Group acceptance and commitment therapy for patients and caregivers in psychosis services: Feasibility of training and a preliminary randomized controlled evaluation.

OBJECTIVE: Psychological interventions reduce the impact of psychosis, but widescale implementation is problematic. We tested the feasibility of group acceptance and commitment therapy for Psychosis (G-ACTp), delivered by frontline staff, and co-facilitated by service-user experts-by-experience (SU-EbyE), for service-users and informal caregivers (ISRCTN: 68540929). We estimated recruitment/retention rates and outcome variability for future evaluation. METHODS: Staff and SU-EbyE facilitators completed 1-day workshops, then delivered closely supervised G-ACTp, comprising four sessions (weeks 1-4) and two boosters (10 and 12 weeks). Participants recruited from adult community psychosis services were randomized to receive G-ACTp immediately or after 12 weeks, completing outcome assessments at 0, 4, and 12 weeks. Service-use/month was calculated for 1-year pre-randomization, weeks 0-12, and 5-year uncontrolled follow-up. RESULTS: Of 41 facilitators trained (29 staff, 12 SU-EbyE), 29 (71%; 17 staff, 12 SU-EbyE) delivered 18 G-ACTp courses. Participant refusal rates were low (9% of service-users [10/112]; 5% of caregivers [4/79]); 60% of those invited to participate attended ≥1 G-ACTp session (64% of service-users [39/61]; 56% of caregivers [35/63]). Randomization of facilitators and participants proved problematic and participant follow-up was incomplete (78% [66/85]; 82% of service-users [36/44]; 73% of caregivers [30/41]). Effect sizes ranged from very small to large mostly favouring treatment. Service-use reductions require cautious interpretation, as very few participants incurred costs. CONCLUSIONS: Implementation appears feasible for service-users; for caregivers, retention needs improving. Outcome variability indicated n = 100-300/arm followed up (α = 0.05, 90% power). Methodological limitations' mean replication is needed: identified sources of potential bias may be reduced in a cluster randomized design with sessional outcome completion. PRACTITIONER POINTS: Group acceptance and commitment therapy can be successfully adapted for people with psychosis and their caregivers. Implementation (training and delivery) is possible in routine community mental health care settings. Clinical and economic outcomes are promising, but replication is needed. Recommendations are made for future studies.

Family intervention in a prison environment: A systematic literature review.

BACKGROUND: The prison population in England and Wales is approximately 85,000, and elevated rates of mental health difficulties have been reported among the prisoners. Despite frequent recommendations for family interventions to optimise prisoner outcomes, the evidence for its use and impact in prison remain unclear. AIM: The aim of the study is to conduct a systematic review of published literature on family interventions in prisons. METHODS: Embase, PsychINFO and Medline were searched using terms for family interventions and for prisoners or young offenders. No limit was imposed on study design, but, for inclusion, we required that papers were written in English and published in peer-reviewed journals. RESULTS: Nine hundred eighty-three titles were retrieved. Twenty-two met criteria for inclusion. Three were case studies, 12 were descriptive, 6 were quasi-experimental and one was a randomised controlled trial. Interventions and study methods were too heterogeneous for meta-analysis. All studies gave positive conclusions about family interventions, but empirical data on effectiveness were slight. CONCLUSIONS: Consistency in findings across the wide-ranging studies suggested that family therapies may indeed be helpful for prisoners and their families, so further research is warranted. The fact that a randomised controlled trial proved feasible should encourage researchers to seek more robust data and to determine which form of intervention is effective and in which circumstances. It would also be useful to develop an improved understanding of mechanisms of change. Copyright © 2016 John Wiley & Sons, Ltd.

Treating Multiple Incident Post-Traumatic Stress Disorder (PTSD) in an Inner City London Prison: The Need for an Evidence Base.

BACKGROUND: Mental health problems have been found to be more prevalent in prison populations, and higher rates of post-traumatic stress disorder (PTSD) have been found in sentenced populations compared to the general population. Evidence-based treatment in the general population however has not been transferred and empirically supported into the prison system. AIMS: The aim of this manuscript is to illustrate how trauma focused work can be applied in a prison setting. METHOD: This report describes a two-phased approach to treating PTSD, starting with stabilization, followed by an integration of culturally appropriate ideas from narrative exposure therapy (NET), given that the traumas were during war and conflict, and trauma-focused cognitive behavioural therapy (TF-CBT). RESULTS: PTSD and scores on paranoia scales improved between start and end of treatment; these improvements were maintained at a 6-month follow-up. CONCLUSION: This case report 1 illustrates successful treatment of multiple incident PTSD in a prison setting using adaptations to TF-CBT during a window of opportunity when individuals are more likely to be free from substances and live in relative stability. Current service provision and evidence-based practice for PTSD is urgently required in UK prisons to allow individuals to engage in opportunities to reduce re-offending, free from mental health symptoms.

Duration of untreated psychosis and need for admission in patients who engage with mental health services in the prodromal phase.

BACKGROUND: It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population. AIMS: To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis. METHOD: We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode. RESULTS: The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment. CONCLUSIONS: Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes.

Exploring perceptions of "wellness" in black ethnic minority individuals at risk of developing psychosis.

BACKGROUND: The NICE Schizophrenia guidelines (NICE, 2009, Update) recommend that services should address cultural differences in treatment, expectations and adherence, and clients' explanatory models of illness should be better understood. Service users from Black African and Black Caribbean communities are overrepresented in psychosis services in the UK, yet there is no literature on how wellness is understood by this group. AIMS: This study explored perceptions of wellness in Black African and Black Caribbean individuals with an At Risk Mental State (ARMS) for psychosis. METHOD: A Q set of potential meanings of wellness was identified from a literature search and interviews with people at risk of developing psychosis. From this, 50 potential definitions were identified; twenty Black African and Black Caribbean ARMS clients ranked these definitions. RESULTS: Following factor analysis of completed Q sorts, six factors emerged that offered insight into perceptions of wellness in this population. These factors included: sense of social purpose explanation, the surviving God's test explanation, the internalization of spirituality explanation, understanding and attribution of symptoms to witchcraft explanation, avoidance and adversity explanation, and seeking help to cope explanation. CONCLUSIONS: Although preliminary, differences between the factors suggests that there may be perceptions of wellness specific to these groups that are distinct from the medical view of wellness promoted within early detection services. These differences may potentially impact upon engagement, particularly factors that clients feel may facilitate or aide their recovery. It is suggested that these differences need to be considered as part of the assessment and formulation process.

Psychosocial predictors of distressing unusual experiences in adolescence: Testing the fit of an adult cognitive model of psychosis.

BACKGROUND: For adults with psychosis, international guidelines recommend individual and family based cognitive behavioural therapy interventions. Recommendations are extended to children and adolescents, based on adult research. It is also recommended that psychological interventions are offered for childhood presentations of psychotic-like or Unusual Experiences (UE), in the absence of a formal diagnosis, when these are Distressing (UEDs). Cognitive models underpinning these interventions require testing in adolescent populations, to further refine therapies. We address this need, by testing for the first time, the application of the adult cognitive model of psychosis to adolescent UEDs. METHODS: We used baseline data from the Coping with Unusual ExperienceS (CUES+) randomised controlled trial for 122 clinically referred adolescents (12-18 years) with self-reported UEDs. Known psychological mechanisms of adult cognitive models of psychosis; negative life events, affect (anxiety and depression), reasoning (jumping to conclusions bias), and schemas were investigated using multiple linear regression models, alongside variables particularly associated with the development and severity of adolescent UEDs and UE type (dissociation, externalising/behavioural problems, managing emotions). RESULTS: The psychological mechanisms of adult cognitive models of psychosis explained 89% of the total variance of adolescent UED severity, F (10, 106) = 99.34, p < .0005, r2 = 0.89, with schemas as the principal significant contributor. Variance explained 40 - 72% across each of the UE types (paranoia, hallucinations, delusions, paranormal thinking and grandiosity). CONCLUSIONS: Findings suggest that the psychological components of adult cognitive models of psychosis, particularly schemas, are also implicated in adolescent UEDs.

Improving Access to psychological therapies for people with severe mental illness (IAPT-SMI): Lessons from the South London and Maudsley psychosis demonstration site.

Implementation of evidence-based cognitive behavioural therapy for psychosis (CBTp) remains low in routine services. The United Kingdom Improving Access to Psychological Therapies for people with Severe Mental Illness (IAPT-SMI) initiative aimed to address this issue. The project evaluated whether existing services could improve access to CBTp and demonstrate effectiveness using a systematic approach to therapy provision and outcome monitoring (in a similar way to the Improving Access to Psychological Therapies (IAPT) model for people with anxiety and depression). We report the clinical outcomes and key learning points from the South London and Maudsley NHS Foundation Trust IAPT-SMI demonstration site for psychosis. Additional funding enabled increased therapist capacity within existing secondary care community mental health services. Self-reported wellbeing and psychotic symptom outcomes were assessed, alongside service use and social/occupational functioning. Accepted referrals/year increased by 89% (2011/12: n = 106/year; 2012-2015: n = 200/year); 90% engaged (attended ≥5 sessions) irrespective of ethnicity, age and gender. The assessment protocol proved feasible, and pre-post outcomes (n = 280) showed clinical improvements and reduced service use, with medium effects. We conclude that, with appropriate service structure, investment allocated specifically for competent therapy provision leads to increased and effective delivery of CBTp. Our framework is replicable in other settings and can inform the wider implementation of psychological therapies for psychosis.

The relationship between ethnicity and service access, treatment uptake and the incidence of psychosis among people at ultra high risk for psychosis.

Black ethnicity is associated with increased risk for psychosis in South London. This study explored the distribution of ethnicity among services users at ultra high risk for psychosis (UHR) and examined the influence of ethnicity on service access, treatment uptake and incidence of psychosis. The ethnic distribution of 228 people at UHR for psychosis, seen in an early detection clinical service over 10 years, was compared with 146 people with first episode psychosis from the same geographic region and census figures for the local population. Black service users were significantly over-represented in the UHR group compared to the background population (34% vs 21%; p < 0.05); but less so than in the first episode sample (58% vs 19%; p < 0.05). Within the UHR sample, there was no strong evidence of differences between ethnic groups in the types of treatment provided, nor in the rate of transition to psychosis over 2 years. The absence of differences between ethnic groups in rates of transition to psychosis raises the possibility that access to mental health care at the high risk stage might have reduced the influence of ethnicity on the incidence of psychosis in this sample. This would need to be replicated in a larger sample.

Psychological distress and risk for suicidal behavior among university students in contemporary China.

BACKGROUND: Psychological distress and suicidal behavior are important mental health problems among university students and warrant research to inform strategies for effective prevention in this young population. The present study aimed to assess psychological distress and suicidal behavior and to unravel their associations among university students. METHODS: A total of 5972 undergraduate students, randomly selected from six universities in central China, comprised the sample. The Chinese version of the Symptom Checklist-90-revised (SCL-90-R) was used to assess various psychological symptoms. Logistic regression analysis was used to examine the relationship between psychological distress and risk for suicidal behavior. RESULTS: 40.7% of the university students reported positive in a least one of the 9 psychological symptom dimensions assessed by the SCL-90-R. 7.6% of the students reported suicidal behavior in the previous twelve months. The risk of suicidal behavior was significantly associated with psychological symptoms of all types, but there were notable differences by sex. For male students, depression and phobic anxiety increased the risk of suicidal behavior. Meanwhile, depression and obsessive-compulsiveness were positively associated with suicidal behavior in female students. Furthermore, increasing risk of suicidal behavior was associated with increasing positive symptom total (PST) score and a statistically significant trend was observed. LIMITATIONS: Data collected from a cross-sectional survey does not allow any examination of causal inference. CONCLUSIONS: Psychological distress and suicidal behavior were both common among university students; and psychological distress was highly associated with suicidal behavior. The findings underscore the importance of mental health care for university students.

Substance use and at-risk mental state for psychosis in 2102 prisoners: the case for early detection and early intervention in prison.

AIM: Prisoners exhibit high rates of substance use and mental health problems. In the present study, we sought to gain a detailed understanding of substance use amongst young prisoners to inform early detection and early intervention strategies in a prison setting. METHODS: This is a cross-sectional study of 2102 prisoners who were screened by the London Early Detection and Prevention in Prison Team (LEAP). Data on the use of substances were collected including age of first use, recent use, duration of use and poly-drug use. The Prodromal Questionnaire - Brief Version was used to screen for the at-risk mental state. RESULTS: We found high rates of lifetime and recent use and low age of first use of a number of substances. We also found strong associations between substance use and screening positive for an at-risk mental state. Logistic regression analysis confirmed that use of any drug in the last year, poly-drug and early use, as well as heavy alcohol use, were related to an increased risk of screening positive. CONCLUSIONS: Substance use in the prison population is not only widespread and heavy but is also strongly linked with a higher risk of developing mental health problems. The need for early detection and early intervention in prison is discussed.

Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study.

A range of complications of pregnancy, abnormal fetal growth and development, and complications of delivery have been associated with increased risk of schizophrenia. Few studies have been able to adjust for a broad range of potential confounding factors. A national population nested case-control study based on Danish longitudinal registers was conducted to investigate the risk of schizophrenia associated with exposure to a range of obstetric events. The sample included 1039 first admissions to, or contacts with Danish psychiatric services with an ICD-8 or ICD-10 diagnosis of schizophrenia and 24, 826 individually matched controls. Adjusting for the other obstetric factors, family psychiatric history, and socio-economic and demographic factors, risk of schizophrenia was associated with maternal non-attendance at antenatal appointments (Incidence Rate Ratio (IRR) 2.08, 95% CI: 1.0, 4.4), gestational age of 37 weeks or below (IRR 1.51, 95% CI: 1.0, 2.2), maternal influenza (IRR 8.2, 95% CI: 1.4, 48.8), preeclampsia (IRR 2.72, 95% CI: 1.0, 7.3), threatened premature delivery (IRR 2.39, 95% CI: 1.4, 4.1), haemorrhage during delivery (IRR 2.43, 95% CI: 1.1, 5.6), manual extraction of the baby (IRR 2.15, 95% CI: 1.1, 4.4), and maternal sepsis of childbirth and the puerperium (IRR 2.91, 95% CI: 1.1, 7.9). There was no significant interaction between the obstetric factors and either sex or family psychiatric history. The data suggest a modest association between prematurity, indicators of hypoxia, maternal infections, and maternal behaviours and risk of the later development of schizophrenia after adjusting for a number of possible confounding factors.

Coping with Unusual ExperienceS for 12-18 year olds (CUES+): a transdiagnostic randomised controlled trial of the effectiveness of cognitive therapy in reducing distress associated with unusual experiences in adolescent mental health services: study protocol for a randomised controlled trial.

BACKGROUND: Childhood 'unusual experiences' (such as hearing voices that others cannot, or suspicions of being followed) are common, but can become more distressing during adolescence, especially for young people in contact with Child and Adolescent Mental Health Services (CAMHS). Unusual experiences that are distressing or have adverse life impact (UEDs) are associated with a range of current and future emotional, behavioural and mental health difficulties. Recommendations for psychological intervention are based on evidence from adult studies, with some support from small, pilot, child-specific evaluations. Research is needed to ensure that the recommendations suit children as well as adults. The CUES+ study (Coping with Unusual ExperienceS for 12-18 year olds) aims to find out whether cognitive behaviour therapy for UEDs (CBT-UED) is a helpful and cost-effective addition to usual community care for 12-18 year olds presenting to United Kingdom National Health Service Child and Adolescent Mental Health Services in four London boroughs. METHODS: The CUES+ study is a randomised controlled trial comparing CBT-UED plus routine care to routine care alone. CBT-UED comprises up to 16 sessions, including up to 12 individual and up to four family support meetings, each lasting around 45-60 min, delivered weekly. The primary outcome is emotional distress. Secondary outcomes are change in UEDs, risk events (self-harm, attendance at emergency services, other adverse events) and health economic outcomes. Participants will be randomised in a 1:1 ratio after baseline assessment. Randomisation will be stratified by borough and by severity of mental health presentation: 'severe' (an identified psychotic or bipolar disorder) or any 'other' condition. Outcomes will be assessed by a trained assessor blind to treatment condition at 0, 16 and 24 weeks. Recruitment began in February, 2015 and is ongoing until the end of March, 2017. DISCUSSION: The CUES+ study will contribute to the currently limited child-specific evidence base for psychological interventions for UEDs occurring in the context of psychosis or any other mental health presentation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ID: ISRCTN21802136 . Prospectively registered on 12 January 2015. Protocol V3 31 August 2015 with screening amended.

Neuropsychological performance over time in people at high risk of developing schizophrenia and controls.

BACKGROUND: Neuropsychological assessments of relatives of schizophrenics have shown subtle impairments in verbal memory, executive and intellectual function, which are stable in those beyond the age of maximum risk for the disorder. We sought to: (1) determine baseline neurocognitive predictors of psychosis, and (2) compare performance over time between relatives within the age of maximum risk, and controls. METHODS: (1) and (2) were examined in 118 individuals at familial high risk of schizophrenia (HR) and 30 controls (C), using one-way analyses of variance (ANOVAs) and repeated measures analyses of covariance (ANCOVAs), controlling for intelligence quotient, time between and number of assessments, and correcting for multiple comparisons. RESULTS: HR who became ill (n = 13) performed nonsignificantly less well at baseline than HR who did not (n = 105) on a test of verbal learning (t(109) = 2.1, p = .03). Across assessments, C performed significantly better than the entire HR group on immediate (F(3,133) = 5.11, p = .002) and delayed (F(3,133) = 5.02, p = .002) story recall. There were no significant interactions of time by group. CONCLUSIONS: Results suggest greater verbal memory impairment in HR who go on to develop schizophrenia. Stable differences between groups over time suggest a trait deficit, which is relatively unaffected by the presence of psychotic symptoms and psychosis onset. Alternatively, small numbers may have precluded detection of group by time interactions.

Association of schizophrenia and autoimmune diseases: linkage of Danish national registers.

OBJECTIVE: Individuals with schizophrenia and their relatives tend to have either higher or lower than expected prevalences of autoimmune disorders, especially rheumatoid arthritis, celiac disease, autoimmune thyroid diseases, and type 1 diabetes. The purpose of the study was to estimate the association of schizophrenia with these disorders as well as a range of other autoimmune diseases in a single large epidemiologic study. METHOD: The Danish Psychiatric Register, the National Patient Register, and a register with socioeconomic information were linked to form a data file that included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 and their parents along with a sample of matched comparison subjects and their parents. The data linkage required that the autoimmune disease occur before the diagnosis of schizophrenia. RESULTS: A history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Nine autoimmune disorders had higher prevalence rates among patients with schizophrenia than among comparison subjects (crude incidence rate ratios ranging from 1.9 to 12.5), and 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (adjusted incidence rate ratios ranging from 1.3 to 3.8). Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren's syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members of schizophrenia patients than among family members of comparison subjects. CONCLUSIONS: Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.

Prison and Community Populations at Ultra-High Risk of Psychosis: Differences and Challenges for Service Provision.

OBJECTIVE: The aim of the study was to explore the feasibility of expanding a community service for early detection of psychosis into a local London prison for men in the United Kingdom. METHODS: All new receptions to a local prison for men in South London were approached for routine screening. Those who met criteria for being at ultra-high-risk of psychosis were compared with a help-seeking sample from the community who met the same criteria. Clinical and sociodemographic characteristics were compared to determine whether the prison and community populations had similar profiles and mental health needs. RESULTS: Of 891 prisoners screened, 44 (5%) met criteria for being at ultra-high risk of psychosis. The community sample consisted of 42 participants. Compared with the community group, prison participants had lower scores on almost all symptom measures, were less likely to have remained in school and completed exams, and were more likely to be in short-term accommodations and to be of black race-ethnicity. Lifetime use of illicit drugs was similar between the groups, but recent use was much higher in the prison group. CONCLUSIONS: Expanding community services into custodial settings should take into account the different environment and needs of the prisoner population. Specifically, early detection and intervention services should target a broad range of mental health problems rather than psychosis alone.

The feasibility and acceptability of a brief Acceptance and Commitment Therapy (ACT) group intervention for people with psychosis: The 'ACT for life' study.

BACKGROUND AND OBJECTIVES: Acceptance and Commitment Therapy (ACT) is a contextual cognitive-behavioural approach with a developing evidence base for clinical and cost-effectiveness as an individually-delivered intervention to promote recovery from psychosis. ACT also lends itself to brief group delivery, potentially increasing access to therapy without inflating costs. This study examined, for the first time, the feasibility and acceptability of ACT groups for people with psychosis (G-ACTp). METHODS: Participants were recruited from community psychosis teams. Ratings of user satisfaction, and pre-post change in self-rated functioning (primary outcome), mood (secondary outcome) and ACT processes were all completed with an independent assessor. Of 89 people recruited, 83 completed pre measures, 69 started the four-week G-ACTp intervention, and 65 completed post measures. RESULTS: Independently assessed acceptability and satisfaction were high. Functioning (Coeff. = -2.4, z = -2.9, p = 0.004; 95% CI: -4.0 to -0.8; within subject effect size (ES) d = 0.4) and mood (Coeff. = -2.3, z = -3.5, p = 0.001; 95% CI: -3.5 to -1.0; d = 0.4) improved from baseline to follow-up. Commensurate changes in targeted ACT processes were consistent with the underlying model. LIMITATIONS: The uncontrolled, pre-post design precluded blinded assessments, and may have inflated effect sizes. Participants may have improved as a result of other factors, and findings require replication in a randomized controlled trial (RCT). CONCLUSIONS: This preliminary study showed that brief group ACT interventions for people with psychosis are feasible and acceptable. Uncontrolled, pre-post assessments suggest small clinical improvements, and changes in psychological processes consistent with an ACT model. Replication in an RCT is required, before implementation can be recommended.

Marital and labor market status in the long run in schizophrenia.

BACKGROUND: Singleness and unemployment increase the risk of schizophrenia. Schizophrenia subsequently increases the risk of singleness and unemployment. OBJECTIVE: To describe long-term changes in marital status and labor market affiliation before and after the first admission with schizophrenia. DESIGN: A case-control study. SETTING AND PARTICIPANTS: The sample included 5341 patients with a diagnosis of schizophrenia at the first admission to a psychiatric facility between 1970 and 1999, and 53 410 matched control subjects. A person admitted in 1999 was followed up in the registers from 1980 to 1997 (ie, from 19 to 2 years before admission). Individuals admitted in 1970 could be followed up from 10 years until 27 years after admission. MAIN OUTCOME MEASURES: Annual socioeconomic indicators. RESULTS: Individuals who were later hospitalized were more frequently living alone, unemployed, receiving social benefits, or otherwise outside the labor market when compared with controls, as early as 19 years before their first admission. For individuals with schizophrenia, the odds ratios of being unmarried or not being fully employed were significantly increased even 25 years after admission. This pattern was especially pronounced for men and for individuals who had more admissions. The ratios increased until admission, with a steeper increase in the years before admission. After admission, the odds declined to the level shown before admission and then stabilized. CONCLUSIONS: Schizophrenia hinders social achievement long before the first admission. The first hospital episode is followed by a period during which social status does not deteriorate further except for the transition into disability pension.

Parental age and risk of schizophrenia: a case-control study.

BACKGROUND: Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors. METHODS: We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history. RESULTS: Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83). CONCLUSION: Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.

Obstetric adversity and age at first presentation with schizophrenia: evidence of a dose-response relationship.

OBJECTIVE: The purpose of the study was to determine if a dose-response relationship exists between obstetric adversity and age at first presentation with schizophrenia. METHOD: The Dublin Psychiatric Case Register was used to identify subjects with schizophrenia. Data on obstetric complications, social class of origin, and family history of psychiatric illness were obtained for those subjects. RESULTS: A total of 409 patients with ICD-9 schizophrenia were identified. Patients with a history of obstetric complications presented earlier to psychiatric services. As the number of complications increased, the mean age at first presentation decreased. This effect was independent of social class of origin and family history of psychiatric illness. CONCLUSIONS: Obstetric adversity exerts an independent influence on the age at first presentation with schizophrenia, in a dose-response manner. This finding supports the existence of a causal relationship between obstetric adversity and age at first presentation with schizophrenia.

Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia.

Neuropsychological assessments were compared among individuals at enhanced genetic risk of schizophrenia (n = 157) and controls (n = 34). The relationship between cognitive impairments and the presence of psychotic symptoms and measures of genetic risk was explored in the high-risk subjects. Neuropsychological differences were identified in many areas of function and were not accounted for by the presence of psychotic symptoms. Genetic liability was not associated with neuropsychological performance or with psychotic symptoms, but exploratory analysis showed some tests were associated with both liability measures. These results suggest that what is inherited is not the disorder itself but a state of vulnerability manifested by neuropsychological impairment, occurring in many more individuals than are predicted to develop the disorder.