During adolescence, cannabis experimentation is common, and its association with interindividual variations in brain maturation well studied. Cellular and molecular underpinnings of these system-level relationships are, however, unclear. We thus conducted a three-step study. First, we exposed adolescent male mice to Δ-9-tetrahydrocannabinol (THC) or a synthetic cannabinoid WIN 55,212-2 (WIN) and assessed differentially expressed genes (DEGs), spine numbers, and dendritic complexity in their frontal cortex. Second, in human (male) adolescents, we examined group differences in cortical thickness in 34 brain regions, using magnetic resonance imaging, between those who experimented with cannabis before age 16 (n = 140) and those who did not (n = 327). Finally, we correlated spatially these group differences with gene expression of human homologs of mouse-identified DEGs. The spatial expression of 13 THC-related human homologs of DEGs correlated with cannabis-related variations in cortical thickness, and virtual histology revealed coexpression patterns of these 13 genes with cell-specific markers of astrocytes, microglia, and a type of pyramidal cells enriched in dendrite-regulating genes. Similarly, the spatial expression of 18 WIN-related human homologs of DEGs correlated with group differences in cortical thickness and showed coexpression patterns with the same three cell types. Gene ontology analysis indicated that 37 THC-related human homologs are enriched in neuron projection development, while 33 WIN-related homologs are enriched in processes associated with learning and memory. In mice, we observed spine loss and lower dendritic complexity in pyramidal cells of THC-exposed animals (vs controls). Experimentation with cannabis during adolescence may influence cortical thickness by impacting glutamatergic synapses and dendritic arborization.

Little is known about molecular pathways mediating the neural response to Delta-9-tetrahydrocannabinol (THC), and their possible role in cannabis-related variations in cortical thickness during adolescence.

Although many studies of the adolescent brain identified positive associations between cognitive abilities and cortical thickness, little is known about mechanisms underlying such brain-behavior relationships. With experience-induced plasticity playing an important role in shaping the cerebral cortex throughout life, it is likely that some of the inter-individual variations in cortical thickness could be explained by genetic variations in relevant molecular processes, as indexed by a polygenic score of neuronal plasticity (PGS-NP). Here, we studied associations between PGS-NP, cognitive abilities, and thickness of the cerebral cortex, estimated from magnetic resonance images, in the Saguenay Youth Study (SYS, 533 females, 496 males: age=15.0 ± 1.8 years of age; cross-sectional), and the IMAGEN Study (566 females, 556 males; between 14 and 19 years; longitudinal). Using Gene Ontology, we first identified 199 genes implicated in neuronal plasticity, which mapped to 155,600 single nucleotide polymorphisms (SNPs). Second, we estimated their effect sizes from an educational attainment meta-GWAS to build a PGS-NP. Third, we examined a possible moderating role of PGS-NP in the relationship between performance intelligence quotient (PIQ), and its subtests, and the thickness of 34 cortical regions.In SYS, we observed a significant interaction between PGS-NP and object assembly vis-à-vis thickness in male adolescents (p = 0.026). A median-split analysis showed that, in males with a ‘high’ PGS-NP, stronger associations between object assembly and thickness were found in regions with larger age-related changes in thickness (r = 0.55, p = 0.00075). Although the interaction between PIQ and PGS-NP was non-significant (p = 0.064), we performed a similar median-split analysis. Again, in the high PGS-NP males, positive associations between PIQ and thickness were observed in regions with larger age-related changes in thickness (r = 0.40, p = 0.018). In the IMAGEN cohort, we did not replicate the first set of results (interaction between PGS-NP and cognitive abilities via-a-vis cortical thickness) while we did observe the same relationship between the brain-behaviour relationship and (longitudinal) changes in cortical thickness (Matrix reasoning: r = 0.63, p = 6.5e-05). No statistically significant results were observed in female adolescents in either cohort. Overall, these cross-sectional and longitudinal results suggest that molecular mechanisms involved in neuronal plasticity may contribute to inter-individual variations of cortical thickness related to cognitive abilities during adolescence in a sex-specific manner.

Background: Over 40 years of research implicates perfectionism in eating disorders in childhood and adolescence. However, the nature of this relationship remains understudied. To address this gap, we performed a systematic review and a meta-analysis to quantify the magnitude of the associations between perfectionism (i.e., unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns) and eating-related symptoms during childhood and adolescence. Methods: The literature search was conducted using five electronic databases in accordance with PRISMA guidelines: MEDLINE, Embase, CINAHL Complete, APA PsycINFO, and EMB Reviews. A total of 904 studies were identified; a total of 126 were included in the systematic review, and 65 in the meta-analysis (N = 29,268). Sensitivity analyses were also carried out to detect potential differences in age and clinical status. Results: All the associations we investigated were both significant and positive. Small effect sizes were found between eating global scores and unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns (res = 0.19, res = 0.21, res = 0.12, respectively) and remained significant in each age group in both clinical and community samples. Perfectionistic concerns were moderately associated with all eating measures, especially in community samples and samples with a mean age under 14. Conclusions: Psychological interventions specially designed to target perfectionistic concerns in the early stages of development may help prevent the onset or reduce the intensity of eating-related symptoms during childhood and adolescence.

Objectives Congenital heart defects (CHD) are responsible for neurodevelopmental delays that were initially attributed to brain injury resulting from cardiac surgery. However, prenatal imaging have shown that brain anomalies are present at birth. The aim of this study was to assess in utero brain injuries before birth in fetuses/neonates with congenital cardiopathies. Methods A complete autopsy evaluation with detailed study of the cardiopathy and neuropathological study was performed in 40 fetuses/neonates. Syndromic congenital cardiopathies were excluded because of the potential other causes of brain injury. The patients were classified into two groups according to their term at death. Results Statistical analyses indicated the mean brain weight was not significantly different between subjects with different morphological types of congenital cardiopathies. However, the brain weight was at or below the fifth percentile in most third-trimester subjects compared to normal brain weight in second-trimester subjects. Low brain weight in third-trimester subjects was also associated with frequent lesions similar to those described in preterm infants, with a particular involvement of white matter and its components. Conclusions These observations allowed us to establish the timing and impact of prenatal neuropathological lesions on brain development, and to correlate them with imaging data reported in the literature.

A prior meta-analyze using behavioral tasks demonstrated that individuals with subclinical delusional ideations jump to conclusion (JTC). The major aim of our systematic review and meta-analyses was to highlight the relationship between cognitive biases and psychotic-like experiences (PLEs) when both are assessed by self-reports measures. In accordance with PRISMA guidelines, four electronic databases were searched. A total of 669 studies were identified, 39 articles met inclusion criteria for the systematic review and 27 for the random effects meta-analysis on healthy and UHR samples investigating cognitive biases (JTC, aberrant salience (ASB), attention to threat (ATB), externalizing bias (ETB), belief inflexibility (BIB), personalizing bias, aggression bias and need for closure). Effect size estimates were calculated using Pearson's correlation coefficients (r). In samples including both healthy and Ultra High Risk (UHR) individuals, positive psychotic-like experiences (PPLEs) were positively associated with ATB (rs = 0.38), ETB (rs = 0.35), BIB (rs = 0.19), JTC (rs = 0.10), and personalizing (rs = 0.24). In community samples, PPLEs were positively associated with ASB (rs = 0.62), ATB (rs = 0.34), ETB (rs = 0.36), BIB (rs = 0.18), JTC (rs = 0.11). In addition, negative PLEs were positively associated with ATB (rs = 0.28), ETB (rs = 0.37), BIB (rs = 0.19) and ASB (rs = 0.18). In UHR samples, positive associations were established between PPLEs and ATB (rs = 0.47), ETB (rs = 0.34), personalizing (rs = 0.36) and the aggression bias (rs = 0.35). Our results support cognitive models of psychosis considering the role of cognitive biases in the onset and the maintenance of psychotic symptoms. Cognitive interventions targeting cognitive biases could potentially prevent transition to psychosis in youth reporting PLEs and in UHR.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.