The issue of whether an association exists between cannabis and psychosis exists, and why, has received considerable attention in recent years (Hall, 1998; Mueser et al. 1998; Blanchard et al. 2000; Degenhardt & Hall, 2002). There are probably a number of reasons for the sustained interest. First, psychotic disorders such as schizophrenia are often chronic or recurring (Mason et al. 1996), are associated with significant disability (Keith et al. 1991) and they place a considerable burden upon the community at large (Hall et al. 1985; Knapp, 1997). Secondly, over the past few decades, high rates of cannabis use and use disorders have been observed among persons with schizophrenia and other psychoses (Barbee et al. 1989; Fowler et al. 1998), suggesting the possibility that cannabis use may be causally related to psychotic disorders. Thirdly, given what is known about the psychotomimetic effects of cannabis (Hall et al. 2001), it is plausible that high doses of cannabis may produce psychotic symptoms. Finally, clinical research with persons with psychotic disorders has found that problematical substance use is correlated with a range of negative outcomes including relapse, rehospitalization, poor medication compliance, poorer social functioning and increased treatment costs (Salyers & Mueser, 2001), suggesting drug use may be related to worsened clinical outcomes.

BRAIN STIMULATION IN THE TREATMENT OF MAJOR DEPRESSION

Repetitive transcranial magnetic stimulation (rTMS) is an experimental medical procedure that is currently under investigation for its potential therapeutic value in major depression and other psychiatric and neurological disorders (Wassermann & Lisanby, 2001). The idea of using brain stimulation to treat depression dates back to the origins of ECT, and includes more recently developed techniques such as deep brain stimulation and vagus nerve stimulation. The value of brain stimulation in psychiatry is still most clearly seen in the, as yet, unparalleled efficacy of ECT in treating severe depression (American Psychiatric Association, 2001). While ECT is the most effective and most rapidly acting treatment for depression, it also causes a variable degree of undesirable cognitive side effects that limit its clinical utility and prevent many patients who could benefit from receiving this often life-saving treatment (McElhiney et al. 1995; Lisanby et al. 2000b). The search for an effective somatic treatment for medication resistant depression with fewer cognitive side effects than ECT has motivated much of the work with rTMS in psychiatry.

Background. The aims of this research were to use data gathered over the course of a 21 year longitudinal study to examine the linkages between cannabis dependence at ages 18 and 21 and rates of psychotic symptoms taking into account previous symptom levels and other confounding factors.

Method. Data were gathered during the course of the Christchurch Health and Development Study (CHDS). The CHDS is a longitudinal study of a birth cohort of 1265 children who have been studied from birth to age 21. As part of this study, data were gathered on cannabis dependence and psychotic symptoms at ages 18 and 21.

Results. Young people meeting DSM-IV criteria for cannabis dependence had elevated rates of psychotic symptoms at ages 18 (rate ratio = 3.7; 95% CI 2.8–5.0; P<0.0001) and 21 (rate ratio = 2.3; 95% CI 1.7–3.2; P<0.0001). These associations were adjusted for previous psychotic symptoms and a range of other confounding factors using a generalized estimating equation model. This analysis showed that after adjustment for confounding factors, those meeting criteria for cannabis dependence still had an increased rate of psychotic symptoms (rate ratio = 1.8; 95% CI 1.2–2.6; P<0.005).

Conclusions. The results show that the development of cannabis dependence is associated with increased rates of psychotic symptoms in young people even when pre-existing symptoms and other background factors are taken into account.

Background. Epidemiological findings suggest that cannabis use is a risk factor for the emergence of psychosis, and that the induction of psychotic symptoms in the context of cannabis use may be associated with a pre-existing vulnerability for psychosis. This study investigated in a non-clinical population the interaction between cannabis use and psychosis vulnerability in their effects on psychotic experiences in daily life.

Method. Subjects (N = 79) with high or low levels of cannabis use were selected among a sample of 685 undergraduate university students. Experience sampling method (ESM) was used to collect information on substance use and psychotic experiences in daily life. Vulnerability to develop psychosis was measured using a clinical interview assessing the level of psychotic symptoms. Statistical analyses were performed using multilevel linear random regression models.

Results. The acute effects of cannabis are modified by the subject's level of vulnerability for psychosis. Subjects with high vulnerability for psychosis are more likely to report unusual perceptions as well as feelings of thought influence than subjects with low vulnerability for psychosis, and they are less likely to experience enhanced feelings of pleasure associated with cannabis. There is no evidence that use of cannabis is increased following occurrence of psychotic experiences as would be expected by the self-medication model.

Conclusion. Cannabis use interacts with psychosis vulnerability in their effects on experience of psychosis in daily life. The public health impact of the widespread use of cannabis may be considerable.

Background. The efficacy and safety of bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, placebo-controlled study.

Method. Nineteen medication-resistant depressed subjects were randomly assigned to 3 weeks of active or sham rTMS. Effects on mood and neuropsychological function were assessed.

Results. Both groups improved significantly in mood over the 3 weeks, but there was no significant difference between active and sham treatments. There were no significant neuropsychological effects.

Conclusions. Bilateral rTMS was not superior to sham in treating resistant depression in this pilot study, but caused no neuropsychological impairment.

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.

Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.

Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.

Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

Background. Individuals with bulimia nervosa report significant symptom fluctuation, and some studies have suggested a premenstrual exacerbation of binge frequency. The purpose of this study is to explore the hormonal correlates of symptom fluctuation in bulimia nervosa.

Method. For five consecutive weeks (one full menstrual cycle), eight women with bulimia nervosa and eight non-eating-disordered control women collected morning saliva samples and recorded several mood characteristics; the bulimic women also recorded binge and purge episodes. Subsequently, salivary cortisol and androgen levels were determined by radioimmunoassay.

Results. Bulimic symptoms were exacerbated in both the mid-luteal and premenstrual phases, when compared with the follicular and ovulatory phases (F(3,21)=3·76, P=0·026; contrast analysis t(7)=3·47, P<0·01). Fluctuation in cortisol was closely correlated with fluctuation of bulimic symptoms, with elevated cortisol secretion following symptom exacerbation (r(24)=0·64, P=0·001).

Conclusions. Bulimic symptom fluctuation appears to be related to two hormonal phenomena – phase of the menstrual cycle and cortisol secretion – with menstrual-cycle phase influencing bulimic symptom severity, and bulimic symptom severity effecting increases in cortisol secretion. Improved understanding of the hormonal causes and consequences of symptom fluctuation may lead to improved psychological and pharmacological treatments for bulimia nervosa.

Background. We aimed to examine factors that influence vulnerability/resiliency of depressed young people to suicidal ideation and suicide attempt.

Method. Data were gathered during a 21-year longitudinal study of a birth cohort of 1265 New Zealand young people. Measures included: suicide attempt; suicidal ideation; major depression; childhood, family, individual and peer factors.

Results. Young people who developed major depression had increased rates of suicidal ideation (OR=5·4; 95% CI 4·5–6·6) and suicide attempt (OR=12·1; 95% CI 7·9–18·5). However, the majority of depressed young people did not develop suicidal ideation or make suicide attempts, suggesting that additional factors influence vulnerability or resiliency to suicidal responses. Factors influencing resiliency/vulnerability to suicidal responses included: family history of suicide; childhood sexual abuse; neuroticism; novelty seeking; self-esteem; peer affiliations; and school achievement. These factors operated in the same way to influence vulnerability/resiliency among those depressed and those not depressed.

Conclusions. Vulnerability/resiliency to suicidal responses among those depressed (and those not depressed) is influenced by an accumulation of factors including: family history of suicide, childhood sexual abuse, personality factors, peer affiliations and school success. Positive configurations of these factors confer increased resiliency, whereas negative configurations increase vulnerability.

Background. There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions.

Method. A sample of terminally ill cancer patients (N=256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998–2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated.

Results. A high WTHD was reported by 14% of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P<0·001): higher levels of depressive symptoms, being admitted to an in-patient hospice setting, a greater perception of being a burden on others, lower family cohesion, lower levels of social support, higher levels of anxiety and greater impact of physical symptoms.

Conclusions. Psychological and social factors are related to a WTHD among terminally ill cancer patients. Greater attention needs to be paid to the assessment of psychological and social issues in order to provide appropriate therapeutic interventions for terminally ill patients.

Background. Maintenance antipsychotic medication is the mainstay of relapse prevention in patients with schizophrenia. Long acting depot antipsychotics were developed to promote treatment adherence and yet their utilization is variable, perhaps due to negative attitudes of both patients and psychiatrists. Recently, a shift away from depots has occurred, in favour of the newer atypical oral antipsychotics.

Method. This study investigated the current attitudes and knowledge concerning depots, with a newly designed questionnaire, in a cross-sectional postal survey of qualified psychiatrists working in south-east England.

Results. A substantial minority of psychiatrists believe that depots are old fashioned (40%), stigmatizing (48%) and are associated with more side-effects than typical oral antipsychotics (38%). Many believe that depots are as efficacious as oral medication (91%) but are less acceptable to patients (69%) and relatives (66%). A large majority consider depots enhance patient compliance (81%) and prevent relapse (94%). Psychiatrists would be persuaded to prescribe depots if they were associated with fewer side-effects, in patients where compliance is an issue, and if atypical depot antipsychotics were available, presumably because they would have a lower incidence of side-effects. Additionally, psychiatrists' knowledge about depots was positively associated with attitudes. More favourable patient-centred attitudes were reported by psychiatrists with higher depot use.

Conclusion. Practising psychiatrists have several strongly endorsed attitudes towards depot medication that are associated with knowledge and prescribing habits. By updating psychiatrists' knowledge about depots, in turn their attitudes may become more positive and prescribing practices may subsequently change.

Background. A variety of factors are related to compliance with medication in schizophrenia, but little attention has been paid to the role of families. Carers' knowledge or expressed emotion (EE) may be related to compliance. The aim of the present study was to evaluate the relevance of these two factors, as well as their relationships with other variables for the prediction of compliance.

Method. A sample of patient–carer pairs (N=79) involved in a family intervention for schizophrenia trial was recruited. Compliance, symptoms, social functioning and attitudes to their carers were assessed in patients. Carers' EE, knowledge and psychopathology were also evaluated.

Results. A number of factors were related to compliance, including carers' EE and patients' psychotic symptoms, which contributed independently to not taking medication. Carers' knowledge about schizophrenia and other groups of symptoms was not related to compliance.

Conclusions. EE may be an important factor to account for in the understanding of patients' compliance and the direction of the relationship between EE and compliance should be the subject of further study.

Background. Relatively few predictors of outcome in first-episode psychosis are potentially malleable and duration of untreated psychosis (DUP) is one. However, the degree to which DUP is mediated by other predictors of outcome is unclear. This study examines the specific effects of DUP on 12-month outcome after adjusting for effects of potential confounders and moderating variables.

Method. The sample comprised 354 first-episode psychosis patients followed up 12-months after remission/stabilization of their psychotic symptoms. Outcome measures included functional outcome, severity of positive symptoms and negative symptoms. Hierarchical multiple regression assessed whether DUP significantly predicted 12-month outcome after adjusting for other predictors. Contrast analysis further clarified the differential effects of DUP on 12-month outcome.

Results. DUP remained a significant predictor of outcome after adjusting for the effects of other variables. This finding remained robust for the subset of patients with schizophrenia or schizophreniform disorder. Functional outcome appeared to decline substantially even after very short treatment delays (>7 days), with more gradual deterioration in functioning until very long DUP (>1 year). Good outcome was variably associated with good pre-morbid adjustment, female gender, diagnosis of affective disorder, short duration of prodromal symptoms, and treatment within the Early Psychosis Prevention and Intervention model in contrast to other models of care.

Conclusions. DUP consistently predicts outcome independently of other variables, and is not simply a proxy for other factors. As one of the few potentially malleable factors influencing outcome, DUP could prove to be a target for secondary preventive efforts in early psychosis.

Background. Lack of insight is frequently observed in schizophrenia. Relationships have been noted between poor insight, clinical symptoms and cognitive impairments but the findings are inconsistent. There have been some recent attempts to relate poor insight to neuro-anatomical measures.

Method. We assessed insight, positive and negative symptoms of schizophrenia, cognitive performance, and whole brain volumes in a sample of 78 DSM-IV male schizophrenics and 36 normal male comparison subjects matched for age and IQ. Subjects underwent a dual-echo MRI brain scan to establish grey, white and whole brain volumes.

Results. Poor Wisconsin Card Sorting Test performance inversely correlated with insight in schizophrenic patients, as did the symptoms alogia, anhedonia, avolition/apathy, affective flattening, inappropriate affect, thought disorder and delusions. The presence of inappropriate affect, delusions and thought disorder, showed the most significant impact on insight levels. There were no significant correlations between whole brain, white and grey matter volume and degree of insight.

Conclusions. The results suggest that poor insight is significantly related to schizophrenic psychopathology, and confirm that there is a relationship between insight and executive performance. Awareness of illness is not related to any global brain measures, suggesting future investigations should pay attention to more specific cortical regions such as the frontal cortex.

Background. Numerous studies have suggested, via the interpretation of negative priming effects, that subjects with schizophrenia are less able than controls to inhibit irrelevant distracting information. Further issues concerning impairment in inhibitory processes are investigated here. First, recent research has revealed that negative priming (NP) effects can be caused by different processes, distractor inhibition or perceptual review. Therefore, conclusions concerning reduced inhibition in patients with schizophrenia are not possible from previous NP research. Secondly, previous NP studies have required subjects to identify some feature of the target. This is the first study to examine NP that uses a spatial task in patients with schizophrenia.

Method. Twenty-eight subjects with schizophrenia and 28 age and sex matched non-psychiatric control subjects completed a computerized NP task that eliminated the possible contribution of perceptual review.

Results. Subjects with schizophrenia had reduced levels of NP compared to control subjects on this spatial NP task (t=2·46, P<0·02). Current age, positive, negative or total PANNS scores did not correlate with negative priming scores, but post hoc analyses revealed that clozapine-treated patients had significantly greater levels of negative priming than patients receiving typical antipsychotic medications.

Conclusions. The present experiment eliminated the contribution of perceptual review to negative priming and demonstrated that when a pure measure of inhibition is taken on a localization task, patients with schizophrenia were less able to inhibit irrelevant distracting stimuli. The fact that NP was reduced in a spatial task suggested a more diffuse reduction in inhibition than previous studies that examined only identification-based responses.

Background. The present study attempted to extend previous research on source monitoring deficits in schizophrenia. We hypothesized that patients would show a bias to attribute self-generated words to an external source. Furthermore, it was expected that schizophrenic patients would be over-confident regarding false memory attributions.

Method. Thirty schizophrenic and 21 healthy participants were instructed to provide a semantic association for 20 words. Subsequently, a list was read containing experimenter- and self-generated words as well as new words. The subject was required to identify each item as old/new, name the source, and state the degree of confidence for the source attribution.

Results. Schizophrenic patients displayed a significantly increased number of source attribution errors and were significantly more confident than controls that a false source attribution response was true. The latter bias was ameliorated by higher doses of neuroleptics.

Conclusions. It is inferred that a core cognitive deficit underlying schizophrenia is a failure to distinguish false from true mnestic contents.

Background. Prader-Willi syndrome (PWS) is a genetic disorder resulting in obesity, short stature, cryptorchidism, learning disabilities (mental retardation) and severe neonatal hypotonia. Associated with the syndrome are a number of behaviours that are sufficiently distinctive that the syndrome is considered to have a specific ‘behavioural phenotype’.

Methods. Through multiple sources we attempted to identify all people with PWS living in one region in the UK. This cohort was augmented by people with PWS from other regions, and a contrast group of people with learning disabilities of varied aetiologies. The main carers were interviewed, using structured and semi-structured interview schedules, to establish the presence and severity of specific behaviours, and PWS diagnostic criteria. The intellectual functioning and attainments of all were determined. Blood samples were obtained for genetic diagnosis from all consenting participants.

Results. Although excessive eating was recognized as a potentially severe problem in those with PWS, it was almost universally controlled by food restriction, and therefore not seen as a ‘problem behaviour’. Those with PWS differed from a learning disabled group of other aetiologies in the prevalence rates of skin picking, temper tantrums, compulsive behaviours and mood fluctuations, and also in the profile of their adaptive behaviours.

Conclusions. The study confirms the distinct behavioural phenotype of PWS. Specific behaviours occurred significantly more frequently in PWS, compared with an age and BMI matched learning disabled comparison group. A factor analysis of the behaviours involved resulted in three factors that we hypothesized to be independent, and to arise from different mechanisms.

Background. Peace-keeping duties are associated with unique stresses for military personnel. There have been few reports on the effects of peace-keeping on psychological health.

Method. We used data from a cross-sectional study originally established to examine health effects of service in the Gulf War, which included a control group who had been deployed in Bosnia (N=2049). This group was examined to establish which demographic, occupational, and deployment-related risk factors were associated with psychological distress measured on the General Health Questionnaire (GHQ-12) and stress symptoms akin to a post-traumatic stress reactions.

Results. The main risk factors for stress symptoms in the Bosnia group were – lower rank, being deployed early in the campaign, having more deployment-related exposures, and serving on staff duties. There was no protective effect of previous deployments to the Falklands or Northern Ireland, and time off following deployment was not protective. For GHQ-12 cases, the main risk factors were: female gender, lower rank, increased deployment-related exposures and serving on staff duties.

Conclusions. This study suggests that stress symptoms and GHQ-12 cases, are strongly predicted both by experiences during deployment and demographic factors.

Background. There have been numerous reports of seasonal trends in psychotic illnesses. In schizophrenia, seasonal trends in incidence have been shown to be especially apparent in first-episode cases. Most previous research has used date of admission as a proxy for date of incidence of disorder; we present results of an investigation into seasonal trends in dates of onset of symptoms in a group of 295 first-episode cases of schizophrenia and schizophreniform disorder.

Method. Data were analysed using statistical methods appropriate for detecting seasonal trends in pooled data over 6 years.

Results. Only male cases of schizophrenia and schizophreniform disorder showed a significant seasonal distribution to dates of onset of symptoms, with a peak in August (winter).

Conclusion. True seasonal patterns are present in schizophrenia incidence, but their consistency with other published studies and wider significance, is difficult to ascertain because of different methods used in dating incidence of disorder.

Background. The level of efficiency of implicit memory in Alzheimer's disease remains unclear as previous studies using stem completion tasks have led to contradictory results.

Method. The present study used target words embedded in significant short texts that subjects were required to read aloud (i.e. to enhance semantic processing). Texts were presented in two perceptual situations: ‘simple’ (blank spaces delimitating words) and ‘complex’ (spaces were filled by ‘8’s). In the completion phase, patients had to write the first word that came to mind in order to complete a three-letter stem. The recognition phase explored explicit memory performance. The performance of 24 Alzheimer patients was compared to a matched sample of healthy controls.

Results. Reading times differed between groups and were shorter for healthy controls. Recognition was dramatically lower in patients, thus confirming the alteration of explicit memory in this pathology. However, a significant priming effect (e.g. the tendency to complete the stem with the aid of a previously explored word) was present in both groups and did not differ between patients and healthy controls.

Conclusions. The absence of a correlation between priming and recognition scores suggests that this result cannot be explained by an explicit memory bias. Moreover, as the priming level was identical whatever the perceptual aspect of the text, we suggest that the priming effect is not only mediated by perceptual processes but also by lexical and conceptual processes, which to some extent are preserved during the light and moderate stages of this disease.