Frontal Dopamine D2/3 Receptor Binding in Drug-Naive First-Episode Schizophrenic Patients Correlates with Positive Psychotic Symptoms and Gender

Glenthøj, Birte; Mackeprang, Torben; Svarer, Claus; Rasmussen, Henrik; Pinborg, Lars H.; Friberg, Lars; Baaré, William F.C.; Hemmingsen, Ralf; Videbæk, Charlotte

doi:10.1016/j.biopsych.2006.01.010

Cited by 80 publications

(75 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, several studies reported reduced D 2/3 in the thalamus in patients with schizophrenia, [51][52][53] whereas Kegeles and colleagues 54 observed increases in thalamic BP ND . Consistent with the results of Glenthoj and colleagues 55 and Talvik and colleagues, 56 we found no significant difference at the level of the whole thalamus.…”

Section: Discussionsupporting

confidence: 92%

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Suridjan

Rusjan²,

Addington³

et al. 2013

J Psychiatry Neurosci

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Suridjan

Rusjan²,

Addington³

et al. 2013

J Psychiatry Neurosci

View full text Add to dashboard Cite

“…Compared with the number of studies of striatum, there have been very few of cortex. Although a decrease was observed in temporal cortex (Tuppurainen et al, 2003) and anterior cingulate cortex (Suhara et al, 2002), two other studies found no difference in frontal cortex, temporal cortex, or thalamus (Talvik et al, 2003;Glenthoj et al, 2006). Therefore it appears that the issue of DRD2 levels in the cortex of schizophrenics is still unresolved.…”

Section: Discussionmentioning

confidence: 93%

Evidence That the BLOC-1 Protein Dysbindin Modulates Dopamine D₂Receptor Internalization and Signaling But Not D₁Internalization

Iizuka¹,

Sei²,

Weinberger³

et al. 2007

J. Neurosci.

121

109

View full text Add to dashboard Cite

The schizophrenia susceptibility gene dystrobrevin-binding protein 1 (DTNBP1) encodes dysbindin, which along with its binding partner Muted is an essential component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin expression is reduced in schizophrenic brain tissue, but the molecular mechanisms by which this contributes to pathogenesis and symptomatology are unknown. We studied the effects of transfection of DTNBP1 siRNA on cell surface levels of dopamine D 2 receptor (DRD2) in human SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. DTNBP1 siRNA decreased dysbindin protein, increased cell surface DRD2 and blocked dopamine-induced DRD2 internalization. MUTED siRNA produced similar effects. In contrast, decreased dysbindin did not change dopamine D 1 receptor (DRD1) levels, or its basal or dopamine-induced internalization. The DRD2 agonist quinpirole reduced phosphorylation of CREB (cAMP response element-binding protein) in dysbindin downregulated cells, demonstrating enhanced intracellular signaling caused by the upregulation of DRD2. This is the first demonstration of a schizophrenia susceptibility gene exerting a functional effect on DRD2 signaling, a pathway that has long been implicated in the illness. We propose a molecular mechanism for pathogenesis in which risk alleles in DTNBP1, or other factors that also downregulate dysbindin, compromise the ability of BLOC-1 to traffic DRD2 toward degradation, but has little effect on DRD1 trafficking. Impaired trafficking of DRD2 decreases dopamine-induced internalization, and with more receptors retained on the cell surface, dopamine stimulation produces excess intracellular signaling. Such an increase in DRD2 signaling relative to DRD1 would contribute to the imbalances in dopaminergic neurotransmission characteristic of schizophrenia.

show abstract

“…Women were excluded from the current study because PPI fluctuates through the menstrual cycle. 32 All participants underwent a comprehensive examination program, including psychopathological ratings, psychophysiological 5,33,34 and neuropsychological examinations, 35,36 singlephoton emission computed tomography (SPECT) 37 or positron emission tomography, 38,39 structural MRI 40,41 and fMRI. 42 We report only on the combined PPI and structural MRI data.…”

Section: Participantsmentioning

confidence: 99%

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Hammer

Oranje

Skimminge

et al. 2013

J Psychiatry Neurosci

Self Cite

View full text Add to dashboard Cite

Frontal Dopamine D2/3 Receptor Binding in Drug-Naive First-Episode Schizophrenic Patients Correlates with Positive Psychotic Symptoms and Gender

Cited by 80 publications

References 54 publications

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Evidence That the BLOC-1 Protein Dysbindin Modulates Dopamine D₂Receptor Internalization and Signaling But Not D₁Internalization

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Contact Info

Product

Resources

About

Frontal Dopamine D2/3 Receptor Binding in Drug-Naive First-Episode Schizophrenic Patients Correlates with Positive Psychotic Symptoms and Gender

Cited by 80 publications

References 54 publications

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Evidence That the BLOC-1 Protein Dysbindin Modulates Dopamine D2Receptor Internalization and Signaling But Not D1Internalization

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Contact Info

Product

Resources

About

Evidence That the BLOC-1 Protein Dysbindin Modulates Dopamine D₂Receptor Internalization and Signaling But Not D₁Internalization