Specifying the association between substance abuse and schizophrenia, with a focus on adolescents and young adults

Schizophrenia, a highly impairing disorder, shortens the life expectancy by 15-years and has the highest per-person socioeconomic burden among all psychiatric disorders.

Substance abuse, another serious societal and health challenge, is associated with schizophrenia regardless of its other adverse impacts.

Despite the research progress, the understanding of the association is not specific enough to effectively inform prevention and intervention. Overall, we aim to elucidate the association from specific perspectives to inform intervention and risk identification.

The specific aims are:(When) How is substance abuse across different age groups associated with schizophrenia?(What) How do specific substance categories used in adolescence relate to schizophrenia?(Who) Are there risk subgroups particularly vulnerable to schizophrenia, under adolescent substance abuse?The Swedish population registers will be linked to define the time windows and construct family designs for optimal confounding control in Aim 1.

The Child and Adolescent Twin Study in Sweden (CATSS) documents detailed substance use during adolescence, allowing us to define specific substance categories and assess their impacts on subsequent psychosis in Aim 2.

We will further elucidate causality by using Mendelian Randomization on published genetic findings of schizophrenia and substance abuse.

In Aim 3, we will stratify the CATSS subjects by their genetic burden, measured by family history and genetic risk scores, and evaluate its interactive effect with substance abuse on the outcome of schizophrenia.The proposal targets health challenges with high societal relevance and further emphasize the critical period of adolescence and early adulthood—the most common onset age of both substance abuse and schizophrenia, yet a socially crucial period to establish one’s social roles and prepare for working-life.

This proposal will advance our knowledge by addressing deeper questions on time window (“when”), substance categories (“what”), and risk subgroups (“who”), which will generate specific and practical knowledge to inform targeted intervention and early identification of at-risk individuals.Our team covers the required skillset in psychiatric epidemiology, genetics, and clinics, and the infrastructures are already set up, making the proposal highly feasible.

We plan to supervise a postdoctoral researcher to finish the proposed projects in three years and generate three high-quality publications.