier to run by the therapist. Individual exposure under high anxiety arousal was no more therapeutic than with lower anxiety. Diazepam is a mild palliative during group exposure but does not facilitate outcome to treatment. Group exposure in vivo is mildly facilitatory for outcome compared with individual exposure. Anxiety evocation during treatment was not therapeutically helpful.

This paper presents a Personal Questionnaire which is sufficiently simple for use in most clinical settings. Following a brief description of Personal Questionnaires, their origin and background are discussed and some subsequent developments delineated. The method involves the use of a general set of adjectives which can be used to qualify the symptoms experienced by any given patient. Successive measurements of the symptoms can be made so that changes in their subjective intensity can be monitored. The internal consistency of ratings of each symptom on each occasion is used as a measure of reliability. As with all previous Personal Questionnaires the symptoms which are measured are unique to the individual, but unlike other methods the format of this Questionnaire is predetermined, which ensures its simplicity and ease of use.

Biochemical studies of manic-depressive psychosis usually correlate biochemical findings with current affective state and hence any significant findings could be secondary to mood change. The present study attempts to correlate measures of the erythrocyte membrane cation carrier with clinical events, remote in time from the biochemical assay.

Erythrocyte sodium concentration, ouabain-sensitive potassium influx and Na-K ATPase were estimated in 11 patients before and after the cross-over point in a 2-year double blind clinical trial of lithium. Patients with the lowest erythrocyte Na-K ATPase and the highest flux sodium ATPase ratio tended to suffer most episodes of affective illness in the 2 years. Patients who had a low initial Na-K ATPase or a high initial flux sodium ATPase ratio, or in whom this ratio fell most with lithium or whose Na-K ATPase rose most with lithium, clinically responded best to lithium.