Notes on Substance-Related Disorders and Their Causes

Substance-Related Disorders: Causes and Prevention

  • Discussion on the causes of substance-related disorders and prevention strategies.

Biological Risk Factors for Substance-Related Disorders

  • Biological risk factors include:
    • Genetics
    • Brain features
    • Neurochemical characteristics

Genetics

  • Genetics has a significant influence on substance-related disorders, especially alcoholism.
    • Heritability estimate for alcoholism is approximately 0.49 (Source: Verhulst, Neale, & Kendler, 2015).
    • Family studies indicate:
    • Individuals with family members who overuse alcohol are 3 to 4 times more likely to misuse alcohol themselves compared to those without such family history.
      • Note: Environmental influences may also contribute to these findings, as children might model parental behavior rather than inherit a genetic predisposition.
    • Genetic influences are generally stronger in:
    • Males than females.
    • Severe cases of alcoholism compared to less severe cases.
    • Alcoholism is likely influenced by multiple genes working together (Sources: Nieratschker, Batra, & Fallgatter, 2013; Schuckit, 2014b).
    • Variants related to alcohol metabolism can lead to differences in processing speed.
    • Some individuals metabolize alcohol faster, making them less susceptible to alcoholism (Source: Rietschel & Treutlein, 2013).
    • Sensitivity to alcohol: Genetics can also affect the low level of response to alcohol, predicting alcoholism risk in offspring.
    • Individuals with a low response require greater quantities of alcohol to achieve the desired psychological effects, increasing their risk for alcoholism (Source: Schuckit, 2014b).
    • Genetics may also influence neurochemistry, affecting cravings or increasing disinhibition when alcohol is consumed (refer to neurochemical section later).

Other Substances

  • The heritability of dependence appears strongest for:
    • Cocaine
    • Opiates, including heroin and prescription painkillers (e.g., OxyContin) (Source: Bryant, Guido, Kole, & Cheng, 2014).
    • Relatives of individuals with substance-related disorders are found to be 8 times more likely to exhibit a substance-related disorder themselves, particularly for opiates and cocaine, but also for marijuana.
    • Multiple genes are likely responsible for this risk (Source: Merikangas & McClair, 2012).
    • Genes may:
    • Influence responsiveness to drugs, such as opiate receptors (Source: Bruchas & Roth, 2016).
    • Affect the development of brain structures associated with substance-related disorders.

Brain Features Related to Substance-Related Disorders

  • Various brain features are linked to substance-related disorders, influencing compulsive drug use through:
    • Priming
    • Drug cues
    • Cravings
    • Stress triggers (Source: Hone-Blanchet, Ciraulo, Pascual-Leone, & Fecteau, 2015).

Definitions:

  • Priming: A situation where a drug dose (e.g., a drink of alcohol or a line of cocaine) triggers uncontrollable binge use.

  • Drug cues: Stimuli related to drug use, such as friends or specific settings that can induce further use.

  • Cravings: An obsessive drive for drug use, significantly impacting life activities.

  • Stress: A common trigger for relapse in individuals with substance-related disorders, often linked to anxiety and depression.

  • The mesolimbic system, a major dopamine pathway, plays a significant role in reward, pleasure, and desire, linking this system to substance use.

    • Starts in the brain's ventral tegmental area and ends in the nucleus accumbens (referencing Figure 9.7).
    • Drugs like crack cocaine stimulate this pathway, leading to priming and intense cravings (Source: Areal et al., 2015).
    • Continued use can become associated with specific cues, promoting addiction (Source: Volkow, Wang, Fowler, & Tomasi, 2015).

Additional Brain Areas Implicated in Addiction

  • The mesolimbic pathway interacts with other critical brain structures, including:
    • Amygdala: Assigns a high reward value to stimuli such as drugs.
    • Plays a role in stress-driven drug-seeking behavior and conditioning of preferences for drug use location.
    • Anterior cingulate: Involved in self-control and problem-solving, particularly relevant to excessive focus on certain drugs (Source: Marhe et al., 2013).
    • Bed nucleus of the stria terminalis: Involved in stress responses, impacting drug-seeking behavior as a coping mechanism (Source: Stamatakis et al., 2014).
    • Hippocampus: Critical for acquiring new information and memories, potentially storing strong memories associated with drug use (Source: Han et al., 2015).
    • Insula: Involved in pain processing and linked to drug cravings (Source: Droutman et al., 2015).
    • Prefrontal cortex: Involved in high-level cognitive processes, regulating behavior, which may be impaired by drug use.
    • Can strongly react to cues predicting drug availability (Source: Jasinska et al., 2015).
    • Orbitofrontal cortex: Associated with decision-making in uncertain situations, where drug-induced changes may lead to impulsive behavior (Source: Smith et al., 2015).

Neuroimaging Studies and Substance Use

  • Neuroimaging provides visual evidence of the effects of excessive substance use on the brain:
    • Reduced blood flow to the prefrontal cortex in individuals with a history of excessive cocaine use reveals diminished metabolic activity in substance users compared to controls.
    • This reduction often leads to a lack of engagement in higher cognitive functions while intoxicated.
    • Conversely, this area is highly stimulated when cues predicting drug availability are present, influenced by the connection to the mesolimbic system and nucleus accumbens.
    • Because of these changes, substance users may prioritize drugs over other stimuli, impacting their ability to regulate consumption (Source: Volkow et al., 2015).

Brain Size and Cognitive Decline

  • Prolonged substance use is linked to:
    • Reduced brain size.
    • Altered brain activity.
    • Lead to cognitive and memory decline beyond the normal aging process (Source: Crunelle et al., 2014).
    • This reduced brain size is also associated with other cognitive disorders, including:
    • Psychotic disorders (Chapter 12)
    • Alzheimer's disease (Chapter 14)
    • Chronic alcohol abuse can result in further cognitive decline, impacting motor function, vision, and speech abilities.