Deep Brain Stimulation for Alcoholism

Introduction and Background

Substance-related addictions, including alcohol addiction, constitute the most frequently occurring psychiatric disease category ( ). Half of the world’s population consumes alcohol, and many of these people meet the World Health Organization criteria for high-risk consumption ( ). The 12-month prevalence of alcohol use disorder is 8.5% among adults in the United States, with higher rates among men (12.4%) compared to women (4.9%), and 5.9% of all global deaths are attributable to alcohol. In the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) alcohol use disorder is characterized by a cluster of behavioral and physical symptoms, summarized in four criteria groups ( ).

• 1.

  Impaired control : consumption in larger amounts or for a longer period of time than was intended; persistent unsuccessful efforts to control alcohol use; a lot of time is spent obtaining, using, or recovering from alcohol; and craving or a strong desire or urge to use alcohol.

• 2.

  Social impairment : failure to fulfill obligations due to alcohol consumption; continued consumption despite persistent or recurrent social problems; important social, occupational, or recreational activities may be given up because of alcohol use.

• 3.

  Risky use : alcohol consumption in situations in which it is physically hazardous; continuous consumption despite the knowledge of psychological or physical problems caused by alcohol.

• 4.

  Pharmacological criteria : tolerance defined as a markedly increased amount of alcohol to achieve desired effect or a diminished effect with continued use of the same amount; withdrawal, manifested by either characteristic withdrawal symptoms (autonomic hyperactivity, increased hand tremor, insomnia, nausea, transient visual tactile or auditory hallucinations or illusions, psychomotor agitation, anxiety, or generalized tonic–clonic seizures); or alcohol or a related substance such as a benzodiazepine is taken to relieve or avoid withdrawal symptoms

Risk factors of alcohol use disorder may be environmental, such as the cultural attitude toward drinking, the availability and price of alcohol, or high levels of stress and suboptimal skills of coping with stress, but genetic factors are also involved. The rate of alcohol use disorder is four times higher in close relatives of an affected person compared to the general population. Genetic contributions also evoke neurobiological predispositions, such as high levels of impulsivity or a down-regulated dopaminergic reward system, that are often associated with a pathological consumption of alcohol ( ).

The current treatment options for alcohol use disorders can be divided into two phases: an acute phase with the aim of detoxification, and a chronic phase with the primary aim of relapse prevention. Therapeutic options in the acute phase have fairly good effect sizes and are commonly considered as sufficient (and are not part of this chapter), but treatment strategies to maintain abstinence (mainly pharmacological and psychosocial interventions) are in the long term unsatisfactory. This is mainly reflected in the high number of relapses in alcohol addiction, as with other substance-related addictions ( ). As a result, the alcohol consumption is most often carried on for a lifetime. As it is associated with many harmful socioeconomic and individual effects, new treatment strategies are urgently required. In this context it is appropriate to evaluate and investigate innovative neuromodulative procedures, such as deep brain stimulation (DBS).

In accordance with the aforementioned risk factors, the etiology of addiction to alcohol is multifactorial to a very high degree. Among others, these factors include social and environmental influences, a person’s individual biography, specific personality traits, and neurobiological dispositions. However, from a neuropathophysiological point of view addiction is considered a chronic disease of the brain resulting from genetic determined dysregulations or impaired prioritization within networks that are associated with reward processing, decision making, and habit formation. These dysregulations and impairments can deteriorate even further by the repeated ingestion of psychotropic substances. Overlapping networks of the intrinsic reward system are believed to be responsible for different stages in addiction. First the basal-ganglia-driven network is associated with binge drinking and intoxication. Herein the ascending mesocortico–striatal dopamine system plays a critical role, not only in alcohol addiction but in nearly all addictions to psychotropic substances. Activation of the dopaminergic system in the midbrain is also involved in mechanisms that lead to cue-induced drug seeking, such as incentive salience and conditioned reinforcement. The amygdala plays a key role in the second stage, the withdrawal and negative affect stage, that is among others aspects characterized by emotional stress and a reduction of motivation. During this stage the human brain is less sensitive to natural rewards ( ) due to decreases in dopamine, serotonin, and GABAergic transmission but an increase in glutamatergic activity in the nucleus accumbens (NAc). And third, the prefrontal cortex circuitry is involved in preoccupation and anticipation of the drug and is therefore a key element of relapse in addiction. The prefrontal cortex has glutamatergic projections to the ventral tegmental area (VTA), and thereby activates mesocortical dopaminergic neurons. Also glutamatergic pathways from prefrontal areas activate both direct and indirect pathways of the basal ganglia. Due to these divergent connections the prefrontal cortex modulates incentive salience and is in charge of the executive control to maintain goal-directed behavior. Hence deficits in executive functions, such as inhibitory control and a reactivation of the reward system, lead to acute craving and relapse ( ).

Apparently, in each of these stages the NAc, being a key structure within the reward system, plays a pivotal role. As an essential part of the ventral striatum (the main entry structure of the basal ganglia) the NAc probably fulfills an important integrative or mediating function in discriminating between the different inputs, e.g., limbic and frontocortical projections. This putative regulative function of the NAc is pertinent to several psychiatric disorders, and depends not only on interactions between D ₁ and D ₂ receptor activation, e.g., by way of the dopaminergic projections from the VTA ( ), but also on a D ₁ -associated coactivation of NMDA receptors, thus also involving the glutamatergic system ( ).