Ian Kelleher

Psychotic-like experiences in the general population: characterizing a high-risk group for psychosis.

Recent research shows that psychotic symptoms, or psychotic-like experiences (PLEs), are reported not only by psychosis patients but also by healthy members of the general population. Healthy individuals who report these symptoms are considered to represent a non-clinical psychosis phenotype, and have been demonstrated to be at increased risk of schizophrenia-spectrum disorder. Converging research now shows that this non-clinical psychosis phenotype is familial, heritable and covaries with familial schizophrenia-spectrum disorder. A review of the research also shows that the non-clinical phenotype is associated extensively with schizophrenia-related risk factors, including social, environmental, substance use, obstetric, developmental, anatomical, motor, cognitive, linguistic, intellectual and psychopathological risk factors. The criterion and construct validity of the non-clinical psychosis phenotype with schizophrenia demonstrates that it is a valid population in which to study the aetiology of psychosis. Furthermore, it suggests shared genetic variation between the clinical and non-clinical phenotypes. Much remains to be learned about psychosis by broadening the scope of research to include the non-clinical psychosis phenotype.

Clinicopathological significance of psychotic experiences in non-psychotic young people: evidence from four population-based studies

BACKGROUND Epidemiological research has shown that hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the population than actual psychotic disorder. These symptoms are especially prevalent in childhood and adolescence. Longitudinal research has demonstrated that psychotic symptoms in adolescence increase the risk of psychotic disorder in adulthood. There has been a lack of research, however, on the immediate clinicopathological significance of psychotic symptoms in adolescence. AIMS To investigate the relationship between psychotic symptoms and non-psychotic psychopathology in community samples of adolescents in terms of prevalence, co-occurring disorders, comorbid (multiple) psychopathology and variation across early v. middle adolescence. METHOD Data from four population studies were used: two early adolescence studies (ages 11-13 years) and two mid-adolescence studies (ages 13-16 years). Studies 1 and 2 involved school-based surveys of 2243 children aged 11-16 years for psychotic symptoms and for emotional and behavioural symptoms of psychopathology. Studies 3 and 4 involved in-depth diagnostic interview assessments of psychotic symptoms and lifetime psychiatric disorders in community samples of 423 children aged 11-15 years. RESULTS Younger adolescents had a higher prevalence (21-23%) of psychotic symptoms than older adolescents (7%). In both age groups the majority of adolescents who reported psychotic symptoms had at least one diagnosable non-psychotic psychiatric disorder, although associations with psychopathology increased with age: nearly 80% of the mid-adolescence sample who reported psychotic symptoms had at least one diagnosis, compared with 57% of the early adolescence sample. Adolescents who reported psychotic symptoms were at particularly high risk of having multiple co-occurring diagnoses. CONCLUSIONS Psychotic symptoms are important risk markers for a wide range of non-psychotic psychopathological disorders, in particular for severe psychopathology characterised by multiple co-occurring diagnoses. These symptoms should be carefully assessed in all patients.

Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies.

BACKGROUND Psychotic symptoms occur more frequently in the general population than psychotic disorder and index risk for psychopathology. Multiple studies have reported on the prevalence of these symptoms using self-report questionnaires or clinical interviews but there is a lack of consensus about the prevalence of psychotic symptoms among children and adolescents. METHOD We conducted a systematic review of all published literature on psychotic symptom prevalence in two age groups, children aged 9-12 years and adolescents aged 13-18 years, searching through electronic databases PubMed, Ovid Medline, PsycINFO and EMBASE up to June 2011, and extracted prevalence rates. RESULTS We identified 19 population studies that reported on psychotic symptom prevalence among children and adolescents. The median prevalence of psychotic symptoms was 17% among children aged 9-12 years and 7.5% among adolescents aged 13-18 years. CONCLUSIONS Psychotic symptoms are relatively common in young people, especially in childhood. Prevalence is higher in younger (9-12 years) compared to older (13-18 years) children.

Childhood trauma and psychosis in a prospective cohort study: Cause, effect, and directionality

OBJECTIVE Using longitudinal and prospective measures, the authors assessed the relationship between childhood trauma and psychotic experiences, addressing the following questions: 1) Does exposure to trauma predict incident psychotic experiences? 2) Does cessation of trauma predict cessation of psychotic experiences? 3) What is the direction of the relationship between childhood trauma and psychotic experiences? METHOD This was a nationally representative prospective cohort study of 1,112 school-based adolescents 13-16 years of age, assessed at baseline and at 3-month and 12-month follow-ups for childhood trauma (physical assault and bullying) and psychotic experiences. RESULTS A bidirectional relationship was observed between childhood trauma and psychosis, with trauma predicting psychotic experiences over time and vice versa. However, even after accounting for this bidirectional relationship with a number of strict adjustments (only newly incident psychotic experiences occurring over the course of the study following exposure to traumatic experiences were examined), trauma was strongly predictive of psychotic experiences. A dose-response relationship was observed between severity of bullying and risk for psychotic experiences. Moreover, cessation of trauma predicted cessation of psychotic experiences, with the incidence of psychotic experiences decreasing significantly in individuals whose exposure to trauma ceased over the course of the study. CONCLUSIONS After a series of conservative adjustments, the authors found that exposure to childhood trauma predicted newly incident psychotic experiences. The study also provides the first direct evidence that cessation of traumatic experiences leads to a reduced incidence of psychotic experiences.

School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial

BACKGROUND Suicidal behaviours in adolescents are a major public health problem and evidence-based prevention programmes are greatly needed. We aimed to investigate the efficacy of school-based preventive interventions of suicidal behaviours. METHODS The Saving and Empowering Young Lives in Europe (SEYLE) study is a multicentre, cluster-randomised controlled trial. The SEYLE sample consisted of 11,110 adolescent pupils, median age 15 years (IQR 14-15), recruited from 168 schools in ten European Union countries. We randomly assigned the schools to one of three interventions or a control group. The interventions were: (1) Question, Persuade, and Refer (QPR), a gatekeeper training module targeting teachers and other school personnel, (2) the Youth Aware of Mental Health Programme (YAM) targeting pupils, and (3) screening by professionals (ProfScreen) with referral of at-risk pupils. Each school was randomly assigned by random number generator to participate in one intervention (or control) group only and was unaware of the interventions undertaken in the other three trial groups. The primary outcome measure was the number of suicide attempt(s) made by 3 month and 12 month follow-up. Analysis included all pupils with data available at each timepoint, excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline. This study is registered with the German Clinical Trials Registry, number DRKS00000214. FINDINGS Between Nov 1, 2009, and Dec 14, 2010, 168 schools (11,110 pupils) were randomly assigned to interventions (40 schools [2692 pupils] to QPR, 45 [2721] YAM, 43 [2764] ProfScreen, and 40 [2933] control). No significant differences between intervention groups and the control group were recorded at the 3 month follow-up. At the 12 month follow-up, YAM was associated with a significant reduction of incident suicide attempts (odds ratios [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and severe suicidal ideation (0·50, 0·27-0·92; p=0·025), compared with the control group. 14 pupils (0·70%) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 (1·51%) in the control group, and 15 pupils (0·75%) reported incident severe suicidal ideation in the YAM group versus 31 (1·37%) in the control group. No participants completed suicide during the study period. INTERPRETATION YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents. These findings underline the benefit of this universal suicide preventive intervention in schools. FUNDING Coordination Theme 1 (Health) of the European Union Seventh Framework Programme.

Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

BACKGROUND Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence. METHOD Psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence. RESULTS In separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use. CONCLUSION Our finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

Psychotic Symptoms and Population Risk for Suicide Attempt A Prospective Cohort Study

IMPORTANCE Up to 1 million persons die by suicide annually. However, a lack of risk markers makes suicide risk assessment one of the most difficult areas of clinical practice. OBJECTIVE To assess psychotic symptoms (attenuated or frank) as a clinical marker of risk for suicide attempt. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 1112 school-based adolescents (aged 13-16 years), assessed at baseline and at 3 and 12 months for self-reported psychopathology, psychotic symptoms, and suicide attempts. MAIN OUTCOMES AND MEASURES Suicide attempts at the 3- and 12-month follow-up and acute suicide attempts (defined as those occurring in the 2 weeks before an assessment). RESULTS Of the total sample, 7% reported psychotic symptoms at baseline. Of that subsample, 7% reported a suicide attempt by the 3-month follow-up compared with 1% of the rest of the sample (odds ratio [OR], 10.01; 95% CI, 2.24-45.49), and 20% reported a suicide attempt by the 12-month follow-up compared with 2.5% of the rest of the sample (OR, 11.27; 95% CI, 4.44-28.62). Among adolescents with baseline psychopathology who reported psychotic symptoms, 14% reported a suicide attempt by 3 months (OR, 17.91; 95% CI, 3.61-88.82) and 34% reported a suicide attempt by 12 months (OR, 32.67; 95% CI, 10.42-102.41). Adolescents with psychopathology who reported psychotic symptoms had a nearly 70-fold increased odds of acute suicide attempts (OR, 67.50; 95% CI, 11.41-399.21). Differences were not explained by nonpsychotic psychiatric symptom burden, multimorbidity, or substance use. In a causative model, the population-attributable fraction of suicide attempts would be 56% to 75% for psychotic symptoms. CONCLUSIONS AND RELEVANCE Adolescents with psychopathology who report psychotic symptoms are at clinical high risk for suicide attempts. More careful clinical assessment of psychotic symptoms (attenuated or frank) in mental health services and better understanding of their pathological significance are urgently needed.

Structural and functional brain correlates of subclinical psychotic symptoms in 11-13 year old schoolchildren.

Studying children experiencing psychotic symptoms provides a unique opportunity to examine the vulnerability to psychosis within the context of development. Using neuroimaging techniques this study investigated cognitive control functions, brain volumetrics and white matter integrity in an at-risk cohort of children. Between-subjects assessment of brain function and structure among 11 school-going, non-treatment seeking children aged 11-13 who were at symptomatic risk for psychosis (AR) and 14 healthy control children aged 11-12 without subclinical psychotic symptoms (CON). MRI assessments included functional measures of response inhibition and error-related processes, whole brain voxel-based morphometry (VBM) of gray matter (GM) and diffusion tensor imaging (DTI) utilizing fractional anisotropy to probe white matter (WM) integrity. fMRI results showed reduced activity in the AR group within right frontal and bilateral temporal cortex for response inhibition and reduced activity within the anterior cingulate, insula and middle frontal gyrus for error-related processing (p<.05, corrected). VBM analysis revealed GM increases in the AR group within middle and superior temporal gyri, angular gyrus, orbitofrontal gyrus and GM decrease within the inferior temporal gyrus (p<.05, corrected). DTI analysis identified WM decreases in the AR group along the inferior fronto-occipital fasciculus, cingulum and inferior longitudinal fasciculus (p<.05, corrected). This multimodal investigation revealed aberrant prefrontal-temporal dysfunction in addition to cingulate and insular dysfunctions which provide potential early neurocognitive risk markers related to the susceptibility for developing psychosis and subsequently the neurodevelopmental trajectory leading to schizophrenia.

Identification and Characterization of Prodromal Risk Syndromes in Young Adolescents in the Community: A Population-Based Clinical Interview Study

While a great deal of research has been conducted on prodromal risk syndromes in relation to help-seeking individuals who present to the clinic, there is a lack of research on prodromal risk syndromes in the general population. The current study aimed first to establish whether prodromal risk syndromes could be detected in non-help-seeking community-based adolescents and secondly to characterize this group in terms of Axis-1 psychopathology and general functioning. We conducted in-depth clinical interviews with a population sample of 212 school-going adolescents in order to assess for prodromal risk syndromes, Axis-1 psychopathology, and global (social/occupational) functioning. Between 0.9% and 8% of the community sample met criteria for a risk syndrome, depending on varying disability criteria. The risk syndrome group had a higher prevalence of co-occurring nonpsychotic Axis-1 psychiatric disorders (OR = 4.77, 95% CI = 1.81-12.52; P < .01) and poorer global functioning (F = 24.5, df = 1, P < .0001) compared with controls. Individuals in the community who fulfill criteria for prodromal risk syndromes demonstrate strong similarities with clinically presenting risk syndrome patients not just in terms of psychotic symptom criteria but also in terms of co-occurring psychopathology and global functioning.

Psychotic experiences in a mental health clinic sample: implications for suicidality, multimorbidity and functioning.

BACKGROUND Recent community-based research has suggested that psychotic experiences act as markers of severity of psychopathology. There has, however, been a lack of clinic-based research. We wished to investigate, in a clinical sample of adolescents referred to a state-funded mental health service, the prevalence of (attenuated or frank) psychotic experiences and the relationship with (i) affective, anxiety and behavioural disorders, (ii) multimorbid psychopathology, (iii) global functioning, and (iv) suicidal behaviour. METHOD The investigation was a clinical case-clinical control study using semi-structured research diagnostic psychiatric assessments in 108 patients newly referred to state adolescent mental health services. RESULTS Psychotic experiences were prevalent in a wide range of (non-psychotic) disorders but were strong markers of risk in particular for multimorbid psychopathology (Z = 3.44, p = 0.001). Young people with psychopathology who reported psychotic experiences demonstrated significantly poorer socio-occupational functioning than young people with psychopathology who did not report psychotic experiences, which was not explained by multimorbidity. Psychotic experiences were strong markers of risk for suicidal behaviour. Stratified analyses showed that there was a greatly increased odds of suicide attempts in patients with a major depressive disorder [odds ratio (OR) 8.89, 95% confidence interval (CI) 1.59-49.83], anxiety disorder (OR 15.4, 95% CI 1.85-127.94) or behavioural disorder (OR 3.13, 95% CI 1.11-8.79) who also had psychotic experiences compared with patients who did not report psychotic experiences. CONCLUSIONS Psychotic experiences (attenuated or frank) are an important but under-recognized marker of risk for severe psychopathology, including multimorbidity, poor functioning and suicidal behaviour in young people who present to mental health services.