TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Kobayashi, Ryohei
A1  - Javadi, Mehrbod Som
A1  - Köck, Zoe
A1  - Wakabayashi, Hiroshi
A1  - Unterecker, Stefan
A1  - Nakajima, Kenichi
A1  - Lapa, Constantin
A1  - Menke, Andreas
A1  - Higuchi, Takahiro
T1  - Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits
JF  - Journal of Nuclear Medicine
N2  - Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results. 
Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 % for desipramine, 25.5 % for venlafaxine, 11.7 % for bupropion and 0.72 % for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake. 
Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.
KW  - MDD
KW  - Antidepressants
KW  - depression
KW  - 123I-mIBG
KW  - antidepressant
KW  - cardiac sympathetic nerve system
KW  - major depressive disorder
KW  - myocardial sympathetic innervation imaging
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161280
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi. Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1099-1103. © SNMMI.
ER  - 
TY  - JOUR
A1  - de Jong, Simone
A1  - Diniz, Mateus Jose Abdalla
A1  - Saloma, Andiara
A1  - Gadelha, Ary
A1  - Santoro, Marcos L.
A1  - Ota, Vanessa K.
A1  - Noto, Cristiano
A1  - Curtis, Charles
A1  - Newhouse, Stephen J.
A1  - Patel, Hamel
A1  - Hall, Lynsey S.
A1  - O'Reilly, Paul F.
A1  - Belangero, Sintia I.
A1  - Bressan, Rodrigo A.
A1  - Breen, Gerome
T1  - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
JF  - Communications Biology
N2  - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
KW  - bipolar disorder
KW  - depression
KW  - genetic association study
KW  - genetic linkage study
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223622
VL  - 1
ER  -