Neurotransmitters are chemicals synthesized inside the brain cells (neuron). Signals from the neuron travel out a thread-like extension called the axon, which connects to the next brain cell through a gap (synapse). There are the target neurons waiting for the signal.

There are many neurotransmitters in the brain. Serotonin, dopamine, acetylcholine are three of them.

Serotonin's role in the body has been associated mainly with mood, but it has major roles in temperature regulation, pain perception, sleep regulation, gut function (irritable bowel syndrome), major vessel constriction and relaxation, blood pressure control, and even neurodegenerative disorders like ALS have been associated with serotonin.

Dopamine is a neurotransmitter involved in motor function, behaviour, and cognition.

Acetylcholine functions both in the brain and peripheral neurons as a neuromodulator, it regulates gut function, sensory and autonomic nervous system, and sleep.

My major research is to define some of these neurotransmitters' involvement in disease.


Improvement of Self-Injury With Dopamine and Serotonin Replacement Therapy in a Patient With a Hemizygous PAK3 Mutation: A New Therapeutic Strategy for Neuropsychiatric Features of an Intellectual Disability Syndrome
Journal of Child Neurology
Gabriella A. Horvath, Maja Tarailo-Graovac, Tanja Bartel, Simone Race, Margot I. Van Allen, Ingrid Blydt-Hansen, Colin J. Ross, Wyeth W. Wasserman, Mary B. Connolly, Clara D. M. van Karnebeek
DOI: 10.1177/0883073817740443

Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy
Journal of the Neurological Sciences
Gabriella A. Horvath, Lorelyn Meisner, Kathryn Selby, Robert Stowe, Bruce Carleton
DOI: 10.1016/j.jns.2017.04.047

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole exome sequencing.
Balci TB, Hartley T, Xi Y, Dyment DA, Beaulieu CL, Bernier FP, Dupuis L, Horvath G, Mendoza-Londono R, Prasad C, Richer J, Yang XR, Armour CM, Bareke E, Fernandez BA, McMillan HJ, Lamont R, Majewski J, Parboosingh J, Narayan Prasad A
DOI: 10.1111/cge.12987
PubMed: 28170084

The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders.
Opladen T, Cortès-Saladelafont E, Mastrangelo M, Horvath G, Pons R, Lopez-Laso E, Fernández-Ramos JA, Honzik T, Pearson T, Friedman J, Scholl-Bürgi S, Wassenberg T, Jung-Klawitter S, Kuseyri O, Jeltsch K, Kurian MA, Garcia-Cazorla À, International Working Group on Neurotransmitter related disorders (iNTD)
DOI: 10.1016/j.ymgmr.2016.09.006
PubMed: 27830117

Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.
Horvath GA, Hukin J, Stockler-Ipsiroglu SG, Aroichane M
DOI: 10.1055/s-0036-1583183
PubMed: 27104484

Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?
Horvath GA, Demos M, Shyr C, Matthews A, Zhang L, Race S, Stockler-Ipsiroglu S, Van Allen MI, Mancarci O, Toker L, Pavlidis P, Ross CJ, Wasserman WW, Trump N, Heales S, Pope S, Cross JH, van Karnebeek CD
DOI: 10.1016/j.ymgme.2015.11.008
PubMed: 26647175

Deep brain stimulation and dantrolene for secondary dystonia in x-linked adrenoleukodystrophy.
van Karnebeek C, Horvath G, Murphy T, Purtzki J, Bowden K, Sirrs S, Honey CR, Stockler S
DOI: 10.1007/8904_2014_305
PubMed: 24718842

Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood.
van Karnebeek CD, Sly WS, Ross CJ, Salvarinova R, Yaplito-Lee J, Santra S, Shyr C, Horvath GA, Eydoux P, Lehman AM, Bernard V, Newlove T, Ukpeh H, Chakrapani A, Preece MA, Ball S, Pitt J, Vallance HD, Coulter-Mackie M, Nguyen H
DOI: 10.1016/j.ajhg.2014.01.006
PubMed: 24530203

A novel recurrent mutation in ATP1A3 causes CAPOS syndrome.
Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM, FORGE Canada Consortium
DOI: 10.1186/1750-1172-9-15
PubMed: 24468074

Long-term outcomes of blood phenylalanine concentrations in children with classical phenylketonuria.
Hartnett C, Salvarinova-Zivkovic R, Yap-Todos E, Cheng B, Giezen A, Horvath G, Lillquist Y, Vallance H, Stockler-Ipsiroglu S
DOI: 10.1016/j.ymgme.2013.01.007
PubMed: 23465864

Three years experience with dried blood spot a-glucosidase screening for Pompe disease in British Columbia, Canada.
Horvath G, Sirrs S, Stockler S, Salvarinova-Zivkovic R, Vallance H, Waters P
DOI: 10.1186/1471-2474-14-s2-p2

Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.
Mercimek-Mahmutoglu S, Horvath GA, Coulter-Mackie M, Nelson T, Waters PJ, Sargent M, Struys E, Jakobs C, Stockler-Ipsiroglu S, Connolly MB
DOI: 10.1542/peds.2011-0123
PubMed: 22529283

The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: a case report.
Salvarinova-Zivkovic R, Hartnett C, Sinclair G, Dix D, Horvath G, Lillquist Y, Stockler-Ipsiroglu S
DOI: 10.1016/j.ymgme.2012.01.007
PubMed: 22305856

Failure of repeated cyclophosphamide pulse therapy in childhood cerebral X-linked adrenoleukodystrophy.
Horvath GA, Eichler F, Poskitt K, Stockler-Ipsiroglu S
DOI: 10.1055/s-0032-1307455
PubMed: 22430161

Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin.
Horvath GA, Selby K, Poskitt K, Hyland K, Waters PJ, Coulter-Mackie M, Stockler-Ipsiroglu SG
DOI: 10.1177/0333102411420584
PubMed: 22013141

Treatment of intractable epilepsy in a female with SLC6A8 deficiency.
Mercimek-Mahmutoglu S, Connolly MB, Poskitt KJ, Horvath GA, Lowry N, Salomons GS, Casey B, Sinclair G, Davis C, Jakobs C, Stockler-Ipsiroglu S
DOI: 10.1016/j.ymgme.2010.08.016
PubMed: 20846889

Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms.
Horvath GA, Stockler-Ipsiroglu SG, Salvarinova-Zivkovic R, Lillquist YP, Connolly M, Hyland K, Blau N, Rupar T, Waters PJ
DOI: 10.1016/j.ymgme.2008.01.003
PubMed: 18276179

Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.
Horvath GA, Davidson AG, Stockler-Ipsiroglu SG, Lillquist YP, Waters PJ, Olpin S, Andresen BS, Palaty J, Nelson J, Vallance H
PubMed: 18767270

Report of a fourth individual with a lethal syndrome of choanal atresia, athelia, evidence of renal tubulopathy, and family history of neck cysts.
Horvath GA, Armstrong L
DOI: 10.1002/ajmg.a.31734
PubMed: 17486625


Current Projects
Neurotransmitter and parasympathetic response in patients with dysautonomia, in collaboration with Dr. Jean-Paul Collet (CFRI). I follow several patients with dysautonomia in clinic, who had their baseline catecholamine measurements and then enroll them in this study to evaluate the effect of Chines massage therapy and Tai-Chi on their parasymapthetic nervous system.

Current Projects
Neurotransmitter changes in patients with presyncope, in collaboration with Dr. Shubayan Sanatani (BCCH) and Dr. Victoria Claydon (SFU) I evaluate pateints in clinic with complex autonomic dysfunction and presyncope, and then enroll them in this study where they have sophisticated investigations with a tilt table test at the SFU Kinesiology Lab. I work on the plasma catecholamine and serotonin level interpretations in relation to the other test findings.

Current Projects
Characterization of a new genetic disorder associated with hemiplagic migraines, coma, progressive spasticity, weakness, seizure disorder, spinal cord atrophy, and systemic serotonin deficiency. The research of a family with the above described phenotype lead to discovery of a new gene that involves cytoskeletal and axonal transport, and will cause cytoskeletal aggregates in neurons, that will keep neurotransmitter transporters (serotonin transporter) and other membrane expressed proteins (e.g. Na/K ATPase). This disorder has similarities with ALS, and could be a major breakthrough in ALS research. this research is done partly in collaboration with Dr. Randy Blakely at the Vanderbilt University in Nashville, who has done the exome sequencing in the family. I spent 6 weeks in his lab to do the molecular and biochemical studies. Before traveling there I developed a radioactive isotope method for measuring the serotonin trasnporter activity in vitro in these patients.


Rare Diseases Foundation: Molecular Genetic Analysis of the MMSD Gene in a Patient with Recurrent Metabolic Coma and Abnormal Urinary Excretion of 3-Hydroxyisobutyric Acid, 2009

Rare Diseases Foundation: Evaluation of choline and acetylcholine pathways in a child with progressive cholinergic failure, 2010

Rare Diseases Foundation:in vivo Phosphorus Magnetic Resonance Spectroscopy of the Muscle in Two Siblings with Unexplained Muscle Weakness, 2009

Honours & Awards

Clinical Investigator Program, two year scholarship awarded (July 2008 to June 2010)

Laura MacRae Award 2007 (awarded to outstanding graduate student in the Dept. of Pediatrics, UBC, by the College of Physicians and Surgeons of British Columbia, June 2007

Rookie of the Year 2007, (awarded by the Pediatric Residents, UBC, at the Annual Graduation and Awards Dinner), June 2007.