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.

How do established developmental risk-factors for schizophrenia change the way the brain develops?

The recognition that schizophrenia is a disorder of neurodevelopment is widely accepted. The original hypothesis was coined more than 30 years ago and the wealth of supportive epidemiologically data continues to grow. A number of proposals have been put forward to suggest how adverse early exposures in utero alter the way the adult brain functions, eventually producing the symptoms of schizophrenia. This of course is extremely difficult to study in developing human brains, so the bulk of what we know comes from animal models of such exposures. In this review, I will summarise the more salient features of how the major epidemiologically validated exposures change the way the brain is formed leading to abnormal function in ways that are informative for schizophrenia symptomology. Surprisingly few studies have examined brain ontogeny from embryo to adult in such models. However, where there is longitudinal data, various convergent mechanisms are beginning to emerge involving stress and immune pathways. There is also a surprisingly consistent alteration in how very early dopamine neurons develop in these models. Understanding how disparate epidemiologically-validated exposures may produce similar developmental brain abnormalities may unlock convergent early disease-related pathways/processes.

Pathways linking adverse environments to emerging adults’ substance abuse and depressive symptoms: A prospective analysis of rural African American men

For African American emerging adult men, developmental challenges are evident in their escalating substance abuse and depressive symptoms; this is particularly true for men from low-resource communities. The present study tests a developmental model linking childhood adversity and contemporaneous contextual stressors to increases in emerging adults’ substance use and depressive symptoms, indirectly, via increases in defensive/hostile relational schemas and social developmental risk factors (e.g., risky peers and romantic partners, lack of involvement in school or work). We also advance exploratory hypotheses regarding DNA methylation in the oxytocin receptor gene (OXTR) as a moderator of the effects of stress on relational schemas. Hypotheses were tested with three waves of data from 505 rural African American men aged 19–25 years. Adverse childhood experiences predicted exposure to emerging adult contextual stressors. Contextual stressors forecast increases in defensive/hostile relational schemas, which increased social developmental risk factors. Social developmental risk factors proximally predicted increases in substance abuse and depressive symptoms. OXTR DNA methylation moderated the effects of contextual stressors on defensive/hostile relational schemas. Findings suggest that early exposures to stress carry forward to affect the development of social developmental risk factors in emerging adulthood, which place rural African American men at risk for increased substance abuse and depressive symptoms during the emerging adult years.