It is no exaggeration to say that, in the 30 years since antidepressants were introduced, they have revolutionised the management of depression, thus fulfilling, at least for depressive illness, Paracelsus' prophetic wish. We now have a group of drugs which can induce remission in a disease which is disabling and not infrequently fatal. Despite intensive research, however, our understanding of the mechanism of action of these drugs is still largely hypothetical. Even our methods of evaluation are sufficient only to enable one to decide whether an antidepressant drug is effective or ineffective; there is no experimental method which can rank them in an overall order of potency, and perhaps this should not be the aim, since there must be subgroups of depressed patients who will respond differently to any one agent.

We have no introspective knowledge of the effects of preconscious processing on our perceptions. We are, therefore, not aware that our expectancies may have prejudiced our perceptions. Expectancies tend to foster perceptions with which they are consonant. Therefore false expectations, driven by false beliefs, may result in misperceptions which reinforce those false beliefs. This morbid cycle is central to the delusional misidentification syndromes. This cycle, with positive feedback, is intrinsically unstable, which helps to explain brief episodes of delusional misidentification. Good sensory data, strong links between sense data and memory, and good judgement will all help to prevent misperceptions. The less these constraints are disrupted, the stronger will be the psychological forces needed to generate a delusional misidentification. It is likely that suspiciousness generates particularly assertive effects on preconscious processing of perceptions. Abnormalities of perceptual processing in patients with schizophrenia explain their proclivity to delusional misidentification.

In 1861 Broca, a Parisian surgeon, reported a postmortem he had carried out on a man who had lost his ability to speak 20 years previously and who in the intervening period had only regained the use of one phrase: “Tan-tan”. Broca found that this man had an old infarct in his left hemisphere, affecting the posterior portions of the second and third frontal gyri.

Memory impairments are handicapping to those who suffer them, and a number of ways of trying to help those afflicted have been devised. Effective psychological approaches are likely to be based on methods designed either to make the most efficient use of remaining memory capacity, or to alter the environment so as to reduce the demands placed on memory. At present the success of such approaches is limited.

In 1989 a crisis occurred in a West Country seaside town. Its psychiatric services had been regarded as a vanguard of community care, having been fully established some three years previously when the in-patient facilities which had been based in a mental hospital some 15 miles away were closed. The framework of the new-style service consisted of five mental health centres scattered throughout the residential area and a 60-bed in-patient unit, based in the grounds of the local district general hospital.

The subject of pain used to be considered the province of the physiologist, physician, and surgeon. In a prominent medical textbook written over 20 years ago, pain was simply defined as “that sensory experience evoked by stimuli that injure” (Mountcastle, 1968). This explanation of tissue damage that generates nervous impulses along recognised pain pathways is appropriate for acute pains. But if pain persists beyond the normal time of healing, which is normally less than three months but can be as long as six months, the correspondence between extent of injury and pain sensation is much less precise.

Predominant psychopathology in a selected population group - adolescents and young adults at school - in a developing country, is described. The highly selective referral to services was supplemented by active case finding in the community over three years. There were 54 cases of somaticised anxiety (brain fag); 22 cases of depressive neurosis characterised by hypochondriasis, cognitive complaints, and culturally determined paranoid ideation; 23 cases of ‘hysteria’ in the form of dissociative states, pseudoseizures and fugues; and 39 cases of brief reactive psychosis which differed from the dissociative states more in duration and intensity than in form. There was a temporal relationship between transient psychosis and the school calendar. Anxiety or depression often predated the florid psychotic reaction which served as a form of help-seeking behaviour or defence in intolerable stress.

Psychological or psychiatric disturbances occur in association with therapeutic abortions but they seem to be marked, severe, or persistent in only a minority (approximately 10%) of women. These consist mostly of caseness depression and anxiety. Psychoses are very uncommon, being repotted in only 0.003% of cases – most of whom have a history of previous psychiatric illness. Certain groups are especially at risk from adverse psychological sequelae; these include those with a past psychiatric history, younger women, those with poor social support, the multiparous, and those belonging to sociocultural groups antagonistic to abortion. This is not to overlook the fact that, adopting a crisis-resolution framework, subsequent termination of an unwanted pregnancy is itself ‘therapeutic‘. A better understanding of the nature of the risk factors would enable clinicians to identify vulnerable women for whom some form of psychological intervention might be beneficial.

In serious mental illness (SMI) even good community care does not usually make a major impact on clinical or social function, but patients and relatives prefer community to hospital care, and it tends to be cheaper. Any gains are lost if the required community services are not resourced, coordinated, and maintained indefinitely. A few SMI patients continue to need asylum under one roof. CPNs see more anxiety/depression than SMI. Their patients come increasingly from GPs, and they tend to work in practices with less need. Their cost-effectiveness is uncertain, although nurse behaviour therapists are cost-effective in anxiety disorders in primary care. Such research is also needed into the work of other mental health professionals. Despite their effectiveness, there is a dearth of behaviour therapists among nurses and psychiatrists. Problem-orientated training is lacking for most professionals with most patients. Behavioural self-treatments have improved phobic disorders and non-severe depression in controlled studies. Gains were as great when self-treatment was guided by a computer or by a manual as by a clinician. Self-help can extend care delivery, with therapists acting as consultants. Computers can also aid clinical audit.

Research on symptoms may often be more fruitful than research on syndromes because: (a) the validities of psychiatric diagnoses remain questionable; (b) interview assessments of a large number of symptoms are inadequate; (c) the diagnostic approach results in problems of misclassification and confounding; (d) the dimensional/categorical issue may be more readily resolved with research using a symptom approach; (e) useful animal models of symptoms are more likely to be developed than useful animal models of syndromes; and (f) symptoms may be better phenotypes than syndromes in genetic research.

Despite the fact that environmental factors have been demonstrated to be important in the genesis of seizures in people with epilepsy, such factors have received scant attention in the education of clinicians or in the provision of services for managing patients with epilepsy. This paper reviews the history of, and literature about, reflex epilepsy, with particular reference to seizures which occur in response to psychological states or stimuli, and discusses the possible implications for management, and the rationale for the use of psychological interventions which may complement drug treatments in the management of epilepsy.

The major assumption underlying all X-linkage studies of bipolar disorder has been that a subgroup of manic–depressive illness follows an X-linked dominant mode of inheritance. An evaluation of the segregation patterns in the pedigrees that have been analysed for X-linkage over the past 20 years does not support this assumption, because the formal genetic criteria for an X-linked dominant mode of inheritance are virtually absent. Not a single pedigree has been ascertained in which the segregation pattern is suggestive of the assumed mode of inheritance. This is mainly because segregation ratios characteristic for X-linked dominant inheritance cannot be observed among the offspring of affected males.

Clozapine shows neuroleptic-like inhibition of locomotor activity and conditioned avoidance responding in rodents, although tolerance develops on repeated treatment. EEG-based studies show strong arousal-inhibiting activity of clozapine as well as neuroleptic-like effects on both caudate spindle duration and rat sleep-waking patterns. Effects such as apomorphine blockade, catalepsy and strong increases of plasma prolactin levels are not seen, however, and chronic treatment does not lead to dopamine D2 receptor supersensitivity. Binding studies show clozapine's highest affinities to be for dopamine D4, 5-HT1c, 5-HT2, α1, muscarinic and histamine H1 receptors, but moderate affinity is also seen for many other receptor subtypes. Microdialysis studies indicate a preferential interaction with striatal D1 receptors, whereas autoradiographical studies indicate upregulation of D1 and downregulation of 5-HT2 receptors after chronic clozapine. Clarification of the mechanisms underlying clozapine's special attributes is often hampered by a failure to examine compounds which show a close chemical relationship to clozapine, but which produce extrapyramidal side-effects in man, such as clothiapine, loxapine and amoxapine.

A syndrome of subcortical dementia has been described in conditions predominantly affecting the basal ganglia or thalamus, structures that have also been implicated in the pathogenesis of schizophrenia. There are similarities between subcortical dementia and the type II syndrome of schizophrenia, in terms of clinical features, pattern of neuropsychological deficits, pathology, biochemistry and data from brain-imaging studies. These similarities raise the possibility that certain schizophrenic symptoms, particularly negative symptoms and disturbance of movement, may reflect subcortical pathology. Neuropsychological deficits of presumed frontal lobe origin have been reported in some schizophrenic subjects. The occurrence of such deficits in a condition in which frontal lobe pathology has not been clearly demonstrated may be explicable in terms of a subcortical deafferentation of the pre-frontal cortex.

Most measurable aspects of normal personality appear to be at least moderately heritable, with direct evidence coming from family, twin and adoption studies and indirect support deriving from psychophysiological research and breeding experiments on animals. Interestingly, genetic studies also shed light on the environmental sources of variation in personality and suggest that shared family environment rarely, if ever, has any positive effect on similarity between relatives. Despite problems of classification, and variations in the use of terms, a survey of the literature provides reasonably consistent evidence of a genetic contribution to several categories of abnormal personality, which we here divide into three groups, antisocial, anxious/avoidant, and schizoid–schizotypal personalities. However, personality disorders are complex traits that do not show simple mendelian patterns of inheritance and so far molecular genetics has been of no help in understanding their aetiology. Fortunately, techniques are now becoming available that enable the detection and potential localisation of genes of small effect and which may help elucidate the molecular basis even of (probably) polygenic traits such as abnormal personality.

It is now generally accepted that stressful life events and chronic difficulties can trigger the onset of depression in predisposed individuals. However, although much is known of the neurobiology of stress, few attempts have been made to provide a biological explanation for the mechanisms whereby life events might trigger depression. Enough is now known of the central control of hypothalamic pituitary adrenal (HPA) function and its response to stress to permit an examination of its role in the neurobiology of the triggering of depression by stress. This evidence is reviewed, and the proposal explored that stress triggers depression by a genomic action of corticosteroids.