Abnormal Striatal Dopamine Transmission in Schizophrenia

Abstract

Despite numerous revisions and reformulations, dopamine (DA) hypothesis of schizophrenia remains a pivotal neurochemical hypothesis of this illness. The aim of this review is to expose and discuss findings from positron emission tomography (PET) or singlephoton-emission computed tomography (SPECT) studies investigating DA function in the striatum of medicated, drug-naïve or drug-free patients with schizophrenia and in individuals at risk compared with healthy volunteers.DA function was studied at several levels: i) at a presynaptic level where neuroimaging studies investigating DOPA uptake capacity clearly show an increase of DA synthesis in patients with schizophrenia; ii) at a synaptic level where neuroimaging studies investigating dopamine transporter availability (DAT) does not bring any evidence of dysfunction; iii) and finally, neuroimaging studies investigating DA receptor density show a mild increase of D2 receptor density in basic condition and, an hyperreactivity of DA system in dynamic condition.These results are discussed regarding laterality, sub-regions of striatum and implications for the at-risk population. Striatal DA abnormalities are now clearly demonstrated in patients with schizophrenia and at risk population and could constitute an endophenotype of schizophrenia. Subtle sub-clinical striatal DA abnormalities in at risk population could be a biomarker of transition from a vulnerability state to the expression of frank psychosis.

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

“…These results partly affirm increased stress-related dorsal striatal DAergic activity in the psychosis spectrum. The mixed results within the striatum are unexpected considering the solid evidence for aberrant striatal DAergic functioning in psychosis (Brunelin et al, 2013;Howes and Kapur, 2009) in combination with the well-validated putative link between stress and psychosis (Howes and Murray, 2014;Myin-Germeys and van Os, 2007).…”

The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue

“…A slightly increased density of D (2)-receptors in basal condition and a significant increase in D (2)-receptors in the striatum of schizophrenia patients has been found (127). This increase of striatal dopamine D (2)-receptors in schizophrenia has also been demonstrated in neuroimaging and molecular imaging studies (128, 129).…”

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

“…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.…”