Skip to main content

CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders

Abstract

Background

The aim of our study was to evaluate the expression of the CASP3 gene at both mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the pathogenesis of depression;

Methods

A total of 290 subjects, including 190 depressed patients and 100 healthy controls, participated in the study. Socio-demographic and clinical data were collected, and the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Venous blood was collected and gene expression was evaluated using RT-PCR and ELISA at the mRNA and protein levels, respectively;

Results

The expression of the CASP3 gene was significantly lower in depressed patients compared to healthy controls at both the mRNA and protein levels. Additionally, a positive correlation was observed between CASP3 gene expression and disease duration as well as the number of depressive episodes;

Conclusions

Further studies are needed to investigate the role of caspase 3 in depressive disorders.

Peer Review reports

Introduction

Depression is considered a scourge of the modern world. According to the reports of World Health Organization around 5% of adults worldwide experience depression [1]. Despite its high prevalence, the underling pathomechanism of depression is not fully understood. Hence, further studies searching for potential factors contributing to the development of this mental disorder are necessary.

The aim of this study was to evaluate the expression of the CASP3 gene at the mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the etiopathogenesis of depression.

Caspase 3 (encoded by CASP3 gene) is a major member of the caspase-family of cysteine proteases. It is considered to be a key mediator of apoptosis in neuronal cells. Studies conducted on animal models also suggest that caspase 3 also functions as a regulatory molecule in neurogenesis and synaptic activity [2,3,4]. Considering the importance of these processes in various mental disorders, including depression, the assessment of the role of caspase 3 in the etiopathogenesis of depressive disorders seems to be justified.

Materials and methods

A total of 290 subjects(183 F, 107 M) aged 18 to 67 (41.29 ± 13.50 years) participated in the study. The study group consisted of 190 hospitalized patients (117 F, 73 M, mean age: 47.51 ± 11.18 yrs.) with depressive disorders, including both recurrent depressive disorders (F33 according to ICD-10 diagnostic criteria) and a depressive episode (F32 according to ICD-10) [5]. The material for the study was collected from patients in the current depressive episode. Participation in the study did not affect the type of administered treatment. Exclusion criteria from the study included serious mental illnesses other than depressive disorders, serious neurological and somatic diseases, in particular autoimmune and neurodegenerative diseases, active cancer, addiction to alcohol or other psychoactive substances. The control group consisted of 100 healthy individuals (66 F, 34 M, mean age: 29.36 ± 8.71 yrs.) with negative history for psychiatric disorders.

Women predominated in both groups. There was no statistically significant difference between the groups in terms of gender (p = 0.4583). Patients from the study group were statistically significantly older than healthy controls (p < 0.0001 for the multifactor generalized linear model fitted, p < 0.001 for “by-group” comparison, p = 0.528 for “by-gender” comparison), which results from the characteristics of depressive disorders and may constitute a certain limitation of this study. However, the study did assess the correlation between the age of the subjects and other variables (see Results).

Clinical data on the duration of the disease (in years), the number of depressive episodes, and the number of hospitalizations (including the current one) were collected from the patients from the study group (Table 1). In patients from the study group, the severity of depressive symptoms was also assessed according to the 17-item Hamilton Depression Rating Scale (HDRS) (Fig. 1) [6]. Due to the fact that the study group consisted of hospitalized patients, most of them had severe depressive symptoms (Fig. 1).

Table 1 Clinical characteristics of the study group
Fig. 1
figure 1

Hamilton Depression Rating Scale (HDRS) results in study group patients

Venous blood was collected from all study participants (study group and control group) on the day of inclusion in the study for further biochemical analysis. RT-PCR was used to evaluate gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to evaluate gene expression at the protein level.

Total RNA isolation from the patients’ blood samples (leukocyte monolayer cells) using a RNA extraction reagent, TRIZOL (Invitrogen Life Technologies, Carlsbad, CA, USA), according to the standard acid-guanidinium-phenol-chlorophorm method was performed using modified Chomczyński metod [7].

The quality of total RNA was checked with Agilent RNA 6000 Nano Kit (Agilent Technologies) in accordance with the manufacturer’s recommendations. The quality of isolated RNA was checked using 2100 Bioanalyzer (Agilent Technologies). The level of degradation of total RNA was determined with the use of an electrophoretogram and RIN values recorded. Only the samples with RIN value > 7 were subject to further analysis [8].

An RT reaction was carried out using TaqMan® RNA Reverse Transcription Kit (Applied Biosystems) based on the manufacturer’s recommendations, using specific Hs 00234387_m1, Hs04194366_g1 probes, specific respectively for CASP3 and RPL13A genes, delivered by Applied Biosystems [8].

Real-Time PCR reaction was conducted using TaqMan® Universal PCR Master Mix, No UNG (Applied Biosystems) according to the protocol provided by the manufacturer. To calculate relative expression of miRNA genes, the Ct comparative method was used [9, 10]. The level of CASP3 gene expression in blood was normalized in relation to RPL13A reference gene [8].

The concentration of protein caspase 3 in the serum of the patients was determined using Human Caspase Elisa Kit from ThermoFischer Scentific (Waltham, MA, USA)according to the protocols provided by the manufacturer. β-actin was used for endogenous control of protein concentration in the samples and determined with the help of Human Actin Beta (ACTb) ELISA Kit (BMASSAY) based on the manufacturer’s recommendations [8].

The statistical analysis was carried out by using IBM SPSS Statistics, v. 28 (IBM Corporation, Armonk, NY, USA). A level of p < 0.05 was deemed statistically significant. All statistical procedures were set as two-tailed. For contingency cross-tables a chi-squared test was used. Generalized linear models with robust standard errors were performed to test differences in numerical traits between the studied groups. All the models were controlled for the participants’ age and gender. The gene (mRNA) expression levels had been log transformed before testing the hypothesis. There were computed the Pearson correlation coefficient for variables measured on the same scale, and Spearman’s rank correlation coefficient for traits measured on various scales.

Results

The expression of the CASP3 gene, both at the mRNA and protein level, was statistically significantly lower in the group of patients with depression than in healthy subjects (Table 2; Figs. 2 and 3).

Table 2 Detailed descriptive statistics for CAPS3 gene expression by study group
Fig. 2
figure 2

CASP3 gene mRNA expression

Fig. 3
figure 3

CASP3 gene expression at the protein level

The relationship between the expressions of the studied gene and clinical variables was also determined (Table 3). There was a positive correlation between the disease duration and the CASP3 gene expression as well as between the number of depressive episodes and the CASP3 gene expression (Table 3).

Table 3 The relationship between the expressions of CASP3 gene and clinical variables

Discussion

The name “caspases” comes from the English words “cysteine-dependent, aspartate-specific peptidases”. They are enzymes from the group of cysteine ​​proteases, which, when activated by apoptosis signals, degrade cellular proteins, cutting the peptide bond behind the aspartate residue. They provide critical links in cell regulatory networks controlling inflammation and cell death [11, 12].

Caspase 3 is an effector caspase, which is activated by caspase 9 (initiator caspase) and plays an important role in apoptosis. Both the extrinsic (death receptor dependent) and intrinsic (mitochrondrial) apoptotic pathways meet at caspase 3. This enzyme is said to be a key mediator of neuronal apoptosis [2]. However, recent studies also indicate important nonapoptotic functions of this enzyme.

Caspase 3 is also involved in the neural differentiation and its activity in neuronal progenitors facilitates neurogenesis [13]. The experiment performed on the clonally derived neurospheres from the striatum of murine embryos showed significant increase in caspase 3 activity during neurosphere differentiation, without the cleavage of PARP (which normally occur during apoptosis), suggesting nonapoptotic role of this caspase in neurogenesis [13]. Additionally the inhibition of caspase 3 activity alters the expression of proteins associated with neurosphere differentiation, like for example nestin or β-III tubulin [13]. Moreover, many proteins that are crucial in synaptic plasticity are substrates for caspase 3 [14], which supports the important role of this enzyme in neuroplasticity. The effects of caspase 3 inhibition (via administration of DEVD-fmk) on learning and memory were also evaluated. The intracerebroventricular administration of z-DEVD-fmk decreased the number of avoidance reactions in active avoidance learning in rats. Application of caspase 3 inhibitor to the cerebellar vermis stimulated the extinction of an acoustic startle reaction [2, 15]. Activated caspase 3 is present, in vivo, in the postsynaptic terminal of neurons in the auditory forebrain of small passerine bird of central Australia and is necessary for the development of long-term habituation to a song [16]. If caspase 3 activity contributes to synaptic plasticity, then a mechanism must also exist for limiting its proteolytic effect at the synapse level avoiding the dismantling of the rest of the neuron. For example, the synaptic caspase 3 activity can be suppressed by nine-amino acid active fragment of activity-dependent neurotrophic factor (ADNF-9) [17]. Caspase 3 can be considered a regulatory molecule in neurogenesis and neuroplasticity.

Understanding of the nonapoptotic function of caspase 3 may have potential implications for the comprehension of pathomechanisms of psychoneurological disorders. Numerous studies have demonstrated the neuroprotective effect of the caspase 3 inhibitor Z-DEVD-FMK on rodent models with traumatic brain injury (TBI) [18]. The caspase 3 inhibitor from Merck Frost Canada, L-826791, was revealed to reduce apoptosis in the hippocampus and piriform cortex in preclinical trials for the treatment of brain injury [19, 20]. Application of caspase 3 inhibitors has also proven efficacy in rescuing the Alzheimer-like phenotypes in mice models [21]. Other studies on AD-animal models indicate that caspase inhibitors might prevent cleavage of tau protein [22], alleviate cognitive impairment and delay cognitive decline [20, 23, 24]. Degeneration of dopaminergic neurons in subjects with Parkinson’s disease by apoptosis has been suggested. Also in case of this neurodegenerative disorder usage of caspase inhibitors lead to significant reduction of dopamine depletion in the striatum and inhibited the loss of dopaminergic neurons in the substantia nigra [20, 25, 26]. The treatment with caspase inhibitors (including caspase 3 inhibitors) was able to provide neuroprotective effects in a rodent model with Huntington’s disease [20, 25, 27]. However, it is worth mentioning that the application of caspase inhibitors is limited to preclinical studies on animal models.

Depressive disorders and neurodegenerative diseases are clinically recognized as two entirely different entities; however, they can often cooccur. The prevalence of depression can be as high as 90% in Alzheimer’s disease and 50% in patients with Parkinson’s disease [28]. This common concomitant presentation of these disorders raises many questions regarding the pathophysiological links between these disorders. There are some overlapping pathomechanism, that are present both in depression and neurodegenerative diseases like neuroinflammation [29] and the disturbances in monoamine neurotransmission [30], hypothalamus-pituitary-axis dysfunction, decreased levels of brain-derived neurotrophic factor (BDNF) and increased oxidative stress levels [29, 31].

Depression leads to neuroplasticity changes in specific regions of the brain which are correlated to symptom severity, negative emotional rumination as well as fear learning. Depression is correlated with atrophy of neurons in the cortical and limbic brain regions that control mood and emotion [32,33,34].

Considering the importance of neurogenesis and neuroplasticity processes in the etiopathogenesis of depression, we decided to investigate the expression of the gene for caspase 3 in patients hospitalized for depressive disorders and in healthy volunteers. In our study the expression of the CASP3 gene, both at the mRNA and protein level, was statistically significantly lower in the group of patients with depression than in healthy controls. We are not aware of any other studies on the expression of the CASP3 gene in this group of patients. In contrast, Szymona et al.. (2019) reported significantly higher expression of CASP3 gene in schizophrenic patients compared to the controls [35]. CASP3 protein was also up-regulated in fibroblasts of patients with Down syndrome [36]. Our study may suggest that apoptotic and neuroplasticity processes are not as important as previously suggested in the etiopathogenesis of depression. However, it is important to remember that expression does not necessarily translate into enzyme activity and the samples in our study were collected from the peripheral blood, not as it is possible on animal models from the neuronal tissue.

Limitations

Studies indicate that determinations from peripheral blood of expression at the mRNA level and at the protein level for genes largely reflect expression in the central nervous system [37], but there is a lack of comparison in the available literature of results for CASP3 gene in patients with depressive disorders.

Hence, the study was conducted on hospitalized psychiatric patients most of them already received treatment before admission. In order to minimalize the effect of treatment on gene expression, the blood was collected at the beginning of the hospitalization, when the depressive symptoms were the most severe and before the modification of existing antidepressant treatment. Although, an effect of treatment on the expression of the studied genes cannot be ruled out.

Conclusions

Despite their high prevalence, the etiopathogenesis of depressive disorders is not fully understood. Seeking for novel biomarkers, contributing factors and possible therapeutic targets in depression is necessary. Numerous preclinical animal model studies provide a lead for further investigations in understanding the exact roles of caspase 3. Our study suggest that CASP3 might play a role in pathogenesis of depression. However further studies are needed to understand the exact role of this enzyme in depression and to provide a better approach for targeting caspases and therapeutic advantage.

Data availability

The data that support the findings of this study are available upon reasonable request from author M.G.

References

  1. World Health Organization. available online: https://www.who.int/news-room/fact-sheets/detail/depression (Accessed July 1st, 2023).

  2. D’Amelio M, Cavallucci V, Cecconi F. Neuronal caspase-3 signaling: not only cell death. Cell Death Differ. 2010;17:1104–14. https://doi.org/10.1038/cdd.2009.180.

    Article  CAS  PubMed  Google Scholar 

  3. Tzeng TT, Tsay HJ, Chang L, et al. Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid. J Biomed Sci. 2013;20:90. https://doi.org/10.1186/1423-0127-20-90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Avdeev DB, Stepanov SS, Gorbunova AV, et al. Immunohistochemical signs of apoptosis and neuroplasticity in the cerebral cortex of white rats after occlusion of the common carotid arteries. Neurosci Behav Physi. 2020;50:804–9. https://doi.org/10.1007/s11055-020-00969-0.

    Article  CAS  Google Scholar 

  5. The ICD-10. Classification of Mental and behavioural Disorders: Diagnostic Criteria for Research. World Health Organization; 1993.

  6. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. https://doi.org/10.1136/jnnp.23.1.56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chomczynski P, Sacchi N. Single - step method of RNA isolation by acid guanidinium thiocyanate- phenol - chloroform extraction. Anal Biochem. 1987;162:156–9.

    Article  CAS  PubMed  Google Scholar 

  8. Gałecka M, Szemraj J, Su KP, Halaris A, Maes M, Skiba A, Gałecki P, Bliźniewska-Kowalska K. Is the JAK-STAT signaling pathway involved in the pathogenesis of Depression? J Clin Med. 2022;11(7):2056. https://doi.org/10.3390/jcm11072056. PMID: 35407663; PMCID: PMC8999744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101–8.

    Article  CAS  PubMed  Google Scholar 

  10. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262.

    Article  CAS  PubMed  Google Scholar 

  11. McLuskey K, Mottram JC. Comparative structural analysis of the caspase family with other clan CD cysteine peptidases. Biochem J. 2015;466(2):219–32. https://doi.org/10.1042/BJ20141324.

    Article  CAS  PubMed  Google Scholar 

  12. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5(4):a008656. https://doi.org/10.1101/cshperspect.a008656. Erratum in: Cold Spring Harb Perspect Biol. 2015;7(4). pii: a026716. doi: 10.1101/cshperspect.a026716.

  13. Fernando P, Brunette S, Megeney LA. Neural stem cell differentiation is dependent upon endogenous caspase 3 activity. FASEB J. 2005;19(12):1671–3. https://doi.org/10.1096/fj.04-2981fje.

    Article  CAS  PubMed  Google Scholar 

  14. Chan SL, Mattson MP. Caspase and calpain substrates: roles in synaptic plasticity and cell death. J Neurosci Res. 1999;58:167–90.

    Article  CAS  PubMed  Google Scholar 

  15. Stepanichev MY, Kudryashova IV, Yakovlev AA, Onufriev MV, Khaspekov LG, Lyzhin AA, et al. Central administration of a caspase inhibitor impairs shuttle-box performance in rats. Neuroscience. 2005;136:579–91.

    Article  CAS  PubMed  Google Scholar 

  16. Huesmann GR, Clayton DF. Dynamic role of postsynaptic caspase-3 and BIRC4 in zebra finch song-response habituation. Neuron. 2006;52:1061–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guo ZH, Mattson MP. Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cereb Cortex. 2000;10:50–7.

    Article  CAS  PubMed  Google Scholar 

  18. Clark RS, Kochanek PM, Watkins SC, Chen M, Edward Dixon C, Seidberg NA, et al. Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem. 2000;74:740–53.

    Article  CAS  PubMed  Google Scholar 

  19. Legos JJ, Lee D, Erhardt JA. Caspase inhibitors as neuroprotective agents. Emerg Drugs. 2001;6:81–94.

    Article  CAS  Google Scholar 

  20. Dhani S, Zhao Y, Zhivotovsky B. A long way to go: caspase inhibitors in clinical use. Cell Death Dis. 2021;12:949. https://doi.org/10.1038/s41419-021-04240-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, et al. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci. 2011;14:69–79.

    Article  PubMed  Google Scholar 

  22. Rohn TT, Head E. Caspases as therapeutic targets in Alzheimer’s disease: is it time to cut to the chase? Int J Clin Exp Pathol. 2009;2:108–18.

    CAS  PubMed  Google Scholar 

  23. Flores J, Noël A, Foveau B, Lynham J, Lecrux C, LeBlanc AC. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model. Nat Commun. 2018;9:3916.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Flores J, Noël A, Foveau B, Beauchet O, LeBlanc AC. Pre-symptomatic caspase-1 inhibitor delays cognitive decline in a mouse model of Alzheimer disease and aging. Nat Commun. 2020;11:4571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang L, Sugama S, Mischak RP, Kiaei M, Bizat N, Brouillet E, et al. A novel systemically active caspase inhibitor attenuates the toxicities of MPTP, malonate, and 3NP in vivo. Neurobiol Dis. 2004;17:250–9.

    Article  CAS  PubMed  Google Scholar 

  26. Viswanath V, Wu Y, Boonplueang R, Chen S, Stevenson FF, Yantiri F, et al. Caspase-9 activation results in downstream caspase-8 activation and bid cleavage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease. J Neurosci. 2001;21:9519–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Toulmond S, Tang K, Bureau Y, Ashdown H, Degen S, O’Donnell R, et al. Neuroprotective effects of M826, a reversible caspase-3 inhibitor, in the rat malonate model of Huntington’s disease. Br J Pharmacol. 2004;141:689–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Depressive symptoms in neurodegenerative diseases. Baquero M, Martín N. World J Clin Cases. 2015;3:682–93.

    Google Scholar 

  29. Neurochemical correlation between major depressive disorder and neurodegenerative diseases, Reus GZ, Titus SE, Abelaira HM, Freitas SM, Tuan T, Quevedo J, Budni J. Life Sci. 2016;158:121–9.

    Article  Google Scholar 

  30. Monoamine oxidase inhibitors. And iron chelators in depressive illness and neurodegenerative disorders. Youdim MBH. J Neural Transm (Vienna). 2018;125:1719–33.

    Article  Google Scholar 

  31. Hussain M, Kumar P, Khan S, Gordon DK, Khan S. Similarities between Depression and neurodegenerative Diseases: Pathophysiology, Challenges in diagnosis and treatment options. Cureus. 2020;12(11):e11613. https://doi.org/10.7759/cureus.11613.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rădulescu I, Drăgoi AM, Trifu SC, Cristea MB. Neuroplasticity and depression: rewiring the brain’s networks through pharmacological therapy (review). Exp Ther Med. 2021;22(4):1131. https://doi.org/10.3892/etm.2021.10565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bliźniewska-Kowalska K, Gałecki P, Szemraj J, Talarowska M. Expression of selected genes involved in neurogenesis in the etiopathogenesis of Depressive Disorders. J Pers Med. 2021;11(3):168. https://doi.org/10.3390/jpm11030168.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gałecki P, Talarowska M. The Evolutionary Theory of Depression. Med Sci Monit. 2017;23:2267–74. https://doi.org/10.12659/msm.901240.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Szymona K, Dudzińska E, Karakuła-Juchnowicz H, Gil-Kulik P, Chomik P, Świstowska M, Gałaszkiewicz J, Kocki J. Analysis of the expression of BAX, BCL2, BIRC6, CASP3, CASP9 apoptosis genes during the first episode of schizophrenia. Psychiatr Pol. 2019;53(6):1293–303. https://doi.org/10.12740/PP/OnlineFirst/99971. English, Polish.

    Article  PubMed  Google Scholar 

  36. Salemi M, Condorelli RA, Romano C, Concetta B, Romano C, Salluzzo MG, Bosco P, Calogero AE. CASP3 protein expression by flow cytometry in Down’s syndrome subjects. Hum Cell. 2014;27(1):43–5. https://doi.org/10.1007/s13577-013-0071-x.

    Article  CAS  PubMed  Google Scholar 

  37. Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(3):261–8. https://doi.org/10.1002/ajmg.b.30272.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

10. The authors appreciate the participants’ contribution to the research on depressive disorders and the contributions of the nurses and medical staff involved in the collection of material for the experiment.

Funding

This work was supported by the Medical University of Lodz, Poland [Research Program Nos. 503/5-062-02/503-51-001-19-00, 503/1-062-02/503-11-001 and 503/1-062-03/503-11-001-19-00]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

Author Contributions: Conceptualization: Katarzyna Bliźniewska-Kowalska, Piotr Gałecki and Małgorzata Gałecka; methodol-ogy: Katarzyna Bliźniewska-Kowalska, Janusz Szemraj (biochemical methodology), Małgorzata Gałecka. formal analysis: Katarzyna Bliźniewska-Kowalska, Małgorzata Gałecka; investigation: Katarzyna Bliźniewska-Kowalska, Piotr Gałecki, Janusz Szmeraj (biochemical analysis), Małgorzata Gałecka; writing—original draft preparation: Katarzyna Bliźniewska-Kowalska, Małgorzata Gałecka; writing—review and editing: Katarzyna Bliźniewska-Kowalska, Piotr Gałecki, Kuan-Pin Su, Jane Pei-Chen Chang and Małgorzata Gałecka; supervision: Piotr Gałecki, Małgorzata Gałecka; funding acquisition: Piotr Gałecki. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Katarzyna Bliźniewska-Kowalska or Małgorzata Gałecka.

Ethics declarations

Ethical approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethical Committee of the Medical University of Lodz (No. RNN/833/11/KB). Informed consent was obtained from all subjects involved in the study.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bliźniewska-Kowalska, K., Gałecki, P., Szemraj, J. et al. CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders. BMC Psychiatry 23, 656 (2023). https://doi.org/10.1186/s12888-023-05153-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12888-023-05153-5

Keywords