Reduced hippocampal volume in adolescents with psychotic experiences: A longitudinal population-based study.

AIMS: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. METHODS: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. RESULTS: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. CONCLUSIONS: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress.

Nonsuicidal self-injury, suicidal thoughts and suicide attempts among sexual minority youth in Ireland during their emerging adult years.

AIM: This study aimed to examine whether or not sexual minority youth constitute an at-risk group for nonsuicidal self-injury, suicidal ideation or suicide attempts during their emerging adult years. METHODS: Using data from the Challenging Times Study, a population-based study of psychopathology and suicide in Ireland, analyses were conducted to test the associations between sexual minority status and the odds of any lifetime experience of nonsuicidal self-injury, suicidal thoughts or suicide attempts among Irish youth aged 19-24 years. RESULTS: Sexual minority youth had 6.6-fold (95% CI 1.7-24.7) increased risk of nonsuicidal self-injury, a 5.0-fold (95% CI 1.3-18.3) increased risk of suicidal ideation, a 7.7-fold (95% CI 1.8-32.0) increased risk of suicide intent and a 6.8-fold (95% CI 1.6-27.6) increased risk of a suicide attempt during their lifetime compared to their heterosexual peers. CONCLUSIONS: This study shows that emerging adulthood is a period of risk for suicide and nonsuicidal self-injurious behaviour among sexual minority youth.

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.

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 Children's 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.

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

BACKGROUND: Psychotic 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. METHODS: In 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. RESULTS: Patients 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. CONCLUSIONS: Non-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.

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.

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.

Psychotic symptoms in adolescence index risk for suicidal behavior: findings from 2 population-based case-control clinical interview studies.

CONTEXT Recent evidence from both clinical and population research has pointed to psychotic symptoms as potentially important markers of risk for suicidal behavior. However, to our knowledge, there have been no epidemiological studies to date that have reported data on psychotic symptoms and suicidality in individuals who have been clinically assessed for suicidal behavior. OBJECTIVES To explore associations between psychotic symptoms in nonpsychotic adolescents and risk for suicidal behavior in (1) the general population, (2) adolescents with psychiatric disorder, and (3) adolescents with suicidal ideation. DESIGN Two independently conducted case-control clinical interview studies. SETTING Population-based studies in Ireland. PARTICIPANTS Study 1 included 212 adolescents aged 11 to 13 years. Study 2 included 211 adolescents aged 13 to 15 years. Participants were recruited from schools. MAIN OUTCOME MEASURES Suicidal behavior and psychotic symptoms, assessed by semi-structured diagnostic clinical interview. RESULTS Psychotic symptoms were associated with a 10-fold increased odds of any suicidal behavior (ideation, plans, or acts) in both the early and middle adolescence studies (odds ratio [OR], 10.23; 95% CI, 3.25-32.26; P < .001 and OR, 10.5; 95% CI, 3.14-35.17; P < .001, respectively). Adolescents with depressive disorders who also experienced psychotic symptoms were at a nearly 14-fold increased odds of more severe suicidal behavior (suicide plans and suicide acts) compared with adolescents with depressive disorders who did not experience psychotic symptoms (OR, 13.7; 95% CI, 2.1-89.6). Among all adolescents with suicidal ideation, those who also reported psychotic symptoms had a nearly 20-fold increased odds of suicide plans and suicide acts compared with adolescents with suicidal ideation who did not report psychotic symptoms (OR, 19.6; 95% CI, 1.8-216.1). CONCLUSIONS Psychotic symptoms are strongly associated with increased risk for suicidal behavior in the general adolescent population and in adolescents with (nonpsychotic) psychiatric disorder. In both studies, an absolute majority of adolescents with more severe suicidal behavior (suicidal plans and acts) reported psychotic symptoms when directly questioned about this as part of a psychiatric interview. Assessment of psychotic symptoms should form a key part of suicide risk assessment.

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.

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.

Are screening instruments valid for psychotic-like experiences? A validation study of screening questions for psychotic-like experiences using in-depth clinical interview.

Individuals who report psychotic-like experiences are at increased risk of future clinical psychotic disorder. They constitute a unique "high-risk" group for studying the developmental trajectory to schizophrenia and related illnesses. Previous research has used screening instruments to identify this high-risk group, but the validity of these instruments has not yet been established. We administered a screening questionnaire with 7 items designed to assess psychotic-like experiences to 334 adolescents aged 11-13 years. Detailed clinical interviews were subsequently carried out with a sample of these adolescents. We calculated sensitivity and specificity and positive predictive value (PPV) and negative predictive value (NPV) for each screening question for the specific symptom it enquired about and also in relation to any psychotic-like experience. The predictive power varied substantially between items, with the question on auditory hallucinations ("Have you ever heard voices or sounds that no one else can hear?") providing the best predictive power. For interview-verified auditory hallucinations specifically, this question had a PPV of 71.4% and an NPV of 90.4%. When assessed for its predictive power for any psychotic-like experience (including, but not limited to, auditory hallucinations), it provided a PPV of 100% and an NPV of 88.4%. Two further questions-relating to visual hallucinations and paranoid thoughts-also demonstrated good predictive power for psychotic-like experiences. Our results suggest that it may be possible to screen the general adolescent population for psychotic-like experiences with a high degree of accuracy using a short self-report questionnaire.

Language, motor and speed of processing deficits in adolescents with subclinical psychotic symptoms.

OBJECTIVES: Neuropsychological impairment is a core feature of schizophrenia. Adolescents reporting subclinical psychotic symptoms are considered to be at greater risk of developing a psychotic illness later in life than adolescents who do not report such symptoms and, thus, may represent an at-risk group for further study. We wished to investigate neuropsychological functioning in early adolescence in relation to reports of psychotic symptoms. METHODS: Participants were recruited from local primary schools after a two-stage screening and parental consent process. In brief, 277 adolescents were screened and 37 attended for testing. Seventeen adolescents who were deemed to report 'definite' psychotic symptoms after clinical interview and 20 control adolescents underwent a clinical interview and a one-hour neuropsychological battery. RESULTS: Adolescents who report psychotic symptoms exhibited significant impairments in receptive language (as measured by the British Picture Vocabulary Scale), motor function (as measured by the Pegboard test) and executive function/speed of processing (as measured by the Trail-Making test). There were no significant differences between the groups on measures of attention, memory or expressive language, abstract reasoning or overall scholastic ability. CONCLUSIONS: Taken together with the results from birth cohort, genetic high risk and prodromal studies, these findings are consistent with a neural inefficiency/disconnectivity hypothesis in those at risk for psychosis. These results highlight the need to investigate developmental brain circuits subserving language and motor function and processing speed and how these change over time in at-risk adolescents.

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.

Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample.

BACKGROUND: Children and adolescents who report psychotic symptoms appear to be at increased risk for psychotic disorders in adulthood - a putative ;symptomatic' high-risk group. However, little research has investigated whether those in this high-risk population have increased rates of exposure to traumatic events in childhood, as seen in patients who have a psychotic illness. AIMS: To examine whether adolescents with psychotic symptoms have an increased rate of traumatic experiences. METHOD: Psychiatric interviews 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 a number of early traumatic events including physical and sexual abuse, exposure to domestic violence and bullying. RESULTS: Fourteen adolescents (6.6% of those interviewed) reported experiencing at least one psychotic symptom. Adolescents who reported psychotic symptoms were significantly more likely to have been physically abused in childhood, to have been exposed to domestic violence and to be identified as a bully/victim (that is, both a perpetrator and victim of bullying) than those who did not report such symptoms. These findings were not confounded by comorbid psychiatric illness or family history of psychiatric history. CONCLUSIONS: Our findings suggest that childhood trauma may increase the risk of psychotic experiences. The characteristics of bully/victims deserve further study.