BackgroundVariation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.MethodsThirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory.ResultsSubjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.ConclusionsOur results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.
SPECT imaging is widely used for the differential diagnosis of degenerative parkinsonisms by exploiting the high affinitiy of the radiotracer (123)I-FP-CIT for the dopamine transporter. Reduced levels of DAT are found in Parkinson Disease (PD), Dementia with Lewy Bodies (DLB), and Progressive Supranuclear Palsy (PSP) compared to in Essential Tremor (ET) and Healthy Controls (HC). However, the extent of the neurodegenerative process may extend beyond nigrostriatal system. We have exploited the affinity of the same radiotracer (123)I-FP-CIT for the serotonin transporter to investigate SERT levels in the midbrain of patients with PD, DLB, PSP, and ET compared to HC. Using MRI images as anatomical templates for midbrain uptake quantification, we found a mild decrease in SERT levels in PD compared to ET and HC, with marked inter-individual variability; on the other side, PSP and DLB patients displayed markedly reduced to undetectable levels of SERT, respectively. These findings show that the neurodegenerative process affects serotoninergic neurons in parkinsonisms, with much more severe involvement in DLB than in PD patients, despite the comparable loss of striatal DAT. SERT-dependent (123)I-FP-CIT uptake may allow a more comprehensive assessment of neurochemical disturbances in degenerative parkinsonisms and may have a value for differential diagnosis.
Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with (123)I-labeled ligand N-delta-(fluoropropyl)-2 beta-carbomethoxy-3beta-(4-iodophenyl)tropene ((123)I-FP-CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, (123)I-FP-CIT imaging was performed in 18 well-characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. The seresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB.
A 22-year-old man diagnosed with neurofibromatosis-I was admitted to the neurology department because of progressive hemianopsia and chronic headache. Magnetic resonance imaging, magnetic resonance spectroscopy (MRS), and F-18 fluorocholine revealed a splenial mass with imaging features compatible with malignant astrocytoma. At follow-up examination, the sharp decrease in F-18 fluorocholine uptake and in choline/creatine ratio supported a conservative management. Molecular imaging of optic pathway gliomas may be a valuable tool in the selection of therapeutic options.
The authors regret this error. In the above-mentioned article, several errors were made in referencing LSVT 1 BIG and LSVT 1 LOUD. The corrected article can be found as supporting information at wileyonlinelibrary.comThe publisher regrets this error.Published online in Wiley Online Library (wileyonlinelibrary. com).
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