Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure: Exploring Pharmacotherapeutic Interventions for Symptom Improvement

Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.

Predicting Adverse Events In A Forensic Psychiatric Population: a Developmental Approach

While adverse events such as inpatient violence, recidivism, and readmission to hospital are extremely common among individuals found not criminally responsible on account of mental disorder (NCRMD), very little is known about developmental risk factors that predict these adverse events in this population. Developmental risk factor research (RFR) focuses on childhood risk factors and later outcomes, and allows for establishing a timeline for events, experiences, and the onset of behaviours or illnesses. The present study is a retrospective file review of inpatients and outpatients at Forensic Mental Health Hospital in South Central Ontario who have been found NCRMD. Developmental risk factors that have been found to predict adverse events in criminal, psychiatric, and forensic psychiatric populations, and adverse events over the period of 1 year were coded. Overall, risk factors occurring in childhood did not predict adverse events. Risk factors occurring in adolescence, specifically trauma, abuse or neglect, predicted adverse events.

Predicting Adverse Events In A Forensic Psychiatric Population: a Developmental Approach

While adverse events such as inpatient violence, recidivism, and readmission to hospital are extremely common among individuals found not criminally responsible on account of mental disorder (NCRMD), very little is known about developmental risk factors that predict these adverse events in this population. Developmental risk factor research (RFR) focuses on childhood risk factors and later outcomes, and allows for establishing a timeline for events, experiences, and the onset of behaviours or illnesses. The present study is a retrospective file review of inpatients and outpatients at Forensic Mental Health Hospital in South Central Ontario who have been found NCRMD. Developmental risk factors that have been found to predict adverse events in criminal, psychiatric, and forensic psychiatric populations, and adverse events over the period of 1 year were coded. Overall, risk factors occurring in childhood did not predict adverse events. Risk factors occurring in adolescence, specifically trauma, abuse or neglect, predicted adverse events.

The role of rs_7927894 FLG gene polymorphism and total IgE in predicting clinical phenotypes of atopic dermatitis in children

Atopic dermatitis (AD) is the most common chronic allergic disease of childhood, the pathogenesis of which is based on endogenous genotype and which manifests by various clinical phenotypes — isolated or combined with other forms of atopy — allergic rhinitis/rhinoconjunctivitis (AR/ARC) and/or bronchial asthma (BA). Currently, one of the most studied genetic markers of AD developmental risk is the single nucleotide polymorphism of the filaggrin gene (SNP FLG), in particular, rs_7927894. The basic AD biomarker is total serum immunoglobulin E (IgE). But, so far, there has been no studies combining the mentioned predictors markers within different clinical AD phenotypes in children. Purpose — to detect the variants of SNP rs_7927894 of FLG gene and serum total IgE concentrations as personalized predictors panel for different AD clinical phenotypes developmental risk in children. Materials and methods. There were recruited 2 groups of patients into the study: the main comprised 39 children with phenotypes of AD isolated and combined with AR/ARC and/or BA; the control group comprised 47 children with disorders of digestive system (functional dyspepsia, chronic gastritis, peptic ulcer, functional biliary disorders) without clinical signs of atopy. The threshold level of statistical significance was set as p<0.05. Results. There were detected the predictor genotype and biomarker for the AD developmental risk as per AD isolated phenotype: 4.11 (95% CI 1.28; 13.18, p<0.05) within C/T SNP rs_7927894 of FLG gene variant and 8.98 (95% CI 2.53, 31.86, p<0.001) for total serum IgE>173 IU/ml. As well, predictor genotype and biomarker for the developmental risk of the AD combined with AR/ARC/BA phenotype were detected: 2.88 (95% 1.07; 8.54, p<0.05) within the C/T SNP rs_7927894 of FLG gene variant and 8.98 (95% CI 2.53; 31.86, p<0.001) for total serum IgE>213 IU/ml. Additionally, the developmental risk for the phenotype of AD combined with AR/ARC/ BA in comparison with AD isolated at a cut-off serum total IgE>1001 IU/ml was detected as 16.00 (95% CI 2.68; 95.44, p<0.01). Conclusions. The C/T SNP rs_7927894 of FLG gene variant and cut(off serum IgE concentrations are significantly associated with the developmental risk of AD clinical phenotypes in children. Total IgE remains a significant predictor biomarker of AD risk in children aged 3 to 18 years at serum concentrations >173 IU/ml for the AD isolated and at serum concentrations >213 IU/ml for the AD combined with AR/ARC/AD phenotypes. The level of total serum IgE>1001 IU/ml is a significant predictor biomarker for the developmental risk of AD phenotype combined with AR/ARC/BA in comparison to the AD isolated phenotype in children. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: atopic dermatitis, children, phenotype, filaggrin gene, single(nucleotide polymorphism, total immune globulin E.