Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems.

To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders.

Systematic review of preclinical and clinical studies.

Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar.

The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Despite the growing recognition of the global burden of psychiatric disease, there are questions about the strength of the evidence base from non-Western societies.

To compare the contribution of Euro-American countries and the rest of the world (RoW) to psychiatric literature.

Survey of the country of origin of papers submitted to and published in six leading psychiatric journals over a 3-year period (1996–1998).

Only 6% of the literature is published from regions of the world that account for over 90% of global population. The three journals published in Europe had a significantly higher proportion of international articles when compared to the three American journals. Less than 1% of all published articles described mental health interventions in the RoW. Acceptance rates were significantly lower for papers submitted from the RoW.

There is a gross under-representation of research from the RoW. This has implications for the development of a truly international psychiatry.

Velo-cardio-facial syndrome (VCFS) is associated with deletions in the q11 band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood.

To investigate brain anatomy in adults with VCFS.

Magnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume.

The subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes.

Deletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS.

Schizophrenia has been linked with psychological problems in childhood but there is little information on precursors of affective psychosis.

To compare childhood psychological antecedents of adult schizophrenia and affective psychosis.

Childhood item sheets, which give standardised information on signs and symptoms of mental illness in the year preceding assessment are completed for all attendees at the children's department of the Maudsley and Bethlem Royal Hospital. We examined item sheet data on individuals with an adult diagnosis of schizophrenia (n=59) or affective psychosis (n=27) and a comparison group with no adult mental illness (n=86) (all had attended the department).

Abnormal suspiciousness or sensitivity and relationship difficulties with peers are associated with later schizophrenia. In contrast, affective psychosis is associated with childhood hysterical symptoms and disturbances in eating.

Childhood psychological precursors for schizophrenia and affective psychosis differ and do not simply reflect non-specific psychiatric disturbance in adolescence.

It is not known whether mothers with psychotic disorders are clinically and socially distinct from women with psychoses who have not had children.

To determine the proportion of mothers in an epidemiologically representative population of women with psychotic disorders, to examine the factors associated with having children, and to examine the factors associated with having children ‘looked after’ by social services.

Descriptive analysis and two case–control studies.

Sixty-three per cent of women with psychotic disorders were mothers. There were no clinical differences between women with or without children, but mothers were more likely to be older and live in unsupported accommodation. Having had a ‘looked after’ child was associated with Mental Health Act detention, younger age, a forensic history and being Black African.

Many women with psychoses are mothers. Mothers with psychoses are as disabled and have as many needs as women with psychoses without children.

Recent research has reported increased risk of aggressive incidents by individuals with psychotic illness.

To examine acts of aggression in first-episode psychosis.

Subjects with a first-episode psychosis were ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3 years (n=166) using clinical interview, informants, health care and forensic records.

Of the subjects, 9.6% demonstrated at least one act of serious aggression (defined as weapon use, sexual assault or victim injury) during at least one psychotic episode and 23.5% demonstrated lesser acts of aggression (defined as all other acts of aggression). For all aggressive subjects (33.1%), unemployment (OR=3.6, 95%CI 1.6–8.0), comorbid substance misuse (OR=3.1, CI 1.1–8.8) and symptoms of overactivity at service contact (OR=6.9, CI 2.7–17.8) had independent effects on risk of aggression.

We confirmed some previously reported demographic and clinical associations with aggression in first-episode psychosis but no relationship with specific psychotic symptoms or diagnostic groups was observed.

Many factors influence the type and quantity of services received by patients and, thus, the total cost of care. Knowledge of these factors can aid budgetary and service-planning decisions.

To investigate factors that influence the cost of caring for patients with severe psychotic illness.

Univariate and multivariate analyses were used to examine associations between baseline characteristics and subsequent 2-year total direct costs in 667 patients from the UK700 case management trial.

Significantly more money was spent on younger patients, those with longer duration of illness, those who had spent less time living independently and those who had spent longer in hospital for psychiatric reasons.

Total costs of caring for patients with severe psychotic illness appear to be influenced to a large extent by age, duration of illness and past levels of dependence on statutory services. The strength of these relationships is greater than the impact of illness severity.

The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown.

To determine the effects of RTD on brain 5-HT2 receptors using positron emission tomography (PET) and 18F-labelled setoperone.

Ten healthy women underwent two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days.

The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT2 receptor binding in various cortical regions following the RTD session.

When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT2 receptors, these findings suggest that a decrease in 5-HT2 binding following RTD might be an adaptive response that provides protection against depressive symptoms.

Brain serotonin (5-HT) function is abnormal in major depression, but the involvement of different 5-HT receptor subtypes has been little studied. The availability of selective ligands now makes it possible to test the sensitivity of 5-HT1D receptors in patients with depression.

The aim of the study was to use the 5-HT1D receptor agonist, zolmitriptan, to test the sensitivity of 5-HT1D receptors in patients with depression before and after treatment with selective serotonin reuptake inhibitors (SSRIs).

We measured the growth hormone response to zolmitriptan (5 mg orally) in patients with major depression before and after SSRI treatment. A matched sample of healthy subjects acted as a control group.

The growth hormone response to zolmitriptan was blunted in patients with a melancholic depressive syndrome. SSRI treatment produced a marked reduction in zolmitriptan-induced growth hormone release.

Patients with melancholic depression have impaired sensitivity of the post-synaptic 5-HT1D receptors that mediate growth hormone release. The reduction in 5-HT1D receptor sensitivity following SSRI treatment is probably an adaptive response to increased levels of synaptic 5-HT.

The UK Government's White Paper Saving Lives: Our Healthier Nation included among its targets a reduction in suicide.

To study causes of change in suicide rate over a 30-year period in Newcastle upon Tyne.

Suicide rates and methods, based on coroners' inquest records, were compared over two periods (1961–1965 and 1985–1994) and differences were related to changes in exposure to poisons and prescribed drugs, and to socio-demographic changes.

Demographic and social changes had taken place which would adversely affect suicide rates. However, a dramatic fall was found in the rate for women, and a modest decline in that for men. Reduced exposure to carbon monoxide and to barbiturates coincided with the fall in rates.

Reduced exposure to lethal methods was responsible for the fall in rate in both genders, while the gender difference in favour of women may be related to their preference for non-violent methods or to their being less affected by the social changes.

Open verdicts are often included in with suicides for research purposes and for setting health targets.

To examine similarities and differences in cases defined by the coroner as suicide and open verdicts and the implications of open verdicts for suicide research.

All cases of open and suicide verdicts recorded in the Newcastle Coroner's Court in the period 1985–1994 were compared on demographic and medical parameters.

Open and suicide verdicts had many similarities, differing only in some respects, of which logistic regression identified the most significant to be a suicide note, method used and age.

Open verdicts should be included in all suicide research after excluding cases in which suicide was unlikely. Objective criteria are needed to facilitate comparison between different studies.

Suicide rates for England and Wales have been decreasing recently, but rates for young adult males remain high.

To review changes in suicide rates for children and adolescents in England and Wales between 1970 and 1998.

Rates for suicide, ‘accidental’ death by causes similar to suicide and ‘undetermined’ death for 10–14- and 15–19-year-olds are calculated between 1970 and 1998 using suicide data and estimated mid-year populations obtained from the Office for National Statistics.

There has been a substantial increase in suicide rate between the 1970s and the 1990s for males aged 15–19 years. This remains true even when ‘undetermined’ and ‘accidental’ death rates for causes similar to suicide are examined. The increase was associated with an increase in self-poisoning with vehicle exhaust gas in the 1980s and an increase in hanging which has continued into the 1990s. Although there was a slight decrease in the official suicide rate for females aged 15–19 years, ‘undetermined’ deaths increased. There is no indication of a major change in suicide rate in 10–14-year-olds.

The substantial increase in suicide rate in 15–19-year-old males may indicate increased psychosocial stress, particularly affecting this group.