An fMRI Study of the Influence of a History of Substance Abuse on Working Memory-Related Brain Activation in Schizophrenia

Abstract

There has been little investigation of the effects of past substance abuse (SA) on working memory (WM) impairments in schizophrenia. This study examined the behavioral and neurobiological impact of past SA (6 months or longer abstinence period) on WM in schizophrenia. Thirty-seven schizophrenia patients (17 with past SA and 20 without) and 32 controls (12 with past SA and 20 without) completed two versions of a two-back WM task during fMRI scanning on separate days. Analyses focused on regions whose patterns of activation replicated across both n-back tasks. Schizophrenia patients were significantly less accurate than controls on both n-back tasks. No main effects or interactions with past SA on WM performance were observed. However, several fronto-parietal-thalamic regions showed an interaction between diagnostic group and past SA. These regions were significantly more active in controls with past SA compared to controls without past SA. Schizophrenia patients with or without past SA either showed no significant differences, or patients with past SA showed somewhat less activation compared to patients without past SA during WM. These results suggest robust effects of past SA on WM brain functioning in controls, but less impact of past SA in schizophrenia. This is consistent with previous literature indicating less impaired neurocognition in schizophrenia with SA.

Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

“…Interestingly, this stress-dampening effect may also be valuable during treatment for opioid users, to prevent relapse. Stress is a known precipitant of relapse in opioid addicts (Sinha, 2001; Lijffijt et al, 2014; Spanagel et al, 2014), and dysregulation of the HPA axis is a hallmark of opioid withdrawal (Zhang et al 2008). While buprenorphine is used clinically at higher doses in opioid replacement therapy, our results suggest that even at low doses, the drug has stress-blunting effects that may contribute to its efficacy in preventing relapse in vulnerable populations.…”

Controllability modulates the neural response to predictable but not unpredictable threat in humans

“…Post-traumatic stress disorder (PTSD), for example, is characterized by symptoms that include re-experiencing, hyperarousal, and avoidance behavior triggered by a life threatening traumatic event beyond one’s control (American Psychiatric Association, 2000). The hyperarousal often observed in PTSD appears to be due to insufficient top-down regulatory control that results in hypersensitivity of subcortical brain areas (e.g., the amygdala) (Briscione et al, 2014; Jovanovic and Ressler, 2010; Milad et al, 2009; Rauch et al, 2006; Robison-Andrew et al, 2014). Further, PTSD is often associated with hypoactivation of the vmPFC and hippocampus (Bremner et al, 2004; Haas et al, 2010; Milad et al, 2009; Rauch et al, 2006).…”

Examining the Crux of Autonomic Dysfunction in Posttraumatic Stress Disorder: Whether Chronic or Situational Distress Underlies Elevated Heart Rate and Attenuated Heart Rate Variability

“…Indeed, PTSD diagnosis and symptom severity have been associated with higher baseline heart rate (HR) (2) and reduced heart-rate variability (HRV) (3), a non-invasive index of autonomic control of cardiac rhythm (4). This is concerning because elevated HR and attenuated HRV are not only indicators of poor cardiovascular health, they are also precursors, conveying heightened risk for arrhythmia (5) and artherosclerosis (6).…”