Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted

Cross-sectional association between metabolic parameters and psychotic-like experiences in a population-based sample of middle-aged and elderly individuals

Background: Metabolic alterations are often found in patients with clinical psychosis early in the course of the disorder. Psychotic-like experiences are observed in the general population, but it is unclear whether these are associated with markers of metabolism. Methods: A population-based cohort of 1890 individuals (mean age 58.0 years; 56.3% women) was included. Metabolic parameters were measured by body-mass index (BMI), concentrations of low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol, triglycerides, and fasting glucose and insulin in blood. Frequency and distress ratings of psychotic-like experiences from the positive symptom dimension of the Community Assessment of Psychic Experience questionnaire were assessed. Cross-sectional associations were analysed using linear regression analyses. Results: Higher BMI was associated with higher frequency of psychotic-like experiences (adjusted mean difference: 0.04, 95% CI 0.02–0.06) and more distress (adjusted mean difference: 0.02, 95% CI 0.01–0.03). Lower LDL-C was associated with more psychotic-like experiences (adjusted mean difference: −0.23, 95% CI −0.40 to −0.06). When restricting the sample to those not using lipid-lowering medication, the results of BMI and LDL-C remained and an association between lower HDL-C and higher frequency of psychotic-like experiences was found (adjusted mean difference: −0.37, 95% CI −0.69 to −0.05). We observed no significant associations between cholesterol, triglycerides, glucose, insulin or homeostatic model assessment and psychotic-like experiences. Conclusions: In a population-based sample of middle-aged and elderly individuals, higher BMI and lower LDL-C were associated with psychotic-like experiences. This suggests that metabolic markers are associated with psychotic-like experiences across the vulnerability spectrum.</p

Callous-unemotional traits and anxiety in adolescents: a latent profile analysis to identify different types of antisocial behavior in a high-risk community sample

OBJECTIVE: Callous-unemotional (CU) traits are associated with a more severe and chronic trajectory of antisocial behavior. The present study aimed to identify different classes of CU and anxiety and to compare these classes on overt and covert antisocial behavior and several clinical correlates. METHOD: In a prospective high-risk cohort of adolescents (N = 679; mean age = 14.77, SD = 0.81), latent profile analysis was conducted using CU traits and anxiety symptoms as indicators, and multi-informant aggressive and rule breaking behavior as distal outcomes. Post-hoc analyses with binary logistic regression and a series of ANCOVA were performed on identified classes assessing violent aggression, property offending, and clinical correlates. RESULTS: Three classes were found, a reference group (low CU, low anxiety; N = 500), a high CU-low anxiety group (N = 98), and an intermediate CU-high anxious group (N = 81). The high CU-low anxiety group scored highest on property offenses, while the intermediate CU-high anxious group scored highest on aggressive behavior. The intermediate CU-high anxious group scored highest on psychotic experiences, while the high CU group scored highest on internet gaming addiction problems and bullying victimization. CONCLUSION: These findings provide further evidence for diverse variants of CU traits in a high-risk community sample. Future prospective studies should point out whether and to what extent adolescents with CU traits with and without anxiety develop criminal careers and psychiatric disorders in adulthood

Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted

Childhood adversity and psychopathology:the dimensions of timing, type and chronicity in a population-based sample of high-risk adolescents

Background: Research on childhood adversity and psychopathology has begun investigating the dimension of timing, however the results have been contradictory depending on the study population, outcome and how adverse life events (ALEs) were operationalized. Additionally, studies so far typically focus only on a narrow range of psychiatric diagnoses or symptoms. The current cross-sectional study aimed to examine the association between timing, type and chronicity of ALEs and adolescent mental health problems. Methods: Adolescents from a population-based cohort oversampled on emotional and behavioral problems (mean age 14.8; range 12–17, N = 861) were included in the current analysis. Primary caregivers were interviewed on what ALEs adolescents experienced. ALEs were defined in two ways: (1) broad operationalization, including school difficulties, parental divorce, and family sickness; and (2) physically threatening abuse only, including physical and sexual violence. After looking at lifetime ALEs, we turned to chronicity, timing and sex differences. We focused on overall psychiatric symptoms as well as specific domains of emotional and behavioral problems, assessed using the Youth Self Report (YSR) and psychotic experiences assessed using the Prodromal Questionnaire-16 (PQ-16). A series of linear models adjusted for sociodemographic and parental factors were used. Results: Lifetime ALEs were associated with all types of psychopathology, with relatively bigger effect sizes for broad than for physical ALEs. The latter associations were found to be more robust to unmeasured confounding. The 9–12 age period of experiencing both broad and physical ALE’s was most saliently associated with any psychopathology. Girls were more at risk after experiencing any ALEs, especially if the adversity was chronic or ALEs took place after the age of 12. Conclusions: Broad as well as physical ALEs are associated with psychopathology, especially ALEs experienced during the 9–12 age period. Physical ALEs may be more useful in investigating specific etiological factors than broad ALEs. Sex differences may not emerge in lifetime measures of ALEs, but can be important for chronic and later childhood adversity.</p

Screening for disruptive behavior in adolescents at risk using the strengths and difficulties questionnaire

Disruptive behavior in adolescents is burdensome and may continue into adulthood if left unidentified. The strengths and difficulties questionnaire (SDQ) can screen for disruptive behavior, but its psychometric properties in high-risk samples and ability to predict delinquency warrant further investigation. In 1022 adolescents, we investigated the predictive validity (on average 1.9 years after screening) of the self-reported SDQ on disruptive behavior disorders and delinquency, measured with multi-informant questionnaires and structured interviews. We compared three scoring methods: total, subscale, and dysregulation profile scoring. In this high-risk sample, SDQ subscale scores predicted disruptive behavior outcomes best. Predictive values for the specific types of delinquency were small. Concluding, the SDQ can be used in high-risk settings for early identification of youth with disruptive behavior

The association between parental chronic physical illness and adolescent functional somatic symptoms

Background: Previous studies have found that adolescents with a chronically ill parent may experience more internalizing problems. It is less clear if this association is sex-related, and whether it is specific for functional somatic symptoms (FSSs) or concerns other internalizing or externalizing problems. Methods: In a prospective cohort of adolescents, oversampled on emotional and behavioral problems (n = 841; mean age 14.9 years), we examined the association between parental chronic illness and adolescent's FSSs, and internalizing and externalizing problems. Adolescent's internalizing and externalizing symptoms were measured using the Youth Self Report; parental chronic physical illness was reported during an interview. Associations were tested using linear regression analyses taking into account socio-demographic confounders. We also explored gender-interaction effects. Results: Having a chronically ill parent (n = 120; 14.3 %) was associated with more FSS in girls (B = 1.05, 95%CI = [0.23, 1.88], p = .013), but not in boys (sex-interaction: p = .013). In girls, an association was also found between parental chronic illness and more internalizing problems (B = 2.68, 95%CI = [0.41, 4.95], p = .021), but this association disappeared when FSSs were excluded from the Internalizing problem scores. Limitations: The current study has a cross-sectional design and relied on self-reported parental chronic physical illness what may have induced misclassification. Conclusion: Findings suggest that having a chronically ill parent is associated with more FSSs in adolescent girls and that this association is specific for FSSs instead of general internalizing problems. Girls with a chronically ill parent may profit from interventions to prevent the development of FSSs

The iBerry study: a longitudinal cohort study of adolescents at high risk of psychopathology

The iBerry study is a population-based cohort study designed to investigate the transition from subclinical symptoms to a psychiatric disorder. Adolescents were selected based on their self-reported emotional and/or behavioral problems assessed by completing the strengths and difficulties questionnaire-youth (SDQ-Y) in their first year of high school. A total of 16,736 SDQ-Y questionnaires completed in the academic years 2014–2015 and 2015–2016 by students in the greater Rotterdam area in the Netherlands were screened. A high-risk group of adolescents was then selected based on the 15% highest-scoring adolescents, and a low-risk group was randomly selected from the 85% lowest-scoring adolescents, with a 2.5:1 ratio between the number of high-risk and low-risk adolescents. These adolescents were invited to come with one parent for a baseline visit consisting of interviews, questionnaires, neuropsychological tests, and biological measurements to assess determinants of psychopathology. A total of 1022 high-risk and low-risk adolescents (mean age at the first visit: 15.0 years) enrolled in the study. The goal of the iBerry study is to follow these adolescents for a 10-year period in order to monitor any changes in their symptoms. Here, we present the study design, response rate, inclusion criteria, and the characteristics of the cohort; in addition, we discuss possible selection effects. We report that the oversampling procedure was successful at selecting a cohort of adolescents with a high rate of psychiatric problems based on comprehensive multi-informant measurements. The future results obtained from the iBerry Study will provide new insights into the way in which the mental health of high-risk adolescents changes as they transition to adulthood. These findings will therefore facilitate the development of strategies designed to optimize mental healthcare and prevent psychopathology