Recreational Marijuana Use, Adolescent Cognitive Development, and Schizophrenia Susceptibility.

Background: We investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk. Methods: In two complementary adolescent samples where the majority reported minimal MJ use, we compared cognitive performances before and after MJ use initiation. The Iowa sample (40 first-degree relatives and 54 second-degree relatives of patients with schizophrenia and 117 control subjects with no schizophrenia family history) underwent a battery of standardized neuropsychological tests at 0, 18, and 36 months. Based on self-administered Timeline Followback interviews, 26.5% of adolescents had emergent MJ use (eMJ) during follow-up. The second sample (n = 3463), derived from a birth cohort, received substance use and sustained attention assessments between ages 10 and 15 years. Mixed linear models and regression analyses tested the effects of eMJ on longitudinal changes in cognitive performance. Results: In the Iowa sample, longitudinal changes in 5 of 8 cognitive domains were significantly associated with eMJ. On sustained attention, visuospatial working memory, and executive sequencing, adolescents with eMJ showed less age-expected improved performance. In addition, first-degree relatives with eMJ were less improved on processing speed and executive reasoning than first-degree relatives without eMJ. In the birth cohort, greater intraindividual variability in reaction times (indicative of poorer sustained attention) was significantly associated with more frequent MJ use and with recreational use levels. Conclusions: Nonheavy MJ use disrupts normal adolescent maturation and compounds aberrant adolescent maturation associated with familial schizophrenia risk. These findings underscore the importance of reducing adolescent MJ access in the context of increased availability to high-potency MJ.

Impulsive decision making, brain cortical thickness and familial schizophrenia risk.

BACKGROUND: Schizophrenia (SZ) patients and their biological relatives are more impulsive than controls. Although greater impulsivity in SZ has been associated with dysfunction in prefrontal neural circuits implicated in reward processing, little is known regarding brain structural correlates of heightened impulsivity in unaffected adolescent relatives of SZ patients. METHODS: Impulsive decision-making was assessed using the delay discounting task in 174 adolescents: 36 first-degree relatives (FDR) and 50 second-degree relatives (SDR) of SZ patients, and 88 healthy controls with no SZ family history (NSFH). We contrasted MRI brain gray matter cortical thickness-discounting constant (k) relationships between these 3 comparison groups using well-validated statistical approaches. RESULTS: FDR had a distinct pattern in cortical thickness-k associations when compared to NSFH and SDR. Preference for immediate rewards (i.e. greater impulsivity) among FDR correlated with less cortical thickness within diffuse brain regions, including dorsolateral prefrontal (cognitive control network and motor/premotor cortex) and lateral temporal (auditory and visual association cortex) brain areas. CONCLUSIONS: Adolescent impulsive decision-making may serve as an informative phenotype of underlying brain circuitry dysfunction associated with SZ risk. Future research focusing on impulsivity in SZ will likely help advance understanding how dysfunctional interactions between cognitive and reward neural circuits contribute to the neurobiological basis of SZ.

Impulsivity in unaffected adolescent biological relatives of schizophrenia patients.

OBJECTIVE: Although schizophrenia is not a prototypic impulse-control disorder, patients report more impulsive behaviors, have higher rates of substance use, and show dysfunction in brain circuits that underlie impulsivity. We investigate impulsivity in unaffected biological relatives of schizophrenia patients to further understand the relationships between schizophrenia risk and impulse control during adolescence. METHOD: Group differences in impulsivity (UPPS-P Impulsive Behavior Scale and delay discounting) were tested in 210 adolescents contrasting 39 first- and 53 second-degree biological relatives of schizophrenia patients, and 118 subjects with no schizophrenia family history (NSFH). RESULTS: Compared to NSFH adolescents and to second-degree relatives, first-degree relatives of schizophrenia patients had increased impulsivity-related behaviors (higher UPPS-P Perseverance, Positive Urgency and Premeditation subscale scores) and greater preference for immediate rewards (smaller AUC and larger discounting constant). Second-degree relatives did not differ significantly from NSFH adolescents on self-report impulsive behaviors or on measures of impulsive decision-making. These group differences remained even after careful consideration of potential confounding factors. CONCLUSION: Impulsivity is associated with schizophrenia risk, and its severity increases with greater familial relatedness to the schizophrenia proband. Additional studies are needed to understand the role impulsivity may play in mediating schizophrenia susceptibility during adolescence.

Cerebral white matter correlates of delay discounting in adolescents.

The adolescent brain undergoes extensive structural white matter (WM) changes. Adolescence is also a critical time period during which cognitive, emotional and social maturation occurs in transition into adulthood. Compared to adults, adolescents are generally more impulsive with increased risk-taking behaviors. The goal of this study is to examine whether adolescent impulsivity may be related to cerebral WM maturation. In 89 healthy adolescents, we assessed impulsivity using the delay discounting task, and MRI WM volumes in brain regions previously implicated in delay discounting behaviors. We found that smaller delay discounting AUC (area under the curve) was associated with larger WM volumes in orbitofrontal, dorsolateral and medial prefrontal cortices (PFC) and motor cortex. There were no significant effects of AUC on WM volumes within somatosensory brain regions. In our sample, younger age was significantly associated with greater WM volumes in orbitofrontal and dorsolateral PFC subregions. Even after accounting for age-related effects, preference for immediate rewards (or greater impulsivity) still correlated with larger WM volumes in prefrontal regions known to mediate cognitive control. Our findings lend further support to the notion that reduced brain WM maturity may limit the ability in adolescents to forgo immediate rewards leading to greater impulsivity.