The neural, behavioral, and epidemiological underpinnings of comorbid alcohol use disorder and post-traumatic stress disorder

Abstract

Alcohol use disorder (AUD) and (PTSD) frequently co-occur and individuals suffering from this dual diagnosis often exhibit increased symptom severity and poorer treatment outcomes than those with only one of these diseases. Although there have been significant advances in our understanding of the neurobiological mechanisms underlying each of these disorders, the neural underpinnings of the comorbid condition remain poorly understood. This chapter summarizes recent epidemiological findings on comorbid AUD and PTSD, with a focus on vulnerable populations, the temporal relationship between these disorders, and the clinical consequences associated with the dual diagnosis. We then review animal models of the comorbid condition and emerging human and non-human animal research that is beginning to identify maladaptive neural changes common to both disorders, primarily involving functional changes in brain reward and stress networks. We end by proposing a neural framework, based on the emerging field of affective valence encoding, that may better explain the epidemiological and neural findings on AUD and PTSD.

Keywords: Alcohol use disorder; Amygdala; Animal models; Functional connectivity; Post-traumatic stress disorder; Prefrontal cortex; Reward circuit; Salience network; Stress circuit; Valence network.

Fig. 1

Brain reward and stress circuitry in the human brain. Diagrammatic illustration of the predominant brain regions and circuits generally though to mediate the processing of reward (green) and stress/fear (red) in the human brain. The nucleus accumbens (NAc) is usually featured as the central node of reward circuit diagrams, which also typically include the DAergic input from the VTA and excitatory input from other limbic structures, like the anterior hippocampus (aHPC). The stress circuit is generally centered around the basolateral AMY (BLA) which has dense, and often reciprocal connectivity with numerous cortical structures including the medial prefrontal cortex, anterior cingulate cortex, insula, the thalamus and aHC as well as nodes of the extended amygdala (CEA, BNST). Illustrated by dashed lines are some of the many additional connections that link elements of both the reward and stress networks that are often omitted from these circuit diagrams.

Fig. 2

Using a human valence network model to visualize the primary alterations in functional connectivity that are common to AUD and PTSD. (A) The major cortical and subcortical brain regions and functional connections involved in assigning a degree of positivity or negativity to all sensory and emotional stimuli, encoding the salience of this input, and orchestrating appropriate behavioral and cognitive responses to this information. (B) Illustration of major maladaptive alterations in valence network connectivity common to both AUD and PTSD, based primarily on data from human functional neuroimaging studies. These changes include an increase in BLA excitability driven, in part, by decreased mPFC and ACC connectivity (thinner line), and increased insula connectivity to this brain region (thicker line).