Introduction. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible alternative to electroconvulsive therapy for the treatment of selected patients with depression, bipolar affective disorder and schizophrenia. The aim of this study was to evaluate the evidence for the effectiveness of rTMS in mood disorders and schizophrenia.

Methods. Studies were identified using MEDLINE (1966 to January 2000), EMBASE/Excerpta Medica (1980 to January 2000), Biological Abstracts and Index to Scientific and Technical Proceedings. A number of biomedical and TMS related websites were also searched. We estimated the number needed to treat to show beneficial effect of rTMS when compared with the placebo controlled group.

Results. Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2·3 with a 95% confidence interval 1·6 to 4·0, total; 81 patients. A single trial of rTMS has also been performed in mania, which shows a beneficial effect of right hemisphere stimulation when compared with left hemisphere stimulation. A controlled trial in schizophrenia failed to show any benefit of rTMS.

Discussion. rTMS has demonstrable beneficial effects in depression. The extent and the duration of the anti-depressant effect of rTMS has yet to be defined. There now needs to be randomized controlled trials to compare rTMS directly with standardized electroconvulsive therapy in order to take this subject forward. With regard to the treatment of other mood disorders and schizophrenia, we are at an early stage in the assessment of further studies that are needed to examine any potential role for rTMS.

Background. It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression.

Methods. By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain.

Results. The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period.

Conclusion. Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.

Background. Due to the limited data available, it is not clear whether the incidence of first-onset depression varies with age in the elderly.

Methods. A representative sample of individuals born 1901–2 (N = 392) was examined at the ages of 70, 75, 79, 81, 83 and 85 years by psychiatrists using a semi-structured schedule. Information on depressive episodes was also collected from self-report and examination of case records. Depression was diagnosed according to the DSM-III-R criteria.

Results. The incidence of depression was 12 per 1000 person-years in men and 30 per 1000 person-years in women between the ages of 70 and 85 (sex difference P = 0·001). The incidence increased from 17 per 1000 person-years (men 8·7, women 23·2, P = 0·007) between the ages of 70 and 79 to 44 per 1000 person years (men 27·0, women 52·8, P = 0·166) between 79 and 85 (age difference: RR 2·6, P < 0·001; men RR 3·1, P = 0·036; women RR 2·3, P = 0·003) . A diagnosis of depression was associated with increased mortality and refusal rate during the 15-year follow-up. Previous episodes of depression were associated with an increased risk of further episodes. The prevalence of depression increased from 5·6% at the age of 70 to 13·0% at the age of 85. The lifetime prevalence of depression was 23% in men and 45% in women.

Conclusions. Both the incidence and prevalence of depression increased with age in this longitudinally followed birth cohort, and the incidence was higher in women than in men.

Background. This study set out to estimate the 12-month prevalence of DSM-III-R major depressive episode (MDE) and to analyse factors associating with psychosocial impairment, episode duration, phenomenology and symptom severity in a representative general population sample of adolescents (15–19-year-olds) and young adults (20–24-year-olds).

Method. The Finnish Health Care Survey '96 (FINHCS '96) was a cross-sectional nationwide epidemiological study. A random sample of 509 adolescents and 433 young adults was interviewed in 1996. MDE was assessed by University of Michigan Composite Diagnostic Interview Short-Form.

Results. The 12-month prevalence of MDE was 5·3% for adolescents (females 6·0%, males 4·4%) and 9·4% for young adults (females 10·7%, males 8·1%). When moderate psychosocial impairment was included in case definition, the prevalences were lowered by 20–25%. Increased impairment was associated with drunkenness at least twice a month, a higher mean number of depressive symptoms and impaired concentration. The median episode duration was 1 month. No factors associating with duration were found. With the exception of symptoms related to appetite being more common among females than males, the phenomenology of MDE was mainly independent of age and gender.

Conclusions. Episodes of major depression among adolescents and young adults in the general population are short but often associated with psychosocial impairment, especially if frequent drunkenness coexists.

Background. Utilizing a prospectively designed community sample, we set out to estimate the rate of newly-incident suicidal ideation and attempts (non-fatal suicide behaviour) in a community sample, to evaluate antecedent sociodemographic characteristics and psychiatric disorders, and to assess use of mental health services in relation to non-fatal suicide behaviour.

Method. Prospectively-gathered data was utilized from 3481 continuing participants in the 13-year follow-up of the Baltimore sample of the NIMH Epidemiologic Catchment Area survey interviewed in 1981, 1982 and 1993/6.

Results. The incidence of suicide attempts was estimated at 148·8 per 100000 person-years and ideation at 419·9 per 100000 person-years. Persons in the youngest age group, in the lowest socio-economic status, and previously married persons were at increased risk for non-fatal suicide behaviour during the follow-up interval. Persons who reported suicidal ideation at baseline were more likely to report having attempted suicide at follow-up (RR = 6·09, 95% CI 2·58–14·36). Psychiatric disorders, especially depression and substance abuse, were associated with new-onset of non-fatal suicidal behaviour. While persons who reported newly-incident suicidal behaviour were more likely to report use of mental health services, few said that suicidal ideation or attempts were the reason for the visits.

Conclusions. Suicidal ideation is a common and important antecedent to suicide attempts and deserves more attention in community and general medical settings.

Background. Stressful life events, such as family conflicts, separation, bereavement, somatic illness and financial problems are common antecedents of suicide. Studies on suicide among younger persons dominate the literature, despite the fact that a large proportion of suicides occur among elderly persons.

Methods. The occurrence of stressful life events was investigated among elderly suicide cases and population controls. The study was conducted in the southwestern part of Sweden and included 85 persons (46 males and 39 females) 65 years and above who had committed suicide from January 1994 to May 1996. Population controls (84 males and 69 females) were randomly selected. Interviews were carried out with the controls and with informants for the suicide cases. Questions on sociodemographic background, mental and somatic health status, and life events (0–6, 7–12 and 13–24 months preceding suicide/interview) were included in the interviews.

Results. Somatic illness, family discord and financial trouble were significant risk factors during all three time periods. Other risk factors were mental disorder, lower education, feelings of loneliness and previous suicide in the family. Factors associated with a decreased risk included active participation in organizations and having a hobby. Variables that remained in the multivariate logistic regression model were mental disorder (men, odds ratio (OR) = 62·4, 95% CI 17·9–217·5; women, OR = 55·9, 95% CI 14·1–222·3) and family discord (men, OR = 10·0, 95% CI 1·7–59·8; women, OR = 9·2, 95% CI 1·9–44·8).

Conclusions. Mental disorder and family discord were the two major risk factors for suicide among elderly men and women.

Background. The prescription of antidepressants has increased substantially over the last 10 years. It is therefore timely to examine trends in mortality associated with overdoses of antidepressants and to compare the relative mortality associated with different antidepressants.

Methods. Data were derived from a newly developed national database of deaths from overdose and poisoning in England and Wales between 1993 and 1997. Age and sex specific death rates associated with overdose and poisoning with antidepressants were calculated together with numbers of deaths per 100000 prescriptions of individual antidepressants.

Results. Twenty per cent (2503) of all deaths from overdose or poisoning were antidepressant related. The number of deaths increased by 18% between 1993 and 1997. Ninety-five per cent of deaths from antidepressants were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. Tricyclic antidepressants were associated with 5·3 deaths per 100000 prescriptions, 4·4 for monoamine oxidase inhibitors and 0·4 for selective serotonin reuptake inhibitors. Annual death rates were highest in men aged 30–44 years (18·2 per million) and women aged 45–59 years (14·8). Death rates from antidepressants were 2·5 times higher in the most deprived fifth than in the least deprived fifth of enumeration districts.

Conclusions. Antidepressants are an important cause of death from poisoning and overdose. SSRIs and newer antidepressants are associated with <10% of the risk of death than the older antidepressants. There is a strong association between area deprivation and deaths from antidepressants.

Background. Concordance for major depressive disorder (MDD) between parents could happen for different reasons. Regardless of the origin and the frequency of the concordance, the effect on offspring of having two parents affected with MDD may be serious. The sex of the affected parent and offspring may also be a important risk factor for MDD in offspring.

Methods. We examined the increased risk of psychopathology among offspring of the four parental mating groups: both parents affected with MDD (N = 53); only mother affected (N = 31); only father affected (N = 65); and, neither parents affected (N = 33). Parents and offspring were assessed by direct interview, conducted blind and independently of each other.

Results. Among the four parental mating groups, offspring of both parents affected had the highest risk of MDD, anxiety disorder and alcohol dependence, and the earliest age of onset for MDD. There were two exceptions: the highest risk of conduct disorder and of drug dependence was in the groups where only the father was affected and where only the mother was affected, respectively. Mother's MDD was a stronger predictor of MDD in male compared to female offspring. Father's MDD was a stronger predictor of MDD in female compared to male offspring.

Conclusion. Having two parents with MDD increases the risk of psychiatric disorders in offspring. A clear dose–response relationship between the number of affected parents and psychiatric disorders in offspring was observed. The sex of the affected parent and of the offspring is important in determining the risk to offspring. For an examination of the risk to psychopathology in offspring, diagnosis status of both parents should be considered.

Background. Treatment resistant depression (TRD) continues to present a formidable challenge to clinicians, accounts for over half of the annual costs associated with treatment for depression and causes great frustration to patients. Although there have been studies attempting to define TRD, little information is available as to the cause of TRD. One suggestion is that patients with TRD have a greater frequency of co-morbid psychiatric disorders, which explains their resistance to standard antidepressant treatments. The objective of this study was to compare the co-morbidity of Axis I disorders between a sample of TRD patients and a sample of non-TRD patients.

Methods. TRD and non-TRD patients, recruited from two separate antidepressant treatment studies, were assessed for Axis I co-morbidity using the SCID-P for the DSM-III-R. Patients for the two samples were then matched for baseline HAM-D-17 total score and gender.

Results. Results reveal that non-TRD patients had a higher rate of both lifetime and current generalized anxiety disorder co-morbidity than did the TRD patients. No other statistically significant differences in Axis I co-morbidity were found.

Conclusions. These findings do not support the idea that current or lifetime Axis I co-morbidity is more common in TRD than non-TRD patients. In fact, the only statistical difference showed non-TRD patients with higher co-morbidity rates.

Background. We pursue an observation that age may influence the clinical features of melancholia and, in particular, psychomotor disturbance.

Methods. Two large clinical databases were amalgamated allowing the clinical features of 124 depressed subjects meeting DSM-III-R and clinical criteria for melancholia to be contrasted with 218 subjects diagnosed as having a non-melancholic depression by both criteria sets. Psychomotor disturbance was assessed by the CORE measure and by seven classical endogeneity symptoms of melancholia which, when summed, created a ENDOG score.

Results. There was no impact of age on ENDOG scores in either the melancholics or non-melancholics. In the melancholics, increasing age was associated with increasing CORE scores and with agitation scale scores in particular. In a set of discriminant function analyses seeking to identify the comparative utility of a set of predictors of melancholic (versus non-melancholic) groups, age was significant, and while CORE and ENDOG scores were individual predictors, their combined entry established that the CORE score alone made the ENDOG score redundant, and that the addition of age then made little impact.

Conclusions. Melancholia appears to have a later age of onset than non-melancholic depression, while its phenotypic expression appears to change with age, with psychomotor disturbance being more distinct in older subjects. Such an effect may have a number of clinical implications, including possible differential effects of varying antidepressant treatments.

Background. We report on the epidemiology of post-traumatic stress disorder (PTSD) in the Australian community, including information on lifetime exposure to trauma, 12-month prevalence of PTSD, sociodemographic correlates and co-morbidity.

Methods. Data were obtained from a stratified sample of 10641 participants as part of the Australian National Survey of Mental Health and Well-being. A modified version of the Composite International Diagnostic Interview was used to determine the presence of PTSD, as well as other DSM-IV anxiety, affective and substance use disorders.

Results. The estimated 12-month prevalence of PTSD was 1·33%, which is considerably lower than that found in comparable North American studies. Although females were at greater risk than males within the subsample of those who had experienced trauma, the large gender differences noted in some recent epidemiological research were not replicated. Prevalence was elevated among the never married and previously married respondents, and was lower among those aged over 55. For both men and women, rape and sexual molestation were the traumatic events most likely to be associated with PTSD. A high level of Axis 1 co-morbidity was found among those persons with PTSD

Conclusions. PTSD is a highly prevalent disorder in the Australian community and is routinely associated with high rates of anxiety, depression and substance disorders. Future research is needed to investigate rates among other populations outside the North American continent.

Background. Trauma is a necessary diagnostic criterion for post-traumatic stress disorder (PTSD). However, the nature of traumas experienced (e.g. assaultive versus non-assaultive) may influence whether any mental disorder will arise. Traumatic experiences may also be associated with other mental disorders, particularly major depressive disorder (MDD). This report examines the relationship of trauma history to the likelihood of full or partial PTSD and MDD. In addition, the study examines the frequency with which assaultive and non-assaultive traumas are reported by patients with full or partial PTSD and MDD.

Methods. Three hundred eighty-six primary care patients completed psychiatric symptom measures during their clinic visit. A subset of 132 participants completed a diagnostic interview within 2 weeks following the screening.

Results. Most patients reporting traumas did not meet criteria for a mental disorder. Patients reporting traumas were more likely to experience current MDD (27·8%) than current full or partial PTSD (20·0%) although a high percentage of patients with traumas (41·1%) had experienced full or partial PTSD diagnosis in their lifetime. Respondents reporting assaultive events as their most severe trauma, when compared with those whose most severe trauma was non-assaultive, were more likely to have met criteria for either full or partial PTSD in their lifetime, and were more likely to have current MDD.

Conclusions. These findings suggest that trauma history is often not associated with psychopathology, and when it is, trauma is often associated with major depression rather than PTSD. The likelihood of psychopathology is increased for individuals reporting assaultive traumas.

Background. We sought to identify personal factors that placed people at risk during an epidemic of medically unexplained illness in a Bhutanese refugee camp in southeastern Nepal.

Methods. We conducted a case–control study, involving 68 cases and 66 controls. Caseness was defined as experiencing at least one attack of medically unexplained fainting or dizziness during the time of the epidemic. We performed hierarchical logistic regression analysis to identify significant predictors of case status.

Results. In terms of Western psychiatric constructs, the illness involved somatoform symptoms of both acute anxiety and dissociation. Sixty per cent reported visual and 28% reported auditory hallucinatory experiences. Cases and controls were similar on all demographic variables, school performance, number of attacks witnessed and psychopathology before the onset of the epidemic. Recent loss, early loss, childhood trauma and pulse-rate were predictors of case status.

Conclusion. We identified trauma, early loss and, especially, recent loss as predictors of attacks during medically unexplained epidemic illness in a Bhutanese refugee community.

Background. Several studies have suggested that visual backward masking (VBM) impairment is present in patients with bipolar disorder, but the clinical features, such as current symptoms, treatment status and past burden of illness that may contribute to the impairment have not been well described. This study examined well-characterized euthymic patients on two VBM tasks to ascertain the extent of VBM impairment in this group and the clinical correlates of this impairment.

Method. Twenty-eight euthymic patients with a DSM-IV diagnosis of bipolar disorder were matched by age, sex and IQ with 28 non-psychiatric control subjects. Both groups completed two VBM tasks; one required subjects to locate the target stimulus, one required identification of the target stimulus. Reaction times and error rates across a range of target-mask inter-stimulus intervals were assessed.

Results. Patients were significantly slower and had more errors on both VBM tasks. There was a significant relation between reaction times on the identification task and past burden of illness, particularly past number of depressions. There was no discernible impact of treatment status on reaction time or performance, including no difference in lithium-treated versus not treated subjects.

Conclusions. These results are consistent with previous reports of neuropsychological deficits in euthymic bipolar disorder patients. The potential benefit to employing tasks such as VBM is that it may provide a method for relating clinical variables such as illness burden with known neural pathways in order to elucidate better the pathophysiology leading to impaired cognitive performance in patients with bipolar disorder.

Background. Verbal working memory (WM), which relies on intact functioning of frontostriatal circuits, has been suggested as a cognitive domain that is preferentially affected in HIV-1 infection. Although several studies have found WM impairments in HIV-1 infected patients, Baddeley's classic WM model has not been studied extensively in this population.

Methods. We used two cognitive neuropsychological approaches to examine verbal WM deficits in 18 HIV-1 seronegative, 16 HIV-1 asymptomatic, and 20 HIV-1 symptomatic patients. First, based on Baddeley's WM model of the Phonological Loop, we used the phonological similarity effect and the irrelevant speech effect to evaluate each individual's phonological store, and the word-length effect and the articulatory suppression effect to evaluate the articulatory control process. Secondly, an individual differences approach, which focuses on the capacity limitation of the WM system and potentially integrates the functions of Baddeley's Central Executive component with the Phonological Loop, was adopted. We evaluated each patient's simultaneous storage and processing of auditory material using the Verbal Memory Span test.

Results. The HIV-1 symptomatic individuals, but not the HIV-1 asymptomatic subjects, demonstrated impaired short-term storage of verbal material in the phonological store on Baddeley's measures. Although the HIV-1 asymptomatic and symptomatic subjects demonstrated intact rehearsal of speech-based material in the articulatory control process, both groups demonstrated impairment on the Verbal Memory Span test.

Conclusions. These findings suggest that deficits in simultaneous short-term storage and processing occur during both early and later stages of HIV-1 infection.

Background. The objective of the study was to develop the cognitive understanding of persecutory delusions. It was hypothesized that safety behaviours contribute to the persistence of persecutory delusions by preventing disconfirmation. It was further hypothesized that emotional distress is associated with aspects of the content of delusions. An investigation was designed to establish whether individuals with persecutory delusions use safety behaviours, and to test predicted associations between delusion content and emotional distress.

Method. A cross-sectional investigation was conducted on 25 individuals with persecutory delusions. A detailed assessment was made of the presence of safety behaviours, the content of delusions and emotional distress.

Results. All participants had used at least one safety behaviour in the last month, most typically avoidance. Higher levels of anxiety were associated with greater use of safety behaviours. New data were obtained on the content of persecutory delusions. Aspects of the content of the delusions were associated with levels of depression, self-esteem, anxiety and delusional distress.

Conclusions. Individuals with persecutory delusions use safety behaviours. The findings may develop the understanding of delusion persistence, acting upon delusions and the negative symptoms of schizophrenia. There are implications for cognitive interventions for psychosis. Support was also found for the hypothesis that emotional distress is linked to the content of delusional beliefs; it is speculated that prior emotional distress influences the content of delusions, and that delusion content in turn influences levels of emotional distress.

Background. This study was undertaken to examine the relationship between anxiety co-morbidity and age of onset of panic disorder.

Methods. Age of onset of panic disorder and co-morbid anxiety disorders were assessed among 201 panic disorder probands with childhood separation anxiety disorder, obsessive–compulsive disorder, obsessive–compulsive symptoms, social phobia and specific phobia as part of a clinician-administered lifetime diagnostic interview. A generalized linear model was used to test the association between each anxiety co-morbidity and age of panic disorder onset while simultaneously controlling for the potential confounding effects of sociodemographic characteristics and other psychiatric co-morbidity.

Results. Earlier onset of panic disorder was found in patients with co-morbid obsessive–compulsive disorder, obsessive–compulsive symptoms and separation anxiety disorder, but not simple phobia or social phobia. Patients with both childhood separation anxiety disorder and obsessive–compulsive disorder had an even earlier panic onset than those with either childhood separation anxiety disorder or obsessive–compulsive disorder.

Conclusions. The association between anxiety co-morbidity and earlier onset of panic disorder is specific to obsessive–compulsive disorder and childhood separation anxiety disorder.

Background. The Interacting Cognitive Subsystems analysis of cognitive vulnerability to depression predicts that subjective experiences of dysphoria in recovered depressed patients will be qualitatively different from those of controls. This study tested this prediction using a new instrument, the Depressed States Checklist.

Methods. Twenty-three recovered recurrently depressed patients and 54 never depressed controls rated the affective and self-devaluative components of a dysphoric experience.

Results. Groups reported similar levels of affective component but recovered depressed patients reported higher self-devaluative dysphoric experience. At zero affective component of dysphoria neither group reported any self-devaluative feelings. With increasing affective component of dysphoria, the self-devaluative component increased significantly more in recovered patients than in controls. The ratio of self-devaluative to affective components of dysphoria significantly differentiated recovered depressed patients from controls.

Conclusions. As predicted, dysphoria in recovered depressed patients is qualitatively different from controls in ways that increase vulnerability to major depression. The Depressed States Checklist is a new, brief, measure of cognitive vulnerability to depression that may be particularly useful in large, prospective, epidemiological studies.