Michelle Harley

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.

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.

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 the population: association with functioning and mental distress

Psychotic experiences are far more common in the population than psychotic disorder. They are associated with a number of adverse outcomes but there has been little research on associations with functioning and distress. We wished to investigate functioning and distress in a community sample of adolescents with psychotic experiences. Two hundred and twelve school-going adolescents were assessed for psychotic experiences, mental distress associated with these experiences, global (social/occupational) functioning on the Childrens Global Assessment Scale, and a number of candidate mediator variables, including psychopathology, suicidality, trauma (physical and sexual abuse and exposure to domestic violence) and neurocognitive functioning. Seventy five percent of participants who reported psychotic experiences reported that they found these experiences distressing (mean score for severity of distress was 6.9 out of maximum 10). Participants who reported psychotic experiences had poorer functioning than participants who did not report psychotic experiences (respective means: 68.6, 81.9; OR=0.25, 95% CI=0.14-0.44). Similarly, participants with an Axis-1 psychiatric disorder who reported psychotic experiences had poorer functioning than participants with a disorder who did not report psychotic experiences (respective means: 61.8, 74.5; OR=0.28, 95% CI=0.12-0.63). Candidate mediator variables explained some but not all of the relationship between psychotic experiences and functioning (OR=0.48, 95% CI=0.22-1.05, P<0.07). Young people with psychotic experiences have poorer global functioning than those who do not, even when compared with other young people with psychopathology (but who do not report psychotic experiences). A disclosure of psychotic experiences should alert treating clinicians that the individual may have significantly more functional disability than suggested by the psychopathological diagnosis alone.

White matter differences among adolescents reporting psychotic experiences : A population-based diffusion magnetic resonance imaging study

IMPORTANCE Abnormal brain connectivity is thought to have a key role in the pathophysiology of schizophrenia and other psychotic disorders. White matter (WM) abnormalities have been reported in patients with schizophrenia and patients with prodromal syndromes. To our knowledge, no studies have yet reported on WM differences among adolescents who report psychotic experiences, a known vulnerability group for later severe psychopathology, including psychotic illness. OBJECTIVE To study WM differences using diffusion-weighted imaging (whole-brain and tractography analyses) in adolescents who report psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS A population-based case-control study of 28 adolescents 13 to 16 years old who reported psychotic experiences and a matched sample of 28 adolescents who did not report psychotic experiences drawn from a sample of 212 young people recruited from primary schools in North Dublin and Kildare, Ireland. The study dates were 2008 to 2011. INTERVENTIONS High-angular resolution diffusion-weighted imaging data were used to conduct whole-brain WM analysis using tract-based spatial statistics. Based on this exploratory analysis, a tractography-based approach with constrained spherical deconvolution was performed. RESULTS Compared with control group participants, adolescents who reported psychotic experiences showed WM differences bilaterally in striatal regions in proximity to the putamen (increased fractional anisotropy, P = .01, false discovery rate corrected), and tractography identified significant WM differences bilaterally in the uncinate fasciculus (increased fractional anisotropy in the right [P = .001] and axial diffusivity in the left [P = .01] uncinate fasciculus, respectively). Similar patterns of WM differences between groups survived adjustment for other psychopathology, indicating some specificity for psychotic experiences. Exploratory along-tract analyses showed WM differences between groups in the frontal projections of the right inferior fronto-occipital fasciculus (reduced radial diffusivity in approximately 32% of the tract segment [P ≤ .0001] and increased fractional anisotropy in approximately 16% of the tract segment [P ≤ .0009]). CONCLUSIONS AND RELEVANCE In a population-based study of adolescents reporting psychotic experiences, we found a number of WM differences in the region of the putamen located between the inferior fronto-occipital fasciculus and the uncinate fasciculus and in the left parietal regions that include the fiber bundle of the superior longitudinal fasciculus. These findings suggest that subtle structural changes to WM microstructure are not merely a consequence of disorder but may index vulnerability to psychosis even at a very early age.

Prevalence of DSM-IV mental disorders, deliberate self-harm and suicidal ideation in early adolescence: an Irish population-based study.

BACKGROUND This study investigated the prevalence of DSM-IV Axis 1 mental disorders, deliberate self-harm and suicidal ideation in a sample of Irish adolescents aged 11-13 years. METHODS A total of 1131 students was surveyed for general psychopathology using the Strengths and Difficulties Questionnaire. Following this, a representative sample of 212 adolescents was assessed for mental disorders, deliberate self-harm and suicidal ideation using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. RESULTS 14.6% of the sample met criteria for a borderline score and 6.9% for an abnormal score on the Strengths and Difficulties Questionnaire. Following clinical diagnostic interviews, 27.4% of participants received a current diagnosis of an Axis 1 disorder and 36.8% received a lifetime diagnosis, those rates falling to 15.4% and 31.2% respectively when specific phobias were excluded. CONCLUSIONS Findings from this study reveal that Irish adolescents aged 11-13 years are experiencing high levels of mental ill-health.

Psychotic symptoms, functioning and coping in adolescents with mental illness.

BackgroundPsychotic symptoms in the context of psychiatric disorders are associated with poor functional outcomes. Environmental stressors are important in the development of psychosis; however, distress may only be pathogenic when it exceeds an individual’s ability to cope with it. Therefore, one interesting factor regarding poor functional outcomes in patients with psychotic symptoms may be poor coping. This paper aimed to address the question whether 1) psychotic symptoms are associated with poorer functioning and 2) whether poor coping moderated the association.MethodsIn a clinical case-clinical control study of 106 newly-referred adolescent patients with non-psychotic psychiatric disorders, coping was investigated using the Adolescents Coping Scale. Severity of impairment in socio-occupational functioning was assessed with the Children’s Global Assessment Scale.ResultsPatients with non-psychotic psychiatric disorders and additional psychotic symptoms (N = 50) had poorer functioning and were more likely to use avoidance-oriented coping compared to patients with non-psychotic psychiatric disorders without psychotic symptoms (N = 56). No differences were found with respect to approach-oriented coping. When stratifying for poor/good coping, only those adolescent patients with psychotic symptoms who applied poor coping (i.e. less use of approach-oriented coping styles [OR 0.24, p < 0.015] and more use of avoidance-oriented coping [OR 0.23, p < 0.034]) had poorer functioning. However, these interactions were not significant.ConclusionsNon-adaptive coping and poorer functioning were more often present in adolescents with non-psychotic psychiatric disorders and additional psychotic symptoms. Due to small subgroups, our analyses could not give definitive conclusions about the question whether coping moderated the association between psychotic symptoms and functioning. Improvement of coping skills may form an important target for intervention that may contribute to better clinical and functional outcomes in patients with psychotic symptoms.

Relationship between the COMT-Val158Met and BDNF- Val66Met Polymorphisms, Childhood Trauma and Psychotic Experiences in an Adolescent General Population Sample

Objective Psychotic experiences occur at a much greater prevalence in the population than psychotic disorders. There has been little research to date, however, on genetic risk for this extended psychosis phenotype. We examined whether COMT or BDNF genotypes were associated with psychotic experiences or interacted with childhood trauma in predicting psychotic experiences. Method Psychiatric interviews and genotyping for COMT-Val158Met and BDNF-Val66Met were carried out on two population-based samples of 237 individuals aged 11-15 years. Logistic regression was used to examine for main effects by genotype and childhood trauma, controlling for important covariates. This was then compared to a model with a term for interaction between genotype and childhood trauma. Where a possible interaction was detected, this was further explored in stratified analyses. Results While childhood trauma showed a borderline association with psychotic experiences, COMT-Val158Met and BDNF-Val66Met genotypes were not directly associated with psychotic experiences in the population. Testing for gene x environment interaction was borderline significant in the case of COMT-Val158Met with individuals with the COMT-Val158Met Val-Val genotype, who had been exposed to childhood trauma borderline significantly more likely to report psychotic experiences than those with Val-Met or Met-Met genotypes. There was no similar interaction by BDNF-Val66Met genotype. Conclusion The COMT-Val158Met Val-Val genotype may be a genetic moderator of risk for psychotic experiences in individuals exposed to childhood traumatic experiences.