Table 2.

Summary of overarching mechanistic concepts, the environmental risk factors and signs that tie into them and the mechanistic pathways that lead to psychotic symptomatology.

Overarching mechanistic concept	Environmental risk factors/signs	Mechanistic pathways
Neurodevelopmental Abnormalities	•Impaired olfactory identification ability •Minor physical anomalies •Non-right handedness •Obstetric complications •Low premorbid intelligence	•Genes > Altered brain development > DA abnormalities & E/I imbalance •Infection > Inflammation > Altered brain development > DA abnormalities & E/I imbalance
Infection and the immune system	•Toxoplasma gondii •Winter/spring season of birth	•Infection > Inflammation > Altered brain development > DA abnormalities & E/I imbalance
Psychosocial Stress	•Childhood trauma •Ethnicity and ethnic density •Migrant status •Stressful life events •Urbanicity	•Psychosocial stress > HPA axis > Inflammation > Brain structure and function > DA abnormalities & E/I imbalance
Substance use	•Cannabis use	•Endocannabinoid system modulation > DA abnormalities & E/I imbalance
DA abnormalities	•Trait anhedonia	•DA abnormalities > Trait anhedonia
E/I imbalance	•Childhood social withdrawal	•E/I imbalance > Childhood social withdrawal
All above	•CHR-P state	•All above

Abbreviations: CHR-P, clinical high risk for psychosis; DA, dopaminergic; E/I, excitation/inhibition; HPA, hypothalamic-pituitary-adrenal