BACKGROUND: Experience of early-life socioeconomic deprivation (ELSD) may increase the risk of mental disorders in young adulthood. This association may be mediated by structural and functional alterations of the hippocampus. METHODS: We conducted a prospective cohort study on 122 participants of the European Longitudinal Study of Pregnancy and Childhood. Information about ELSD was collected via questionnaire from mothers during the first 18 months of participants' lives. At age 23-24, participants underwent examination by structural magnetic resonance imaging, resting-state functional connectivity and assessment of depressive symptoms (Mood and Feelings Questionnaire) and anxiety (Spielberger State-Trait Anxiety Inventory). The association of ELSD with brain outcomes in young adulthood was assessed with correlations, linear regression (adjusting for sex, socioeconomic position and mother's mental health) and moderated mediation analysis. RESULTS: Higher ELSD was associated with greater depressive symptoms (B = 0.22; p = 0.001), trait anxiety (B = 0.07; p = 0.02) and lower global connectivity of the right hippocampus (B = -0.01; p = 0.02). These associations persisted when adjusted for covariates. In women, lower global connectivity of the right hippocampus was associated with stronger trait anxiety (B = -4.14; p = 0.01). Global connectivity of the right hippocampus as well as connectivity between the right hippocampus and the left middle temporal gyrus mediated the association between ELSD and trait anxiety in women. Higher ELSD correlated with a lower volume of the right hippocampus in men, but the volume of the right hippocampus was not related to mental health. CONCLUSIONS: Early preventive strategies targeted at children from socioeconomically deprived families may yield long-lasting benefits for the mental health of the population.

2nd Faculty of Medicine Charles University Prague Prague Czech Republic

3rd Faculty of Medicine Charles University Prague Prague Czech Republic

Brain and Mind Research Central European Institute of Technology Masaryk University Brno Czech Republic

Faculty of Science RECETOX Brno MU Czech Republic

National Institute of Mental Health Klecany Czech Republic

Zobrazit více v PubMed

Angelini, V., Howdon, D. D., & Mierau, J. O. (2018). Childhood socioeconomic status and late-adulthood mental health: Results from the Survey on Health, Ageing and Retirement in Europe. The Journals of Gerontology: Series B, 74, 95–104. doi: 10.1093/geronb/gby028 PubMed DOI PMC

Angold, A., & Costello, E. (1987). Mood and feelings questionnaire (MFQ). Durham, NC: Developmental Epidemiology Program, Duke University. Retrieved from: https://devepi.duhs.duke.edu/measures/the-mood-and-feelings-questionnaire-mfq/

Arnone, D., McKie, S., Elliott, R., Juhász, G., Thomas, E., Downey, D., … Anderson, I. (2013). State-dependent changes in hippocampal grey matter in depression. Molecular Psychiatry, 18, 1265–1272. doi: 10.1038/mp.2012.150 PubMed DOI

Barch, D., Pagliaccio, D., Belden, A., Harms, M. P., Gaffrey, M., Sylvester, C. M., … Luby, J. (2016). Effect of hippocampal and amygdala connectivity on the relationship between preschool poverty and school-age depression. The American Journal of Psychiatry, 173, 625–634. doi: 10.1176/appi.ajp.2015.15081014 PubMed DOI PMC

Besteher, B., Squarcina, L., Spalthoff, R., Bellani, M., Gaser, C., Brambilla, P., & Nenadić, I. (2019). Hippocampal volume as a putative marker of resilience or compensation to minor depressive symptoms in a nonclinical sample. Frontiers in Psychiatry, 10. doi: 10.3389/fpsyt.2019.00467 PubMed DOI PMC

Bobak, M., Pikhart, H., Pajak, A., Kubinova, R., Malyutina, S., Sebakova, H., … Marmot, M. (2006). Depressive symptoms in urban population samples in Russia, Poland and the Czech Republic. British Journal of Psychiatry, 188, 359–365. doi: 10.1192/bjp.188.4.359 PubMed DOI

Bobak, M., Pikhart, H., Rose, R., Hertzman, C., & Marmot, M. (2000). Socioeconomic factors, material inequalities, and perceived control in self-rated health: Cross-sectional data from seven post-communist countries. Social Science & Medicine, 51, 1343–1350. doi: 10.1016/S0277-9536(00)00096-4 PubMed DOI

Brito, N. H., & Noble, K. G. (2014). Socioeconomic status and structural brain development. Frontiers in Neuroscience, 8, 276. doi: 10.3389/fnins.2014.00276 PubMed DOI PMC

Burghy, C. A., Stodola, D. E., Ruttle, P. L., Molloy, E. K., Armstrong, J. M., Oler, J. A., … Essex, M. J. (2012). Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience, 15, 1736. doi: 10.1038/nn.3257 PubMed DOI PMC

Cao, X., Liu, Z., Xu, C., Li, J., Gao, Q., Sun, N., … Zhang, K. (2012). Disrupted resting-state functional connectivity of the hippocampus in medication-naive patients with major depressive disorder. Journal of Affective Disorders, 141, 194–203. doi: 10.1016/j.jad.2012.03.002 PubMed DOI

Cermakova, P., Formanek, T., Kagstrom, A., & Winkler, P. (2018). Socioeconomic position in childhood and cognitive aging in Europe. Neurology, 91, e1602–e1610. doi: 10.1212/WNL.0000000000006390 PubMed DOI PMC

Cermakova, P., Pikhart, H., Kubinova, R., & Bobak, M. (2020a). Education as inefficient resource against depressive symptoms in the Czech Republic: Cross-sectional analysis of the HAPIEE study. European Journal of Public Health, 30(5), 948–952. doi: 10.1093/eurpub/ckaa059. PubMed DOI PMC

Cermakova, P., Pikhart, H., Ruiz, M., Kubinova, R., & Bobak, M. (2020b). Socioeconomic position in childhood and depressive symptoms in later adulthood in the Czech Republic. Journal of Affective Disorders, 272, 17–23. doi: 10.1016/j.jad.2020.03.099. PubMed DOI

Cha, J., Greenberg, T., Song, I., Blair Simpson, H., Posner, J., & Mujica-Parodi, L. R. (2016). Abnormal hippocampal structure and function in clinical anxiety and comorbid depression. Hippocampus, 26, 545–553. doi: 10.1002/hipo.22566 PubMed DOI PMC

Chaloner, A., & Greenwood-Van Meerveld, B. (2013). Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model. The Journal of Pain, 14, 270–280. doi: 10.1016/j.jpain.2012.11.008 PubMed DOI

Chandola, T., Bartley, M., Sacker, A., Jenkinson, C., & Marmot, M. (2003). Health selection in the Whitehall II study, UK. Social Science & Medicine, 56, 2059–2072. doi: 10.1016/s0277-9536(02)00201-0 PubMed DOI

Chen, A. C., & Etkin, A. (2013). Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder. Neuropsychopharmacology, 38, 1889–1898. doi: 10.1038/npp.2013.122 PubMed DOI PMC

Chen, E., & Miller, G. E. (2012). ‘Shift-and-persist’ strategies: Why low socioeconomic status isn't always bad for health. Perspectives on Psychological Science, 7, 135–158. doi: 10.1177/1745691612436694 PubMed DOI PMC

Cusick, S. E., & Georgieff, M. K. (2016). The role of nutrition in brain development: The golden opportunity of the ‘first 1000 days’. The Journal of Pediatrics, 175, 16–21. doi: 10.1016/j.jpeds.2016.05.013 PubMed DOI PMC

De La Plata, C. D. M., Garces, J., Kojori, E. S., Grinnan, J., Krishnan, K., Pidikiti, R., … McColl, R. (2011). Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury. Archives of Neurology, 68, 74–84. doi: 10.1001/archneurol.2010.342 PubMed DOI PMC

Erikson, R., Goldthorpe, J. H., & Portocarero, L. (1979). Intergenerational class mobility in three Western European societies: England, France and Sweden. The British Journal of Sociology, 30, 415–441. doi: 10.2307/589632 PubMed DOI

Galobardes, B., Shaw, M., Lawlor, D. A., Lynch, J. W., & Davey Smith, G. (2006a). Indicators of socioeconomic position (part 1). Journal of Epidemiology and Community Health, 60, 7–12. doi: 10.1136/jech.2004.023531 PubMed DOI PMC

Galobardes, B., Shaw, M., Lawlor, D. A., Lynch, J. W., & Davey Smith, G. (2006b). Indicators of socioeconomic position (part 2). Journal of Epidemiology and Community Health, 60, 95–101. doi: 10.1136/jech.2004.028092 PubMed DOI PMC

Gorka, A. X., Hanson, J. L., Radtke, S. R., & Hariri, A. R. (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. Biology of Mood & Anxiety Disorders, 4, 12. Retrieved from: https://biolmoodanxietydisord.biomedcentral.com/articles/10.1186/2045-5380-4-12 PubMed PMC

Hayakawa, Y. K., Sasaki, H., Takao, H., Mori, H., Hayashi, N., Kunimatsu, A., … Ohtomo, K. (2013). Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging. Journal of Affective Disorders, 144, 263–268. doi: 10.1016/j.jad.2012.10.023 PubMed DOI

Hayes, A. (2018). PROCESS macro for SPSS and SAS. The PROCESS macro for SPSS and SAS. Introduction to mediation, moderation, and conditional PROCESS analysis, second edition: A regression-based approach. Retrieved from: http://processmacro.org/papers.html

Heeren, A., & McNally, R. J. (2016). An integrative network approach to social anxiety disorder: The complex dynamic interplay among attentional bias for threat, attentional control, and symptoms. Journal of Anxiety Disorders, 42, 95–104. doi: 10.1016/j.janxdis.2016.06.009 PubMed DOI

Horackova, K., Kopecek, M., Machů, V., Kagstrom, A., Aarsland, D., Motlova, L. B., & Cermakova, P. (2019). Prevalence of late-life depression and gap in mental health service use across European regions. European Psychiatry, 57, 19–25. doi: 10.1016/j.eurpsy.2018.12.002 PubMed DOI

Javanbakht, A., Kim, P., Swain, J. E., Evans, G. W., Phan, K. L., & Liberzon, I. (2016). Sex-specific effects of childhood poverty on neurocircuitry of processing of emotional cues: A neuroimaging study. Behavioral Sciences (Basel), 6. doi: 10.3390/bs6040028 PubMed DOI PMC

Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry, 62, 593–602. doi: 10.1001/archpsyc.62.6.593 PubMed DOI

Koolschijn, P. C. M., van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., & Crone, E. A. (2013). Hippocampal volume and internalizing behavior problems in adolescence. European Neuropsychopharmacology, 23, 622–628. doi: 10.1016/j.euroneuro.2012.07.001 PubMed DOI

Liao, W., Xu, Q., Mantini, D., Ding, J., Machado-de-Sousa, J. P., Hallak, J. E., … Chen, H. (2011). Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder. Brain Research, 1388, 167–177. doi: 10.1016/j.brainres.2011.03.018 PubMed DOI

Liu, F., Zhu, C., Wang, Y., Guo, W., Li, M., Wang, W., … Zeng, L. (2015). Disrupted cortical hubs in functional brain networks in social anxiety disorder. Clinical Neurophysiology, 126, 1711–1716. doi: 10.1016/j.clinph.2014.11.014 PubMed DOI

Lyons, D. M., Yang, C., Sawyer-Glover, A. M., Moseley, M. E., & Schatzberg, A. F. (2001). Early life stress and inherited variation in monkey hippocampal volumes. Archives of General Psychiatry, 58, 1145–1151. doi: 10.1001/archpsyc.58.12.1145 PubMed DOI

Mareckova, K., Klasnja, A., Andryskova, L., Brazdil, M., & Paus, T. (2019a). Developmental origins of depression-related white matter properties: Findings from a prenatal birth cohort. Human Brain Mapping, 40, 1155–1163. doi: 10.1002/hbm.24435 PubMed DOI PMC

Mareckova, K., Klasnja, A., Bencurova, P., Andryskova, L., Brazdil, M., & Paus, T. (2019b). Prenatal stress, mood, and gray matter volume in young adulthood. Cerebral Cortex, 29, 1244–1250. doi: 10.1093/cercor/bhy030 PubMed DOI PMC

Mareckova, K., Marecek, R., Bencurova, P., Klanova, J., Dusek, L., & Brazdil, M. (2018). Perinatal stress and human hippocampal volume: Findings from typically developing young adults. Scientific Reports, 8, 4696. doi: 10.1038/s41598-018-23046-6 PubMed DOI PMC

Marmot, M. (2004). Status syndrome. Significance, 1, 150–154. doi: 10.1111/j.1740-9713.2004.00058.x. DOI

Marques, A. A., Bevilaqua, M. C. D. N., da Fonseca, A. M. P., Nardi, A. E., Thuret, S., & Dias, G. P. (2016). Gender differences in the neurobiology of anxiety: Focus on adult hippocampal neurogenesis. Neural Plasticity, 2016. doi: 10.1155/2016/5026713 PubMed DOI PMC

McCormick, C. M., Smythe, J. W., Sharma, S., & Meaney, M. J. (1995). Sex-specific effects of prenatal stress on hypothalamic-pituitary-adrenal responses to stress and brain glucocorticoid receptor density in adult rats. Developmental Brain Research, 84, 55–61. doi: 10.1016/0165-3806(94)00153-q PubMed DOI

McEwen, B. S. (2000). Effects of adverse experiences for brain structure and function. Biological psychiatry, 48, 721–731. doi: 10.1016/s0006-3223(00)00964-1 PubMed DOI

McLaren, M. E., Szymkowicz, S. M., O'Shea, A., Woods, A. J., Anton, S. D., & Dotson, V. M. (2016). Dimensions of depressive symptoms and cingulate volumes in older adults. Translational Psychiatry, 6, e788. doi: 10.1038/tp.2016.49 PubMed DOI PMC

Murgatroyd, C., & Spengler, D. (2011). Epigenetic programming of the HPA axis: Early life decides. Stress, 14, 581–589. doi: 10.3109/10253890.2011.602146 PubMed DOI

Najman, J. M., Hayatbakhsh, M. R., Clavarino, A., Bor, W., O'Callaghan, M. J., & Williams, G. M. (2010). Family poverty over the early life course and recurrent adolescent and young adult anxiety and depression: A longitudinal study. American Journal of Public Health, 100, 1719–1723. doi: 10.2105/AJPH.2009.180943 PubMed DOI PMC

Orbach, L., Herzog, M., & Fritz, A. (2019). Relation of state- and trait-math anxiety to intelligence, math achievement and learning motivation. Journal of Numerical Cognition, 5(3), 371–399. doi: 10.5964/jnc.v5i3.204 DOI

Parker, G., Wilhelm, K., Mitchell, P., Austin, M.-P., Roussos, J., & Gladstone, G. (1999). The influence of anxiety as a risk to early onset major depression. Journal of Affective Disorders, 52, 11–17. doi: 10.1016/s0165-0327(98)00084-6 PubMed DOI

Piler, P., Kandrnal, V., Kukla, L., Andrýsková, L., Švancara, J., Jarkovský, J., … Klánová, J. (2017). Cohort profile: The European Longitudinal Study of Pregnancy and Childhood (ELSPAC) in the Czech Republic. International Journal of Epidemiology, 46, 1379–1379f. doi: 10.1093/ije/dyw091 PubMed DOI PMC

Pruessner, J. C., Dedovic, K., Khalili-Mahani, N., Engert, V., Pruessner, M., Buss, C., … Lupien, S. (2008). Deactivation of the limbic system during acute psychosocial stress: Evidence from positron emission tomography and functional magnetic resonance imaging studies. Biological Psychiatry, 63, 234–240. doi: 10.1016/j.biopsych.2007.04.041 PubMed DOI

Qiao, J., Li, A., Cao, C., Wang, Z., Sun, J., & Xu, G. (2017). Aberrant functional network connectivity as a biomarker of generalized anxiety disorder. Frontiers in Human Neuroscience, 11, 626. doi: 10.3389/fnhum.2017.00626 PubMed DOI PMC

Qiu, A., Rifkin-Graboi, A., Chen, H., Chong, Y., Kwek, K., Gluckman, P., … Meaney, M. (2013). Maternal anxiety and infants' hippocampal development: Timing matters. Translational Psychiatry, 3, e306. doi: 10.1038/tp.2013.79 PubMed DOI PMC

Rao, U., Chen, L.-A., Bidesi, A. S., Shad, M. U., Thomas, M. A., & Hammen, C. L. (2010). Hippocampal changes associated with early-life adversity and vulnerability to depression. Biological Psychiatry, 67, 357–364. doi: 10.1016/j.biopsych.2009.10.017 PubMed DOI PMC

Rice, D., & Barone, Jr. S. (2000). Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environmental Health Perspectives 108, 511–533. doi: 10.1289/ehp.00108s3511 PubMed DOI PMC

Rusch, B. D., Abercrombie, H. C., Oakes, T. R., Schaefer, S. M., & Davidson, R. J. (2001). Hippocampal morphometry in depressed patients and control subjects: Relations to anxiety symptoms. Biological Psychiatry, 50, 960–964. doi: 10.1016/s0006-3223(01)01248-3 PubMed DOI

Russell, A. E., Ford, T., & Russell, G. (2015). Socioeconomic associations with ADHD: Findings from a mediation analysis. PLoS ONE, 10(6), e0128248. doi: 10.1371/journal.pone.0128248. PubMed DOI PMC

Sakaguchi, Y., & Sakurai, Y. (2017). Left-right functional asymmetry of ventral hippocampus depends on aversiveness of situations. Behavioral Brain Research, 325, 25–33. doi: 10.1016/j.bbr.2017.02.028 PubMed DOI

Singh-Manoux, A., Marmot, M. G., & Adler, N. E. (2005). Does subjective social status predict health and change in health status better than objective status? Psychosomatic Medicine, 67, 855–861. doi: 10.1097/01.psy.0000188434.52941.a0 PubMed DOI

Spasojevic, N., Stanisavljevic, D., Gavrilovic, L., Jovanovic, P., Cucakovic, A., & Dronjak, S. (2012). Hippocampal asymmetry in expression of catecholamine synthesizing enzyme and transporters in socially isolated rats. Neuro Endocrinology Letters, 33, 631–635. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/23160224/ PubMed

Spence, S. H., Najman, J. M., Bor, W., O'Callaghan, M. J., & Williams, G. M. (2002). Maternal anxiety and depression, poverty and marital relationship factors during early childhood as predictors of anxiety and depressive symptoms in adolescence. Journal of Child Psychology and Psychiatry, 43, 457–469. doi: 10.1111/1469-7610.00037 PubMed DOI

Spielberger, C. D., & Gorsuch, R. L. (1983). State-trait anxiety inventory for adults: Manual and sample: Manual, instrument and scoring guide. USA: Consulting Psychologists Press. doi: 10.1037/t06496-000. DOI

Staff, R. T., Murray, A. D., Ahearn, T. S., Mustafa, N., Fox, H. C., & Whalley, L. J. (2012). Childhood socioeconomic status and adult brain size: Childhood socioeconomic status influences adult hippocampal size. Annals of Neurology, 71, 653–660. doi: 10.1002/ana.22631 PubMed DOI

Suzuki, H., Botteron, K. N., Luby, J. L., Belden, A. C., Gaffrey, M. S., Babb, C. M., … Barch, D. M. (2013). Structural-functional correlations between hippocampal volume and cortico-limbic emotional responses in depressed children. Cognitive, Affective, & Behavioral Neuroscience, 13, 135–151. doi: 10.3758/s13415-012-0121-y PubMed DOI PMC

Videbech, P., & Ravnkilde, B. (2004). Hippocampal volume and depression: A meta-analysis of MRI studies. American Journal of Psychiatry, 161, 1957–1966. doi: 10.1176/appi.ajp.161.11.1957 PubMed DOI

Weinstock, M. (2007). Gender differences in the effects of prenatal stress on brain development and behaviour. Neurochemical Research, 32, 1730–1740. doi: 10.1007/s11064-007-9339-4 PubMed DOI

Whitfield-Gabrieli, S., & Nieto-Castanon, A. (2012). Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity, 2, 125–141. doi: 10.1089/brain.2012.0073. PubMed DOI

Yun, J.-Y., Kim, J.-C., Ku, J., Shin, J.-E., Kim, J.-J., & Choi, S.-H. (2017). The left middle temporal gyrus in the middle of an impaired social-affective communication network in social anxiety disorder. Journal of Affective Disorders, 214, 53–59. doi: 10.1016/j.jad.2017.01.043 PubMed DOI

Zhang, R., Chen, Z., Liu, P., & Feng, T. (2020). The neural substrates responsible for how trait anxiety affects delay discounting: Right hippocampal and cerebellar connectivity with bistable right inferior parietal lobule. Psychophysiology, 57, e13495. doi: 10.1111/psyp.13495 PubMed DOI

Socioeconomic and cognitive roots of trait anxiety in young adults