Striatal dopamine transporter availability with [123I]β-CIT SPECT is unrelated to gender or menstrual cycle

Best, Susan E.; Sarrel, Philip M.; Malison, Robert T.; Laruelle, Marc; Zoghbi, Sami S.; Baldwin, Ronald M.; Seibyl, John; Innis, Robert B.; Dyck, Christopher H. van

doi:10.1007/s00213-005-0158-5

Cited by 44 publications

(24 citation statements)

References 56 publications

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“…However, although all subjects evidenced a luteal-phase rise in progesterone, 4 subjects did not have luteal-phase progesterone levels greater than 3 ng/mL, suggesting an anovulatory cycle as occurs in as many as 38% of cycles in young women (27) and is consistent with other studies (28). Results did not differ when these subjects were eliminated from the analyses.…”

Section: Study 2: the Effect Of Menstrual Cyclesupporting

confidence: 86%

“…The influence of menstrual phase and sexsteroid hormones on other neurotransmitter and receptor systems has been underresearched. Striatal dopamine transporters do not vary with menstrual cycle phase (28), and there is conflicting evidence on variations in dopamine D 2 receptors by phase of cycle (49,50). Serotonin transporter availability also does not fluctuate (28), whereas the serotonin 2A receptor (51) may fluctuate with menstrual cycle phase.…”

Section: The Effect Of Menstrual Cycle Phase On B 2 -Nachr Availabilitymentioning

confidence: 99%

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123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Cosgrove

Mitsis

Bois

et al. 2007

Journal of Nuclear Medicine

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The study of the effects of sex and hormones on brain chemistry and neurotransmission is of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. We examined the availability of nAChR containing the b 2 subunit in healthy men and women and the influence of menstrual phase among women. Methods: Ten men and 19 women nonsmokers underwent one 123 I-5-IA-85380 ( 123 I-5-IA) SPECT scan and one MRI scan. A subset of 9 women, aged 18-39 y, underwent a second 123 I-5-IA scan. These 9 women were scanned during the early follicular (days 4-7 in 8 subjects and day 11 in 1 subject) and mid-luteal (days 19-25) phases of their menstrual cycle. Hormone levels were measured in all women to confirm the phase of the cycle. Results: Regional brain activity (kBq/cm 3 ) was higher (39%-54%) in women than in men nonsmokers. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (V T 9), differences of 10%-16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (V T ), there was less than a 4% difference by sex in regional brain b 2 -nAChR availability. These sex differences in kBq/cm 3 and V T 9 resulted from significantly higher levels of total plasma parent, free fraction (f 1 ), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain b 2 -nAChR availability were observed across the menstrual cycle for any outcome measure. Conclusion: Overall, these findings demonstrate no significant difference in brain b 2 -nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate sex differences in radiotracer metabolism and plasma protein binding and highlight the critical need to measure plasma radiotracer levels and f 1 in studies that include both sexes. The importance of studying sex differences in brain neurochemistry has become increasingly evident with the recent demonstration of differences between men and women in symptomatology and treatment for many neuropsychiatric disorders. Evidence of differences in brain structure, function, neurotransmission, and receptor availability between men and women is mounting (1). Sex differences exist in a variety of behaviors related to tobacco smoking, such as craving, sensitivity to nicotine, and response to nicotine replacement therapy (2,3); however, the mechanisms underlying these differences are unclear. Women often experience more difficulty in quitting smoking than men (4-9), and rates of success may differ by menstrual phase. For example, women who quit smoking during the luteal phase of the menstrual cycl...

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Section: Study 2: the Effect Of Menstrual Cyclesupporting

confidence: 86%

Section: The Effect Of Menstrual Cycle Phase On B 2 -Nachr Availabilitymentioning

confidence: 99%

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Cosgrove

Mitsis

Bois

et al. 2007

Journal of Nuclear Medicine

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“…Several studies have reported a similar effect of sex on DAT, with females showing greater DAT uptake than males (24,28). However, other studies could not confirm this association (29). We did not find any association between striatal DAT availability and age, an established factor of influence (24).…”

Section: Discussioncontrasting

confidence: 61%

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Giessen¹,

Win²,

Tanck³

et al. 2008

J Nucl Med

145

110

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Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with human striatal DAT expression, but the exact effects on DAT expression are not clear. A variable number of tandem repeats (VNTR) in the 39 untranslated region of the DAT gene was previously investigated in relation to striatal DAT availability, but the results were inconclusive. Other polymorphisms in the DAT gene were not extensively studied. Therefore, we investigated whether polymorphisms in both 39 and 59 ends of the DAT gene show association with in vivo striatal DAT expression. Methods: The subjects were an ethnically homogeneous group of 79 healthy young adults. Striatal DAT availability was measured with 123 I-(2-b-carbomethoxy-3-b(4-iodophenyl)-tropane) ( 123 I-b-CIT) SPECT. The 40-base-pair VNTR in the 39 untranslated region of the DAT gene and the 2 single nucleotide polymorphisms (SNPs) rs2652511 and rs2937639 in the 59 end of the DAT gene were genotyped. Multiple-regression analysis was performed for each of the 3 polymorphisms. Analysis of the combination of the polymorphisms (haplotype analysis) was conducted for the triad rs2652511-rs2937639-VNTR. Results: For the VNTR, the 9-repeat (9R) allele was associated with significantly higher striatal DAT expression than was the 10-repeat (10R) allele (P 5 0.002). Subanalysis suggested a dominant effect for the 9R allele. Neither SNP rs2652511 nor SNP rs2937639 was associated with striatal DAT availability. The haplotype T-A-9R (rs2652511-rs2937639-VNTR) was significantly more associated with higher striatal DAT expression than were the other haplotypes (P 5 0.009). Conclusion: The DAT VNTR 9R carriers have higher striatal DAT availability than do 10R homozygotes. This finding replicates former studies that included healthy subjects and also used 123 I-b-CIT SPECT. Our haplotype analysis identified a subgroup of 9R carriers, the T-A-9R, which appears to be mainly responsible for the association with higher striatal DAT availability. Thus, a combination of polymorphisms in both the 39 and the 59 ends of the DAT gene is associated with in vivo striatal DAT expression. This finding in healthy subjects may contribute to research on DAT availability and genotype in neuropsychiatric disorders.

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“…Replacement of testosterone in castrated male rats increases SERT mRNA and SERT availability [37]. Since we did not measure sex hormones, and Best et al [38] found no relationship between menstrual cycle or sex hormones and SERT availability in healthy individuals, these explanations remain speculative and should be examined further.…”

Section: Methodological Explanations For Inconsistent Findingsmentioning

confidence: 84%

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Ruhé

Booij

Reitsma

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods We included 49 depressed outpatients (mean±SD 42.3±8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [ 123 I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP ND ) in the midbrain and diencephalon with cerebellar binding as a reference. Results In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p=0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p=0.002) and an additional smoking×gender (p=0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p=0.018) with higher SERT availability in winter. Conclusion Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

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Striatal dopamine transporter availability with [123I]β-CIT SPECT is unrelated to gender or menstrual cycle

Cited by 44 publications

References 56 publications

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

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