Showing papers by "Diego A. Pizzagalli published in 2011"

Effects of early life stress on cognitive and affective function: an integrated review of human literature.

Abstract: Rationale The investigation of putative effects of early life stress (ELS) in humans on later behavior and neurobiology is a fast developing field. While epidemiological and neurobiological studies paint a somber picture of negative outcomes, relatively little attention has been devoted to integrating the breadth of findings concerning possible cognitive and emotional deficits associated with ELS. Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae.

Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1) Genetic Variation and Stress Interact to Influence Reward Learning

Abstract: Stress is a general risk factor for psychopathology, but the mechanisms underlying this relationship remain largely unknown. Animal studies and limited human research suggest that stress can induce anhedonic behavior. Moreover, emerging data indicate that genetic variation within the corticotropin-releasing hormone type 1 receptor gene (CRHR1) at rs12938031 may promote psychopathology, particularly in the context of stress. Using an intermediate phenotypic neurogenetics approach, we assessed how stress and CRHR1 genetic variation (rs12938031) influence reward learning, an important component of anhedonia. Psychiatrically healthy female participants (n = 75) completed a probabilistic reward learning task during stress and no-stress conditions while 128-channel event-related potentials were recorded. Fifty-six participants were also genotyped across CRHR1. Response bias, an individual9s ability to modulate behavior as a function of reward, was the primary behavioral variable of interest. The feedback-related positivity (FRP) in response to reward feedback was used as a neural index of reward learning. Relative to the no-stress condition, acute stress was associated with blunted response bias as well as a smaller and delayed FRP (indicative of disrupted reward learning) and reduced anterior cingulate and orbitofrontal cortex activation to reward. Critically, rs12938031 interacted with stress to influence reward learning: both behaviorally and neurally, A homozygotes showed stress-induced reward learning abnormalities. These findings indicate that acute, uncontrollable stressors reduce participants9 ability to modulate behavior as a function of reward, and that such effects are modulated by CRHR1 genotype. Homozygosity for the A allele at rs12938031 may increase risk for psychopathology via stress-induced reward learning deficits.

Asymmetry in Resting Intracortical Activity as a Buffer to Social Threat

Abstract: Social rejection can create powerful changes in people’s brains and bodies. In the study reported here, we examined brain-based individual differences associated with buffering against cardiovascular threat responses to social rejection. Using EEG source-localization techniques, we examined differences in intracortical asymmetry. We predicted that individuals with greater left relative to right dorsolateral prefrontal activity would show a more approach-motivated response to social rejection. Eighty-four female participants were randomly assigned to one of three stressful situations: social rejection, social evaluation without rejection, or self-evaluation. Among participants assigned to the social-rejection condition, greater left relative to right prefrontal intracortical activity at baseline was associated with more adaptive cardiovascular profiles and more self-reported approach-oriented emotions. Participants in the other conditions did not show these relationships. Our data are the first to show tha...

Measuring extrastriatal dopamine release during a reward learning task

Abstract: Objectives: Reward learning is critical for survival. Animal research emphasizes the role of dopaminergic (DA) mesocorticolimbic pathways in reward learning, but few studies have evaluated extrastriatal DA functioning in humans. The purpose of this study was to examine presynaptic DA release in extrastriatal regions of the reward circuit by measuring displacement of the high affinity D2/D3 radioligand ( 18 F)Fallypride during a reward task. Design: Ten healthy volunteers underwent a ( 18 F)Fallypride positron emission tomography protocol while performing a reward task, allowing us to assess participants' ability to modulate behavior as a function of reward. DA receptor ligand displace- ment was correlated with task performance and self-reported anhedonia. Observations: Parametric t-maps revealed significant decrease in ( 18 F)Fallypride binding in the medial orbitofrontal cortex (mOFC), ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC), indicat- ing endogenous DA release in these regions. Increasing anhedonic symptoms correlated with DA release in the left vmPFC, left dACC, and right dACC emerged (all r's > 0.65, P's < 0.05). Similarly, reduced reward learning correlated with higher DA release in left vmPFC, right vmPFC, and left dACC (all r's < � 0.64, P's < 0.05). Left dACC (r ¼ 0.66, P ¼ 0.04) and left vmPFC (r ¼ 0.74, P ¼ 0.01) DA release showed a significant positive correlation with impaired tendency to modulate behavior as a function of prior positive reinforcements. Conclusions: These findings support the hypothesis that DA release in mOFC, vmPFC, and dACC regions plays an important role in reinforcement learning in the human brain. Hum Brain Mapp 34:575-586, 2013. V C 2011 Wiley Periodicals, Inc.

From Basic Processes to Real-World Problems: How Research on Emotion and Emotion Regulation Can Inform Understanding of Psychopathology, and Vice Versa

Abstract: Research on emotion and emotion regulation is expected to improve our understanding of psychopathology. However, achieving this understanding requires overcoming several obstacles, including the paucity of objective markers of specific emotions or psychiatric diagnoses, and the fact that emotion regulation is a concept that can be difficult to operationalize. We review affective neuroscience research that has addressed these issues by focusing on psychological and neural mechanisms implicated in approach and avoidance behaviors, as revealed by studies of fear, anxiety, and reward processing. Dysfunction in these mechanisms may serve as risk markers for psychopathology, while emotion regulation research demonstrates that some of them are susceptible to volitional control. The conclusion acknowledges limitations of affective neuroscience and highlights goals for future work.

Changes in depressive symptoms and social functioning in the sequenced treatment alternatives to relieve depression study.

Abstract: Major depressive disorder (MDD) profoundly affects social func- tioning, including the ability to enjoy social activities with peers, friends, and family members. We sought to compare changes in social functioning and depressive symptoms in the first level of the Sequenced Treatment Alterna- tives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated using flexible doses of citalopram for up to 14 weeks. We compared the change over the course of treatment in the social activities item of the Work and Social Adjustment Scale to the change in individual items of the Quick Inventory of Depressive SymptomsYSelf- Rated (QIDS-SR). Improvement in social functioning was modestly positively correlated with improvement in sad mood, concentration/decision making, in- volvement, and energy/fatigability. Only 16% to 22% of the variance in the change in social functioning was accounted for by these symptoms, and only 32% was accounted for by the total QIDS-SR score. In this large real-world sample of outpatients treated using citalopram, changes in depressive symptoms do not entirely explain improvements in social functioning.

Varenicline as a smoking cessation aid in schizophrenia: Effects on smoking behavior and reward sensitivity

Abstract: Rationale Smoking rates are up to five times higher in people with schizophrenia than in the general population, placing these individuals at high risk for smoking-related health problems. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, is a promising aid for smoking cessation in this population. To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia.