Skip to main content
SpringerLink
Log in

Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18–35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737–rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Lara DR, Bisol LW, Brunstein MG, Reppold CT, de Carvalho HW, Ottoni GL (2012) The affective and emotional composite temperament (AFECT) model and scale: a system-based integrative approach. J Affect Disord 140:14–37. https://doi.org/10.1016/j.jad.2011.08.036

    Article  PubMed  Google Scholar 

  2. Clark LA (2005) Temperament as a unifying basis for personality and psychopathology. J Abnorm Psychol 114:505–521. https://doi.org/10.1037/0021-843X.114.4.505

    Article  PubMed  Google Scholar 

  3. Pawlak J, Dmitrzak-Węglarz M, Maciukiewicz Kapelski P, Czerski P, Leszczyńska-Rodziewicz A, Zaremba D, Hauser J (2017) Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder. Acta Neuropsychiatr 29:115–121. https://doi.org/10.1017/neu.2016.43

    Article  CAS  PubMed  Google Scholar 

  4. Yang T, Lam RW, Huang J, Su Y, Liu J, Yang X, Yang L, Zhu N, Zhao G, Mao R, Zhou R, Xia W, Liu H, Wang Z, Chen J, Fang Y et al (2021) Exploring the effects of temperament on gray matter volume of frontal cortex in patients with mood disorders. Neuropsychiatr Dis Treat 17:183–193. https://doi.org/10.2147/NDT.S287351

    Article  PubMed  PubMed Central  Google Scholar 

  5. Qiu F, Akiskal HS, Kelsoe JR, Greenwood TA (2017) Factor analysis of temperament and personality traits in bipolar patients: correlates with comorbidity and disorder severity. J Affect Disord 207:282–290. https://doi.org/10.1016/j.jad.2016.08.031

    Article  PubMed  Google Scholar 

  6. Fico G, Caivano V, Zinno F, Carfagno M, Steardo LJ, Sampogna G, Luciano M, Fiorillo A (2019) Affective temperaments and clinical course of bipolar disorder: an exploratory study of differences among patients with and without a history of violent suicide attempts. Medicina (Kaunas) 55:390. https://doi.org/10.3390/medicina55070390

    Article  PubMed  Google Scholar 

  7. Akiskal HS, Downs J, Jordan P, Watson S, Daugherty D, Pruitt DB (1985) Affective disorders in referred children and younger siblings of manic-depressives. Mode of onset and prospective course. Arch Gen Psychiatry 42:996–1003. https://doi.org/10.1001/archpsyc.1985.01790330076009

    Article  CAS  PubMed  Google Scholar 

  8. Quilty LC, Sellbom M, Tackett JL, Bagby RM (2009) Personality trait predictors of bipolar disorder symptoms. Psychiatry Res 169:159–163. https://doi.org/10.1016/j.psychres.2008.07.004

    Article  PubMed  Google Scholar 

  9. Wilks Z, Perkins AM, Cooper A, Pliszka B, Cleare AJ, Young AH (2020) Relationship of a big five personality questionnaire to the symptoms of affective disorders. J Affect Disord 277:14–20. https://doi.org/10.1016/j.jad.2020.07.122

    Article  PubMed  Google Scholar 

  10. Evans L, Akiskal HS, Keck PE Jr, McElroy SL, Sadovnick AD, Remick RA, Kelsoe JR (2005) Familiality of temperament in bipolar disorder: support for a genetic spectrum. J Affect Disord 85:153–168. https://doi.org/10.1016/j.jad.2003.10.015

    Article  PubMed  Google Scholar 

  11. Kesebir S, Vahip S, Akdeniz F, Yüncü Z, Alkan M, Akiskal H (2005) Affective temperaments as measured by TEMPS-A in patients with bipolar I disorder and their first-degree relatives: a controlled study. J Affect Disord 85:127–133. https://doi.org/10.1016/j.jad.2003.10.013

    Article  PubMed  Google Scholar 

  12. Saguem BN, Mtiraoui A, Nakhli J, Mannaï J, Ben Salah N, El Kissi Y, Ben Nasr S (2021) Affective temperaments and their relationships with life events in bipolar patients and siblings: a controlled study. J Ment Health 30:36–42. https://doi.org/10.1080/09638237.2019.1608924

    Article  PubMed  Google Scholar 

  13. Sanchez-Roige S, Gray JC, MacKillop J, Chen CH, Palmer AA (2018) The genetics of human personality. Genes Brain Behav 17:e12439. https://doi.org/10.1111/gbb.12439

    Article  CAS  PubMed  Google Scholar 

  14. Lo MT, Hinds DA, Tung JY et al (2017) Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders. Nat Genet 49:152–156. https://doi.org/10.1038/ng.3736

    Article  CAS  PubMed  Google Scholar 

  15. Mick E, McGough J, Deutsch CK, Frazier JA, Kennedy D, Goldberg RJ (2014) Genome-wide association study of proneness to anger. PLoS ONE 9:e87257. https://doi.org/10.1371/journal.pone.0087257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Luciano M, Hagenaars SP, Davies G, Hill WD, Clarke TK, Shirali M, Harris SE, Marioni RE, Liewald DC, Fawns-Ritchie C, Adams MJ, Howard DM, Lewis CM, Gale CR, McIntosh AM, Deary IJ (2018) Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nat Genet 50:6–11. https://doi.org/10.1038/s41588-017-0013-8

    Article  CAS  PubMed  Google Scholar 

  17. Belonogova NM, Zorkoltseva IV, Tsepilov YA, Axenovich TI (2021) Gene-based association analysis identifies 190 genes affecting neuroticism. Sci Rep 11:2484. https://doi.org/10.1038/s41598-021-82123-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ferreira MA, O’Donovan MC, Meng YA et al (2008) Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 40:1056–1058. https://doi.org/10.1038/ng.209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Psychiatric GWAS Consortium Bipolar Disorder Working Group (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 43:977–983. https://doi.org/10.1038/ng.943

    Article  CAS  Google Scholar 

  20. Mullins N, Forstner AJ, O’Connell KS et al (2021) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet 53:817–829. https://doi.org/10.1038/s41588-021-00857-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Erk S, Meyer-Lindenberg A, Schnell K, Opitz von Boberfeld C, Esslinger C, Kirsch P, Grimm O, Arnold C, Haddad L, Witt SH, Cichon S, Nöthen MM, Rietschel M, Walter H (2010) Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 67:803–811. https://doi.org/10.1001/archgenpsychiatry.2010.94

    Article  PubMed  Google Scholar 

  22. Strohmaier J, Amelang M, Hothorn LA, Witt SH, Nieratschker V, Gerhard D, Meier S, Wüst S, Frank J, Loerbroks A, Rietschel M, Stürmer T, Schulze TG (2013) The psychiatric vulnerability gene CACNA1C and its sex-specific relationship with personality traits, resilience factors and depressive symptoms in the general population. Mol Psychiatry 18:607–613. https://doi.org/10.1038/mp.2012.53

    Article  CAS  PubMed  Google Scholar 

  23. Roussos P, Giakoumaki SG, Georgakopoulos A, Robakis NK, Bitsios P (2011) The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males. Bipolar Disord 13:250–259. https://doi.org/10.1111/j.1399-5618.2011.00924.x

    Article  PubMed  Google Scholar 

  24. Takeuchi H, Tomita H, Taki Y et al (2019) A Common CACNA1C gene risk variant has sex-dependent effects on behavioral traits and brain functional activity. Cereb Cortex 29:3211–3219. https://doi.org/10.1093/cercor/bhy189

    Article  PubMed  Google Scholar 

  25. Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947. https://doi.org/10.1101/cshperspect.a003947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Feng T, Kalyaanamoorthy S, Barakat K (2018) L-type calcium channels: structure and functions. In: Shad KF (ed) Ion Channels in Health and Sickness. IntechOpen, London. https://doi.org/10.5772/intechopen.77305

    Chapter  Google Scholar 

  27. Kabir ZD, Martínez-Rivera A, Rajadhyaksha AM (2017) From gene to behavior: L type calcium channel mechanisms underlying neuropsychiatric symptoms. Neurotherapeutics 14:588–613. https://doi.org/10.1007/s13311-017-0532-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jogia J, Ruberto G, Lelli-Chiesa G, Vassos E, Maierú M, Tatarelli R, Girardi P, Collier D, Frangou S (2011) The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Mol Psychiatry 16:1070–1071. https://doi.org/10.1038/mp.2011.49

    Article  CAS  PubMed  Google Scholar 

  29. Bigos KL, Mattay VS, Callicott JH, Straub RE, Vakkalanka R, Kolachana B, Hyde TM, Lipska BK, Kleinman JE, Weinberger DR (2010) Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67:939–945. https://doi.org/10.1001/archgenpsychiatry.2010.96

    Article  PubMed  PubMed Central  Google Scholar 

  30. Starnawska A, Demontis D, Pen A, Hedemand A, Nielsen AL, Staunstrup NH, Grove J, Als TD, Jarram A, O’Brien NL, Mors O, McQuillin A, Børglum AD, Nyegaard M (2016) CACNA1C hypermethylation is associated with bipolar disorder. Transl Psychiatry 6:e831. https://doi.org/10.1038/tp.2016.99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bastos CR, Xavier J, Camerini L, Dewes SS, Moreira FP, Wiener CD, Jansen K, Kaster MP, de Mattos SLD, da Silva RA, Oses JP, Portela LV, Lara DR, Tovo-Rodrigues L, Ghisleni G (2022) BDNF levels according to variations in the CACNA1C gene: sex-based disparity. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-022-01189-5.10.1007/s10571-022-01189-5

    Article  PubMed  Google Scholar 

  32. Carvalho HW, Cogo-Moreira H, Jansen K, Souza L, Branco J, Silva R, Lara D (2020) The latent structure and reliability of the emotional trait section of the affective and emotional composite temperament scale (AFECTS). Arch Clin Psychiatr (São Paulo) 47:25–29. https://doi.org/10.1590/0101-60830000000225

    Article  Google Scholar 

  33. Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444. https://doi.org/10.1093/nar/19.19.5444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Eckart N, Song Q, Yang R, Wang R, Zhu H, McCallion AS, Avramopoulos D et al (2016) Functional characterization of schizophrenia-associated variation in CACNA1C. PLoS ONE 11:e0157086. https://doi.org/10.1371/journal.pone.0157086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Preacher KJ, Hayes AF (2008) Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 40:879–891. https://doi.org/10.3758/brm.40.3.879

    Article  PubMed  Google Scholar 

  36. Barnett JH, Huang J, Perlis RH, Young MM, Rosenbaum JF, Nierenberg AA, Sachs G, Nimgaonkar VL, Miklowitz DJ, Smoller JW (2011) Personality and bipolar disorder: dissecting state and trait associations between mood and personality. Psychol Med 41:1593–1604. https://doi.org/10.1017/S0033291710002333

    Article  CAS  PubMed  Google Scholar 

  37. Sparding T, Pålsson E, Joas E, Hansen S, Landén M (2017) Personality traits in bipolar disorder and influence on outcome. BMC Psychiatry 17:159. https://doi.org/10.1186/s12888-017-1332-0

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hanke N, Penzel N, Betz LT, Rohde M, Kambeitz-Ilankovic L, Kambeitz J (2022) Personality traits differentiate patients with bipolar disorder and healthy controls–a meta-analytic approach. J Affect Disord 302:401–411. https://doi.org/10.1016/j.jad.2022.01.067

    Article  PubMed  Google Scholar 

  39. Nowakowska C, Strong CM, Santosa CM, Wang PW, Ketter TA (2005) Temperamental commonalities and differences in euthymic mood disorder patients, creative controls, and healthy controls. J Affect Disord 85:207–215. https://doi.org/10.1016/j.jad.2003.11.012

    Article  PubMed  Google Scholar 

  40. Soto CJ (2016) The little six personality dimensions from early childhood to early adulthood: mean-level age and gender differences in parents’ reports. J Pers 84:409–422. https://doi.org/10.1111/jopy.12168

    Article  PubMed  Google Scholar 

  41. De Bolle M, De Fruyt F, McCrae RR et al (2015) The emergence of sex differences in personality traits in early adolescence: a cross-sectional, cross-cultural study. J Pers Soc Psychol 108:171–185. https://doi.org/10.1037/a0038497

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bunnet ER (2020) Gender differences in perceived traits of men and women. Wiley Encycl Pers Ind Diff. https://doi.org/10.1002/9781119547174.ch207

    Article  Google Scholar 

  43. Smedler E, Abé C, Pålsson E, Ingvar M, Landén M (2019) CACNA1C polymorphism and brain cortical structure in bipolar disorder. J Psychiatry Neurosci 45:182–187. https://doi.org/10.1503/jpn.190029

    Article  PubMed  PubMed Central  Google Scholar 

  44. Soeiro-de-Souza MG, Bio DS, Dias VV, Vieta E, Machado-Vieira R, Moreno RA (2013) The CACNA1C risk allele selectively impacts on executive function in bipolar type I disorder. Acta Psychiatry Scand 128:362–369. https://doi.org/10.1111/acps.12073

    Article  CAS  Google Scholar 

  45. Uemura T, Green M, Warsh JJ (2016) CACNA1C SNP rs1006737 associates with bipolar I disorder independent of the Bcl-2 SNP rs956572 variant and its associated effect on intracellular calcium homeostasis. World J Biol Psychiatry 17:525–534. https://doi.org/10.3109/15622975.2015.1019360

    Article  PubMed  Google Scholar 

  46. Arnsten AFT, Datta D, Wang M (2021) The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex. Mol Psychiatry 26:3684–3700. https://doi.org/10.1038/s41380-020-00973-3

    Article  CAS  PubMed  Google Scholar 

  47. Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J (1998) Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry 55:663–664. https://doi.org/10.1001/archpsyc.55.7.663

    Article  CAS  PubMed  Google Scholar 

  48. Altshuler L, Bookheimer S, Proenza MA, Townsend J, Sabb F, Firestine A, Bartzokis G, Mintz J, Mazziotta J, Cohen MS (2005) Increased amygdala activation during mania: a functional magnetic resonance imaging study. Am J Psychiatry 162:1211–1213. https://doi.org/10.1176/appi.ajp.162.6.1211

    Article  PubMed  Google Scholar 

  49. Damme KSF, Alloy LB, Young CB, Kelley NJ, Chein J, Ng TH, Titone MK, Black CL, Nusslock R (2020) Amygdala subnuclei volume in bipolar spectrum disorders: insights from diffusion-based subsegmentation and a high-risk design. Hum Brain Mapp 41:3358–3369. https://doi.org/10.1002/hbm.25021

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lancaster TM, Foley S, Tansey KE, Linden DE, Caseras X (2016) CACNA1C risk variant is associated with increased amygdala volume. Eur Arch Psychiatry Clin Neurosci 266:269–275. https://doi.org/10.1007/s00406-015-0609-x

    Article  CAS  PubMed  Google Scholar 

  51. Tesli M, Skatun KC, Ousdal OT, Brown AA, Thoresen C, Agartz I, Melle I, Djurovic S, Jensen J, Andreassen OA (2013) CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls. PLoS ONE 8:e56970. https://doi.org/10.1371/journal.pone.0056970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP (2011) The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord 13:696–700. https://doi.org/10.1111/j.1399-5618.2011.00963.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, DelBello MP, Frangou S, McIntosh A, Phillips ML, Sussman JE, Townsend JD (2012) The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord 14:313–325. https://doi.org/10.1111/j.1399-5618.2012.01022.x

    Article  PubMed  Google Scholar 

  54. Bi B, Che D, Bai Y (2022) Neural network of bipolar disorder: Toward integration of neuroimaging and neurocircuit-based treatment strategies. Transl Psychiatry 12:143. https://doi.org/10.1038/s41398-022-01917-x

    Article  PubMed  PubMed Central  Google Scholar 

  55. Dao DT, Mahon PB, Cai X, Kovacsics CE, Blackwell RA, Arad M, Shi J, Zandi PP, O’Donnell P, Knowles JA, Weissman MM, Coryell W, Scheftner WA, Lawson WB, Levinson DF, Thompson SM, Potash JB, Gould TD, Bipolar Genome Study (BiGS) Consortium (2010) Mood disorder susceptibility gene CACNA1C modifies mood-related behaviors in mice and interacts with sex to influence behavior in mice and diagnosis in humans. Biol Psychiatry 68:801–810. https://doi.org/10.1016/j.biopsych.2010.06.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Banciu A, Banciu DD, Mustaciosu CC, Radu M, Cretoiu D, Xiao J, Cretoiu SM, Suciu N, Radu BM (2018) Beta-estradiol regulates voltage-gated calcium channels and estrogen receptors in telocytes from human myometrium. Int J Mol Sci 19:1413. https://doi.org/10.3390/ijms19051413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sarkar SN, Huang RQ, Logan SM, Yi KD, Dillon GH, Simpkins JW (2008) Estrogens directly potentiate neuronal L type Ca2+ channels. Proc Natl Acad Sci USA 105:15148–15153. https://doi.org/10.1073/pnas.0802379105

    Article  PubMed  PubMed Central  Google Scholar 

  58. Lai YJ, Zhu BL, Sun F, Luo D, Ma YL, Luo B, Tang J, Xiong MJ, Liu L, Long Y, Hu XT, He L, Deng XJ, Zhang JH, Yang J, Yan Z, Chen GJ et al (2019) Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice. Aging Cell 18:e12961. https://doi.org/10.1111/acel.12961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. He L, Hu XT, Lai YJ, Long Y, Liu L, Zhu BL, Chen GJ (2016) Regulation and the mechanism of estrogen on Cav1.2 gene in rat-cultured cortical astrocytes. J Mol Neurosci 60:205–213. https://doi.org/10.1007/s12031-016-0803-y

    Article  CAS  PubMed  Google Scholar 

  60. Witt SH, Kleindienst N, Frank J, Treutlein J, Mühleisen T, Degenhardt F, Jungkunz M, Krumm B, Cichon S, Tadic A, Dahmen N, Schwarze CE, Schott B, Dietl L, Nöthen MM, Mobascher A, Lieb K, Roepke S, Rujescu D, Rietschel M, Schmahl C, Bohus M (2014) Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder. Psychiatr Genet 24:262–265. https://doi.org/10.1097/YPG.0000000000000060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kantojärvi K, Liuhanen J, Saarenpää-Heikkilä O, Satomaa AL, Kylliäinen A, Pölkki P, Jaatela J, Toivola A, Milani L, Himanen SL, Porkka-Heiskanen T, Paavonen J, Paunio T (2017) Variants in calcium voltage-gated channel subunit alpha1 C-gene (CACNA1C) are associated with sleep latency in infants. PLoS ONE 12:e0180652. https://doi.org/10.1371/journal.pone.0180652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bastos CR, Tovo-Rodrigues L, Ardais AP, Xavier J, Salerno P, Camerini L, Jansen K, de Mattos Souza LD, da Silva RA, Lara DR, Ghisleni G (2020) The role of CACNA1C gene and childhood trauma interaction on bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 101:109915. https://doi.org/10.1016/j.pnpbp.2020.109915

    Article  CAS  PubMed  Google Scholar 

  63. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381:1371–1379. https://doi.org/10.1016/S0140-6736(12)62129-1

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

The assistance of our research team is greatly acknowledged. The authors are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES) for their research fellowships, and PRONEX-FAPERGS (08/2009-Pronex, grant number 10/0055-0) by funding.

Author information

Authors and Affiliations

  1. Post-Graduation Program in Health and Behavior, Center of Health Science, Catholic University of Pelotas, 373, 324C Gonçalves Chaves Street, Pelotas, Rio Grande do Sul, CEP 96015-560, Brazil

    Clarissa Ribeiro Bastos, Bertha Bueno Bock, Janaina Xavier, Laísa Camerini, Samantha Seibt Dewes, Karen Jansen, Ricardo Azevedo da Silva, Ricardo Tavares Pinheiro, Luciano de Mattos Souza & Gabriele Ghisleni

  2. Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Clarissa Ribeiro Bastos & Mateus Grellert

  3. Department of Psychology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil

    Hudson Wander de Carvalho

  4. Institute of Biological Sciences, Federal University of Rio Grande, Rio Grande, Rio Grande do Sul, Brazil

    Jean Pierre Oses

  5. Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Luis Valmor Portela

  6. Department of Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Diogo Rizzato Lara

  7. Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil

    Luciana Tovo-Rodrigues

Authors
  1. Clarissa Ribeiro Bastos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertha Bueno Bock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janaina Xavier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laísa Camerini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samantha Seibt Dewes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mateus Grellert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hudson Wander de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karen Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ricardo Azevedo da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ricardo Tavares Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luciano de Mattos Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jean Pierre Oses
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Luis Valmor Portela
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Diogo Rizzato Lara
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Luciana Tovo-Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Gabriele Ghisleni
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors mentioned in the paper have significantly contributed to the research. CRB conceptualization, investigation, writing–original draft. GG supervision, conceptualization, methodology, formal analysis. LTR conceptualization, methodology, formal analysis. MG, HWC methodology and formal analysis. BBB, JX, LC, SSD investigation. RTP, RAS, KJ, JPO, LDS, LVP, DRL supervision and project administration. All authors: writing–review and editing.

Corresponding author

Correspondence to Gabriele Ghisleni.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of ethics

The study protocol was approved by the Ethics Committee of Catholic University of Pelotas, Pelotas, Brazil (Protocol number 2010/15), and was performed in accordance with the ethical standards as laid down in the Declaration of Helsinki

Consent to participate

Informed consent was obtained from all individual participants included in the study

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 383 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bastos, C.R., Bock, B.B., Xavier, J. et al. Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women. Eur Arch Psychiatry Clin Neurosci 273, 41–50 (2023). https://doi.org/10.1007/s00406-022-01493-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-022-01493-7

Keywords

Search

Navigation