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Neural correlates of prenatal stress in young women

Published online by Cambridge University Press:  19 March 2015

A. Favaro ,
E. Tenconi ,
D. Degortes ,
R. Manara  and
P. Santonastaso
A. Favaro*
Affiliation:
Department of Neurosciences, University of Padova, Padova, Italy Cognitive Neuroscience Center, University of Padova, Padova, Italy
E. Tenconi
Affiliation:
Department of Neurosciences, University of Padova, Padova, Italy Cognitive Neuroscience Center, University of Padova, Padova, Italy
D. Degortes
Affiliation:
Department of Neurosciences, University of Padova, Padova, Italy
R. Manara
Affiliation:
Department of Medicine, University of Salerno, Salerno, Italy IRCSS San Camillo, Venice, Italy
P. Santonastaso
Affiliation:
Department of Neurosciences, University of Padova, Padova, Italy Cognitive Neuroscience Center, University of Padova, Padova, Italy
*
*Address for correspondence: A. Favaro, MD, PhD, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy. (Email: angela.favaro@unipd.it)
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Abstract

Background

Prenatal stress is hypothesized to have a disruptive impact on neurodevelopmental trajectories, but few human studies have been conducted on the long-term neural correlates of prenatal exposure to stress. The aim of this study was to explore the relationship between prenatal stress exposure and gray-matter volume and resting-state functional connectivity in a sample of 35 healthy women aged 14–40 years.

Method

Voxel-based morphometry and functional connectivity analyses were performed on the whole brain and in specific regions of interest (hippocampus and amygdala). Data about prenatal/postnatal stress and obstetric complications were obtained by interviewing participants and their mothers, and reviewing obstetric records.

Results

Higher prenatal stress was associated with decreased gray-matter volume in the left medial temporal lobe (MTL) and both amygdalae, but not the hippocampus. Variance in gray-matter volume of these brain areas significantly correlated with depressive symptoms, after statistically adjusting for the effects of age, postnatal stress and obstetric complications. Prenatal stress showed a positive linear relationship with functional connectivity between the left MTL and the pregenual cortex. Moreover, connectivity between the left MTL and the left medial-orbitofrontal cortex partially explained variance in the depressive symptoms of offspring.

Conclusions

In young women, exposure to prenatal stress showed a relationship with the morphometry and functional connectivity of brain areas involved in the pathophysiology of depressive disorders. These data provide evidence in favor of the hypothesis that early exposure to stress affects brain development and identified the MTL and amygdalae as possible targets of such exposure.

Keywords

Amygdalaanxietydepressionprenatal stress
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 12 , September 2015 , pp. 2533 - 2543
Copyright
Copyright © Cambridge University Press 2015 

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References

Alexander, N, Rosenlocher, F, Stalder, T, Linke, J, Distler, W, Morgner, J, Kirschbaum, C (2012). Impact of antenatal synthetic glucocorticoid exposure on endocrine stress reactivity in term-born children. Journal of Clinical Endocrinology and Metabolism 97, 3538–3544.Google Scholar
Ball, T, Rahm, B, Eickhoff, SB, Schulze-Bonhage, A, Speck, O, Mutschler, I (2007). Response properties of human amygdala subregions: evidence based on functional MRI combined with probabilistic anatomical maps. PLoS One 2, e307.Google Scholar
Bingham, BC, Rani, CSS, Frazer, A, Strong, R, Morilak, DA (2013). Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior. Psychoneuroendocrinology 38, 2746–2757.Google Scholar
Biswal, BB, Mennes, M, Zuo, XN, Gohel, S, Kelly, C, Smith, SM, Beckmann, CF, Adelstein, JS, Buckner, RL, Colcombe, S, Dogonowski, A-M, Ernst, M, Fair, D, Hampson, M, Hoptman, MJ, Hyde, JS, Kiviniemi, VJ, Kotter, R, Li, S-J, Lin, C-P, Lowe, MJ, Mackay, C, Madden, DJ, Madsen, KH, Margulies, DS, Mayberg, HS, McMahon, K, Monk, CS, Mostofsky, SH, Nagel, BJ, Pekar, JJ, Peltier, SJ, Petersen, SE, Riedl, V, Rombouts, SARB, Rypma, B, Schlaggar, BL, Schmidt, S, Seidler, RD, Siegle, GJ, Sorg, C, Teng, G-J, Veijola, J, Villringer, A, Walter, M, Wang, L, Weng, X-C, Whitfield-Gabrieli, S, Williamson, P, Windischberger, C, Zang, Y-F, Zhang, H-Y, Castellanos, FX, Milham, MP (2010). Toward discovery science of human brain function. Proceedings of the National Academy of Sciences USA 107, 4734–4739.Google Scholar
Buka, SL, Goldstein, JM, Seidman, LJ, Tsuang, MT (2000). Maternal recall of pregnancy history: accuracy and bias in schizophrenia research. Schizophrenia Bulletin 26, 335–350.Google Scholar
Buss, C, Davis, EP, Muftuler, LT, Head, K, Sandman, CA (2010). High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6–9-year-old children. Psychoneuroendocrinology 35, 141–153.Google Scholar
Buss, C, Davis, EP, Shahbaba, B, Pruessner, JC, Head, K, Sandman, CA (2012). Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volume and affective problems. Proceedings of the National Academy of Sciences USA 109, E1312–E1319.Google Scholar
Catani, M, Dell'Acqua, F, Thiebaut de Schotten, M (2013). A revised limbic system model for memory, emotion and behaviour. Neuroscience and Biobehavioral Reviews 37, 1724–1737.Google Scholar
Charil, A, Laplante, DP, Vaillancourt, C, King, S (2010). Prenatal stress and brain development. Brain Research Reviews 65, 56–79.Google Scholar
Class, QA, Abel, KM, Khashan, AS, Rickert, ME, Dalman, C, Larsson, H, Hultman, CM, Langstrom, N, Lichtenstein, P, D'Onofrio, BM (2014). Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress. Psychological Medicine 44, 71–84.Google Scholar
Class, QA, Lichtenstein, P, Langstrom, N, D'Onofrio, BM (2011). Timing of prenatal maternal exposure to severe life events and adverse pregnancy outcomes: a population study of 2.6 million pregnancies. Psychosomatic Medicine 73, 234–241.CrossRefGoogle ScholarPubMed
Colombo, L, Sartori, G, Brivio, C (2002). Estimation of intelligence quotient by means of the Brief Intelligence Test [in Italian]. Giornale di Psicologia 3, 613–637.Google Scholar
Davis, EP, Glynn, LM, Waffarn, F, Sandman, CA (2011). Prenatal maternal stress programs infant stress regulation. Journal of Child Psychology and Psychiatry 52, 119–129.Google Scholar
Davis, EP, Sandman, CA, Buss, C, Wing, DA, Head, K (2013). Fetal glucocorticoid exposure is associated with preadolescent brain development. Biological Psychiatry 74, 647–655.Google Scholar
de Kwaasteniet, B, Ruhe, E, Caan, M, Rive, M, Olabarriaga, S, Groefsema, M, Heesink, L, van Wingen, G, Denys, D (2013). Relation between structural and functional connectivity in major depressive disorder. Biological Psychiatry 74, 40–47.Google Scholar
Derogatis, LR, Lipman, R, Rickels, K, Uhlenhath, E, Covi, L (1974). The Hopkins Symptoms Check List (HSCL): a self-report symptoms inventory. Behavioral Science 19, 1–15.Google Scholar
Fatemi, SH, Folsom, TD (2009). The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophrenia Bulletin 35, 528–548.Google Scholar
Favaro, A, Tenconi, E, Bosello, R, Degortes, D, Santonastaso, P (2011). Perinatal complications in unaffected sisters of anorexia nervosa patients: testing a covariation model between genetic and environmental factors. European Archives of Psychiatry and Clinical Neuroscience 261, 391–396.Google Scholar
Favaro, A, Tenconi, E, Santonastaso, P (2006). Perinatal factors and the risk of developing anorexia nervosa and bulimia nervosa. Archives of General Psychiatry 63, 82–88.CrossRefGoogle ScholarPubMed
Favaro, A, Tenconi, E, Santonastaso, P (2010). The interaction between perinatal factors and childhood abuse in the risk of developing anorexia nervosa. Psychological Medicine 40, 657–665.Google Scholar
Gluckman, PD, Hanson, MA (2004). Living with the past: evolution, development, and patterns of disease. Science 305, 1733–1736.Google Scholar
Haukvik, UK, Rimol, LM, Roddey, JC, Hartberg, CB, Lange, EH, Vaskinn, A, Melle, I, Andreassen, OA, Dale, A, Agartz, I (2014). Normal birth weight variation is related to cortical morphology across the psychosis spectrum. Schizophrenia Bulletin 40, 410–419.Google Scholar
Kang, HJ, Kawasawa, YI, Cheng, F, Zhu, Y, Xu, X, Li, M, Sousa, AM, Pletikos, M, Meyer, KA, Sedmak, G, Guennel, T, Shin, Y, Johnson, MB, Krsnik, Z, Mayer, S, Fertuzinhos, S, Umlauf, S, Lisgo, SN, Vortmeyer, A, Weinberger, DR, Mane, S, Hyde, TM, Huttner, A, Reimers, M, Kleinman, JE, Sestan, N (2011). Spatio-temporal transcriptome of the human brain. Nature 478, 483–489.Google Scholar
Kolb, B, Mychasiuk, R, Muhammad, A, Li, Y, Frost, DO, Gibb, R (2012). Experience and the developing prefrontal cortex. Proceedings of the National Academy of Sciences USA 109 (Suppl. 2), 17186–17193.Google Scholar
Li, J, Wang, ZN, Chen, YP, Dong, YP, Shuai, HL, Xiao, XM, Reichetzeder, C, Hocher, B (2011). Late gestational maternal serum cortisol is inversely associated with fetal brain growth. Neuroscience and Biobehavioral Reviews 36, 1085–1092.Google Scholar
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience 10, 434–445.Google Scholar
McNeil, TF, Cantor-Graae, E, Sjöström, K (1994). Obstetric complications as antecedents of schizophrenia: empirical effects of using different obstetric complication scales. Journal of Psychiatric Research 28, 519–530.Google Scholar
Mychasiuk, R, Gibb, R, Kolb, B (2011). Prenatal stress produces sexually dimorphic and regionally specific changes in gene expression in hippocampus and frontal cortex of developing rat offspring. Developmental Neuroscience 33, 531–538.Google Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.Google Scholar
Pagliaccio, D, Luby, JL, Bogdan, R, Agrawal, A, Gaffrey, MS, Belden, AC, Botteron, KN, Harms, MP, Barch, DM (2014). Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology 39, 1245–1253.Google Scholar
Patenaude, B, Smith, SM, Kennedy, D, Jenkinson, M (2011). A Bayesian Model of Shape and Appearance for Subcortical Brain. Neuroimage 56, 907–922.Google Scholar
Peng, J, Liu, J, Nie, B, Li, Y, Shan, B, Wang, G, Li, K (2011). Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study. European Journal of Radiology 80, 395–399.Google Scholar
Reynolds, RM (2013). Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis – 2012 Curt Richter Award Winner. Psychoneuroendocrinology 38, 1–11.Google Scholar
Rifkin-Graboi, A, Bai, J, Chen, H, Bak'r Hameed, W, Wee Sim, L, Thway Tint, M, Leutscher-Broekman, B, Chong, Y-S, Gluckman, PD, Fortier, MV, Meaney, MJ, Qiu, A (2013). Prenatal maternal depression associates with microstructure of right amygdala in neonates at birth. Biological Psychiatry 74, 837–844.Google Scholar
Sacher, J, Neumann, J, Funfstuck, T, Soliman, A, Villringer, A, Schroeter, ML (2012). Mapping the depressed brain: a metaanalysis of structural and functional alterations in major depressive disorder. Journal of Affective Disorders 140, 142–148.CrossRefGoogle Scholar
Sah, P, Faber, ES, Lopez De Armentia, M, Power, J (2003). The amygdaloid complex: anatomy and physiology. Physiological Reviews 83, 803–834.Google Scholar
Sandman, CA, Buss, C, Head, K, Davis, EP (2015). Fetal exposure to maternal depressive symptoms is associated with cortical thickness in late childhood. Biological Psychiatry 77, 324–334.CrossRefGoogle ScholarPubMed
Schmitt, A, Malchow, B, Hasan, A, Falkai, P (2014). The impact of environmental factors in severe psychiatric disorders. Frontiers of Neuroscience 8, 19.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 22–33.Google Scholar
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23 (Suppl. 1), S208–S219.Google Scholar
Smith, SM, Nichols, TE (2009). Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44, 83–98.Google Scholar
Spielberger, CD, Gorsuch, RL, Lushene, RE (1970). Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press: Palo Alto, CA.Google Scholar
Squire, LR, Zola-Morgan, S (1991). The medial temporal lobe memory system. Science 253, 1380–1386.Google Scholar
Teicher, MH, Andersen, SL, Polcari, A, Anderson, CM, Navalta, CP, Kim, DM (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience and Biobehavioral Reviews 27, 33–44.Google Scholar
Tottenham, N, Sheridan, MA (2009). A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Frontiers of Human Neuroscience 3, 68.Google Scholar
Walhovd, KB, Fjell, AM, Brown, TT, Kuperman, JM, Chung, Y, Hagler, DJ Jr, Roddey, JC, Erhart, M, McCabe, C, Akshoomoff, N, Amaral, DG, Bloss, CS, Libiger, O, Schork, NJ, Darst, BF, Casey, BJ, Chang, L, Ernst, TM, Frazier, J, Gruen, JR, Kaufmann, WE, Murray, SS, van Zijl, P, Mostofsky, S, Dale, AM, Pediatric Imaging, Neurocognition, and Genetics Study (2012). Long-term influence of normal variation in neonatal characteristics on human brain development. Proceedings of the National Academy of Sciences USA 109, 20089–20094.Google Scholar
Weinstock, M (2008). The long-term behavioural consequences of prenatal stress. Neuroscience and Biobehavioral Reviews 32, 1073–1086.Google Scholar
Weissman, MM, Wickramaratne, P, Adams, P, Wolk, S, Verdeli, H, Olfson, M (2000). Brief screening for family psychiatric history: the family history screen. Archives of General Psychiatry 57, 675–682.Google Scholar
Wyrwoll, CS, Holmes, MC (2011). Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinology 95, 47–55.Google Scholar
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