Author: James Anderson

How Does Stress Relate to Drug or Alcohol Abuse?

The above discussion of the primary players (PV, BDNF/TrkB, and glutamate) have on opening and closing sensitive periods should be taken into account for future studies. Work-related stress may include factors such as the demands of the job, the ability to have control over decisions, and the degree of social support within the workplace. People in jobs where they don’t perceive themselves to have a lot of control are susceptible to developing clinical anxiety and depression, as well as stress-related medical conditions like ulcers and diabetes (Marmot, 2006). Effective treatment for addiction provides social support and teaches coping and problem-solving skills to help people reduce and manage their stress during recovery.

Stress and Addiction: When a Robust Stress Response Indicates Resiliency

In addition to its actions on the HPA axis, amphetamine also stimulates adrenergic response as evidenced by increased norepinephrine, blood pressure (Nurnberger et al., 1984), blood pressure (Nurnberger et al., 1984), and heart rate (de Wit et al., 2007). Amphetamine acutely activates the ANS of experienced, but not dependent, methamphetamine users as indexed by the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) (Harris et al., 2006). In summary, these studies confirmed attenuated pain sensitivity in persons at high risk for hypertension, but they did not support a role for the EOS nor for enhanced baroreceptor activation as explanatory mechanisms for the hypoalgesia observed in hypertension-prone individuals. In light of the earlier observations that this group exhibits stress-response dysregulation, we speculated that alterations within the stress response systems could contribute to pain alteration in this population. The Romanian orphan study is a superb example of how children with a significant history of early life stress (Johnson et al., 1992) show low cortisol levels, ADHD, and peer difficulties and have fewer problems when placed into foster home (Pitula et al., 2017). Rodent studies have shown that different levels of social buffering are evident in differences in maternal care.

In both humans and animals, deficits in executive function including the regulation of affect and reward are involved in risk behaviors. Behaviors such as aggression, impulsivity, and poor social function are risk factors for increased substance use and are found in both humans and animals following exposure to early adversity. The inter-relationship between risk behaviors and substance use has been characterized more in association studies in humans than in animals. Animal studies have examined the developmental expression of risk behaviors in early stress models; the relationship between stress, early expression of risk factors and subsequent drug use is sorely missing. Understanding how different forms of abuse (physical, sexual, or neglect) or its duration influence risk behavior and subsequent drug-taking may offer insight for preventative treatment. Thus, we performed a subsequent study to examine HPA responses to stress following the first 24 hours of a quit attempt in predicting relapse over a four-week period (198).

2. Drug-related factors influencing stress responses

Salivary cortisol levels and mood reports were assessed during the evening and morning over 24 hours of ad libitum smoking and during the first 24 hours of abstinence. Not surprisingly, participants reported significant withdrawal symptoms on the first day that they were abstinent. Smokers who relapsed during the first week of abstinence reported greater craving for cigarettes and greater overall distress during the first 24-hour period of abstinence than those who maintained abstinence over the same period. Though all participants showed the expected diurnal changes in cortisol levels, smokers who relapsed within the first week of the quit attempt exhibited a greater decline in cortisol levels on the abstinence day compared to the ad libitum day.

1. Relatedly, dopamine (Flagel et al.),2010) and opiate changes (Ploj et al., 2003) following maternal separation are reviewed.
2. Through structural equation modeling, the associations between the age of maltreatment and morphometric MRI changes were determined and believed to reflect times when the region is most sensitive to exposure to adversity (Andersen et al., 2008; Pechtel et al., 2014).
3. Depending on the nature of the stressor (physical, cognitive) and duration of stress exposure, there could be a need to mobilize energy and acute inflammation toward host defense and physical survival processes (30, 31, 34).
4. A well-established literature of arousal and motivation exists, whereby individuals are motivated to seek an optimal level of arousal (Yerkes-Dodson) and emotional arousal enhances perception of salient information; arousal also heightens the ability to learn (Berlyne, 1969).

Stress and the role of externalizing and internalizing behaviors in addiction

To succeed in long-term sobriety, it is important to properly manage stress and avoid the people, places and situations that may lead to relapse. Trauma in early childhood is a key factor for making people more vulnerable in later life (Keating, 2017). High levels of stress experienced in early life can cause methylation of key genes that control the stress system. Fight-or-flight is a normal response to stress; all the blood goes to the muscles so that you’re ready for action.

1. The role of GABA and BDNF in externalizing and internalizing behaviors

Their addictive behavior is the result of their experiences and the environments in which they were brought up. In fact, some individuals, like sensation-seekers, chase “stressful” situations that promote the release of stress hormones. However, intense, unpredictable, prolonged stressors,—such as interpersonal conflict, loss of loved ones, and unemployment—can produce learned helplessness and depressive-like symptoms. Chronic stress increases the risk for developing depression, the common cold, influenza, tension headaches, grinding teeth, and tensing the neck and shoulders (McEwen, 2003). Stress is a key risk factor in addiction initiation, maintenance, relapse, and thus treatment failure (Sinha & Jastreboff, 2013). Stressful life events combined with poor coping skills may impact the risk of addiction by increasing impulsive responding and self-medication.

(C) Based on research evidence, a schematic of the disruptions in the adaptive stress response phases with chronic repeated stress and with early-life stress/childhood maltreatment. The second mechanism that we examined to explain hypoalgesia in hypertension-prone individuals was a blunting of normal opioidergic inhibitory regulation of hypothalamic activities. This work was based on previous opioid blockade research (118–120); therefore, we examined the effect of opiate blockade on HPA responses to a painful stressor in individuals with and without a parental history of hypertension. In this research, we used a double-blind, counterbalanced design to administer the blockade (placebo or naltrexone) prior to assessing nociceptive flexion reflex threshold.

Finally, reducing glutamatergic activity with treatment with adinazolam and MK-801, but not by augmenting serotonin activity with tianeptine (Leussis et al., 2008) was shown to reduce the effects of a social stressor in rats (see Fig. 1, Fig. 2). By adulthood, females have more PV neurons in the amygdala and medial prefrontal cortex than males (Rowniak et al., 2015; Wischhof et al., 2015). ERβ receptors co-localize exclusively on PV neurons in layer V in PFC (Blurton-Jones and Tuszynski, 2002; Kritzer, 2002), with less expression of ERα on BDNF containing neurons (Blurton-Jones and Tuszynski, 2006). Estrogen increases general neuronal loss between puberty (P35) and adulthood (P90) in the prefrontal cortex of rats (Juraska and Markham, 2004; Markham et al., 2007). Intracellular androgen receptors are neither detected on PV neurons nor are PV neurons affected by gonadectomy in males; instead androgen receptors are predominantly localized to pyramidal cells in the PFC (Kritzer, 2004).

Furthermore, this review covers the most commonly used drugs of nicotine, alcohol, cannabis, psychostimulants (i.e., cocaine and amphetamines), and opioids. Can the stress pathophysiology of addiction risk and relapse be targeted to restore the adaptive stress response for normal, healthy reward via social, cognitive, and behavioral coping in order to reduce drug intake and relapse and improve treatment outcomes? Research is underway to address this question, with the goal of normalizing adaptive stress response processes and improving SUD treatment outcomes. There are two specific considerations in developing interventions to target the stress pathophysiology of addiction. First, whereas there are multilevel disruptions in stress responses that encompass this pathophysiology, genetic, demographic, and clinical moderators may influence the magnitude and profile of stress pathophysiology of addiction that contribute to the significant heterogeneity discussed below. These moderators are listed in Table 3 (top) and may vary by the specific type of SUD being targeted and the specific phase of the addiction risk cycle.

These biobehavioral disruptions related to SUD processes and outcomes have jointly been characterized as the “stress pathophysiology of addiction” (114), and the specific predictors in prevention, intervention, and treatment are listed in Table 2. The next section describes three specific types of high, repeated, and chronic levels of stress that can overwhelm the exquisitely wired adaptive stress response system with substantial, sustained disruption of the dynamic flexible responses. This disruption can change the basal subjective state and physiologic tone, the phasic stress response, as well as the stress recovery phase without a return to homeostasis, as discussed in previous psychosocial and psychobiological stress adaptation models (43, 44) and illustrated in Figure 1, C and D. Substance use disorders (SUDs) incur a significant burden to society in the United States and worldwide.

Here, we posit that a pre-existing condition of inflammation due to early life stress will increase the vulnerability to develop as substance use disorder (Frank et al., 2011). The timing of stress exposure interacts with a sensitive period to uniquely effect behavior (Andersen and Teicher, 2008b). Experiences that occur during a sensitive period will have maximal effect on regional brain development to fine-tune neuronal circuits (Andersen, 2003; Greenough et al., 1987). Sensitive periods differ from critical periods, which require specific information to guide development (Greenough et al., 1987). The limited time course of development of ocular dominance columns is a classic example of a critical period (Lensjo et al., 2017). Alternatively, sensitive periods may represent a critical period that occurs during the second phase of synaptic overproduction and elimination.