Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms
Abstract
Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Abnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have been implicated in suicide.
“Abnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have also been implicated in suicide.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [32]
Alterations in CB1 receptor expression in the dorsolateral prefrontal cortex of suicide victims, particularly among those with comorbid substance use, implicate the endocannabinoid system in emotional regulation and stress response.
“Alterations in CB1 receptor expression in the dorsolateral prefrontal cortex (PFC) of suicide victims, particularly among those with comorbid substance use, further implicate the endocannabinoid system in emotional regulation and stress response (32–34).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [32]
Cites
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
(1997) · American Psychiatric Press eBooks · Cited by 3,056 · see citing works
Sheehan, D., Lecrubier, Y., Harnett Sheehan, K., Janavs, J., Weiller, E., Keskiner, A., Schinka, J., Knapp, E., Sheehan, M., & Dunbar, G. (1997) · European Psychiatry · doi:10.1016/s0924-9338(97)83297-x · Cited by 2,149 · see citing works
Lachman, H. M., Papolos, D. F., Saito, T., Yu, Y.-M., Szumlanski, C. L., & Weinshilboum, R. M. (1996) · Pharmacogenetics · doi:10.1097/00008571-199606000-00007 · Cited by 1,788 · see citing works
A functional polymorphism in the monoamine oxidase A gene promoter
Sabol, S. Z., Hu, S., & Hamer, D. (1998) · Human Genetics · doi:10.1007/s004390050816 · Cited by 1,079 · see citing works
Schizophrenia, “just the facts” 4. Clinical features and conceptualization
Tandon, R., Nasrallah, H. A., & Keshavan, M. S. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.03.005 · Cited by 1,031 · see citing works
Wallwork, R. S., Fortgang, R. G., Hashimoto, R., Weinberger, D. R., & Dickinson, D. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.01.031 · Cited by 843 · see citing works
Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR
Vandenbergh, D. J., Persico, A. M., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., & Uhl, G. R. (1992) · Genomics · doi:10.1016/s0888-7543(05)80138-7 · Cited by 708 · see citing works
Reliability and validity of a depression rating scale for schizophrenics
Addington, D., Addington, J., Maticka-Tyndale, E., & Joyce, J. (1992) · Schizophrenia Research · doi:10.1016/0920-9964(92)90003-n · Cited by 651 · see citing works
Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation
McDermott, R., Tingley, D., Cowden, J., Frazzetto, G., & Johnson, D. D. P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808376106 · Cited by 384 · see citing works
Glatt, S. J., Faraone, S. V., & Tsuang, M. T. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.3.469 · Cited by 343 · see citing works
Specificity of the Calgary Depression Scale for schizophrenics
Addington, D. E., ADDINGTON, J., & Maticka‐Tyndale, E. (1994) · Schizophrenia Research · doi:10.1016/0920-9964(94)90017-5 · Cited by 267 · see citing works
Fan, J., Zhang, C.-S., Gu, N., Li, X.-W., Sun, W.-W., Wang, H.-Y., Feng, G.-Y., Clair, D. S., & He, L. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.018 · Cited by 259 · see citing works
A network of dopaminergic gene variations implicated as risk factors for schizophrenia.
Talkowski, M. E., Kirov, G., Bamne, M., Georgieva, L., Torres, G. E., Mansour, H. A., Chowdari, K., Milanova, V., Wood, J., McClain, L., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm347 · Cited by 154 · see citing works
Factor structure and external validity of the PANSS revisited
van den Oord, E. J. C. G., Rujescu, D., Robles, J. R., Giegling, I., Birrell, C. E., Bukszár, J., Murrelle, L., Möller, H., Middleton, L. T., & Muglia, P. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2005.09.002 · Cited by 151 · see citing works
Malhotra, A. K., Goldman, D. A., Mazzanti, C. M., Clifton, A. D., Breier, A. F., & Pickar, D. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000412 · Cited by 132 · see citing works
Fan, J., & Sklar, P. B. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001690 · Cited by 130 · see citing works
Meta-analysis of association between genetic variants in COMT and schizophrenia: An update
Okochi, T., Ikeda, M., Kishi, T., Kawashima, K., Kinoshita, Y., Kitajima, T., Yamanouchi, Y., Tomita, M., Inada, T., Ozaki, N., et al. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.02.019 · Cited by 126 · see citing works
Chen, X., Wang, X., O’Neill, F. A., Walsh, D., & Kendler, K. S. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001519 · Cited by 125 · see citing works
Strous, R. D., Nolan, K. A., Lapidus, R., Diaz, L., Saito, T., & Lachman, H. M. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20021 · Cited by 115 · see citing works
The role of the serotonergic system at the interface of aggression and suicide
Bortolato, M., Pivac, N., Šeler, D. M., Perković, M. N., Pessia, M., & Giovanni, G. D. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.015 · Cited by 110 · see citing works
Majadas, S., Olivares, J. M., Galan, J., & Díez, T. (2011) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2011.03.009 · Cited by 102 · see citing works
Serotonin transporter gene (5-HTTLPR) and major psychoses
Serretti, A., Lilli, R., Lorenzi, C., Lattuada, E., Cusin, C., & Smeraldi, E. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000936 · Cited by 92 · see citing works
Norton, N., Kirov, G., Zammit, S., Jones, G., Jones, S., Owen, R., Krawczak, M., Williams, N. M., O’Donovan, M. C., & Owen, M. J. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10517 · Cited by 90 · see citing works
Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia
Zammit, S., Jones, G., Jones, S. J., Norton, N., Sanders, R. D., Milham, C., McCarthy, G. M., Jones, L. A., Cardno, A. G., Gray, M. Y., et al. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30021 · Cited by 80 · see citing works
Association between Val108/158met polymorphism of theCOMTgene and schizophrenia
Wonodi, I., Stine, O. C., Mitchell, B. D., et al. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20037 · Cited by 77 · see citing works
Costas, J., Sanjuán, J., Ramos‐Ríos, R., Paz, E., Agra, S., Ivorra, J. L., Páramo, M., Brenlla, J., & Arrojo, M. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.04.021 · Cited by 70 · see citing works
Goghari, V. M., & Sponheim, S. R. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.05.015 · Cited by 69 · see citing works
Kuželová, H., Ptáček, R., & Maçek, M. (2010) · PubMed · Cited by 68 · see citing works
Han, D. H., Park, D. B., Na, C., Kee, B. S., & Lee, Y. S. (2004) · Psychiatry Research · doi:10.1016/j.psychres.2004.06.013 · Cited by 62 · see citing works
Wang, Y., Fang, Y., Shen, Y., & Xu, Q. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2009.03.029 · Cited by 58 · see citing works
Association between a promoter variant in the monoamine oxidase A gene and schizophrenia
Jönsson, E. G., Norton, N., Forslund, K., Mattila-Evenden, M., Rylander, G., Åsberg, M., Owen, M. J., & Sedvall, G. C. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00224-4 · Cited by 57 · see citing works
Bayle, F., Leroy, S., Gourion, D., Millet, B., Olié, J., Poirier, M. F., & Krebs, M. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10037 · Cited by 55 · see citing works
Sazcı, A., Ergül, E., Küçükali, C. İ., Kılıç, G., Kaya, G., & Kara, İ. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.09.005 · Cited by 54 · see citing works
Schennach, R., Obermeier, M., Seemüller, F., Jäger, M., Schmauß, M., Laux, G., Pfeiffer, H., Naber, D., Schmidt, L., Gäebel, W., et al. (2012) · Psychopathology · doi:10.1159/000336729 · Cited by 53 · see citing works
COMT Val158Met and BDNF C270T polymorphisms in schizophrenia: a case-control study
Galderisi, S., Maj, M., Kirkpatrick, B. W., et al. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.06.017 · Cited by 48 · see citing works
Goldberg, T. E., Kotov, R., Lee, A. T., Gregersen, P. K., Lencz, T., Bromet, E. J., & Malhotra, A. K. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.03.021 · Cited by 45 · see citing works
Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features
Bergen, S. E., Fanous, A. H., Walsh, D., O’Neill, F. A., & Kendler, K. S. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.02.009 · Cited by 40 · see citing works
Gamma, F., Faraone, S. V., Glatt, S. J., Yeh, Y.-C., & Tsuang, M. T. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.09.020 · Cited by 40 · see citing works
Functional catechol-O-methyltransferase gene polymorphism and susceptibility to schizophrenia
Park, T. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)00030-5 · Cited by 40 · see citing works
Huang, S.-Y., Chen, H., Ma, K.-H., Shy, M.-J., Chen, J.-H., Lin, W.-C., & Lu, R.-B. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2009.10.004 · Cited by 39 · see citing works
Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese
Wei, Y., Li, C., Li, S., Liu, Y., & Hu, L. (2011) · Behavioral and Brain Functions · doi:10.1186/1744-9081-7-42 · Cited by 39 · see citing works
Platelet serotonin concentration and depressive symptoms in patients with schizophrenia
Peitl, V., Vidrih, B., Karlović, Z., Getaldić, B., Peitl, M., & Karlović, D. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.03.006 · Cited by 39 · see citing works
Self-citationStrous, R. D., Lapidus, R., Viglin, D., Kotler, M., & Lachman, H. M. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.09.067 · Cited by 37 · see citing works
The genetic relationship of personality to major depression and schizophrenia
Fanous, A. H., & Kendler, K. S. (2004) · Neurotoxicity Research · doi:10.1007/bf03033295 · Cited by 35 · see citing works
Meta‐study on association between the monoamine oxidase A gene (MAOA) and schizophrenia
Li, D., & He, L. (2007) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30570 · Cited by 31 · see citing works
Nunokawa, A., Watanabe, Y., Muratake, T., Kaneko, N., Koizumi, M., & Someya, T. (2007) · Neuroscience Research · doi:10.1016/j.neures.2007.03.015 · Cited by 29 · see citing works
Han, D. H., Park, D. B., Choi, T. Y., Joo, S. Y., Lee, M. K., Park, B. R. G., Nishimura, R., Chu, C.-C., & Renshaw, P. F. (2008) · Neuroreport · doi:10.1097/wnr.0b013e32830867ad · Cited by 29 · see citing works
Catechol‐O‐methyltransferase and the clinical features of psychosis
McClay, J. L., Fanous, A. H., van den Oord, E. J. C. G., Webb, B. T., Walsh, D., O’Neill, F. A., Kendler, K. S., & Chen, X. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30401 · Cited by 28 · see citing works
Monoamine Oxidase A and B Gene Polymorphisms and Negative and Positive Symptoms in Schizophrenia
Camarena, B., Fresán, A., Aguilar, A., et al. (2012) · ISRN Psychiatry · doi:10.5402/2012/852949 · Cited by 28 · see citing works
Qiu, H., Meng, H. Q., Song, C., Xiu, M. H., Chen, D. C., Zhu, F. Y., Wu, G. Y., Kosten, T. A., Kosten, T. R., & Zhang, X. (2009) · Brain Research · doi:10.1016/j.brainres.2009.06.072 · Cited by 27 · see citing works
Chen, C., Lu, R., Yeh, Y., Shih, M.-C., & Huang, S. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00670.x · Cited by 27 · see citing works
Ikeda, M., Iwata, N., Suzuki, T., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., & Ozaki, N. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0349-6 · Cited by 27 · see citing works
HapMap tag-SNP analysis confirms a role forCOMTin schizophrenia risk and reveals a novel association
Voisey, J., Swagell, C. D., Hughes, I. P., Lawford, B. R., Young, R. M., & Morris, C. P. (2010) · European Psychiatry · doi:10.1016/j.eurpsy.2010.08.004 · Cited by 26 · see citing works
Martorell, L., Costas, J., Valero, J., Gutiérrez-Zotes, A., Phillips, C., Torres, M., Brunet, A., Garrido, G., Carracedo, Á., Guillamat, R., et al. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2007.11.001 · Cited by 25 · see citing works
Carlström, E. L., Saetre, P., Rosengren, A., Thygesen, J. H., Djurovic, S., Melle, I. S., Andreassen, O. A., Werge, T. M., Agartz, I., Hall, H., et al. (2012) · Behavioral and Brain Functions · doi:10.1186/1744-9081-8-24 · Cited by 24 · see citing works
Pelayo‐Terán, J. M., Crespo‐Facorro, B., Carrasco-Marı́n, E., Pérez‐Iglesias, R., Mata, I. F., Arranz, M. J., Leyva‐Cobián, F., & Vázquez‐Barquero, J. L. (2007) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30639 · Cited by 24 · see citing works
Sun, Y., Zhang, J., Yuan, Y., Yu, X., Shen, Y., & Xu, Q. (2011) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32009 · Cited by 23 · see citing works
Lee, H.-Y., Kim, D., Lee, H., Choi, J.-E., & Kim, Y. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.11.013 · Cited by 23 · see citing works
Contreras, J., Hare, L., Camarena, B., Glahn, D. C., Dassori, A. M., Medina, R., Contreras, S. A., Ramirez, M., Armas, R., MUNOZ, R. A., et al. (2008) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01273.x · Cited by 22 · see citing works
Tovilla‐Zárate, C. A., Camarena, B., Fresán, A., López‐Narváez, M. L., González‐Castro, T. B., Juárez‐Rojop, I. E., Ramírez‐Bello, J., Genis, A. D., & Nicolini, H. (2012) · Molecular Biology Reports · doi:10.1007/s11033-012-2264-x · Cited by 22 · see citing works
Serotonin transporter polymorphism and depressive‐related symptoms in schizophrenia
Голимбет, В. Е., Алфимова, М. В., Shchebatykh, T. V., Abramova, L. I., Каледа, В. Г., & Rogaev, E. I. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20135 · Cited by 22 · see citing works
Association between the SLC6A3 A1343G polymorphism and schizophrenia
Cordeiro, Q., Siqueira-Roberto, J., & Vallada, H. (2010) · Arquivos de Neuro-Psiquiatria · doi:10.1590/s0004-282x2010000500008 · Cited by 19 · see citing works
Konneker, T., Crowley, J. J., Quackenbush, C. R., Keefe, R. S. E., Perkins, D. O., Stroup, T. S., Lieberman, J. A., van den Oord, E. J. C. G., & Sullivan, P. F. (2010) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31077 · Cited by 17 · see citing works
Stöber, G., Sprandel, J., Jabs, B. E., et al. (2006) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-006-0657-3 · Cited by 17 · see citing works
Serotonin transporter polymorphism (5-HTTLPR) in Croatian population
Culej, J., Štefanović, M., Ćelap, I., Nikolac, N., & Karlović, D. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3800-7 · Cited by 6 · see citing works
Self-citationSerotonin Transporter Polymorphism in Relation to Depression
Peitl, V., Karlović, D., Štefanović, M., & Vrkić, N. (2015) · Hrčak Portal of scientific journals of Croatia (University Computing Centre) · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Zhuang, Z., Yang, R., Wang, W., Qi, L., & Huang, T. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01961-8 · Cited by 220 · see citing works
Salehi, M., Saeidi, M., Amanat, M., Barias, T., Anyeji, U., Alzein, O., & Gunturu, S. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1738009
“Alterations in CB1 receptor expression in the dorsolateral prefrontal cortex (PFC) of suicide victims, particularly among those with comorbid substance use, further implicate the endocannabinoid system in emotional regulation and stress response (32 – 34).”
- Authors
- Peitl, V., Štefanović, M., & Karlović, D.
- Affiliations
- University Hospital Centre Zagreb (HR)
- Corresponding author
- Karlović, Dalibor
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 77
- Pages
- 209-215
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2605536328
- Cited by
- 48
- References
- 67
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 9 · 2019: 8 · 2018: 8
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- depressive symptoms, schizophrenia, genetic polymorphism, serotonin transporter, 5-HTTLPR, COMT Val158Met, dopamine transporter, serotonergic neurotransmission, dopamine signaling, suicidality, negative symptoms, sex differences
- MeSH terms
- Adult, Catechol O-Methyltransferase, Depression, Dopamine, Factor Analysis, Statistical, Female, Humans, Male, Monoamine Oxidase, Polymorphism, Genetic, Schizophrenia, Serotonin, Case-Control Studies, Minisatellite Repeats, Dopamine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
