Early Life Stress and Substance Use Disorders: Underlying Neurobiology and Pathways to Adverse Outcomes

Abstract

Early life stress (ELS) has been established as a major risk factor for a multitude of psychiatric and medical disorders. ELS is highly prevalent in the general population and constitutes a major public health concern. The current review will focus on the clinical literature that suggests a link between adverse early life experiences and vulnerability for adolescent and adult substance use disorders. It will investigate the characteristics of ELS that appear to increase risk for disorder onset and a more severe disease course, characterized by earlier onset, greater risk of relapse, and treatment resistance. The authors explore how ELS may increase risk for adverse substance use outcomes through long-lasting changes in the HPA axis and development of stress, reward, and executive control brain systems. The review will also discuss potential pathways to substance use disorder following ELS, with a focus on the role of comorbid mood and anxiety disorders and other modifiable traits. Finally, the authors will discuss how the current body of work presents the potential for prevention and intervention strategies to reduce the psychosocial consequences following early life stress and minimize adverse substance use outcomes.

Anger and substance abuse: a systematic review and meta-analysis

“…The literature reinforces that the simultaneous use of alcohol and cocaine potentiates withdrawal symptoms in the body, including irritation and anger. 38,[75][76][77][78] The main limitation of the cross-sectional design of the included studies is that they did not allow for the determination of different anger profiles and the amount of PSU over time. All possible analyses were carried out between anger and depression, anger and type of psychoactive substances, anger and withdrawal time, anger in men and women, anger and age.…”

Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder

“…Group (FH+ vs. FH−) by total CTQ interactions, covarying sex and age of alcohol initiation, were also modeled with alcohol use measures as the dependent variables. Age of alcohol initiation was included as a covariate because childhood maltreatment is associated with earlier age of alcohol initiation 36 , earlier initiation is associated with greater alcohol use 37 – 39 , and earlier initiation is associated with family history of problematic alcohol and other substance use 40 , which is commonly observed in individuals with familial risk for bipolar disorder. Following a significant interaction, relations between total CTQ and alcohol use were modeled within each group, covarying sex and age of alcohol initiation, to investigate group differences driving a significant interaction.…”

“…ELS also increases risk for substance use disorders (SUDs), including alcohol use disorders (AUDs) 15 , and ELS is associated with higher prevalence of comorbid SUDs in bipolar disorder, compared to prevalence of SUDs in healthy adults 16 . Substance use has been suggested to be an intermediate step between ELS and bipolar disorder 15 , and greater GMV differences following ELS in bipolar disorder may relate to high rates of SUDs in this population 17 , 18 .…”

“…ELS also increases risk for substance use disorders (SUDs), including alcohol use disorders (AUDs) 15 , and ELS is associated with higher prevalence of comorbid SUDs in bipolar disorder, compared to prevalence of SUDs in healthy adults 16 . Substance use has been suggested to be an intermediate step between ELS and bipolar disorder 15 , and greater GMV differences following ELS in bipolar disorder may relate to high rates of SUDs in this population 17 , 18 . Genes that confer risk for bipolar disorder may also increase risk for SUDs 19 , however, it is unknown if familial risk for bipolar disorder interacts with ELS and associated brain changes to contribute to substance use during young adulthood, further structural brain changes following ELS, and ultimately risk for the development of bipolar disorder, SUDs, and their comorbidity.…”

Inaugural Editorial

“…Kirlic, Cohen, & Singh (2020) review interventions targeting behavioral and neurobiological effects of adversity on children and adolescents, applying basic neuroscience research on early life stress to improve the effectiveness of novel and scalable preventive interventions. Kirsch, Nemeroff, & Lippard (2020) discuss the relationship between early life adversity, neurobiological adaptations, and subsequent adolescent and adult substance use disorders, discussing the potential for improved prevention and treatment outcomes by identifying potential pathways involving genetic vulnerabilities associated with mood and anxiety disorders. Teicher, Ohashi, & Khan (2020) extend their previous research on a proposed network model to explain patterns of susceptibility or resilience to childhood adversity (Ohashi, Anderson, Bolger, Khan, McGreenery, & Teicher, 2019), showing that timing, type, and number of adverse experiences are predictive of psychiatric outcomes during late adolescence and early adulthood.…”