Changes in Regional Brain Glucose Metabolism Measured With Positron Emission Tomography After Paroxetine Treatment of Major Depression

Kennedy, Sidney H.; Evans, Kenneth R.; Krüger, Stephanie; Mayberg, Helen S.; Meyer, Jeffrey H.; McCann, Sonia; Arifuzzman, Andrew I.; Houle, Sylvain; Vaccarino, Franco J.

doi:10.1176/appi.ajp.158.6.899

Cited by 625 publications

(362 citation statements)

References 48 publications

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“…However, elevating serotonergic function pharmacologically by chronic treatment with SSRIs improved the dysregulated cerebral blood flow and metabolic activity seen in mPFC of depressed subjects (Kennedy et al, 2001), consistent with the observation that SCIT prevented the CUS-induced deficit in ED set shifting in the present study. Thus, there must be some convergence of effect of SSRI and selective NRI treatment in improving mPFC function.…”

Section: Discussionsupporting

confidence: 91%

“…Depressed patients show altered responses on verbal fluency and attentional set-shifting tasks (Austin et al, 2001;Beats et al, 1996;Purcell et al, 1997), as well as diminished motivation and impaired extradimensional set shifting (Miller and Lewis, 1977;Murphy et al, 1999). Consistent with such neuropsychological findings, imaging studies have shown hypoactive function of prefrontal cortex in depression (Rogers et al, 2004;Sheline, 2003), which was improved upon treatment with antidepressant drugs, such as paroxetine (Kennedy et al, 2001;Prasko et al, 2004).…”

Section: Introductionmentioning

confidence: 80%

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Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

348

263

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Chronic stress is a risk factor for the development of many psychopathological conditions in humans, including major depression and anxiety disorders. There is a high degree of comorbidity of depression and anxiety. Moreover, cognitive impairments associated with frontal lobe dysfunction, including deficits in cognitive set-shifting and behavioral flexibility, are increasingly recognized as major components of depression, anxiety disorders, and other stress-related psychiatric illnesses. To begin to understand the neurobiological mechanisms underlying the cognitive and emotional consequences of chronic stress, it is necessary to employ an animal model that exhibits similar effects. In the present study, a rat model of chronic unpredictable stress (CUS) consistently induced a cognitive impairment in extradimensional set shifting capability in an attentional set shifting test, suggesting an alteration in function of the medial prefrontal cortex. CUS also increased anxiety-like behavior on the elevated plus-maze. Further, chronic treatment both with the selective norepinephrine reuptake blocker, desipramine (7.5 mg/kg/day), and the selective serotonin reuptake blocker, escitalopram (10 mg/kg/ day), beginning 1 week before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced deficit in extradimensional set-shifting. Chronic desipramine treatment also prevented the CUS-induced increase in anxiety-like behavioral reactivity on the plus-maze, but escitalopram was less effective on this measure. Thus, CUS induced both cognitive and emotional disturbances that are similar to components of major depression and anxiety disorders. These effects were prevented by chronic treatment with antidepressant drugs, consistent also with clinical evidence that relapse of depressive episodes can be prevented by antidepressant drug treatment.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 80%

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

348

263

View full text Add to dashboard Cite

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“…The ACC plays a central role in processing positively valenced emotions [239] and other rewards [240], and in coding value representations of anticipated rewards [241], as shown in studies of sleep deprivation [242-245], psychopharmacological intervention [246-250], cognitive behavioral therapy [251,252] and a combined approach of therapy and psychopharmacological intervention [231]. …”

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

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This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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“…Imaging studies have shown associations between cognitive dysfunction and altered activity in prefrontal cortex in depression (Rogers et al 2004;Sheline 2003). Successful treatment with cognitive behavioral therapy, or antidepressant drugs such as paroxetine, produced concomitant changes in prefrontal cortical function, also revealed in neuroimaging studies (Goldapple et al 2004;Kennedy et al 2001;Prasko et al 2004). …”

Section: Introductionmentioning

confidence: 99%

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

et al. 2008

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Rationale-Chronic stress perturbs modulatory brain neurotransmitter systems, including serotonin (5-HT), and is a risk factor for psychiatric disorders such as depression. Deficits in cognitive flexibility, reflecting prefrontal cortical dysfunction, are prominent in such disorders. Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT.Objectives-Assess the effects of chronic intermittent cold (CIC) stress, a potent metabolic stressor, on performance of rats in an attentional set shifting test (AST). Assess a possible role for serotonin in CIC-induced deficits, and test the effects of acute serotonin reuptake blockade. Methods-MaleSprague-Dawley rats were exposed to CIC stress (14 days × 6 hr/day at 4 °C) before testing on the AST. In subsequent experiments, brain 5-HT was depleted in naïve rats with para-chlorophenylalanine, or 5-HT release was increased acutely in CIC-stressed rats with citalopram (5 mg/kg, s.c.) given 30 min prior to the first reversal task. Microdialysis was used to assess CICinduced changes in 5-HT release in OFC during testing.Results-CIC-stressed rats exhibited a selective impairment on the first reversal task in the AST. 5-HT depletion induced a similarly selective deficit in reversal learning. The CIC-induced impairment in reversal learning was attenuated by acute 5-HT reuptake blockade. 5-HT release was reduced in OFC of CIC-stressed rats during behavioral testing.Conclusions-The CIC stress-induced impairment of cognitive flexibility may involve dysregulation of 5-HT modulatory function in OFC. Such deficits may thus model relevant symptoms of neuropsychiatric disorders that respond positively to SSRI treatment.

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Changes in Regional Brain Glucose Metabolism Measured With Positron Emission Tomography After Paroxetine Treatment of Major Depression

Abstract: These results provide further support for a dysfunction in cortical-limbic circuitry in depression, which is at least partly reversed after successful paroxetine treatment.

Cited by 625 publications

References 48 publications

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

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