Acute and Lifetime Stress and Psychotic Illness: The Roles of Reward and Salience Networks

Abstract

Affective reactions to acute stressors often evoke exacerbations of psychotic symptoms and sometimes de novo psychotic symptoms and initial psychotic episodes. Across the lifespan, affective reactions to acute stressors are enhanced by successive adverse childhood experiences (ACEs), in a process called "behavioral sensitization". The net effects of behavioral sensitization of acute stress responses are to alter responsivity to positive and negative feedback and to unexpected events, regardless of valence, leading to the maladaptive assignment of salience to stimuli and events. The assignment of "aberrant" salience to stimuli and events has profound consequences for learning and decision-making, which can influence both the positive and negative symptoms of psychosis. In this review, we discuss some of the psychological and neural mechanisms by which affective reactivity to acute stress, and its sensitization through the experience of stress and trauma across the lifespan, impact both the positive and negative symptoms of psychosis. We recount how the reward and salience networks of the brain, together with inputs from the dopamine and serotonin neurotransmitter systems, are implicated in both affective reactivity to stress and the symptoms of psychosis, likely mediate the effects of stress and trauma on the symptoms of psychosis and could serve as targets for interventions.

Keywords: affective reactivity; dopamine; insula; prediction error; reinforcement learning; sensitization; serotonin; striatum.

Figure 1.

The hypothalamic-pituitary-adrenal (HPA) axis. The release of corticotropin-releasing factor (CRF) by the hypothalamus promotes release of adrenocorticotrophic hormone (ACTH) by the pituitary gland, which, in turn, signals the adrenal glands to begin releasing glucocorticoids into the blood. Glucocorticoids (such as cortisol) travel via the bloodstream and attach to glucocorticoid receptors in the brain. The hippocampus and amygdala can, in turn, influence the activity of the hypothalamus. Adapted from Hyman [56], with permission copyright ©2009 Springer Nature.

Figure 2.

Nodes of the Salience and Reward Networks. (A) Salience network: anterior insula, dorsal pregenual anterior cingulate cortex (dorsal pgACC), anterior mid cingulate cortex (aMCC). Reward network: hypothalamus, orbitofrontal cortex (OFC), the ventral striatum (VS), including the nucleus accumbens and ventral putamen, ventral tegmental area (VTA), substantia nigra, midbrain regions (caudate, pallidum). As Haber and Knutson (2010) have noted, other structures including the amygdala, hippocampus, lateral habenular (LHb) nucleus, and brainstem structures, such as the pedunculopontine nucleus and the raphe nuclei, play key roles in regulating the reward network. (B) Adapted from Gupta et al. [57], with permission copyright © 2015 Elsevier.

Figure 3.

Tract tracing studies have shown that striatocortical connections run in three parallel pathways. Motor areas project to the caudal putamen; dorsolateral prefrontal cortex to caudate and rostral putamen; and limbic areas to the ventral (limbic) striatum. These subdivisions have been termed the sensorimotor, associative, and ventral (limbic) striatum. The ventral tegmental area and medial substantia nigra (SN) project primarily to limbic striatum, while central/ventrolateral parts of the SN project to the associative and sensorimotor striatum. Striatal efferents projecting back to the midbrain. In addition to these reciprocal connections, feedforward striato-nigro-striatal connections allow information to pass along the striatum from limbic to motor regions via the associative striatum. Adapted from McCutcheon et al. [27], an open access article distributed under the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

Figure 4.

Adverse Childhood Experiences (ACEs) act through sensitization of dopamine systems to impact sensitivity to stressors, punishments, and rewards and the attribution of salience to events (which range from mundane to biologically-important). Conversion to psychotic illness and the expression of psychotic symptoms are influenced by affective reactivity to stimuli and events and the attribution of salience to these stimuli and events. Negative symptoms may emerge as a consequence of noisy dopamine signaling, if (1) people attribute insufficient motivational salience to biologically-important stimuli and events, or if (2) reductions in prefrontal cortical activity levels are associated with striatal hyperactivity, leading to deficits in reward sensitivity, motivation, and decision-making. Some negative symptoms in psychotic illness may result from mechanisms separate from sensitization of dopamine systems, as growing evidence suggests that negative symptoms are more closely tied to neglect and deprivation in childhood/adolescent, whereas positive symptoms are more closely tied to abuse.