Mary Clarke

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.

Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia.

OBJECTIVE The authors sought to determine whether prenatal exposure to infection and a positive family history of psychotic disorders interact synergistically to increase the risk of later developing schizophrenia. METHOD The authors linked two national registers, the Medical Birth Register and the Finnish Population Register, to identify all women in Helsinki who received hospital treatment during pregnancy for an upper urinary tract infection (N=9,596) between 1947 and 1990. The Finnish Hospital Discharge Register was used to ascertain psychiatric outcomes in adulthood of offspring exposed to infection prenatally. Family history of psychotic disorders was determined by linking the Hospital Discharge Register and the Population Register. The authors used an additive statistical interaction model to calculate the amount of biological synergism between positive family history and prenatal exposure to infection. RESULTS Prenatal exposure to infection did not significantly increase the risk of schizophrenia. However, the effect of prenatal exposure to pyelonephritis was five times greater in those who had a family history of psychosis compared to those who did not. The synergy analysis suggested that an estimated 38%-46% of the offspring who developed schizophrenia and had both prenatal exposure to infection and a positive family history of psychotic disorders did so as a result of the synergistic action of both risk factors. CONCLUSIONS These findings support a mechanism of gene-environment interaction in the causation of schizophrenia.

Early insight predicts depression and attempted suicide after 4 years in first‐episode schizophrenia and schizophreniform disorder

Objective:  To map the development of insight in the 4 years after presentation with first‐episode schizophrenia and schizophreniform disorder and to determine the effects of evolving insight on depression and the likelihood of attempted suicide.

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.

Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis

BACKGROUND The critical period hypothesis proposes that deterioration occurs aggressively during the early years of psychosis, with relative stability subsequently. Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits. AIMS To test the critical period hypothesis by determining whether outcome in non-affective psychosis stabilises beyond the critical period and whether DUP correlates with 8-year outcome; to determine whether duration of untreated illness (DUI) has any independent effect on outcome. METHOD We recruited 118 people consecutively referred with first-episode psychosis to a prospective, naturalistic cohort study. RESULTS Negative and disorganised symptoms improved between 4 and 8 years. Duration of untreated psychosis predicted remission, positive symptoms and social functioning at 8 years. Continuing functional recovery between 4 and 8 years was predicted by DUI. CONCLUSIONS These results provide qualified support for the critical period hypothesis. The critical period could be extended to include the prodrome as well as early psychosis.

Schizophrenia and the city: A review of literature and prospective study of psychosis and urbanicity in Ireland

Urbanicity has been repeatedly associated with increased incidence of schizophrenia. This article (a) presents results of a prospective study of urbanicity and schizophrenia in Ireland and (b) reviews the literature relating to urbanicity and schizophrenia. We prospectively compared incidence of schizophrenia and other psychoses in urban and rural catchment areas (over 4years and 7years, respectively) using face-to-face, DSM-III-R diagnostic interviews. Incidence of schizophrenia in males was higher in urban compared to rural areas, with an age-adjusted incidence rate ratio (IRR) of 1.92 (1.52-2.44) for males and 1.34 (1.00-1.80) for females. Incidence of affective psychosis was lower in urban compared to rural areas for males (IRR 0.48; 0.34-0.67) and females (IRR 0.60; 0.43-0.83). These findings are consistent with the literature, which provides persuasive evidence that risk for schizophrenia increases with urban birth and/or upbringing, especially among males. Register-based studies support this conclusion more consistently than studies using face-to-face diagnostic interviews, the difference being related to power. The mechanism of association is unclear but may relate to biological or social/environmental factors or both, acting considerably before psychotic symptoms manifest. There is a diversity of potential candidates, including air pollution, cannabis and social exclusion. Urbanicity may have a synergistic effect with genetic vulnerability. Future research is likely to focus on the relationship between urbanicity and neural maldevelopment, the possibility of rural protective factors (e.g. social capital, low social fragmentation), urbanicity in developing countries, cultural variables and geographical location, and associations between urbanicity and other disorders (e.g. affective psychosis).

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.

Incidence and clinical correlates of aggression and violence at presentation in patients with first episode psychosis

This study aimed to identify the incidence and clinical correlates of aggression and violence in first episode psychosis. We prospectively recruited subjects with a first episode of DSM-psychosis presenting from a geographically defined catchment area to a secondary referral psychiatric service over a four-year period (n = 157). We used the Modified Overt Aggression Scale to retrospectively assess aggression (a hostile or destructive mental attitude, including verbal aggression, physical aggression and/or violence) and violence (the exercise of physical force), blind to diagnosis. One in three patients with psychosis was aggressive at the time of presentation. One patient in 14 engaged in violence that caused, or was likely to cause, injury to other people. Aggression was independently associated with drug misuse (odds ratio (OR) 2.80, 95% confidence interval 1.12-6.99) and involuntary admission status (OR = 3.62, 95% CI 1.45-9.01). Violence in the week prior to presentation was associated with drug misuse (OR = 2.75, CI 1.04-7.24) and involuntary admission status (OR = 3.21, CI 1.21-8.50). Violence in the week following presentation was associated with poor insight (OR 2.97, CI 1.03-8.56) and pre-contact violence (OR 3,82, CI 1.34-10.88). In patients with schizophrenia, violence in the week following presentation was associated with drug misuse (OR = 7.81, CI 1.33-45.95) and high psychopathology scores (OR = 20.59, CI 1.66-254.96). Overall, despite a high rate of verbal aggression, physical violence towards other people is uncommon in individuals presenting with first episode psychosis.

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.