addiction

Co-Occurring Mental and Substance Use Disorders: The Neurobiological Effects of Chronic Stress

ptsd_dual_diagnosis-2

PART 2

PTSD and Substance use Disorders

One of the overarching issues is the question of why substance use and other mental disorders so often co-occur. Are there genetic mediators and/or neurobiological connections between these disorders that drive the comorbidity? Do different psychiatric disorders have differing relationships with various substances of abuse? Better understanding of the connection between substance use disorder and mental illness could have a profound effect on both prevention and treatment. In this blog we focus on PTSD.

PTSD and Substance Use Disorders

The high prevalence of the comorbidity of substance use disorders and PTSD has been reported in a number of studies. Initial reports focused on veterans with PTSD, of whom 64%–84% met the criteria for a lifetime alcohol use disorder and 40%–44% met the criteria for a lifetime drug use disorder, including nicotine dependence (54, 55).

In civilian populations with PTSD, estimates of the lifetime prevalence of substance use disorders range from 22% to 43% (56, 57), far higher than the estimates for substance use disorders in the general population. As in other comorbidities, PTSD and substance use disorders have a number of connecting pathways. Substance intoxication may heighten the likelihood of exposure to trauma, hence the likelihood of developing PTSD.

Furthermore, chronic substance use and withdrawal may increase anxiety/arousal states, making it more likely that individuals with substance use disorders will develop PTSD after trauma exposure. On the other hand, PTSD could increase the risk of developing a substance use disorder, because individuals may abuse substances in an attempt to relieve symptoms of PTSD.

Substance use could also exacerbate symptoms and/or prolong the course of PTSD by preventing habituation to traumatic memories. These pathways are not mutually exclusive, and new evidence is emerging concerning the neurobiological underpinnings of potential causal pathways.

In one recent study (58), individuals who had experienced any trauma and developed PTSD had an increased risk for the development of drug dependence, particularly nicotine dependence, but not alcohol dependence. This finding suggests specificity between substance of abuse and psychopathology.

The HPA axis, extrahypothalamic CRF, and the noradrenergic system are all intimately involved in the stress response, PTSD, and the pathophysiology of substance use disorders. Evidence is accumulating to support a role for CRF in mediating the effects of stress in increasing self-administration of drugs. Studies in rats have also demonstrated that withdrawal from chronic cocaine (59) or alcohol administration (60) in rats is associated with increases in CRF in the hypothalamus, amygdala, and basal forebrain. Elevated CSF CRF has been found in humans during alcohol withdrawal (61). Two studies examining CSF concentrations of CRF have demonstrated higher levels in individuals with PTSD, compared to healthy subjects (62, 63). This finding is of particular interest because elevated brain CRF levels, especially in the amygdala, potentiate fear-related behavioral responses (64).

As such, elevated levels of CRF may mediate both the symptoms of hyperarousal and the increased risk for substance use disorders in PTSD. Increased CRF may enhance the reinforcing properties of some drugs, worsen the severity of withdrawal symptoms, and exacerbate symptoms of PTSD. Evidence implicating abnormalities in noradrenergic systems has been found for both PTSD and substance use disorders. Individuals with PTSD have elevated urinary excretion of both norepinephrine and epinephrine and elevated plasma levels of norepinephrine (65).

Markers of noradrenergic activity are increased in both alcohol and opioid withdrawal (66–68). Brain CRF and noradrenergic systems modulate each other in a number of ways. Stress increases CRF in the locus ceruleus (69), and intraventricular administration of CRF increases norepinephrine turnover in the hypothalamus, hippocampus, and prefrontal cortex (70). In the amygdala, norepinephrine stimulates the release of CRF (71). Koob and colleagues (72, 73) hypothesized that interactions between CRF and the noradrenergic systems can function as a “feed-forward” system, with progressive augmentation of the stress response with repeated stress exposure.

Specifically, substance use or withdrawal or other stress may stimulate CRF release in the locus ceruleus, leading to the release of norepinephrine in the cortex, which would, in turn, stimulate the release of CRF in the hypothalamus and amygdala. This interaction could help to explain the attempt to self-medicate PTSD symptoms with substances of abuse, the worsening of PTSD symptoms during substance withdrawal, and the increase in vulnerability to the development of PTSD in traumatized individuals with substance use disorders. Neuroimaging studies have shed light on the connection between PTSD, other anxiety disorders, and substance use disorders. Amygdala activation occurs during symptom provocation in PTSD, panic disorder, and social phobia (74). As mentioned earlier, increased amygdalar blood flow is also seen in cocaine-dependent individuals presented with cocaine-related cues (50, 75).

Conclusions

Although the nature of the relationship between psychiatric disorders and substance use disorders is complex and multifaceted, there are likely to be unifying constructs. Neuroadaptations in brain stress and reward pathways associated with chronic stress may predispose or unmask a vulnerability to psychiatric disorders, substance use disorders, or both. Dysfunction in the prefrontal cortex and frontal cortex associated with deficits in self-monitoring and behavioral control are evident

Reference

a. Brady, K. T., & Sinha, R. (2005). Co-occurring mental and substance use disorders: the neurobiological effects of chronic stress. American Journal of Psychiatry.

Advertisements

Categories: addiction, co-morbidity, PTSD

Tagged as: , ,

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s