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Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

ABSTRACT: Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20,586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10,000 patient-years. No increased risk was found during MPH-exposed compared with non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.

SUBMITTER: Man KK

PROVIDER: S-EPMC5314128 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

Man K K C KK Coghill D D Chan E W EW Lau W C Y WC Hollis C C Liddle E E Banaschewski T T McCarthy S S Neubert A A Sayal K K Ip P P Wong I C K IC

Translational psychiatry 20161115 11

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001-2014). Using the self-controlled case series design, relativ ...[more]

PMID: 27845780

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Project description:Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n?=?205; Schizoaffective disorder, n?=?112; Schizophrenia, n?=?163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p?=?0.037, OR?=?0.65, 95% CI?=?0.43-0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p?=?0.035, Cohen's d?=?0.194), as well as significantly greater DLPFC (p?<?0.05, Cohen's d?=?-0.21) and parahippocampal volumes (p?<?0.01, Cohen's d?=?-0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.

Project description:Introduction: Although attenuated psychotic symptoms often occur for the first time during adolescence, studies focusing on adolescents are scarce. Attenuated psychotic symptoms form the criteria to identify individuals at increased clinical risk of developing psychosis. The study of individuals with these symptoms has led to the release of the DSM-5 diagnosis of Attenuated Psychosis Syndrome (APS) as a condition for further research. We aimed to characterize and compare hospitalized adolescents with DSM-5-APS diagnosis vs. hospitalized adolescents without a DSM-5-APS diagnosis. Methods: Interviewing help-seeking, hospitalized adolescents (aged 12-18 years) and their caregivers independently with established research instruments, we (1) evaluated the presence of APS among non-psychotic adolescents, (2) characterized and compared APS and non-APS individuals regarding sociodemographic, illness and intervention characteristics, (3) correlated psychopathology with levels of functioning and severity of illness and (4) investigated the influence of individual clinical, functional and comorbidity variables on the likelihood of participants to be diagnosed with APS. Results: Among 248 consecutively recruited adolescents (age=15.4 ± 1.5 years, females = 69.6%) with non-psychotic psychiatric disorders, 65 (26.2%) fulfilled APS criteria and 183 (73.8%) did not fulfill them. Adolescents with APS had higher number of psychiatric disorders than non-APS adolescents (3.5 vs. 2.4, p < 0.001; Cohen's d = 0.77), particularly, disruptive behavior disorders (Cramer's V = 0.16), personality disorder traits (Cramer's V = 0.26), anxiety disorders (Cramer's V = 0.15), and eating disorders (Cramer's V = 0.16). Adolescents with APS scored higher on positive (Cohen's d = 1.5), negative (Cohen's d = 0.55), disorganized (Cohen's d = 0.51), and general symptoms (Cohen's d = 0.84), and were more severely ill (Cohen's d = 1.0) and functionally impaired (Cohen's d = 0.31). Negative symptoms were associated with lower functional levels (Pearson ? = -0.17 to -0.20; p = 0.014 to 0.031). Global illness severity was associated with higher positive, negative, and general symptoms (Pearson ? = 0.22 to 0.46; p = 0.04 to p < 0.001). APS status was independently associated with perceptual abnormalities (OR = 2.0; 95% CI = 1.6-2.5, p < 0.001), number of psychiatric diagnoses (OR = 1.5; 95% CI = 1.2-2.0, p = 0.002), and impaired stress tolerance (OR = 1.4; 95% CI = 1.1-1.7, p = 0.002) (r 2 = 0.315, p < 0.001). Conclusions: A considerable number of adolescents hospitalized with non-psychotic psychiatric disorders meet DSM-5-APS criteria. These help-seeking adolescents have more comorbid disorders and more severe symptoms, functional impairment, and severity of illness than non-APS adolescents. Thus, they warrant high intensity clinical care.

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Project description:ObjectivesThe heterogeneity and comorbidity of major mental disorders presenting in adolescents and young adults has fostered calls for trans-diagnostic research. This study examines early expressions of psychopathology and risk and trans-diagnostic caseness in a community cohort of twins and non-twin siblings.MethodsUsing data from the Brisbane Longitudinal Twin Study, we estimated median number of self-rated psychiatric symptoms, prevalence of subthreshold syndromes, family history of mood and/or psychotic disorders, and likelihood of subsequent trans-diagnostic caseness (individuals meeting diagnostic criteria for mood and/or psychotic syndromes). Next, we used cross-validated Chi-Square Automatic Interaction Detector (CHAID) analyses to identify the nature and relative importance of individual self-rated symptoms that predicted trans-diagnostic caseness. We examined the positive and negative predictive values (PPV; NPV) and accuracy of all classifications (Area under the Curve and 95% confidence intervals: AUC; 95% CI).ResultsOf 1815 participants (Female 1050, 58%; mean age 26.40), more than one in four met caseness criteria for a mood and/or psychotic disorder. Examination of individual factors indicated that the AUC was highest for subthreshold syndromes, followed by family history then self-rated psychiatric symptoms, and that NPV always exceeded PPV for caseness. In contrast, the CHAID analysis (adjusted for age, sex, twin status) generated a classification tree comprising six trans-diagnostic symptoms. Whilst the contribution of two symptoms (need for sleep; physical activity) to the model was more difficult to interpret, CHAID analysis indicated that four self-rated symptoms (sadness; feeling overwhelmed; impaired concentration; paranoia) offered the best discrimination between cases and non-cases. These four symptoms showed different associations with family history status.ConclusionsThe findings need replication in independent cohorts. However, the use of CHAID might provide a means of identifying specific subsets of trans-diagnostic symptoms representing clinical phenotypes that predict transition to caseness in individuals at risk of onset of major mental disorders.

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Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

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Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

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