Why Do Drug Use Disorders Often
Co-Occur With Other Mental Illnesses?
The high prevalence of comorbidity between drug use disorders and other mental illnesses does not mean that
one caused the other, even if it appeared first. In fact, establishing causality or directionality is difficult for several reasons. Some symptoms of a mental disorder may not be recognized until the illness has substantially progressed, and imperfect recollections of when drug use/abuse started can also present
timing issues. Still, three scenarios
- Drugs of abuse can cause abusers to experience one or more symptoms of another mental illness. The increased risk of psychosis in some marijuana abusers has been offered as evidence for this possibility.
- Mental illnesses can lead to drug abuse. Individuals with overt, mild, or even subclinical mental disorders may abuse drugs as a form of self-medication. For example, the use of tobacco products by patients with schizophrenia is believed to lessen the symptoms of the disease and improve cognition ("Smoking and Schizophrenia: Self-Medication or Shared Brain Circuitry?").
- Both drug use disorders and other mental illnesses are caused by overlapping
factors such as underlying brain deficits, genetic vulnerabilities, and/or early exposure to stress or trauma.
All three scenarios probably
contribute, in varying degrees, to how
and whether specific comorbidities manifest themselves.
Overlapping Conditions– Shared Vulnerability
High Prevalence of Drug Abuse and Dependence Among Individuals With Mood and Anxiety Disorders
High Prevalence of Mental Disorders Among Patients With Drug Use Disorders
Higher Prevalence Smoking Among Patients With Mental Disorders
Because mood disorders increase vulnerability to drug abuse and addiction, the diagnosis and treatment
of the mood disorder
can reduce the risk of subsequent drug use. Because the inverse may also be true, the diagnosis and treatment of drug use disorders may reduce the risk of developing other mental illnesses and, if they do occur, lessen their severity or make them more amenable to effective
treatment. Finally, because more than 40 percent of the cigarettes smoked in this country are smoked by individuals with a psychiatric disorder, such as major depressive disorder; alcoholism; post-traumatic stress disorder (PTSD); schizophrenia; or bipolar disorder, smoking by patients with mental
illness contributes greatly to their increased morbidity
Overlapping Genetic Vulnerabilities.
A particularly active area
of comorbidity research involves
the search for genes that might
predispose individuals to develop
both addiction and other mental
illnesses, or to have a greater risk
of a second disorder occurring after
the first appears. It is estimated that
40-60 percent of an individual's
vulnerability to addiction is attributable
to genetics; most of this
vulnerability arises from complex
interactions among multiple genes
and from genetic interactions with
environmental influences. In some
instances, a gene product may act
directly, as when a protein influences
how a person responds to a
drug (e.g., whether the drug experience
is pleasurable or not) or how
long a drug remains in the body.
But genes can also act indirectly by
altering how an individual responds
to stress or by increasing the likelihood
of risk-taking and novelty-seeking
behaviors, which could
influence the development of both
drug use disorders and other mental
illnesses. Several regions of the human
genome have been linked to
increased risk of both, including associations
with greater vulnerability
to adolescent drug dependence and
The rate of smoking
in patients with
ranged as high as
Involvement of Similar Brain
Regions. Some areas of the brain
are affected by both drug use disorders
and other mental illnesses.
For example, the circuits in the
brain that use the neurotransmitter
dopamine–a chemical that carries
messages from one neuron to another–
are typically affected by addictive
substances and may also be
involved in depression, schizophrenia,
and other psychiatric disorders.
Indeed, some antidepressants and essentially all antipsychotic medications
target the regulation of dopamine in this system directly, whereas others may have indirect effects. Importantly, dopamine pathways have also been implicated
in the way in which stress can increase vulnerability to drug addiction. Stress is also a known risk factor for a range of mental disorders and therefore provides one likely common neurobiological link between the disease processes of addiction and those of other mental disorders.
The overlap of brain areas involved
in both drug use disorders and other mental illnesses suggests
that brain changes stemming from one may affect the other. For example, drug abuse that precedes the first symptoms of a mental illness may produce changes in brain structure and function that kindle an underlying propensity to develop that mental illness. If the mental disorder develops first, associated changes in brain activity
may increase the vulnerability to abusing substances by enhancing
their positive effects, reducing awareness of their negative effects, or alleviating the unpleasant
effects associated with the mental disorder or the medication used to treat it.
Smoking and Schizophrenia: Self-
Medication or Shared Brain Circuitry?
Patients with schizophrenia have higher rates of alcohol, tobacco,
and other drug abuse than the general population. Based on nationally
representative survey data, 41 percent of respondents with past-month
mental illnesses are current smokers, which is about double the rate of
those with no mental illness. In clinical samples, the rate of smoking in
patients with schizophrenia has ranged as high as 90 percent.
Various self-medication hypotheses have been proposed to explain
the strong association between schizophrenia and smoking, although
none have yet been confirmed. Most of these relate to the nicotine
contained in tobacco products: Nicotine may help compensate for
some of the cognitive impairments produced by the disorder and may
counteract psychotic symptoms or alleviate unpleasant side effects of
antipsychotic medications. Nicotine or smoking behavior may also help
people with schizophrenia deal with the anxiety and social stigma of
Research on how both nicotine and schizophrenia affect the brain has
generated other possible explanations for the high rate of smoking
among people with schizophrenia: The presence of abnormalities in
particular circuits of the brain may predispose individuals to schizophrenia;
increase the rewarding effects of drugs like nicotine; or reduce
an individual's ability to quit smoking. The involvement of common
mechanisms is consistent with the observation that both nicotine and
the medication clozapine (which also acts at nicotine receptors) can
improve attention and working memory in an animal model of
schizophrenia. Clozapine is effective in treating individuals with schizophrenia.
It also reduces their smoking levels. Understanding how and
why patients with schizophrenia use nicotine is likely to help us develop
new treatments for both schizophrenia and nicotine dependence.
The Influence of Developmental Stage
Adolescence–A Vulnerable Time. Although drug abuse and addiction can happen at any time during a person's life, drug use typically starts in adolescence, a period when the first signs of mental illness commonly appear. It is therefore not surprising that comorbid disorders can already be seen among youth. Significant changes in the brain occur during adolescence, which may enhance vulnerability to drug use and the development of addiction and other mental disorders. Drugs of abuse affect brain circuits involved in reward, decisionmaking, learning and memory, and behavioral control, all of which are still maturing into early adulthood. Thus, understanding the long-term impact of early drug exposure is a critical area of comorbidity research.
The brain continues to develop into adulthood and undergoes dramatic changes during adolescence.
One of the brain areas still maturing during adolescence is the prefrontal cortex– the part of the brain that enables us to assess situations, make sound decisions, and keep our emotions and desires under control. The fact that this critical part of an adolescent's brain is still a work in progress puts them at increased risk for poor decisions (such as trying drugs or continuing abuse). Thus, introducing drugs while the brain is still developing
may have profound and long-lasting consequences.
The high rate of comorbidity between drug abuse and addiction and other mental disorders argues for a comprehensive approach to intervention that identifies, evaluates, and treats each disorder concurrently.
Early Occurrence Increases Later Risk. Strong evidence has emerged showing early drug use to be a risk factor for later substance abuse problems; additional findings
suggest that it may also be a risk factor for the later occurrence of other mental illnesses. However,
this link is not necessarily a simple one and may hinge upon genetic vulnerability, psychosocial experiences, and/or general environmental
influences. A recent study highlights this complexity, with the finding that frequent
marijuana use during adolescence can increase the risk of psychosis in adulthood, but only in individuals
who carry a particular gene variant (see sidebar, "The Influence
of Adolescent Marijuana Use on Adult Psychosis Is Affected by
The Influence of Adolescent Marijuana Use on Adult Psychosis Is Affected by Genetic Variables
Percentage of Individuals Meeting Diagnostic Criteria for Schizophreniform Disorder at Age 26
The above figure shows that variations in a gene can affect the likelihood of developing psychosis in adulthood following exposure to cannabis. The Catechol-O-Methyltransferase gene regulates an enzyme that breaks down dopamine, a brain chemical involved in schizophrenia. It comes in two forms: Met and Val. Individuals with one or two copies of the Val
variant have a higher risk of developing schizophrenic-type disorders if they used cannabis during adolescence (dark bars). Those with only the Met variant were unaffected by cannabis use. These findings hint at the complexity of factors that contribute to comorbid conditions; however, more research is needed.
It is also true that having a mental disorder in childhood or adolescence can increase the risk of later drug abuse problems,
as frequently occurs with conduct disorder and untreated attention-deficit hyperactivity disorder (ADHD). This presents a challenge when treating children with ADHD, since effective treatment
often involves prescribing stimulant medications with abuse potential. This issue has generated strong interest from the research community, and although the results
are not yet conclusive, most studies suggest that ADHD medications
do not increase the risk of drug abuse among children with ADHD ("Childhood ADHD and Later Drug Problems").
Regardless of how comorbidity develops, it is common in youth as well as adults. Given the high prevalence of comorbid mental disorders and their likely adverse
impact on substance abuse treatment outcomes, drug abuse programs for adolescents should include screening and, if needed, treatment for comorbid mental disorders.