TY  - JOUR
A1  - Palladino, Viola Stella
A1  - Chiocchetti, Andreas G.
A1  - Frank, Lukas
A1  - Haslinger, Denise
A1  - McNeill, Rhiannon
A1  - Radtke, Franziska
A1  - Till, Andreas
A1  - Haupt, Simone
A1  - Brüstle, Oliver
A1  - Günther, Katharina
A1  - Edenhofer, Frank
A1  - Hoffmann, Per
A1  - Reif, Andreas
A1  - Kittel-Schneider, Sarah
T1  - Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD
JF  - Journal of Clinical Medicine
N2  - The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.
KW  - ADHD
KW  - hiPSC
KW  - PARK2
KW  - mitochondria
KW  - disease modelling
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220074
SN  - 2077-0383
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - McNeill, Rhiannon V.
A1  - Ziegler, Georg C.
A1  - Radtke, Franziska
A1  - Nieberler, Matthias
A1  - Lesch, Klaus‑Peter
A1  - Kittel‑Schneider, Sarah
T1  - Mental health dished up — the use of iPSC models in neuropsychiatric research
JF  - Journal of Neural Transmission
N2  - Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.
KW  - hiPSC
KW  - iPSC
KW  - stem cells
KW  - mental disorders
KW  - affective disorders
KW  - ADHD
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235666
SN  - 0300-9564
VL  - 127
ER  -