Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies

Kambeitz, Joseph; Abi‐Dargham, Anissa; Kapur, Shitij; Howes, Oliver

doi:10.1192/bjp.bp.113.132308

Cited by 101 publications

(72 citation statements)

References 84 publications

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“…Deviations in prefrontal DAergic activity may perhaps not be expected based on inconclusive findings in the existing literature on DA in psychosis (Kambeitz et al, 2014), although recent work seems to suggest blunted amphetamine-induced DAergic activity in SZ as measured with FLB457 (Slifstein et al, 2015). Again, replication samples and especially the use of high-affinity D2/3 tracers may provide insight into altered stress-induced cortical DAergic activity associated with psychosis (vulnerability).…”

Section: The Dysregulated Stress Responsementioning

confidence: 99%

“…DA is a catecholamine that is functionally involved in cognition, movement, reward motivation and salience attribution -the assignment of importance to a stimulus (Arnsten et al, 1994;Berridge and Robinson, 1998;Goldman-Rakic, 1998). Most importantly however, changes in brain DA function have been related to stress-related psychopathological conditions such as substance abuse (Robinson and Berridge, 1993), post-traumatic stress disorder (De Bellis et al, 1999;Glover et al, 2003;Hamner and Diamond, 1993;Lemieux and Coe, 1995;Spivak et al, 1999;Yehuda et al, 1992) and psychosis (Howes and Kapur, 2009;Kambeitz et al, 2014). Especially the latter disorder has consistently been associated with increased striatal DA synthesis capacity and release (Fusar-Poli and Meyer-Lindenberg, 2013;Howes et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The dopaminergic response to acute stress in health and psychopathology: A systematic review

Vaessen

Hernaus

Myin-Germeys

et al. 2015

Neuroscience & Biobehavioral Reviews

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Section: The Dysregulated Stress Responsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The dopaminergic response to acute stress in health and psychopathology: A systematic review

Vaessen

Hernaus

Myin-Germeys

et al. 2015

Neuroscience & Biobehavioral Reviews

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“…Postiron emission tomography (PET) studies with displaceable DA D2/D3 receptor (D2/D3R) radioligands show that low striatal D2/D3R availability may be associated with impulsivity (Clark et al, 2012), addiction to alcohol (Volkow et al, 1996; Martinez et al, 2005), substance abuse (Volkow et al, 1990; Volkow et al, 2001; Martinez et al, 2004; Fehr et al, 2008), and obesity (Wang et al, 2001; Haltia et al, 2007; de Weijer et al, 2011) whereas high D2/D3R availability has been associated with risk for schizophrenia (Laruelle, 1998), although this finding has not been replicated (Howes et al, 2012; Kambeitz et al, 2014). Similarly, the A1 (T) allele of the single nucleotide polymorphism (SNP) TaqIA (rs1800497), located in the ankyrin repeat and kinase domain containing 1 ( ANKK1 ) 10 kb downstream from the DA D2 receptor ( DRD2 ) gene (Grandy et al, 1989), is associated with addictive behavior including gambling (Comings et al, 1996), substance abuse (Noble et al, 1993; Persico et al, 1996; Lawford et al, 2000; Chen et al, 2004; Messas et al, 2005), and binge eating (Davis et al, 2012) and with obesity (Noble et al, 1994; Spitz MR, 2000; Thomas et al, 2001; Stice et al, 2008; Duran-Gonzalez et al, 2011) while the A2 (C) allele is associated with risk for schizophrenia (Parsons et al, 2007; Dubertret et al, 2010; Arab and Elhawary, 2015).…”

Section: Introductionmentioning

confidence: 99%

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

Eisenstein

Bogdan

Love‐Gregory

et al. 2016

Synapse

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In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are non-selective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N‐[11C]methyl)benperidol ([11C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in 2 independent samples. Sample 1 (n = 39) was composed of obese and non-obese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5-12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1−), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1− was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [11C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states. GRAPHICAL ABSTRACT We investigated the difference in striatal dopamine D2 receptor binding, as measured by PET with (N-[11C]methyl)benperidol ([11C]NMB), between A1 allele carriers (A1+) and individuals homozygous for the A2 allele (A1−) of the DRD2/ANKK1 TaqIA single nucleotide polymorphism. In Study 1, A1+ had 5-12% less striatal [11C]NMB binding than A1−.

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“…13,14 In patients with schizophrenia, the presynaptic DA marker [ 18 F]DOPA has been shown to be elevated, whereas studies on postsynaptic DA receptors have produced discrepant results. 15,16 Striatal D 2/3 dopamine receptor availability has been found to be reduced in most substance use disorders 17,18 but negative findings have also been reported. [19][20][21] Various studies of the serotonin 5-HT 1A receptor in depression have shown decreased, increased or unaltered levels.…”

Section: Introductionmentioning

confidence: 99%

Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

et al. 2015

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The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.

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Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies

Cited by 101 publications

References 84 publications

The dopaminergic response to acute stress in health and psychopathology: A systematic review

The dopaminergic response to acute stress in health and psychopathology: A systematic review

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

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