A History of Trauma is Associated with Aggression, Depression, Non-Suicidal Self-Injury Behavior, and Suicide Ideation in First-Episode Psychosis.

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms-such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior-for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) and a history of trauma, we need to understand the impact of trauma on their whole presentation. FEP participants were recruited from an Early Psychosis Program (N = 187, ages 12-35, 72.2% male). Clinicians gathered history of trauma, aggression, and suicide data, and rated current symptom severity and functioning. Data was coded using clinician rated measures, self-report measures, and retrospective clinical chart review. Regression analyses examined whether trauma was associated with a history of aggression, suicidal ideation, suicide behavior, NSSIB, symptoms, and functioning. Trauma was associated with aggression, aggression severity and type of aggression (aggression towards others). Trauma was also associated with depression severity, suicide ideation, most severe suicide ideation, and NSSIB. Trauma was not associated with suicide behavior, severity of suicide behavior or psychosocial functioning. Integrating trauma treatment into FEP care could reduce rates of depression, aggression, suicide ideation, and NSSIB for those with a history of trauma. To reduce suicide attempt occurrence and improve functioning, more research is needed

Uncharted Waters: Treating Trauma Symptoms in the Context of Early Psychosis.

Psychosis is conceptualized in a neurodevelopmental vulnerability-stress framework, and childhood trauma is one environmental factor that can lead to psychotic symptoms and the development of psychotic disorders. Higher rates of trauma are associated with higher psychosis risk and greater symptom frequency and severity, resulting in increased hospitalization rates and demand on outpatient primary care and mental health services. Despite an estimated 70% of individuals in the early stages of psychosis reporting a history of experiencing traumatic events, trauma effects (post-traumatic anxiety or depressive symptoms) are often overlooked in psychosis treatment and current interventions typically do not target commonly comorbid post-traumatic stress symptoms. We presented a protocol for Trauma-Integrated Cognitive Behavioral Therapy for Psychosis (TI-CBTp), an approach to treating post-traumatic stress symptoms in the context of early psychosis care. We provided a brief summary of TI-CBTp as implemented in the context of Coordinated Specialty Care and presented preliminary data supporting the use of TI-CBTp in early psychosis care. The preliminary results suggest that individuals with comorbid psychosis and post-traumatic stress symptoms can be appropriately and safely treated using TI-CBTp within Coordinated Specialty Care

A Novel Role for the Periaqueductal Gray in Consummatory Behavior

The periaqueductal gray (PAG) has a well-established role in pain processing, autonomic function and behavioral responses to fear. Anatomical work suggests the PAG may mediate food intake and reward processing as it has extensive reciprocal connections within brain circuits that mediate appetitive processes and consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala, parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005). Therefore, we investigated if the PAG of hungry rats has a functional role in appetitive and consummatory behaviors. To address this, PAG was pharmacologically inactivated during a spatial working memory task with muscimol (0.1–0.3 μg), a GABAA agonist via intracranial infusion. Inactivation of PAG led to reduced intake of food rewards and increased errors on this task. To focus on the specific effects PAG inactivation had on food consumption, PAG was inactivated during two separate food intake tasks in a separate group of rats. Again, PAG inactivation resulted in a significant decrease in food consumption, as well as an increased latency to consume food. We next investigated PAG neural responses to reward encounters. A different group of rats performed the same task used in Experiment 1 while the in vivo activity of PAG neurons was recorded. In a subset of PAG neurons, reward encounters elicited phasic excitation. A separate subset of PAG neurons were inhibited during reward encounters. These responses scaled with the size of the reward, with sustained excitation or inhibition in response to large rewards compared to small. Our data also show that separate groups of PAG neurons in awake behaving animals display either increased and decreased neural responses to reward encounters. Additionally, a proportion of neurons were modulated by the animals’ velocity. This study is the first to show that PAG neurons process reward-related information, perhaps to mediate consummatory behaviors related to food consumption

Investigating the Contributions of Hippocampal Memory and Reward Valuation Systems to Cost-Benefit Decision Making

Thesis (Ph.D.)--University of Washington, 2017-06The hippocampus has for many decades been thought of as an essential brain region for learning about new events, often described in terms of the contexts within which particular associations, actions and outcomes occur. However, little is understood about how hippocampal context analyses impact downstream decision processes. Comparison of current events to past experiences influences our evaluation of salient stimuli, allows memory to serve a prospective organizational function, and the use of past experiences to guide current decision making processes is essential for optimal decision making. However, we know that it is rare to observe phasic neural responses to rewards, or to cues that predict rewards, by hippocampal cells in the same way that we would observe in other neurons, such as ventral tegmental area (VTA) dopamine neurons. Therefore, we sought to understand how reward and value information was represented at the level of hippocampal processing during complex decision making. To do this, we recorded hippocampal neural activity while rats performed a complex decision-making task: a maze based probability discounting task. We assessed whether the hippocampal neurons would differentiate the context based on dynamic reward contingencies. In addition, we compared timing of these changing neural representations to VTA dopamine neural processing on the same task as they are functionally and anatomically connected to the hippocampus. It is important to understand how brain regions in decision-relevant circuits process goal relevant stimuli differentially that can feed into memory representations of what is and isn’t salient. Our first region of interest was the periaqueductal gray (PAG) as it has previously been demonstrated that it is anatomically connected to the VTA. This connection may provide a modulatory effect over the functional loop of the VTA-hippocampus by which behavior, learning, and memory mediated by the VTA are influenced by information processed in the PAG. However, it has not previously been demonstrated that the PAG encodes rewarding stimuli. Therefore, another one of the aims of this dissertation is to ascertain whether PAG neurons encode appetitive stimuli. To do this, we recorded the in-vivo activity of PAG neurons while rats performed a differential-reward working memory task. Lastly, another goal of the current dissertation was to try to assess how these decision-making and memory functions may be affected with age. It is thought that age-related decline in separate neural systems occurs independently from each other. However, because the hippocampus is so intricately linked within a circuit that processes rewards and is essential to differentiating contexts, a functional decline in the hippocampus over time may impact decision making. Therefore, we examined the relationship between declines in spatial working memory performance and changes in risky decision making in aged rats and young controls. Additionally, we wanted to assess if observed changes in risk-based decision making behavior was linked to a functional decline in VTA neural processes on rewards and reward-relevant stimuli

A Novel Role for the Periaqueductal Gray in Consummatory Behavior.

The periaqueductal gray (PAG) has a well-established role in pain processing, autonomic function and behavioral responses to fear. Anatomical work suggests the PAG may mediate food intake and reward processing as it has extensive reciprocal connections within brain circuits that mediate appetitive processes and consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala, parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005). Therefore, we investigated if the PAG of hungry rats has a functional role in appetitive and consummatory behaviors. To address this, PAG was pharmacologically inactivated during a spatial working memory task with muscimol (0.1-0.3 μg), a GABAA agonist via intracranial infusion. Inactivation of PAG led to reduced intake of food rewards and increased errors on this task. To focus on the specific effects PAG inactivation had on food consumption, PAG was inactivated during two separate food intake tasks in a separate group of rats. Again, PAG inactivation resulted in a significant decrease in food consumption, as well as an increased latency to consume food. We next investigated PAG neural responses to reward encounters. A different group of rats performed the same task used in Experiment 1 while the in vivo activity of PAG neurons was recorded. In a subset of PAG neurons, reward encounters elicited phasic excitation. A separate subset of PAG neurons were inhibited during reward encounters. These responses scaled with the size of the reward, with sustained excitation or inhibition in response to large rewards compared to small. Our data also show that separate groups of PAG neurons in awake behaving animals display either increased and decreased neural responses to reward encounters. Additionally, a proportion of neurons were modulated by the animals velocity. This study is the first to show that PAG neurons process reward-related information, perhaps to mediate consummatory behaviors related to food consumption

Analysis of morphine-induced changes in the activity of periaqueductal gray neurons in the intact rat

•Different subsets of PAG neurons are excited and inhibited by noxious stimuli.•Morphine has mixed effects on the activity of PAG neurons in anesthetized rats.•Morphine causes a small increase in the activity of most PAG neurons in awake rats. Microinjection of morphine into the periaqueductal gray (PAG) produces antinociception. In vitro slice recordings indicate that all PAG neurons are sensitive to morphine either by direct inhibition or indirect disinhibition. We tested the hypothesis that all PAG neurons respond to opioids in vivo by examining the extracellular activity of PAG neurons recorded in lightly anesthetized and awake rats. Spontaneous activity was less than 1Hz in most neurons. Noxious stimuli (heat, pinch) caused an increase in activity in 57% and 75% of the neurons recorded in anesthetized and awake rats, respectively. The same noxious stimuli caused a decrease in activity in only 17% and 6% of neurons recorded in anesthetized and awake rats. Systemic administration of morphine caused approximately equal numbers of neurons to increase, decrease, or show no change in activity in lightly anesthetized rats. In contrast, administration of morphine caused an increase in the activity of 22 of the 27 neurons recorded in awake rats. No change in activity was evident in the remaining five neurons. Changes in activity caused by morphine were surprisingly modest (a median increase from 0.7 to 1.3Hz). The small inconsistent effects of morphine are in stark contrast to the large changes produced by morphine on the activity of rostral ventromedial medulla (RVM) neurons or the widespread inhibition and excitation of PAG neurons treated with opioids in in vitro slice experiments. The relatively modest effects of morphine in the present study suggest that morphine produces antinociception by causing small changes in the activity of many PAG neurons

Loss of Sensitivity to Rewards by Dopamine Neurons May Underlie Age-Related Increased Probability Discounting.

Normative aging is known to affect how decisions are made in risky situations. Although important individual variability exists, on average, aging is accompanied by greater risk aversion. Here the behavioral and neural mechanisms of greater risk aversion were examined in young and old rats trained on an instrumental probability discounting task. Consistent with the literature, old rats showed greater discounting of reward value when the probability of obtaining rewards dropped below 100%. Behaviorally, reward magnitude discrimination was the same between young and old rats, and yet these same rats exhibited reduced sensitivity to positive, but not negative, choice outcomes. The latter behavioral result was congruent with additional findings that the aged ventral tegmental neurons (including dopamine cells) were less responsive to rewards when compared to the same cell types recorded from young animals. In sum, it appears that reduced responses of dopamine neurons to rewards contribute to aging-related changes in risky decisions