Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study.

BACKGROUND: Children with conduct disorder (CD) are at increased risk of developing antisocial personality disorder (ASPD) and psychopathy in adulthood. The biological basis for this is poorly understood. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of psychopathic antisocial adults reported significant differences from controls in the fractional anisotropy (FA) of the uncinate fasciculus (UF), a white-matter tract that connects the amygdala to the frontal lobe. However, it is unknown whether developmental abnormalities are present in the UF of younger individuals with CD. METHOD: We used DT-MRI tractography to investigate, for the first time, the microstructural integrity of the UF in adolescents with CD, and age-related differences in this tract. We compared FA and perpendicular diffusivity of the UF in 27 adolescents with CD and 16 healthy controls (12 to 19 years old) who did not differ significantly in age, IQ or substance use history. To confirm that these findings were specific to the UF, the same measurements were extracted from two non-limbic control tracts. Participants in the CD group had a history of serious aggressive and violent behaviour, including robbery, burglary, grievous bodily harm and sexual assault. RESULTS: Individuals with CD had a significantly increased FA (p = 0.006), and reduced perpendicular diffusivity (p = 0.002), in the left UF. Furthermore, there were significant age-related between-group differences in perpendicular diffusivity of the same tract (Z obs = 2.40, p = 0.01). Controls, but not those with CD, showed significant age-related maturation. There were no significant between-group differences in any measure within the control tracts. CONCLUSIONS: Adolescents with CD have significant differences in the 'connectivity' and maturation of UF.

A multi-site randomized controlled trial of a cognitive skills programme for male mentally disordered offenders: social-cognitive outcomes.

BACKGROUND: Cognitive skills programmes have been associated with improvements on psychometric measures and reductions in antisocial behaviour in mentally disordered offenders (MDOs). However, to date there have been no randomized controlled trials (RCTs) of such programmes with this population. In the first RCT of a cognitive skills programme with MDOs we aimed to determine if participation in the Reasoning and Rehabilitation (R&R) programme was associated with improvements in social-cognitive skills and thinking styles. METHOD: A total of 84 men with a primary diagnosis of psychotic disorder and a history of violence were recruited from medium-secure forensic units and allocated to receive R&R (n=44) or treatment as usual (TAU; n=40). At baseline and post-treatment interviews, participants completed questionnaires to assess social problem-solving, criminal attitudes, anger experience, blame externalizing and perspective-taking. Researchers were not blind to group status. RESULTS: The R&R group demonstrated significant improvements on measures of social problem-solving relative to the TAU group, some of which were maintained at 12 months post-treatment. Only half of those allocated to receive R&R completed the full programme. In post-hoc analyses programme completers showed improvements in social problem-solving at the end of treatment and changes in criminal attitudes at 12 months post-treatment. CONCLUSIONS: Among male MDOs, R&R participation was associated with improvements in social-cognitive skills, some of which were maintained for up to 12 months post-treatment. Our finding that programme completers do better may reflect pre-treatment patient characteristics. This study establishes that multi-site RCTs can be conducted in medium-secure forensic units.

Violent behaviour in U.K. military personnel returning home after deployment.

BACKGROUND: There is growing concern about an alleged rise in violent behaviour amongst military personnel returning from deployment to Iraq and Afghanistan. The aims of this study were to determine the prevalence of violence in a sample of U.K. military personnel following homecoming from deployment in Iraq and to examine the impact of deployment-related experiences, such as combat trauma, on violence, and the role of sociodemographics and pre-enlistment antisocial behaviour. METHOD: This study used baseline data from a cohort study of a large randomly selected sample of U.K. Armed Forces personnel in service at the time of the Iraq war (2003). Regular personnel (n=4928) who had been deployed to Iraq were included. Data, collected by questionnaire, included information on deployment experiences, sociodemographic and military characteristics, pre-enlistment antisocial behaviour, post-deployment health outcomes and a self-report measure of physical violence in the weeks following return from deployment. RESULTS: Prevalence of violence was 12.6%. This was strongly associated with pre-enlistment antisocial behaviour [adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.9-4.4]. After controlling for pre-enlistment antisocial behaviour, sociodemographics and military factors, violence was still strongly associated with holding a combat role (aOR 2.0, 95% CI 1.6-2.5) and having experienced multiple traumatic events on deployment (aOR for four or more traumatic events 3.7, 95% CI 2.5-5.5). Violence on homecoming was also associated with mental health problems such as post-traumatic stress disorder (aOR 4.8, 95% CI 3.2-7.2) and alcohol misuse (aOR 3.1, 95% CI 2.5-3.9). CONCLUSIONS: Experiences of combat and trauma during deployment were significantly associated with violent behaviour following homecoming in U.K. military personnel. Post-deployment mental health problems and alcohol misuse are also associated with increased violence.

Altered connections on the road to psychopathy.

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

Predictors of violent victimization amongst those with psychosis.

OBJECTIVE: The aim of this study was to establish the prevalence and predictors of violent victimization amongst a community-dwelling sample of individuals with psychosis. METHOD: The 2-year prevalence of self-reported violent victimization was estimated for a sample of 708 individuals with chronic psychosis living in the community in four urban UK centres. Baseline socio-demographic and clinical factors were examined as possible risk factors for victimization over the 2-year follow-up period. RESULTS: The 2-year prevalence of violent victimization in the sample was 23%. Four factors were found to be independently predictive of victimization - history of victimization, less than daily family contact, young age at illness onset and the presence of co-morbid Cluster B personality disorder. CONCLUSION: Those with psychotic illnesses are at elevated risk of being assaulted. Given the likely adverse health implications, clinicians should routinely enquire about victimization in their assessments of those with psychotic disorders particularly amongst those who are socially isolated, with a younger age of illness onset and in those with co-morbid personality disorder.

Do care patterns change over time in a newly established mental health service? A report from the UK700 trial.

PURPOSE: Data on the process of mental health care is scant. Most studies focus on services at their inception when activity may be atypical and then usually present data only mean values for the reported variables over the whole study period. We aimed to test whether care delivery changes over time, and to describe any changes at the individual patient and team levels. METHODS: Process data on 272 patients in three new intensive case management (ICM) teams were collected over 2 years. Interventions were prospectively recorded using clinician-derived categories. Changes over time are described at both patient and team level. RESULTS: The number of contacts and the proportion of face-to-face activity were remarkably constant after the first month at the patient level. The proportion of 'psychiatric' interventions (main focus on medication or a specific 'mental health' intervention performed) increased greatly after the first 6 months. The care activity received by individual patients varied considerably. Overall, teams varied significantly in the extent to which their activity rates were sustained over time. CONCLUSIONS: New ICM teams deliver highly individualised care with more marked differences in treatment patterns between patients in the same team than mean differences between teams. The early 'engagement' period is marked by a greater focus on social care. There is evidence of differences in sustainability of the services by site.

Aripiprazole in schizophrenia: consensus guidelines.

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Pregnancy and birth complications in patients with schizophrenia in Trinidad and London.

It has been shown that an excess of pregnancy and birth complications (PBCs) does not contribute to the excess rates of schizophrenia reported for the population of Caribbean origin in Britain compared with the native Caucasian British population. We therefore attempted to compare the rate of PBCs between a sample of schizophrenics in Britain with that of a sample from Trinidad where some of the Caribbean migrants to Britain originated. First contact patients with schizophrenia according to the CATEGO system diagnosis were identified in Trinidad and London. Their mothers, where available, were interviewed using the Lewis-Murray scale for pregnancy and birth complications. Data from Trinidad and Tobago concerning 56 patients were compared with those of the Caucasian (n = 61) and African-Caribbean (n = 50) patients in London. The rate of PBCs was similar for the Caucasian British patients (24.6%) and the patients in Trinidad and Tobago (21.7%). The rates were lowest in the African-Caribbean patients in London (14.0%), though this difference was not statistically significant. These findings suggest that pregnancy and birth complications are a risk factor for a substantial minority of patients with schizophrenia in Trinidad and London. It also confirms that the excess rates of schizophrenia reported for the Caribbean population in Britain are not due to these complications.

Does co-morbid personality disorder increase the risk of suicidal behaviour in psychosis?

OBJECTIVE: To examine the association between co-morbid personality disorder (PD) and suicidal behaviour over a 2-year period in a sample of patients with psychosis. METHOD: A total of 670 patients with established psychotic illness were interviewed using a battery of instruments including a screen for co-morbid PD. The prevalence of attempted and completed suicide was measured over the next 2 years using multiple data sources. Logistic regression was used to examine whether those with co-morbid PD were at greater risk of suicidal behaviour compared with others. RESULTS: One hundred and eighty six patients (28%) were rated as having a co-morbid PD. After adjusting for all covariates, patients with co-morbid PD were significantly more likely to attempt or complete suicide over the 2-year period (adjusted odds ratio: 1.87; 95% CI: 1.02-3.42). CONCLUSION: Co-morbid PD is independently associated with an increased risk of suicidal behaviour in psychosis. Early assessment of personality status should be part of the routine assessment of all psychiatric patients.

Risperidone in chronic schizophrenia: a detailed audit, open switch study and two-year follow-up of patients on depot medication.

Little information exists on the medium- to long-term outcome of switching patients with schizophrenia from traditional depot to atypical oral antipsychotic agents. By detailed clinical audit, we identified a representative group of 102 patients of an Irish psychiatric service with DSM-IV chronic schizophrenia and on depot neuroleptics for a mean of 15 years. Of 69 eligible to participate, 33 entered a 6-month switch study of risperidone, with limited follow-up of consenters and non-consenters at 1 and 2 years. At 6 months, 23 of 33 were still on risperidone and had small significant improvements in clinical and extrapyramidal side effects, QOL and adjunct medication measures over baseline. At 12 months, 19 of 33 were still on risperidone, reducing to 13 of 33 at 2 years. At 2 years, of 32 surviving consenters to switch, 19 had suffered clinically detrimental events and were no longer on risperidone, compared to none of the 33 surviving non-consenters, who were all still on depot. These findings suggest that switching from depot to risperidone may encounter high rates of refusal and attrition subsequent to switch. While a majority of switched patients may improve to least 6 months, audit plus switch may have clinically unfavourable effects on others over a 2-year follow-up period [corrected].

Do schizophrenic patients who managed to get to university have a non-developmental form of illness?

BACKGROUND: Many people who develop schizophrenia have impairments in intellectual and social functioning that are detectable from early childhood. However, some patients do not exhibit such deficits, and this suggests that they may have suffered less neurodevelopmental damage. We hypothesized that the aetiology and form of schizophrenia may differ in such patients. We therefore studied a group of schizophrenic patients who were functioning well enough to enter university prior to illness onset. METHODS: The casenotes of 46 university-educated patients and 48 non-university-educated patients were rated on several schedules including the OPCRIT checklist, and the two groups were compared using univariate statistical techniques. Principal components analysis was then performed using data from all patients, and the factor scores for each principal component were compared between groups. RESULTS: Univariate analyses showed the university-educated patients had an excess of depressive symptoms, and a paucity of core schizophrenic symptoms. Four principal components emerged in the principal components analysis: mania, biological depression, schizophrenic symptoms, and a reactive depression. University-educated patients scored significantly higher on the reactive depression principal component, and lower on the schizophrenic symptoms principal component, than the non-university-educated patients.

Reducing violence in severe mental illness: randomised controlled trial of intensive case management compared with standard care.

OBJECTIVES: To establish whether intensive case management reduces violence in patients with psychosis in comparison with standard case management. DESIGN: Randomised controlled trial with two year follow up. SETTING: Four inner city community mental health services. PARTICIPANTS: 708 patients with established psychotic illness allocated at random to intervention (353) or control (355) group. INTERVENTION: Intensive case management (caseload 10-15 per case manager) for two years compared with standard case management (30-35 per case manager). MAIN OUTCOME MEASURE: Physical assault over two years measured by interviews with patients and case managers and examination of case notes. RESULTS: No significant reduction in violence was found in the intensive case management group compared with the control group (22.7% v 21.9%, P=0.86). CONCLUSIONS: Intensive case management does not reduce the prevalence of violence in psychotic patients in comparison with standard care.

Quality of life outcome in a randomized controlled trial of case management.

BACKGROUND: This paper presents the quality of life (QOL) outcome results from the UK700 randomised controlled trial of case management. METHOD: A total of 708 patients with severe mental illness were randomly assigned to intensive and standard forms of case management in four sites in the UK. QOL was assessed using the Lancashire Quality of Life Profile, which provides a self-reported objective and subjective appraisal of eight life domains (finances, work, leisure, family, social relations, living situation, safety and health). The outcome after 2 years was examined using univariate and multivariate analyses. RESULTS: Significant improvements in QOL over the 2 years were observed. The QOL outcome did not differ significantly by case management treatment conditions or by diagnosis. A better outcome was associated with improvements in depression and with the location (site) of treatment. In one site there were significant improvements in all eight domains and overall QOL, with moderate or better effect sizes (> 0.4) in three domains and overall QOL. CONCLUSIONS: Depression should be assessed when subjective QOL measures are used. Better means for describing service organisations and the context/place in which they operate should be developed in order to explain more of the variance in QOL outcomes.

Relatives of patients with severe psychotic disorders: factors that influence contact frequency. Report from the UK700 trial.

BACKGROUND: The isolation experienced by many patients with severe psychotic disorders is generally assumed to be due to their social withdrawal. An alternative possibility is that relatives avoid frequent contact with patients because they find the situation distressing. AIMS: To examine the predictors of frequent patient-relative contact, in particular the role of relatives' experience. METHOD: UK700 trial data were used to determine baseline predictors of frequent contact and establish whether relatives' experience at baseline predicted continued frequent contact 2 years later. RESULTS: Neither characteristics associated in the literature with relatives' 'burden' nor relatives' experience predicted patient-relative contact frequency. Instead, the predictors were mainly demographic. CONCLUSIONS: Many relatives experience considerable distress, but the evidence does not suggest that they avoid frequent contact with the patient as a consequence.

Relatives of patients with severe psychotic illness: factors that influence appraisal of caregiving and psychological distress.

BACKGROUND: Research shows considerable variability in the effect on relatives of patients' mental illness but the determinants of relatives' experience remain unclear. We investigated the influence of demographic, social and clinical characteristics on relatives' experience when conceptualised using a stress-appraisal-coping paradigm. METHODS: Our sample was drawn from relatives of patients recruited to the UK700 case management study (n = 154). Demographic, social and clinical data were collected from patients, and relatives completed the Experience of Caregiving Inventory and the General Health Questionnaire. We predicted that patients' symptomatology in particular would influence relatives' experience, and that relatives who appraised caregiving more negatively and less positively would experience greater psychological distress. RESULTS: Linear regression analyses revealed that relatives' appraisal was not predicted by patients' symptomatology. Instead, relatives appraised caregiving more negatively if the patient was unemployed or younger, and less positively if the patient had been ill for longer or had poorer social functioning. Little of the variance in appraisal was explained by these variables, however. Consistent with the stress-coping model, relatives' negative appraisal was a strong predictor of psychological distress and accounted for a substantial proportion of its variance. Positive appraisal did not predict psychological distress, however. None of the demographic, social or clinical characteristics tested had any significant effect on relatives' psychological distress once appraisal was adjusted for. There was an unexpected positive correlation between the two appraisal scales, with relatives who appraised caregiving more negatively also appraising it more positively. CONCLUSIONS: Our results support a stress-coping model of caregiving but further research is required to determine more influential predictors of relatives' appraisal. Our findings indicate that interventions aimed at patients' social functioning and relatives' negative appraisal of caregiving may assist in reducing relatives' psychological distress.

Effects of case-load size on the process of care of patients with severe psychotic illness. Report from the UK700 trial.

BACKGROUND: Studies of intensive case management (ICM) for patients with psychotic illnesses have produced conflicting results in terms of outcome. Negative results have sometimes been attributed to a failure to deliver differing patterns of care. AIMS: To test whether the actual care delivered in a randomised clinical trial of ICM v. standard case management (the UK700 trial) differed significantly. METHOD: Data on 545 patients' care were collected over 2 years. All patient contacts and all other patient-centred interventions (e.g. telephone calls, carer contacts) of over 15 minutes were prospectively recorded. Rates and distributions of these interventions were compared. RESULTS: Contact frequency was more than doubled in the ICM group. There were proportionately more failed contacts and carer contacts but there was no difference in the average length of individual contacts or the proportion of contacts in the patients' homes. CONCLUSIONS: The failure to demonstrate outcome differences in the UK700 study is not due to a failure to vary the treatment process. UK standard care contains many of the characteristics of assertive outreach services and differences in outcome may require that greater attention be paid to delivering evidence-based interventions.