I am glad to have this opportunity to talk about an unfortunate consequence of developments in the Health Service over recent years. My theme will be what is now happening to mentally disordered people who have committed criminal offences. At present, many of them are going to prison. The prison system—already severely overcrowded—contains some hundreds of mentally disordered offenders who in the opinion of prison medical officers need and are capable of gaining benefit from care, management and treatment in psychiatric hospitals. When using the term ‘mental disorder’ I shall, of course, be referring to those states of mind which have been classified and defined in Section 4 of the Mental Health Act 1959: members of the College who work in the National Health Service will be relieved to know that I do not share the view of the citizens of Samuel Butler's Erewhon that crime itself is an illness, whose sufferers should all be placed in the hands of the omniscient psychopathologists. Indeed, when one has the practical responsibility for the provision of health care for prisoners, it is quite irrelevant whether or not they committed their offences as a result of a mental disorder or whether their mental disorder developed before or after the offence or trial. The only thing that matters is their present condition. If a prisoner is suffering from mental disorder of a nature or degree that warrants his detention in hospital for treatment, then the prison medical officer will want to bring about his admission to hospital under the appropriate section of the 1959 Act. This is wholly in accordance with the philosophy of the Act, which does not limit hospital admission to cases in which the criminal offence was causally related to a mental disorder. In this talk I shall want to consider why in so many cases hospital places cannot be found.

Eleven patients with obsessive thoughts were treated in two pilot studies. In the first of these patients were given thought-stopping, and this was contrasted with relaxation therapy. In the second study patients were treated by a technique described here as ‘satiation’, and this was followed by thought-stopping and finally a course of amitriptyline. The overall results were poor, but one type of obsessive thought responded well to satiation.

Forty-one out-patients with a history of at least three attacks of depressive illness were randomly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets, or to lithium tablets once daily plus placebo mianserin tablets. After one year, the dosage of mianserin was increased to 30 mg t.d.s. for a further six months. All but three of the patients had previously been stabilized on prophylactic lithium therapy. Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT. The overall affective morbidity index, calculated from global rating, showed no significant difference between drugs, but the index of the mianserin group was higher in the second six months than in the first. The lithium group showed no such change. Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness.

The prevalence of abnormal serum total thyroxine (T4) and triiodothyronine (T3) concentrations were determined in 1,206 in-patients in two associated psychiatric hospitals. The biochemical pattern of primary hypothyroidism occurred in five females and one male (prevalence 0.5 per cent), but in only one patient was the diagnosis clinically obvious. Eight patients (all female) were clinically hyperthyroid (prevalence 0.7 per cent), of whom six were previously undiagnosed. There was no evidence that phenothiazines or benzodiazepine therapy had any significant effect on thyroid hormone levels. The small differences in thyroid hormone levels between psychiatric diagnostic groups could be explained by differences in age distribution.

The effect of thyrotoxicosis upon the recurrence of manic-depressive psychoses has been studied by the use of a routine follow-up system. In this system 267 patients had three or more affective illnesses. Five of these patients had eight well-documented episodes of thyrotoxicosis. Only three of these eight episodes coincided with an affective illness, and in each case an alternative explanation for the association was available. These findings suggest that thyrotoxicosis has little effect upon the occurrence of a manic-depressive episode.

In a six-month study of psychiatric hospital in-patients, it was found that accidents more often occurred among females and among patients on psychogeriatric wards. Falls were the most common form of accident. Accidents resulting from the aggressive behaviour of other patients usually occurred on long-stay and rehabilitation wards, with middle-aged patients the victims.

In Fijian, matiruku means literally ‘low tide in the morning’ and figuratively somebody periodically insane. In this study, the conceptual basis of matiruku was examined by means of a questionnaire completed by 24 Fijians which explored its occurrence, aetiology and precipitation, phenomenology, management and prognosis. It was concluded that matiruku corresponds to hypomania, which may have special features in Fiji: short duration, frequent recurrence and an intensification of symptoms in the morning.

After a brief review of the characteristic somatic and psychotropic effects of benzodiazepines evidence is presented which supports a specific facilitatory action of these drugs on GABA ergic synapses within the mammalian central nervous system. Benzodiazepines enhance presynaptic inhibition in the spinal cord and dorsal column nuclei as well as postsynaptic inhibition in dorsal column nuclei, hippocampus, hypothalamus, cerebral cortex, cerebellar cortex, which are all examples of recurrent and collateral inhibition mediated by GABA ergic intrinsic neurones. In addition, the compounds also enhance the inhibitory effect of GABA ergic long projection neurones in the substantia nigra and the lateral vestibular nucleus of Deiters. Several problems remain to be solved, such as the exact site at which benzodiazepines initiate their action (pre-synaptically at GABA ergic nerve endings or postsynaptically at the target cells) and the possible existence of endogenous ligands for the benzodiazepine receptor. Some suspected implications which studies on benzodiazepine binding sites could have for a deeper understanding of the mode of action of these drugs are discussed.

Two types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 μM), the other type (A) has two populations of receptors which have a high (0.16 μM) and a low (.02 μM) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 x 10-7M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity.

Brain membranes from rat and human contain a single class of brain specific binding sites for pharmacologically and clinically active benzodiazepines. There is good correlation between the pharmacological effects of benzodiazepines and the affinity for the 3H-diazepam binding site.

Benzodiazepine binding sites are not present on glial cells. Selective neuronal degeneration experiments in rats indicate a neuronal localization. 3H-Flunitrazepam is a very suitable ligand for affinity binding and it binds to the same class of binding sites as 3H-diazepam.

Our results indicate that the in vitro3H-diazepam and 3H-flunitrazepam binding sites are the receptors which in vivo mediate various pharmacological and clinical effects of benzodiazepines.

Benzodiazepines bind with high affinity to a specific benzodiazepine receptor, which occurs exclusively in the central nervous system. The affinity of various benzodiazepines to the receptor closely parallels their pharmacological and therapeutic potency. Binding to the receptor is stereospecific. The receptor is mainly localized in the synaptic membrane fraction and has its highest density in cortical areas of the brain. In Huntington's chorea a decrease in benzodiazepine receptor binding is found in caudate nucleus and putamen, which, at least in putamen, is due to a loss of benzodiazepine receptors apparently located on GABA neurones, which degenerate in Huntington's chorea. The loss of benzodiazepine receptors might explain why the ameliorative effects of benzodiazepines in the early stages of the disease are not sustained in the later stages.