Although antipsychotic medications are extremely valuable in both the acute and long-term management of schizophrenia, a substantial subgroup of patients derive little or only partial benefit. A variety of strategies to treat such patients are reviewed.

Abnormal premorbid personality has long been considered to be an important feature of patients who develop schizophrenia, or schizophrenic-like psychoses late in life. Schizoid and paranoid personality traits in particular are repeatedly reported to have preceded the development of psychosis by many years. Such personality abnormalities have been viewed as part of a schizophrenic spectrum disorder, causally invoked in the aetiology of psychosis, or even regarded as an adaptive protection of vulnerable individuals against psychotic breakdown. An ICD-10 diagnosable personality disorder, however, is seen in only about 50% of patients who develop a paranoid psychosis late in life. The premorbid personality abnormalities encountered in late-onset paranoid states and delusional disorder are different from those reported in schizophrenia and there appears to be a genetic basis for these differences. The role of such personality disturbance in the aetiology of psychosis is controversial but probably only minor.

Cognitive abnormalities may occur in the physically asymptomatic phases of the infection with the human immunodeficiency virus (HIV), and poor education may represent a risk factor for their development. These abnormalities are usually mild, and apparently do not affect subjects’ daily living performance, although this notion should be regarded as preliminary, due to the present primitive stage of development of the instruments which assess functioning in daily living activities. The above evidence has emerged from the cross-sectional phase of the WHO Neuropsychiatric AIDS Study, carried out in the five geographic areas predominantly affected by the HIV epidemic (sub-Saharian Africa, Latin America, North America, South-East Asia, Western Europe), on subject samples that are representative of the whole population of HIV-infected persons living in those areas. The professional implications of HIV-associated early cognitive dysfunction are open to research: for example the current debate on the impact of dysfunction on aviation-related skills emphasizes the need for test batteries with a higher predictive potential than those presently available.

Data from an ongoing family interview study suggest that schizoaffective probands - including even those with a very brief history of a major depressive or manic syndrome - display a high prevalence of major mood disorders in their first-degree relatives. In this respect, schizoaffective probands proved significantly different from ‘pure’ schizophrenic probands, but not significantly different from bipolar probands.

This review studies the epidemiology of anxiety disorders of childhood and adolescence, including prevalence rates, comorbidity patterns, risk factors and course. Comorbidity is very important: most children with anxiety disorders also have one or several other anomalies, usually anxiety or mood disorders. The authors point out the main evidence suggesting that a number of risk factors are associated with childhood anxiety disorders: age, sex, low socioeconomic setting; child's personality, and lastly, familial risk factors which have a very strong influence: children of parents with current or past anxiety disorders are more at risk of having anxiety disorders. Concerning the course of disorders, we have tentatively defined subsets of children or adolescents with anxiety disorders, and tried to clarify the recovery rate of these subsets. Future directions for research are suggested.

The role of the neuropeptide cholecystokinin in schizophrenia has been widely explored because of its modulating action on midbrain dopamine neurons. The recent discovery of more specific receptor subtype cholecystokinin antagonists should be considered as potential treatment for schizophrenia with fewer side effects. This paper reviews cholecystokinin/dopamine interactions in animal and human studies. Clinical trials with cholecystokinin agonists and antagonists in schizophrenia are updated.

A number of Meso-American artifacts which appear to depict subjects presenting severe depressive episodes have been identified, showing that concern with depressive disorders is not a recent phenomenon. Atypical presentations of depression in modern Mexico are characterized by a high degree of somatization, perhaps to avoid the stigma of “mental disorders”. Other characteristics are mood reactivity, substantial anxiety, phobias and the reversed vegetative manifestations. There is a high comorbidity with panic disorder and with bipolar depression. Nosological terminology is not fully standardized, and commonly encountered diagnoses include “neurasthenia”, “neurotic depression”, “mixed depression”, “resistant depression”, etc. Treatment involves a variety of modalities, including TCAs, MAOIs, and anxiolytics, together with a number of drug combinations; open trials are underway with newer agents such as SAMe, SSRIs and the RIMAs.

As with other drugs it is necessary to look for changes induced by anxiolytics on vital signs, laboratory parameters and adverse events. In return, in a more specific way for anxiolytics, we will look at side effects at the central nervous system level with psychological and physiological battery tests. We will also assess the safety of use of anxiolytics in certain specific conditions, such as overdose or withdrawal and in certain populations such as the elderly, neonates and children. The assessment of safety and side effects, whatever the drug type studied, must come early in the developing process of a drug (phases I, II and III).

Although a great deal of biological research has been carried out on several psychiatric disorders, it is disappointing to see how little progress has been made in the field of the biology of personality. The authors underline the methodological problems that arise in the investigation of biological substrates of human personality and review both currently available and putative peripheral markers of the central nervous system that might be used in further human studies.

The concordance and degree of overlap between 13 diagnostic systems for schizophrenia, including the five European systems of Berner, Bleuler, Langfeldt, Pull and Schneider, were evaluated in a cross-sectional study (N = 51) taking the phase of illness (acute or residual) into account. The diagnostic assessments were processed by computer using a 183-item standardised checklist and a data-processing program in GW-Basic language. The inter-rater reliability, as assessed by Kappa coefficient, was good to excellent for each diagnostic system established by this method (K from 0.5 to 1). When comparing the concordance between pairs of 13 diagnostic systems for schizophrenia in acute and residual phase groups, results showed that only two significant relationships were not influenced by the phase of illness (Carpenter x RDC; Catego x Schneider), while 24 were. These included only two relationships in the acute group (Carpenter Catego; Carpenter Schneider) and 22 links between pairs of systems in the residual group. In the acute group, no diagnosis of schizophrenia, including duration criteria such as those of DSM III-R, Feighner, Langfeldt, Pull and RDC, was linked to other systems. In the residual group, the operational systems such as Catego, DSM III-R, Feighner, Newhaven, Pull and RDC had more than five relationships with the other systems whereas the non-operational systems of Bleuler, ICD9, Langfeldt and Schneider had less than four relationships with the others. Except Pull's criteria, the European diagnostic systems, in particular Berner's and Bleuler's, seemed to differ from the others because of the few relationships displayed. The results underline the importance of taking the phase of illness into account when comparing between studies utilizing different diagnostic systems for schizophrenia. They also show the relationships between European and international diagnostic systems, insufficiently established so far.

In 55 chronic DSM III-R schizophrenics the occurrence of obstetric complications (OCs) was investigated using the familial/sporadic strategy and Leonhard's unsystematic/systematic distinction. The overall frequency and severity of OCs did not differ between patients and controls. A sub-sample of patients, whose genetic risk was supposed to be high in both classification systems (diagnosis of unsystematic and familial schizophrenia), had significantly fewer OCs than controls on the Lewis and Murray scale (P < 0.05). With reference to previous reports of increased mortality rates in the offspring of schizophrenics, high genetic risk and additional perinatal stressors may increase perinatal mortality. In contrast, patients whose genetic risk was supposed to be low in both systems (diagnosis of systematic and sporadic schizophrenia) showed a trend to an increased frequency of OCs in the Fuchs scale. In the context of the recently reported highly significantly increased rate of maternal infections during midgestation in these patients, it was supposed that perinatal complications may be of some aetiological importance in schizophrenics with low genetic risk.

One hundred and sixteen patients with RDC unipolar recurrent depressive disorder, melancholic subtype, were treated with imipramine or phenelzine and followed-up for six months. None of the patients had a first-degree relative with bipolar I disorder. Twenty-six patients (22.4%) presented an hypomanic episode (‘hypomanic group’). This group of patients, when depressed, had a significantly lower age of onset of the disorder and higher response to antidepressant therapy than patients who did not present an hypomanic episode. Significantly more patients (88%) of the ‘hypomanic group’ had at least one first-degree relative with a history of major depressive disorder. These patients displayed some of the typical features of bipolar II disorder. Overall results support the continuum in clinical phenomena between unipolar and bipolar disorders.

In the UK, the majority of patients with depressive disorders are treated by general practitioners, and there is little agreement on the nomenclature for atypical disorders including dysthymia, atypical depression, neurasthenia and recurrent brief depression. Mixed depressive and anxiety symptoms are considered to be the norm, and antidepressant drugs are increasingly being used in place of benzodiazepines. Unfortunately, antidepressant regimens prescribed by GPs tend to be inadequate in terms of both duration and dosage, and an educational campaign is underway to remedy this problem. British psychiatrists employ the full range of available antidepressant drugs for depression, and the severity of the disorder is not a primary determinant for choice of drug; on the other hand, ECT is reserved primarily for psychotic depression. Neurasthenia is frequently diagnosed as “chronic fatigue syndrome”, or “myalgic encephalomyelitis”, and a psychological treatment protocol has given encouraging initial results.

In order to evaluate the validity of the Montgomery and Asberg Depression Rating Scale (MADRS) in a Black African context, the MADRS construction study was replicated in Benin (West Africa) following the same initial procedure. Ninety-two Beninese French-speaking, major depressed out-patients were rated with the French version of the CPRS and were administered 75 mg/day clomipramine for 4 weeks. Forty-nine patients were rated at the end of the period. A list of items with a frequency higher than 70% was pre-selected from this data in strict accordance with the Montgomery and Asberg procedure; the ten items most sensitive to change Were then extracted from this list. The new scale shared eight of the ten MADRS items. Only pessimistic and suicidal thoughts, perhaps culture-bound, were absent and replaced in the new list by reported muscular tension and reduced sexual interest. None of the classic African symptoms involving somatic complaints or persecution ideas were selected by the procedure. The interest of using a shortened version of the MADRS, limited to the common eight items, is discussed.

The incidences of major psychiatric syndromes (DSM III-R, axis I) in the age group 18–49 years were investigated. Incidence was defined as first ever admission rates during a period of 1 year.. The study base was a well-defined catchment area of 217,649 persons. Selection bias was analyzed by the use of a population-based psychiatric case register. Information bias was minimized by the use of a semi-structured interview, the Present State Examination, 10th edition. Comorbidity defined as significant cooccurrence of Axis I disorders was analyzed by multivariate statistics. One hundred and sixty-six patients were interviewed. PSE-10, now published by WHO, proved to be as reliable as its predecessors, and appropriate for the severely ill psychiatric patient. Incidences of schizophrenia, other psychoses stratified for the presence of psychoactive substance use disorders, and mood disorders stratified for anxiety disorders were reported. The sample was biased towards younger individuals with more severe psychopathology.