Laboratory of Molecular Neuropsychiatry

Laboratory of Molecular Neuropsychiatry

Laboratory of Molecular Neuropsychiatry investigates the role of endocrine and neurotransmitters systems and their corresponding genes in the etiology and treatment of neuropsychiatric and stress related disorders.

Head

DVM, PhD Nela Pivac

+385 1 457 1207
Fax: +3851 4561010
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Since the etiological and psychobiological basis of neuropsychiatric disorders is still unclear, but should be the consequence of interaction between genetic and environmental factors and specific proteins, the role of serotonergic, catecholaminergic, immunological, neurotrophic and neuroendocrine systems in psychiatric (depression, schizophrenia, posttraumatic stress disorders, alcoholism, suicidal and aggressive behaviour) and neurological (Alzheimer’s disease, epilepsy) disorders are the main topics of intensive research in the Laboratory of Molecular Neuropsychiatry.

The aims of the research are to determine the neurobiological variables and polymorphism of genes that are coding for proteins of serotonergic, catecholaminergic, immunological, neurotrophic and neuroendocrine systems in neuropsychiatric disorders and are specifically focused on the search of biomarkers for the best pharmacotherapy according to biochemical and/or molecular characteristics of patients.

D Muck-Šeler (2005. year) and N Pivac (2009. year) obtained National Science Award for the results in the research of biochemical and molecular markers of psychiatric and stress related disorders.

Between years 2002 -2011 the results were published in 64 scientific articles in journal cited in Current Contents base.

Dubravka Švob Štrac
Ph.D.

Senior Research Associate
+385 1 457 1365
1749

Gordana Nedić Erjavec
PhD

Senior assistant
+385 1 457 1265
1818

Matea Nikolac Perković
PhD

research assistant
1818

Nela Pivac
DVM, PhD

senior scientist
+385 1 457 1207
1321 1749
_

Genetic factors as markers of suicide

Glavni istraživač / voditelj: Nela Pivac

Molecular basis and treatment of psychiatric and stress related disorders

Glavni istraživač / voditelj: Nela Pivac

Stress related (acute stress reaction, posttraumatic stress disorder) and eating disorders, addictions (alcoholism), aggressive/suicidal behavior, and attention deficit hyperactivity disorder are frequent multifactorial and polygenic psychiatric disorders that induce a great suffering in patients and their families, and carry financial burden to the whole society. Molecular basis of these disorders involves the changes in neurotransmitter (primarily serotonin - 5-HT, noradrenalin, dopamine) and neuroendocrine systems, and functional gene polymorphisms controlling  the activity of the corresponding proteins.

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Pharmacogenomics and proteomics of serotonergic and catcholaminergic system

Glavni istraživač / voditelj: Dorotea Mueck Šeler

Serotonergic and catecholaminergic (dopaminergic, noradrenergic) neurotransmitter systems regulate physiological functions and are also connected to the etiology of complex and polygenic neuropsychiatric disorders (Alzheimer’s disease /AD/, frontotemporal dementia, schizophrenia and depression). Etiology and psychobiological mechanisms of neuropsychiatric disorders is not well understood, but could be the result of interaction of genetic factors, specific proteins and environment.

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Stress, GABA-A receptors and mechanisms of action of neuropsychoactive drugs

Stress, GABA-A receptors and mechanisms of action of neuropsychoactive drugs

Glavni istraživač / voditelj: Dubravka Švob Štrac

The purpose of the present research is to improve our understanding of the mechanisms of action of neuropshycoactive drugs, especially during their chronic administration and modification by stress. Particular emphasis is placed on the research of benzodiazepines and antidepressants, used to treat anxiety, insomnia and depression, which are acting via GABAergic and serotonergic systems in the brain. Therefore, we investigate the changes in the expression and function of GABA-A receptor in vitro after prolonged exposure to benzodiazepines, known to induce the development of tolerance and dependence. Moreover, by using experimental animals, we have been also investigating the interactions between the effects of stress and benzodiazepines and antidepressants, primarily on the susceptibility to convulsions, as well as the role of the serotonergic system in controlling brain excitability.

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1. Pivac N, Knezevic A, Gornik O, Pucic M, Igl W, Peeters H, Crepel A, Steyaert J, Novokmet M,  Redzic I, Nikolac M, Novkovic Hercigonja V, Dodig Curkovic K, Curkovic M, Nedic G, Mück-Seler D, Borovecki F, Rudan I, Lauc G. (2011) Human plasma glycome in attention-deficit hyperactivity disorder and autism spectrum disorders. Mol Cell Proteomics, 10.1: 1-7. IF=8,79

2. Pivac N, Nikolac M, Nedic G, Mustapic M, Borovecki F, Hajnsek S, Presecki P, Pavlovic M, Mimica N, Mück-Seler D (2011). Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer’s disease. Progr Neuro-Psychopharmacol Biol Psychiatry, 35: 356-362. IF=2,82

3. Mück-Seler D, Pivac N. (2011) Serotonin. Periodicum biologorum, 113: 29-41

4. Mück-Seler D, Sagud M, Mihaljevic-Peles A, Jakovljevic, Pivac N (2011) Baseline lipid levels and acute treatment response to paroxetine and tianeptine in depressed women. Letters to the Editors. J Clin Psychopharmacology, 31: 387-390. IF=5,09

5. Pregelj P, Nedic G, Videtic Paska A, Zupanc T, Nikolac M, Balazic J,  Tomori M, Komel R, Mück-Seler D, Pivac N. (2011) The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide. J Affect Disord, 128: 287-290. IF=3,763

6. Nedic G, Nikolac M, Nenadic Sviglin K, Mück-Seler D, Borovecki F, Pivac N (2011): Association study of a functional catechol-o-methyltransferase (COMT) val108/158Met and suicide attempts in patients with alcohol dependence. Int J Neuropsychopharmacol 14: 377-388. IF=4,874

7.Nenadic-Sviglin K, Nedic G, Nikolac M, Kozaric-Kovacic D, Stipcevic T, Mück-Seler D,  Pivac N. (2011) Suicide attempt, comorbid depression and platelet serotonin in alcohol dependence. Alcohol, 45: 209-216. IF=2,41

8.Nedic G, Pivac N, Kocijan Hercigonja D, Jovancevic M, Dodig Curkovic K, Mück-Seler D Platelet monoamine oxidase activity in children with attention-deficit/hyperactivity disorder (2010) Psychatry Res, 175: 252-255. IF=2,373

9.Nedic G, Nikolac M,  Borovecki F,  Hajnsek S, Mück-Seler D, Pivac N. (2010) Association study of a functional catechol-O-methyl-transferase polymorphism and smoking in healthy Caucasian subjects. Neurosci Lett., 473: 216-219.  IF=1,93

10.Sagud M, Mihaljevic Peles A, Pivac N, Jakovljevic M, Mück- Seler D (2009)  Lipid levels in female patients with affective disorders. Psychiatry Res, 168: 218-221 IF=2,37

11.Stipcevic T, Kusacic-Kuna S,   Dezeljin M,   Dodig D, Korsic M, Pivac N, Mück-Seler D (2009) Platelet serotonin concentration and monoamine oxidase activity in hypothyroid patients. Hormone Research, 71: 207-212. IF=1,73

12.Pivac N, Kim B, Nedic G, Joo YH, Kozaric-Kovacic D, Hong JP, Mück-Seler D (2009) Ethnic differences in the brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy subjects. Croat Med J, 50, 43-48. IF=1,37

13.Pivac N,  Nedic G, Mustapic M,  Babic A, Stipcevic T,  Borovecki F,  Hajnsek S, Mück-Seler D. (2009) The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy  subjects. Neurosci Lett 462: 45-48. IF=1,93

14.Mück-Seler D, Presecki P, Mimica N, Mustapic M, Pivac N, Babic A,  Nedic G, Folnegovic-Smalc V (2009). Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer’s disease. Progr Neuro-Psychopharmacol Biol Psychiatry, 33: 1226-1231.  IF=2,82

15. Sagud M, Pivac N, Nedic G, Mihaljevic Peles A, Kramaric M, Jakovljevic M, Mück-Seler D (2008) The effect of lamotrigine on platelet serotonin concentration in patients with bipolar depression. Letter to the editors. Psychopharmacology, 4: 683-685. IF=4,103

16.Mück-Seler D, Sagud M, Mustapic M, Nedic G, Babic A, Mihaljevic Peles A, Jakovljevic M, Pivac N (2008). The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression. Progress Neuro-Psychopharmacol Biological Psychiatry, 32: 1195-1198. IF=2,82

17.Noskova T, Pivac N, Nedic G, Kazantseva A, Gaysina D, Faskhutdinova G, Gareeva A, Khalilova Z, Khusnutdinova E, Kozaric Kovacic D, Kovacic Z, Jokic M, Mück-Seler D (2008)  Ethnic differences in the serotonin transporter polymorphism (5-HTTLPR) in several European populations. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32, 1735-1739. IF=2,82

18.Sagud M, Mihaljevic-Peles A, Pivac N, Jakovljevic M, Mück-Seler D (2007) Platelet serotonin and serum lipids in psychotic mania. J. Affect. Disord., 97: 247-251. IF=3,763

19.Pivac N, Knezevic J, Kozaric-Kovacic  D, Dezeljin M, Mustapic M, Rak D, Matijevic T, Pavelic J, Mück-Seler D (2007) Monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity in combat related posttraumatic stress disorder, J Affect Disord., 103, 131-138. IF=3,763

20.Mustapic M, Pivac N, Kozaric-Kovacic D, Dezeljin M, Cubells JF, Mück-Seler D (2007) Dopamine beta-hydroxylase (DBH) activity and -1021C/T polymorphism ofDBHgene in combat-related posttraumatic stress disorder. Am J Med Genetics Part B Neuropsychiatry Genetics, 144B: 1087-1089. IF=3,481

21.Pivac N, Knezevic J, Mustapic M, Dezeljin M, Mück-Seler D,  Kozaric-Kovacic D, Balija M, Matijevic T, Pavelic J (2006) The lack of association between monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO activity among men. Life Sci., 79, 45-49. IF=2.583

22.Pivac N, Kozaric-Kovacic D, Mustapic M, Dezeljin D, Borovecki A, Grubisic-Ilic M, Mück-Seler D (2006) Platelet serotonin in combat related posttraumatic stress disorder with psychotic symptoms. J. Affect. Disord., 93, 223-227. IF=3.763

23.Sagud M, Mihaljevic-Peles A, Mück-Seler D, Jakovljevic M,  Pivac N (2006) Quetiapine augmentation in treatment-resistant depression: a naturalistic study. Psychopharmacology, 187, 511-514., IF=4103

24.Kozaric-Kovacic D, Pivac N, Mück-Seler D, Rothbaum BO (2005) Risperidone in psychotic combat related posttraumatic stress disorder: an open trial. J. Clin. Psychiatry, 66,  922-927.  IF=5,218

25.Pivac N, Mück-Seler D, Kozaric-Kovacic D, Mustapic M, Nenadic-Sviglin K, Dezeljin M  (2005) Platelet monoamine oxidase in alcoholism. Psychopharmacology, Letter to the Editors., 182,  194-196. IF=4.103

26..Pivac N, Kozaric-Kovacic D, Mück-Seler D (2004) Olanzapine versus fluphenazine in an open trial in patients with psychoptic combat related posttraumatic stress disorder. Psychopharmacology, 175, 451-456. IF=4.103

27.Mück-Seler D, Pivac N, Mustapic M, Crncevic Z, Jakovljevic M, Sagud M (2004) Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. Psychiatry Res., 127, 217-226. IF=2,373

28.Pivac N, Mück-Seler D, Mustapic M, Nenadic-Sviglin K, Kozaric-Kovacic D (2004) Platelet serotonin concentration in alcoholic subjects. Life Sci., 76, 521-531. IF=2,56

29.Mück-Seler D, Pivac N, Jakovljevic M, Sagud M, Mihaljevic-Peles A (2003) Platelet 5-HT concentration and comorbid depression in war veterans with or without posttraumatic stress disorder. J. Affect. Disord., 75, 171-179 IF=3,763

30.Pivac N, Mück-Seler D, Diksic M (2003) Effects of desipramine on regional serotonin synthesis in the rat brain: acute and chronic autoradiographic studies. Neurochem. Int., 43, 611-619. IF=3,541

31.Pivac N, Mück-Seler D, Sagud M, Jakovljevic M, Mustapic M, Mihaljevic-Peles A (2003) Long-term sertraline treatment and peripheral biochemical markers in female depressed patients. Prog. Neuro-Psychopharmacol. Biol. Psychiat.,  27, 759-765. IF=2,82

32.Mück-Seler D, Pivac N (2003) The effect of natural clinoptilolite on the serotonergic receptors in the brain of mice with mammary carcinoma. Life Sci., 73, 2059-2069. IF=2,560

33.Sagud M, Pivac N, Mück-Seler D, Jakovljevic M, Mihaljevic-Peles A, Korsic M (2002) Effects of sertraline treatment on plasma cortisol, prolactin and thyroid hormones in female depressed patients. Neuropsychobiology, 45, 139-143. IF=2,15

34.Pivac N, Mück-Seler D, Sagud M, Jakovljevic M (2002) Platelet serotonergic markers in posttraumatic stress disorder. Prog. Neuro-Psychopharmacol. Biol. Psychiat., 26, 1193-1198. IF=2,82

35. Mück-Seler D, Pivac N, Sagud M,  Jakovljevic M, Mihaljevic-Peles A (2002) The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression. Prog. Neuro-Psychopharmacol. Biol. Psychiat., 26, 1235-1243. IF=2,82

 

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