Associations of age with reward delay discounting and response inhibition in adolescents with bipolar disorders.

OBJECTIVES: Bipolar disorders' (BD) onset before age 18 is a potential marker for a more severe illness course. Adolescence is also a period of significant normative maturation of inhibitory control and reward-relevant decision-making processes, such as decreased delay discounting (i.e., decreased preference for smaller, immediate versus larger, delayed rewards). Adults with BD exhibit elevated delay discounting rates. Very little is known about developmental changes in delay discounting in adolescents with BD, or about associations between inhibitory control and delay discounting in BD. The present study addresses these questions. METHODS: The sample included 78 participants, ages 13 to 23, with BD or without history of mental illness. Group differences and group by age interaction effects on delay discounting (32 BD, 32 controls with valid responses), probability discounting (34 BD, 37 controls) and inhibitory control indices (34 BD, 38 controls) were assessed. RESULTS: Among healthy controls, less discounting of delayed rewards was associated with older age, whereas adolescents with BD did not show age-related associations. There were no group differences in probability discounting or inhibitory control. LIMITATIONS: The cross-sectional nature of the study cannot fully rule out the less likely interpretation of group differences in cohort effects. CONCLUSIONS: The lack of age-related improvement in delay tolerance in BD suggests disrupted development of executive control processes within reward contexts, which in turn may contribute to understanding more severe course of pediatric onset BD. Longitudinal studies are needed to examine delay discounting in relation to maturation of neural reward systems among adolescents with BD.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

Clinical and neurocognitive course in early-onset psychosis: a longitudinal study of adolescents with schizophrenia-spectrum disorders.

AIM: Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents. METHOD: Thirty-six subjects, aged 10 to 17 years, were included at baseline. All had Diagnostic and Statistical Manual-Fourth Edition diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder and psychosis - not otherwise specified, as determined by Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children structured interviews. Patients were administered a neuropsychological battery, and Positive and Negative Syndrome Scale ratings were completed at baseline and again at 1 year (n = 14). Most participants were inpatients at baseline, and 13 of 14 were on atypical antipsychotic medication during both sessions. RESULTS: At baseline, the patients demonstrated impairments in working memory, processing speed, executive function and verbal learning. No significant cognitive change was detected at 1-year follow-up. In contrast, clinical symptoms were variable across 1 year, with an improvement in positive symptoms at 1 year. No relationships between clinical and cognitive symptoms were observed, with the exception of baseline IQ predicting negative symptoms at 1 year. CONCLUSIONS: Young patients with schizophrenia-spectrum disorders displayed neurocognitive impairments at baseline. Despite measurable fluctuations in clinical symptoms over the year, no significant changes were measured in cognition. Lower IQ at baseline was predictive of more negative symptoms at 1 year.

A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders.

OBJECTIVE: There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics (SGAs) have been undertaken. To plan the design of a subsequent randomized controlled trial (RCT), the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocols. METHOD: Thirty children and adolescents (20 males, 10 females), ages 10-18 years, who met unmodified Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for a schizophrenia-spectrum disorder (schizophrenia, schizoaffective, schizophreniform, psychotic disorder not otherwise specified) were randomized to receive 12 weeks of open-label, flexibly dosed treatment with either risperidone (mean [standard deviation, SD] dose = 3.4 mg [1.5]), olanzapine (mean [SD] dose = 14.0 mg [4.6]) or quetiapine (mean [SD] dose = 611 mg [253.4]). RESULTS: Twenty one (70%) of 30 subjects completed the study. There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale (PANSS) total scores in treatment efficacy observed (F((2,24)) = 3.13, p = 0.06). However, the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine (risperidone vs. quetiapine, d = 1.10 [95% confidence interval, CI, 0.09-2.01]) was suggested by the point estimate. CONCLUSIONS: These preliminary data, viewed together with the extant literature, suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinically significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses. Additional challenges and considerations for mounting a larger RCT are explored.