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The interaction between OXTR rs2268493 and perceived maternal care is associated with amygdala–dorsolateral prefrontal effective connectivity during explicit emotion processing

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Abstract

Previous studies have indicated a link between socio-emotional processing and the oxytocin receptor. In this regard, a single nucleotide polymorphism in the oxytocin receptor coding gene (OXTR rs2268493) has been linked with lower social functioning, increased risk for autism spectrum disorders (ASDs) and with post-mortem OXTR mRNA expression levels. Indeed, the levels of expression of OXTR in brain regions involved in emotion processing are also associated with maternal care. Furthermore, maternal care has been associated with emotional correlates. Taken together, these previous findings suggest a possible combined effect of rs2268493 and maternal care on emotion-related brain phenotypes. A crucial biological mechanism subtending emotional processing is the amygdala–dorsolateral prefrontal cortex (DLPFC) functional connection. On this basis, our aim was to investigate the interaction between rs2268493 and maternal care on amygdala–DLPFC effective connectivity during emotional evaluation. We characterized through dynamic causal modeling (DCM) patterns of amygdala–DLPFC effective connectivity during explicit emotion processing in healthy controls (HC), profiled based on maternal care and rs2268493 genotype. In the whole sample, right top-down DLPFC-to-amygdala pattern was the most likely directional model of effective connectivity. This pattern of connectivity was the most likely for all rs2268493/maternal care subgroups, except for thymine homozygous (TT)/low maternal care individuals. Here, a right bottom-up amygdala-to-DLPFC was the most likely directional model. These results suggest a gene by environment interaction mediated by the oxytocin receptor on biological phenotypes relevant to emotion processing.

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References

  1. Bosch OJ, Neumann ID (2012) Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: from central release to sites of action. Horm Behav 61(3):293–303. https://doi.org/10.1016/j.yhbeh.2011.11.002

    Article  CAS  PubMed  Google Scholar 

  2. Maud C, Ryan J, McIntosh JE, Olsson CA (2018) The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review. BMC Psychiatry 18(1):154. https://doi.org/10.1186/s12888-018-1740-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jurek B, Neumann ID (2018) The oxytocin receptor: from intracellular signaling to behavior. Physiol Rev 98(3):1805–1908. https://doi.org/10.1152/physrev.00031.2017

    Article  CAS  PubMed  Google Scholar 

  4. Kogan A, Saslow LR, Impett EA, Oveis C, Keltner D, Rodrigues Saturn S (2011) Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition. Proc Natl Acad Sci USA 108(48):19189–19192. https://doi.org/10.1073/pnas.1112658108

    Article  PubMed  Google Scholar 

  5. Tops S, Habel U, Radke S (2019) Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior. Horm Behav 108:84–93. https://doi.org/10.1016/j.yhbeh.2018.03.002

    Article  CAS  PubMed  Google Scholar 

  6. Bernhard RM, Chaponis J, Siburian R, Gallagher P, Ransohoff K, Wikler D, Perlis RH, Greene JD (2016) Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment. Soc Cognit Affect Neurosci 11(12):1872–1881. https://doi.org/10.1093/scan/nsw103

    Article  Google Scholar 

  7. Chen X, Nishitani S, Haroon E, Smith AK, Rilling JK (2019) OXTR methylation modulates exogenous oxytocin effects on human brain activity during social interaction. Genes Brain Behav. https://doi.org/10.1111/gbb.12555

    Article  PubMed  Google Scholar 

  8. Lancaster K, Goldbeck L, Puglia MH, Morris JP, Connelly JJ (2018) DNA methylation of OXTR is associated with parasympathetic nervous system activity and amygdala morphology. Soc Cognit Affect Neurosci 13(11):1155–1162. https://doi.org/10.1093/scan/nsy086

    Article  Google Scholar 

  9. Marusak HA, Furman DJ, Kuruvadi N, Shattuck DW, Joshi SH, Joshi AA, Etkin A, Thomason ME (2015) Amygdala responses to salient social cues vary with oxytocin receptor genotype in youth. Neuropsychologia 79(Pt A):1–9. https://doi.org/10.1016/j.neuropsychologia.2015.10.015

    Article  PubMed  PubMed Central  Google Scholar 

  10. Triana-Del Río R, van den Burg E, Stoop R, Hegoburu C (2019) Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction. Psychopharmacology 236(1):339–354. https://doi.org/10.1007/s00213-018-5030-5

    Article  CAS  PubMed  Google Scholar 

  11. Fan Y, Herrera-Melendez AL, Pestke K, Feeser M, Aust S, Otte C, Pruessner JC, Böker H, Bajbouj M, Grimm S (2014) Early life stress modulates amygdala–prefrontal functional connectivity: implications for oxytocin effects. Hum Brain Mapp 35(10):5328–5339. https://doi.org/10.1002/hbm.22553

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lischke A, Berger C, Prehn K, Heinrichs M, Herpertz SC, Domes G (2012) Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected. Psychoneuroendocrinology 37(4):475–481. https://doi.org/10.1016/j.psyneuen.2011.07.015

    Article  CAS  PubMed  Google Scholar 

  13. Peltola MJ, Strathearn L, Puura K (2018) Oxytocin promotes face-sensitive neural responses to infant and adult faces in mothers. Psychoneuroendocrinology 91:261–270. https://doi.org/10.1016/j.psyneuen.2018.02.012

    Article  CAS  PubMed  Google Scholar 

  14. Keech B, Crowe S, Hocking DR (2018) Intranasal oxytocin, social cognition and neurodevelopmental disorders: a meta-analysis. Psychoneuroendocrinology 87:9–19. https://doi.org/10.1016/j.psyneuen.2017.09.022

    Article  CAS  PubMed  Google Scholar 

  15. Grace SA, Rossell SL, Heinrichs M, Kordsachia C, Labuschagne I (2018) Oxytocin and brain activity in humans: a systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology 96:6–24. https://doi.org/10.1016/j.psyneuen.2018.05.031

    Article  CAS  PubMed  Google Scholar 

  16. Groppe SE, Gossen A, Rademacher L, Hahn A, Westphal L, Gründer G, Spreckelmeyer KN (2013) Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain. Biol Psychiatry 74(3):172–179. https://doi.org/10.1016/j.biopsych.2012.12.023

    Article  CAS  PubMed  Google Scholar 

  17. Campbell DB, Datta D, Jones ST, Batey Lee E, Sutcliffe JS, Hammock EA, Levitt P (2011) Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. J Neurodev Disord 3(2):101–112. https://doi.org/10.1007/s11689-010-9071-2

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D (2009) Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci USA 106(50):21437–21441. https://doi.org/10.1073/pnas.0909579106

    Article  CAS  PubMed  Google Scholar 

  19. Zhang R, Zhang HF, Han JS, Han SP (2017) Genes Related to Oxytocin and Arginine-Vasopressin Pathways: associations with autism spectrum disorders. Neurosci Bull 33(2):238–246. https://doi.org/10.1007/s12264-017-0120-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. LoParo D, Waldman ID (2015) The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry 20(5):640–646. https://doi.org/10.1038/mp.2014.77

    Article  CAS  PubMed  Google Scholar 

  21. Velikonja T, Fett AK, Velthorst E (2019) Patterns of nonsocial and social cognitive functioning in adults with autism spectrum disorder: a systematic review and meta-analysis. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2018.3645

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ribeiro LD, Vargas-Pinilla P, Kappel DB, Longo D, Ranzan J, Becker MM, Dos Santos Riesgo R, Schuler-Faccini L, Roman T, Schuch JB (2018) Evidence for association between OXTR gene and ASD clinical phenotypes. J Mol Neurosci 65(2):213–221. https://doi.org/10.1007/s12031-018-1088-0

    Article  CAS  Google Scholar 

  23. Cataldo I, Azhari A, Esposito G (2018) A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder. Front Mol Neurosci 11:27. https://doi.org/10.3389/fnmol.2018.00027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Damiano CR, Aloi J, Dunlap K, Burrus CJ, Mosner MG, Kozink RV, McLaurin RE, Mullette-Gillman OA, Carter RM, Huettel SA, McClernon FJ, Ashley-Koch A, Dichter GS (2014) Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards. Mol Autism 5(1):7. https://doi.org/10.1186/2040-2392-5-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Di Napoli A, Warrier V, Baron-Cohen S, Chakrabarti B (2014) Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome. Mol Autism 5(1):48. https://doi.org/10.1186/2040-2392-5-48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Consortium G (2013) The genotype-tissue expression (GTEx) project. Nat Genet 45(6):580–585. https://doi.org/10.1038/ng.2653

    Article  CAS  Google Scholar 

  27. Bales KL, Perkeybile AM (2012) Developmental experiences and the oxytocin receptor system. Horm Behav 61(3):313–319. https://doi.org/10.1016/j.yhbeh.2011.12.013

    Article  CAS  PubMed  Google Scholar 

  28. Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30(4):534–547. https://doi.org/10.1016/j.yfrne.2009.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Galbally M, Lewis AJ, Ijzendoorn M, Permezel M (2011) The role of oxytocin in mother-infant relations: a systematic review of human studies. Harv Rev Psychiatry 19(1):1–14. https://doi.org/10.3109/10673229.2011.549771

    Article  PubMed  Google Scholar 

  30. Lukas M, Bredewold R, Neumann ID, Veenema AH (2010) Maternal separation interferes with developmental changes in brain vasopressin and oxytocin receptor binding in male rats. Neuropharmacology 58(1):78–87. https://doi.org/10.1016/j.neuropharm.2009.06.020

    Article  CAS  PubMed  Google Scholar 

  31. Champagne F, Diorio J, Sharma S, Meaney MJ (2001) Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci USA 98(22):12736–12741. https://doi.org/10.1073/pnas.221224598

    Article  CAS  PubMed  Google Scholar 

  32. Szymanska M, Schneider M, Chateau-Smith C, Nezelof S, Vulliez-Coady L (2017) Psychophysiological effects of oxytocin on parent-child interactions: a literature review on oxytocin and parent-child interactions. Psychiatry Clin Neurosci 71(10):690–705. https://doi.org/10.1111/pcn.12544

    Article  CAS  PubMed  Google Scholar 

  33. McDonald NM, Baker JK, Messinger DS (2016) Oxytocin and parent-child interaction in the development of empathy among children at risk for autism. Dev Psychol 52(5):735–745. https://doi.org/10.1037/dev0000104

    Article  PubMed  PubMed Central  Google Scholar 

  34. Taurisano P, Blasi G, Romano R, Sambataro F, Fazio L, Gelao B, Ursini G, Lo Bianco L, Di Giorgio A, Ferrante F, Papazacharias A, Porcelli A, Sinibaldi L, Popolizio T, Bertolino A (2013) DAT by perceived MC interaction on human prefrontal activity and connectivity during emotion processing. Soc Cognit Affect Neurosci 8(8):855–862. https://doi.org/10.1093/scan/nss084

    Article  Google Scholar 

  35. Antonucci LA, Taurisano P, Coppola G, Cassibba R (2018) Attachment style: the neurobiological substrate, interaction with genetics and role in neurodevelopmental disorders risk pathways. Neurosci Bio Behav Rev 95:515–527. https://doi.org/10.1016/j.neubiorev.2018.11.002

    Article  Google Scholar 

  36. Ong MY, Eilander J, Saw SM, Xie Y, Meaney MJ, Broekman BFP (2018) The influence of perceived parenting styles on socio-emotional development from pre-puberty into puberty. Eur Child Adolesc Psychiatry 27(1):37–46. https://doi.org/10.1007/s00787-017-1016-9

    Article  PubMed  Google Scholar 

  37. Castelli RD, Quevedo LD, Coelho FM, Lopez MA, da Silva RA, Böhm DM, Souza LD, de Matos MB, Pinheiro KA, Pinheiro RT (2015) Association between perception of maternal bonding styles and social anxiety disorder among young women. Braz J Psychiatry 37(4):331–333. https://doi.org/10.1590/1516-4446-2015-1668

    Article  PubMed  Google Scholar 

  38. Ebner NC, Chen H, Porges E, Lin T, Fischer H, Feifel D, Cohen RA (2016) Oxytocin’s effect on resting-state functional connectivity varies by age and sex. Psychoneuroendocrinology 69:50–59. https://doi.org/10.1016/j.psyneuen.2016.03.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Seeley SH, Chou YH, O’Connor MF (2018) Intranasal oxytocin and OXTR genotype effects on resting state functional connectivity: a systematic review. Neurosci Bio Behav Rev 95:17–32. https://doi.org/10.1016/j.neubiorev.2018.09.011

    Article  CAS  Google Scholar 

  40. Riem MM, van lJzendoorn MH, Tops M, Boksem MA, Rombouts SA, Bakermans-Kranenburg MJ (2013) Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal. Eur Neuropsychopharmacol 23(10):1288–1295. https://doi.org/10.1016/j.euroneuro.2013.01.011

    Article  CAS  PubMed  Google Scholar 

  41. Zhang T, Wu J, Li F, Caffo B, Boatman-Reich D (2015) A dynamic directional model for effective brain connectivity using electrocorticographic (ECoG) time series. J Am Stat Assoc 110(509):93–106. https://doi.org/10.1080/01621459.2014.988213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Delgado MR, Nearing KI, Ledoux JE, Phelps EA (2008) Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron 59(5):829–838. https://doi.org/10.1016/j.neuron.2008.06.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cognit Neurosci 14(8):1215–1229. https://doi.org/10.1162/089892902760807212

    Article  Google Scholar 

  44. Ochsner KN, Silvers JA, Buhle JT (2012) Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Ann N Y Acad Sci 1251:E1–24. https://doi.org/10.1111/j.1749-6632.2012.06751.x

    Article  PubMed  PubMed Central  Google Scholar 

  45. Phelps EA, LeDoux JE (2005) Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48(2):175–187. https://doi.org/10.1016/j.neuron.2005.09.025

    Article  CAS  PubMed  Google Scholar 

  46. Banks SJ, Eddy KT, Angstadt M, Nathan PJ, Phan KL (2007) Amygdala–frontal connectivity during emotion regulation. Soc Cognit Affect Neurosci 2(4):303–312. https://doi.org/10.1093/scan/nsm029

    Article  Google Scholar 

  47. Ochsner KN, Ray RR, Hughes B, McRae K, Cooper JC, Weber J, Gabrieli JD, Gross JJ (2009) Bottom-up and top-down processes in emotion generation: common and distinct neural mechanisms. Psychol Sci 20(11):1322–1331. https://doi.org/10.1111/j.1467-9280.2009.02459.x

    Article  PubMed  PubMed Central  Google Scholar 

  48. Quarto T, Paparella I, De Tullio D, Viscanti G, Fazio L, Taurisano P, Romano R, Rampino A, Masellis R, Popolizio T, Selvaggi P, Pergola G, Bertolino A, Blasi G (2017) Familial risk and a genome-wide supported DRD2 variant for schizophrenia predict lateral prefrontal–amygdala effective connectivity during emotion processing. Schizophr Bull. https://doi.org/10.1093/schbul/sbx128

    Article  PubMed Central  Google Scholar 

  49. Huijgen J, Dinkelacker V, Lachat F, Yahia-Cherif L, El Karoui I, Lemaréchal JD, Adam C, Hugueville L, George N (2015) Amygdala processing of social cues from faces: an intracrebral EEG study. Soc Cognit Affect Neurosci 10(11):1568–1576. https://doi.org/10.1093/scan/nsv048

    Article  Google Scholar 

  50. Bethlehem RA, Baron-Cohen S, van Honk J, Auyeung B, Bos PA (2014) The oxytocin paradox. Front. Behav Neurosci 8:48. https://doi.org/10.3389/fnbeh.2014.00048

    Article  CAS  Google Scholar 

  51. Bethlehem RA, van Honk J, Auyeung B, Baron-Cohen S (2013) Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies. Psychoneuroendocrinology 38(7):962–974. https://doi.org/10.1016/j.psyneuen.2012.10.011

    Article  CAS  PubMed  Google Scholar 

  52. Lo Bianco L, Blasi G, Taurisano P, Di Giorgio A, Ferrante F, Ursini G, Fazio L, Gelao B, Romano R, Papazacharias A, Caforio G, Sinibaldi L, Popolizio T, Bellantuono C, Bertolino A (2013) Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli. Psychol Med 43(2):279–292. https://doi.org/10.1017/S0033291712001134

    Article  CAS  PubMed  Google Scholar 

  53. Parker G, Tupling H, Brown LB (1979) A parental bonding instrument vol 52. Br J Med Psychol. https://doi.org/10.1111/j.2044-8341.1979.tb02487.x

    Article  Google Scholar 

  54. Stephan KE, Friston KJ (2010) Analyzing effective connectivity with functional magnetic resonance imaging. Wiley Interdiscip Rev Cognit Sci 1(3):446–459. https://doi.org/10.1002/wcs.58

    Article  Google Scholar 

  55. Birnbaum R, Weinberger DR (2013) Functional neuroimaging and schizophrenia: a view towards effective connectivity modeling and polygenic risk. Dialog Clin Neurosci 15(3):279–289

    Google Scholar 

  56. Beitchman JH, Zai CC, Muir K, Berall L, Nowrouzi B, Choi E, Kennedy JL (2012) Childhood aggression, callous-unemotional traits and oxytocin genes. Eur Child Adolesc Psychiatry 21(3):125–132. https://doi.org/10.1007/s00787-012-0240-6

    Article  PubMed  Google Scholar 

  57. van Harmelen AL, van Tol MJ, van der Wee NJ, Veltman DJ, Aleman A, Spinhoven P, van Buchem MA, Zitman FG, Penninx BW, Elzinga BM (2010) Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biol Psychiatry 68(9):832–838. https://doi.org/10.1016/j.biopsych.2010.06.011

    Article  PubMed  Google Scholar 

  58. Gorka AX, Hanson JL, Radtke SR, Hariri AR (2014) Reduced hippocampal and medial prefrontal gray matter mediate the association between reported childhood maltreatment and trait anxiety in adulthood and predict sensitivity to future life stress. Biol Mood Anxiety Disord 4:12. https://doi.org/10.1186/2045-5380-4-12

    Article  PubMed  PubMed Central  Google Scholar 

  59. LoPilato AM, Goines K, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman L, Perkins DO, Tsuang MT, Woods SW, Walker EF (2019) Impact of childhood adversity on corticolimbic volumes in youth at clinical high-risk for psychosis. Schizophr Res. https://doi.org/10.1016/j.schres.2019.01.048

    Article  PubMed  Google Scholar 

  60. Dannlowski U, Kugel H, Grotegerd D, Redlich R, Opel N, Dohm K, Zaremba D, Grögler A, Schwieren J, Suslow T, Ohrmann P, Bauer J, Krug A, Kircher T, Jansen A, Domschke K, Hohoff C, Zwitserlood P, Heinrichs M, Arolt V, Heindel W, Baune BT (2016) Disadvantage of social sensitivity: interaction of oxytocin receptor genotype and child maltreatment on brain structure. Biol Psychiatry 80(5):398–405. https://doi.org/10.1016/j.biopsych.2015.12.010

    Article  CAS  PubMed  Google Scholar 

  61. Tomoda A (2016) Preliminary evidence for impaired brain activity of neural reward processing in children and adolescents with reactive attachment disorder. Yakugaku Zasshi 136(5):711–714. https://doi.org/10.1248/yakushi.15-00262-5

    Article  CAS  PubMed  Google Scholar 

  62. Miguel PM, Pereira LO, Silveira PP, Meaney MJ (2019) Early environmental influences on the development of children’s brain structure and function. Dev Med Child Neurol. https://doi.org/10.1111/dmcn.14182

    Article  PubMed  Google Scholar 

  63. Dannlowski U, Stuhrmann A, Beutelmann V, Zwanzger P, Lenzen T, Grotegerd D, Domschke K, Hohoff C, Ohrmann P, Bauer J, Lindner C, Postert C, Konrad C, Arolt V, Heindel W, Suslow T, Kugel H (2012) Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biol Psychiatry 71(4):286–293. https://doi.org/10.1016/j.biopsych.2011.10.021

    Article  PubMed  Google Scholar 

  64. Dannlowski U, Kugel H, Huber F, Stuhrmann A, Redlich R, Grotegerd D, Dohm K, Sehlmeyer C, Konrad C, Baune BT, Arolt V, Heindel W, Zwitserlood P, Suslow T (2013) Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Hum Brain Mapp 34(11):2899–2909. https://doi.org/10.1002/hbm.22112

    Article  PubMed  Google Scholar 

  65. First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press Inc, Washington

    Google Scholar 

  66. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9(1):97–113

    Article  CAS  Google Scholar 

  67. Hollingshead AB (1975) Four factor index of social status. Unpublished manuscript, Yale University, New Haven, CT

  68. Wechsler D (1981) WAIS-R: Wechsler adult intelligence scale-revised. New York, N.Y.: Psychological Corporation

  69. Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70(1):41–55

    Article  Google Scholar 

  70. Ho D, Imai K, King G, Stuart EA (2011) MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw 42(8):28. https://doi.org/10.18637/jss.v042.i08

    Article  Google Scholar 

  71. Buss C, Lord C, Wadiwalla M, Hellhammer DH, Lupien SJ, Meaney MJ, Pruessner JC (2007) Maternal care modulates the relationship between prenatal risk and hippocampal volume in women but not in men. J Neurosci 27(10):2592–2595. https://doi.org/10.1523/JNEUROSCI.3252-06.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pruessner JC, Champagne F, Meaney MJ, Dagher A (2004) Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride. J Neurosci 24(11):2825–2831. https://doi.org/10.1523/JNEUROSCI.3422-03.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pruessner JC, Dedovic K, Pruessner M, Lord C, Buss C, Collins L, Dagher A, Lupien SJ (2010) Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populations—2008 Curt Richter Award Winner. Psychoneuroendocrinology 35(1):179–191. https://doi.org/10.1016/j.psyneuen.2009.02.016

    Article  PubMed  Google Scholar 

  74. Tottenham N, Tanaka JW, Leon AC, McCarry T, Nurse M, Hare TA, Marcus DJ, Westerlund A, Casey BJ, Nelson C (2009) The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Res 168(3):242–249. https://doi.org/10.1016/j.psychres.2008.05.006

    Article  PubMed  PubMed Central  Google Scholar 

  75. Blasi G, Lo Bianco L, Taurisano P, Gelao B, Romano R, Fazio L, Papazacharias A, Di Giorgio A, Caforio G, Rampino A, Masellis R, Papp A, Ursini G, Sinibaldi L, Popolizio T, Sadee W, Bertolino A (2009) Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans. J Neurosci 29(47):14812–14819. https://doi.org/10.1523/JNEUROSCI.3609-09.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Blasi G, Hariri AR, Alce G, Taurisano P, Sambataro F, Das S, Bertolino A, Weinberger DR, Mattay VS (2009) Preferential amygdala reactivity to the negative assessment of neutral faces. Biol Psychiatry 66(9):847–853. https://doi.org/10.1016/j.biopsych.2009.06.017

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ashburner J, Friston KJ (1999) Nonlinear spatial normalization using basis functions. Hum Brain Mapp 7(4):254–266

    Article  CAS  Google Scholar 

  78. Friston KJ, Harrison L, Penny W (2003) Dynamic causal modelling. Neuroimage 19(4):1273–1302

    Article  CAS  Google Scholar 

  79. Penny WD, Stephan KE, Mechelli A, Friston KJ (2004) Comparing dynamic causal models. Neuroimage 22(3):1157–1172. https://doi.org/10.1016/j.neuroimage.2004.03.026

    Article  CAS  PubMed  Google Scholar 

  80. Ochsner KN, Ray RD, Cooper JC, Robertson ER, Chopra S, Gabrieli JD, Gross JJ (2004) For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage 23(2):483–499. https://doi.org/10.1016/j.neuroimage.2004.06.030

    Article  PubMed  Google Scholar 

  81. Ochsner KN, Gross JJ (2005) The cognitive control of emotion. Trends Cognit Sci 9(5):242–249. https://doi.org/10.1016/j.tics.2005.03.010

    Article  Google Scholar 

  82. Dolan RJ, Vuilleumier P (2003) Amygdala automaticity in emotional processing. Ann N Y Acad Sci 985:348–355. https://doi.org/10.1111/j.1749-6632.2003.tb07093.x

    Article  CAS  PubMed  Google Scholar 

  83. Golkar A, Lonsdorf TB, Olsson A, Lindstrom KM, Berrebi J, Fransson P, Schalling M, Ingvar M, Ohman A (2012) Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation. PLoS One 7(11):e48107. https://doi.org/10.1371/journal.pone.0048107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Morawetz C, Bode S, Baudewig J, Heekeren HR (2017) Effective amygdala–prefrontal connectivity predicts individual differences in successful emotion regulation. Social Cognit Affect Neurosci 12(4):569–585. https://doi.org/10.1093/scan/nsw169

    Article  Google Scholar 

  85. Morawetz C, Bode S, Baudewig J, Kirilina E, Heekeren HR (2016) Changes in effective connectivity between dorsal and ventral prefrontal regions moderate emotion regulation. Cereb Cortex 26(5):1923–1937. https://doi.org/10.1093/cercor/bhv005

    Article  PubMed  Google Scholar 

  86. Rigoux L, Stephan KE, Friston KJ, Daunizeau J (2014) Bayesian model selection for group studies—revisited. Neuroimage 84:971–985. https://doi.org/10.1016/j.neuroimage.2013.08.065

    Article  CAS  PubMed  Google Scholar 

  87. Kass RE, Raftery AE (1995) Bayes factors. J Am Stat Assoc 90(430):773–795

    Article  Google Scholar 

  88. Gainotti G (2018) A historical review of investigations on laterality of emotions in the human brain. J Hist Neurosci. https://doi.org/10.1080/0964704x.2018.1524683

    Article  PubMed  Google Scholar 

  89. Pessoa L, Rossi A, Japee S, Desimone R, Ungerleider LG (2009) Attentional control during the transient updating of cue information. Brain Res 1247:149–158. https://doi.org/10.1016/j.brainres.2008.10.010

    Article  CAS  PubMed  Google Scholar 

  90. Quirk GJ, Armony JL, LeDoux JE (1997) Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala. Neuron 19(3):613–624

    Article  CAS  Google Scholar 

  91. Adolphs R (1999) Social cognition and the human brain. Trends Cognit Sci 3(12):469–479

    Article  CAS  Google Scholar 

  92. Adolphs R (2003) Is the human amygdala specialized for processing social information? Ann N Y Acad Sci 985:326–340

    Article  Google Scholar 

  93. Shen F, Wang N, Qi C, Li YJ, Cui CL (2014) The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the acquisition of morphine-induced place preference. Behav Neurosci 128(4):446–459. https://doi.org/10.1037/a0036964

    Article  CAS  PubMed  Google Scholar 

  94. Mueller SC, Maheu FS, Dozier M, Peloso E, Mandell D, Leibenluft E, Pine DS, Ernst M (2010) Early-life stress is associated with impairment in cognitive control in adolescence: an fMRI study. Neuropsychologia 48(10):3037–3044. https://doi.org/10.1016/j.neuropsychologia.2010.06.013

    Article  PubMed  PubMed Central  Google Scholar 

  95. Thomaes K, Dorrepaal E, Draijer N, de Ruiter MB, Elzinga BM, van Balkom AJ, Smit JH, Veltman DJ (2012) Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder. Psychol Med 42(11):2337–2349. https://doi.org/10.1017/S0033291712000499

    Article  CAS  PubMed  Google Scholar 

  96. Duncan NW, Hayes DJ, Wiebking C, Tiret B, Pietruska K, Chen DQ, Rainville P, Marjańska M, Ayad O, Doyon J, Hodaie M, Northoff G (2015) Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: a preliminary multimodal rsfMRI-fMRI-MRS-dMRI study. Hum Brain Mapp 36(11):4622–4637. https://doi.org/10.1002/hbm.22941

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bluhm RL, Williamson PC, Osuch EA, Frewen PA, Stevens TK, Boksman K, Neufeld RW, Theberge J, Lanius RA (2009) Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J Psychiatry Neurosci 34(3):187–194

    PubMed  PubMed Central  Google Scholar 

  98. Howells FM, Stein DJ, Russell VA (2012) Childhood trauma is associated with altered cortical arousal: insights from an EEG Study. Front Integr Neurosci 6:120. https://doi.org/10.3389/fnint.2012.00120

    Article  PubMed  PubMed Central  Google Scholar 

  99. Hentze C, Walter H, Schramm E, Drost S, Schoepf D, Fangmeier T, Mattern M, Normann C, Zobel I, Schnell K (2016) Functional correlates of childhood maltreatment and symptom severity during affective theory of mind tasks in chronic depression. Psychiatry Res 250:1–11. https://doi.org/10.1016/j.pscychresns.2016.02.004

    Article  Google Scholar 

  100. Gould F, Clarke J, Heim C, Harvey PD, Majer M, Nemeroff CB (2012) The effects of child abuse and neglect on cognitive functioning in adulthood. J Psychiatr Res 46(4):500–506. https://doi.org/10.1016/j.jpsychires.2012.01.005

    Article  PubMed  PubMed Central  Google Scholar 

  101. Majer M, Nater UM, Lin JM, Capuron L, Reeves WC (2010) Association of childhood trauma with cognitive function in healthy adults: a pilot study. BMC Neurol 10:61. https://doi.org/10.1186/1471-2377-10-61

    Article  PubMed  PubMed Central  Google Scholar 

  102. Schneider-Hassloff H, Straube B, Jansen A, Nuscheler B, Wemken G, Witt SH, Rietschel M, Kircher T (2016) Oxytocin receptor polymorphism and childhood social experiences shape adult personality, brain structure and neural correlates of mentalizing. Neuroimage 134:671–684. https://doi.org/10.1016/j.neuroimage.2016.04.009

    Article  CAS  PubMed  Google Scholar 

  103. Liu X, Kawamura Y, Shimada T, Otowa T, Koishi S, Sugiyama T, Nishida H, Hashimoto O, Nakagami R, Tochigi M, Umekage T, Kano Y, Miyagawa T, Kato N, Tokunaga K, Sasaki T (2010) Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. J Hum Genet 55(3):137–141. https://doi.org/10.1038/jhg.2009.140

    Article  CAS  PubMed  Google Scholar 

  104. Isgett SF, Algoe SB, Boulton AJ, Way BM, Fredrickson BL (2016) Common variant in OXTR predicts growth in positive emotions from loving-kindness training. Psychoneuroendocrinology 73:244–251. https://doi.org/10.1016/j.psyneuen.2016.08.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Choi D, Minote N, Watanuki S (2017) Associations between the oxytocin receptor gene (OXTR) rs53576 polymorphism and emotional processing of social and nonsocial cues: an event-related potential (ERP) study. J Physiol Anthropol 36(1):12. https://doi.org/10.1186/s40101-016-0125-3

    Article  PubMed  PubMed Central  Google Scholar 

  106. Duncan LE, Keller MC (2011) A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. Am J Psychiatry 168(10):1041–1049. https://doi.org/10.1176/appi.ajp.2011.11020191

    Article  PubMed  PubMed Central  Google Scholar 

  107. Franke B (2016) Heritability of a general psychopathology factor in the population: potential implications for classification and treatment. J Am Acad Child Adolesc Psychiatry 55(12):1016–1017. https://doi.org/10.1016/j.jaac.2016.10.003

    Article  PubMed  Google Scholar 

  108. Gotlib IH, Mount JH, Cordy NI, Whiffen VE (1988) Depression and perceptions of early parenting: a longitudinal investigation. Br J Psychiatry 152:24–27

    Article  CAS  Google Scholar 

  109. Wilhelm K, Niven H, Parker G, Hadzi-Pavlovic D (2005) The stability of the parental bonding instrument over a 20-year period. Psychol Med 35(3):387–393

    Article  Google Scholar 

  110. Swartz JR, Wiggins JL, Carrasco M, Lord C, Monk CS (2013) Amygdala habituation and prefrontal functional connectivity in youth with autism spectrum disorders. J Am Acad Child Adolesc Psychiatry 52(1):84–93. https://doi.org/10.1016/j.jaac.2012.10.012

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Rita Masellis, Riccarda Lomuscio, Dr Leonardo Fazio, Dr Raffaella Romano, Dr Barbara Gelao and Dr Silvia Torretta (Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro) for making data acquisition possible. We also thank Prof. Gabrielle Coppola (Department of Educational Science, Psychology and Communication Science) for crucial methodological insights.

Funding

This work was supported by a “Capitale Umano ad Alta Qualificazione” grant by Fondazione Con Il Sud, by the “Ricerca Finalizzata” grant (number: PE-2011-02347951) and by the 2014-2016 PhD program of the Department of Educational Science, Psychology and Communication Science, University of Bari Aldo Moro. The funding bodies had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Section for Neurodiagnostic Applications, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians Universität, 80336, Munich, Germany

    Linda A. Antonucci

  2. Department of Educational Science, Psychology and Communication Science, University of Bari “Aldo Moro”, 70121, Bari, Italy

    Linda A. Antonucci, Eleonora Dispoto & Rosalinda Cassibba

  3. Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare, 11, 70124, Bari, Italy

    Linda A. Antonucci, Giulio Pergola, Roberta Passiatore, Paolo Taurisano, Tiziana Quarto, Antonio Rampino, Alessandro Bertolino & Giuseppe Blasi

  4. IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, 71013, Foggia, Italy

    Paolo Taurisano

  5. Psychiatry Unit, Bari University Hospital, 70124, Bari, Italy

    Antonio Rampino, Alessandro Bertolino & Giuseppe Blasi

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  1. Linda A. Antonucci
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Correspondence to Giuseppe Blasi.

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Conflict of interest

Giuseppe Blasi received lecture fees from Jannsen and Lundbeck. Antonio Rampino has received travel fees from Lundbeck. Alessandro Bertolino is a stockholder of Hoffmann-La Roche Ltd. He has also received consulting fees from Biogen and lecture fees from Otsuka, Janssen, Lundbeck. All other authors have no biomedical financial interests and no potential conflicts of interest.

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Antonucci, L.A., Pergola, G., Passiatore, R. et al. The interaction between OXTR rs2268493 and perceived maternal care is associated with amygdala–dorsolateral prefrontal effective connectivity during explicit emotion processing. Eur Arch Psychiatry Clin Neurosci 270, 553–565 (2020). https://doi.org/10.1007/s00406-019-01062-5

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