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Department of Psychiatry and Behavioral Sciences

Department of Psychiatry and Behavioral Sciences

Psychopharmacology

Neurobiological processes of panic disorder

Principal Investigator:  Richard J. Maddock, M.D.

The panic response is an "alarm" mechanism which may have adaptive value in the face of threat.  However, in patients with panic disorder, this response repeatedly occurs at inappropriate times.  The regulatory web that governs this neurobiological process appears to be disordered.  Current research in my laboratory attempts to elucidate the nature of this dysfunction using a variety of neuroscience methods, including cognitive, metabolic and pharmacological challenge studies and functional neuroimaging.  The most consistent cognitive finding in panic disorder is that such patients exhibit longer response latencies to emotionally salient words on various cognitive tasks, including color naming and lexical decision tasks.  FMRI studies in our lab have shown that emotionally salient words consistently activate the retrosplenial region of the posterior cingulate gyrus, and the right amygdala in normal subjects.  Differences in the brain response to such stimuli in panic patients may suggest brain regions implicated in the pathogenesis of panic disorder.  Comparative studies in panic disorder patients are undergoing data analysis.  Several lines of evidence suggest that panic patients respond abnormally to metabolic challenges which affect the regulation of pH, including sodium lactate infusions and CO2 inhalation.  In our lab we have shown that panic patients consistently have an exaggerated systemic lactic acid response to alkalosis.  More recently, Dager and colleagues have reported the same abnormality within the brains of panic patients.  Magnetic resonance spectroscopy studies of brain energy metabolism and pH regulation in response to metabolic challenges in panic patients are being planned to test competing models of the mechanism of this metabolic abnormality.

Effects of lisdexamfetamine on cognitive control and reward response in adolescents and young adults with ADHD: neural and clinical outcomes

Principal Investigator:  Julie Schweitzer, Ph.D.

The goal of this project is to identify the effect of a commonly used stimulant (lisdexamfetamine; LDX) in adolescents and young adults with ADHD. This is a developmental period associated with high-risk taking activity in typical development, but particularly in individuals with ADHD. Everyday challenges in risk-taking for this population include issues that have the potential for long-term consequences including poor academic functioning, reckless automobile driving, substance abuse and unprotected sex. The cognitive control neural system likely mediates the ability to monitor and control behaviors associated with these actions. The effects of pharmacological intervention on the neural processes of cognitive control that mediate these behaviors, particularly in this developmental period, are unknown. Similarly the effects of stimulants to treat ADHD on the neural processes underlying self-control associated with this developmental period are unknown. We will use a delay discounting paradigm to quantify the neural and cognitive changes in self-control associated with LDX and placebo. Delay discounting paradigms measure decision-making between sooner, smaller rewards versus larger, more delayed rewards and provide a quantitative measure of self-control. We will investigate how the cognitive control and reward/self-control mechanisms, interact. We will use a combination of behavioral and neuroimaging measures in an 8-week, randomized, double-blind, placebo-controlled, parallel-groups titrated optimal dose trial of LDX oral once daily.