Prefrontal cortical dopamine systems and the elaboration of functional corticostriatal circuits: implications for schizophrenia and Parkinson's disease

Ay, Deutch

doi:10.1007/bf01245232

Cited by 205 publications

(105 citation statements)

References 126 publications

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“…As low prefrontal cortical control is suggested to promote impulsivity (Meyer-Lindenberg et al, 2006), the results of our investigation may be explained in terms of prefrontal function. This interpretation is in line with the observation that diminished frontal dopaminergic neurotransmission leads to an upregulation of midbrain dopamine activity (Deutch, 1993;Tsai et al, 2004). It is known from animal experiments that unfamiliar environments are accompanied by a robust increase of dopamine (Ihalainen et al, 1999) and a rapid respond of dopamine neurons with burst of spikes (Ljungberg et al, 1992).…”

Section: Discussionsupporting

confidence: 85%

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Lang

Bajbouj

Sander

et al. 2007

Neuropsychopharmacol

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The gene encoding cathechol-O-methyltransferase (COMT) contains a common functional missense polymorphism (Val158Met) that regulates dopamine in an allele-dependent manner. A pivotal role of dopamine neurotransmission in the prefrontal cortex has been implicated in drug-seeking behavior and related personality traits, such as sensation seeking, with some evidence for a gender-specific association. Here, we tested the hypothesis that the COMT Val158Met polymorphism modulates the personality dimension, sensation seeking, in a gender-dependent manner. Study sample included 214 male (age 38.1712.6 years) and 218 female (age 36.1713.6 years) healthy volunteers, who were assessed with Zuckerman's sensation-seeking scale and genotyped for the Val158Met polymorphism (dbSNP:rs4680). Univariate analysis of variance showed that the sensation seeking score was significantly affected by a COMT genotype Â gender interaction (F ¼ 5.330, df ¼ 2, p ¼ 0.005). The Val158Met polymorphism was associated with the sensation seeking personality trait in women only. The highest scores in the sensation-seeking scale and in three of the four subscales were observed in female subjects with the Val/Val genotype relative to women carrying the Met allele. Our results suggest that high COMT enzyme activity associated with the Val allele predisposes to high sensation seeking scores in female subjects and add to increasing evidence for a gender specific role of COMT in normal and dysfunctional behavior.

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Section: Discussionsupporting

confidence: 85%

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Lang

Bajbouj

Sander

et al. 2007

Neuropsychopharmacol

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“…These findings suggest that reduced DA transmission in the PFC is implicated in the pathogenesis of depression. A similar relationship has been suggested in patients with Parkinson's disease accompanied by depression (Cummings, 1992;Deutch, 1993). Depression occurs in large populations of patients with Parkinson's disease, and depressed patients with Parkinson's disease have greater frontal lobe dysfunction and greater involvement of a reduced dopaminergic system than nondepressed patients with the disease.…”

Section: Clinical Relevancementioning

confidence: 63%

“…However, in humans, an overresponse to stress can be maladaptive, resulting in the expression or exacerbation of many neuropsychiatric disorders, including a number of features that indicate abnormal functioning of the PFC (Mattes, 1980;Weinberger et al, 1986;Deutch, 1993;Fibiger, 1995). The influence of dopaminergic neurons in the PFC on the PFC functions in neuropsychiatric disorders remains obscure, but some observations support the idea that these neurons play a role in the pathogenesis of certain neuropsychiatric disorders.…”

Section: Clinical Relevancementioning

confidence: 99%

“…All these disorders involve a working memory deficit caused by prefrontal cortical (PFC) dysfunction (Mattes, 1980;Weinberger et al, 1986;Deutch, 1993;Fibiger, 1995). Several antidepressants increase dopamine (DA) levels in the PFC (Tanda et al, 1994), and raising the DA level in patients with Parkinson's disease with L-3,4-dihydroxyphenylalanine improves their working memory deficit (Lange et al, 1992).…”

Section: Abstract: Chronic Stress; Working Memory; Prefrontal Cortexmentioning

confidence: 99%

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Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction

et al. 2000

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Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 g/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders.Key words: chronic stress; working memory; prefrontal cortex; dopaminergic neuron; D1 receptor; cognitive deficit Exposure to stress is known to precipitate or exacerbate many neuropsychiatric disorders such as depression, Parkinson's disease, schizophrenia, and others (Schwab and Zieper, 1965;Mazure, 1995). All these disorders involve a working memory deficit caused by prefrontal cortical (PFC) dysfunction (Mattes, 1980;Weinberger et al., 1986;Deutch, 1993;Fibiger, 1995). Several antidepressants increase dopamine (DA) levels in the PFC (Tanda et al., 1994), and raising the DA level in patients with Parkinson's disease with L-3,4-dihydroxyphenylalanine improves their working memory deficit (Lange et al., 1992). These findings suggest that a reduced dopaminergic transmission in the PFC is responsible for the working memory deficits in the neuropsychiatric disorders.In animals, reduced PFC dopaminergic function or blockade of DA receptor in the PFC of monkeys and rats impairs working memory function (Brozoski et al., 1979;Simon et al., 1980;Bubser and Schmidt, 1990), which supports the observations in the neuropsychiatric disorders. In addition, an exposure to acute stress in monkeys or rats has been reported to produce working memory impairment, which can be blocked by...

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“…Others have found increased reaction time variability in a response inhibition task in CT heterozygotes (Gurvich & Rossell, 2014). Prefrontal cortical D2 receptors are also proposed to affect responsivity to stress via subcortical projections by attenuating dopamine release in the midbrain via a negative feedback system (Deutch, 1993). …”

Section: Introductionmentioning

confidence: 99%

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

et al. 2017

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IntroductionPrevious research has indicated that variation in genes encoding catechol‐O‐methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults.MethodsOne hundred and twenty‐two healthy adult males (mean age 35.2 years, range 21–63) were enrolled in the study. Cognitive function was assessed using Cambridge Neuropsychological Test Automated Battery and early life stress was assessed using the Childhood Traumatic Events Scale (Pennebaker & Susman, 1988).Results DRD2 C957T was significantly associated with executive function, with CC homozygotes having significantly reduced performance in spatial working memory and spatial planning. A significant genotype–trauma interaction was found in Rapid Visual Information Processing test, a measure of sustained attention, with CC carriers who had experienced early life stress exhibiting impaired performance compared to the CC carriers without early life stressful experiences. There were no significant findings for COMT Val158Met.ConclusionsThis study supports previous findings that DRD2 C957T significantly affects performance on executive function related tasks in healthy individuals and shows for the first time that some of these effects may be mediated through the impact of childhood traumatic events. Future work should aim to clarify further the effect of stress on neuronal systems that are known to be vulnerable in mental health disorders and more specifically what the impact of this might be on cognitive function.

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Prefrontal cortical dopamine systems and the elaboration of functional corticostriatal circuits: implications for schizophrenia and Parkinson's disease

Cited by 205 publications

References 126 publications

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Gender-Dependent Association of the Functional Catechol-O-Methyltransferase Val158Met Genotype with Sensation Seeking Personality Trait

Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

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