Striatal Dopamine Transporter Binding in Neuroleptic-Naive Patients With Schizophrenia Studied With Positron Emission Tomography

Abstract

Average striatal dopamine transporter density is unaltered in neuroleptic-naive patients with schizophrenia. However, patients lack asymmetry in caudate dopamine transporter binding, which conforms with disrupted brain lateralization in this disorder.

Association between Dopamine Transporter (DAT1) Genotype, Left-Sided Inattention, and an Enhanced Response to Methylphenidate in Attention-Deficit Hyperactivity Disorder

“…While there is, as yet, little direct evidence for this assumption, a number of studies do suggest a cerebral asymmetry in transporter densities. For example, Laakso et al (2000) reported higher striatal dopamine transporter binding in healthy subjects within the right, relative to left, striatum. Cheon et al (2003) also reported that DAT binding ratios within the basal ganglia of children with ADHD, relative to controls, were elevated by 51% on the right and 40% on the left.…”

Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

“…Recent studies in schizophrenia support a decreased cerebral asymmetry rather than altered directional asymmetry as the potential candidate phenotype of abnormal lateralization that could contribute to individual susceptibility to schizophrenia (Sommer et al, 2001). In vivo imaging studies also pointed to the loss of asymmetry as a candidate marker to better characterize schizophrenia-associated deficits (Hietala et al, 1999(Hietala et al, , 1995Hsiao et al, 2003;Laakso et al, 2000). Our data, showing that hyperdopaminergia directly impairs the degree of lateralization without affecting the direction, further support the magnitude of lateralization as the relevant and informative variable for the study of asymmetry.…”

“…Similarly, in the meta-analysis of three prospective followup studies, pre-schizophrenic subjects were significantly more often non-right-handed than the general population (Sommer et al, 2001). Furthermore, in vivo imaging studies of schizophrenia have provided evidence that the right-left asymmetry of the dopamine (DA) synthesis capacity and of the dopamine transporter (DAT) binding in the caudate are both lost in antipsychotic-naive patients (Hietala et al, 1999(Hietala et al, , 1995Hsiao et al, 2003;Laakso et al, 2000). In addition, neuroleptics are able to change the balance of hemispheric activity, thus improving left-hemispheric attentional processes (for a review, see Gruzelier, 1999), and a recent study demonstrated that haloperidol-induced downregulation of DA synthesis was significantly greater in the left than in the right striatum (Grunder et al, 2003).…”

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

“…b-CIT also MiniReview has affinity to the serotonin transporter (Boja et al 1994), which makes the interpretation of the analysis of radioactivity distribution difficult in brain areas possessing high density of both 5-HT-and dopamine transporters. With PET, b-CFT (Hantraye et al 1992) as well as other cocaine analogues (Halldin et al 1996) have been developed and used in a variational of applications in studying neurologic and neuropsychiatric disorders (Laakso et al 2000a).…”

“…The dopamine transporter is therefore an important element for the action of dopamine on locomotion, cognition, affect and neuroendocrine functions (Giros & Caron 1993;Hoffman 1994;Vizi 2000). Alterations in dopamine transporter have been described in several neurologic and neuropsychiatric disorders (Verhoeff 1999) such as Parkinson's disease (Janowsky et al 1987), Alzheimer's disease (Allard et al 1990), depression (Laasonen-Balk et al, 1999), alcoholism (Tiihonen et al 1995;Laine et al 1999;Repo et al 1999;Tupala et al 2000), schizophrenia (Laakso et al 2000a(Laakso et al & 2001, attention deficit hyperactivity disorder (Krause et al 2000), and social phobia (Tiihonen et al 1997). This review deals with in vitro and in vivo imaging methods for studying the dopamine transporter distribution and function.…”