Skip to main content
SpringerLink
Log in

A Dimensional and Dynamic Approach to the Neurobiology of Mood Disorders: On Intermediate Phenotypes and Their Interaction with Early Stress

  • Chapter
  • First Online:
Etiopathogenic Theories and Models in Depression

Part of the book series: Depression and Personality ((DP))

Abstract

The neurobiological theories of depression find their main pitfall when searching associations between specific pathophysiological mechanisms and a clinical syndrome with diffuse limits and high heterogeneity, such as depressive syndrome. In order to improve treatment effectiveness, recent studies have focused on identification of intermediate phenotypes (quantifiable physiological traits or processes that are interposed between gene and clinical phenotype) that could identify the subgroup of patients with depression with more homogeneous symptoms, similar physiological features, and consistent responses to treatment. This chapter will provide a critical review of neurobiological studies with a dimensional approach in patients with mood disorders. Focusing on neurobiological evidence about intermediate phenotypes, such as cognitive functioning in patients with depression, it emphasizes the relevance of building bridges between neuroscience research and clinical field to lead to greater understanding of the causes of depressive illness.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aas, M., Dazzan, P., Fisher, H., Morgan, C., Reichenberg, A., Zanelli, J., Fearon, P., Jones, P. B., Murray, R. M., & Pariante, C. (2011a). Childhood trauma and cognitive function in first-episode affective and non-affective psychosis. Schizophrenia Research, 129(1), 9–12. https://doi.org/10.1016/j.schres.2011.03.017

    Article  Google Scholar 

  • Aas, M., Dazzan, P., Mondelo, V., Toulopoulou, T., Reichenberg, A., Di Forti, M., Fisher, H. L., Handley, R., Hepgul, N., Marques, T., Miorelli, A., Taylor, H., Russo, M., Wiffen, B., Papadopoulos, A., Aitchison, K. J., Morgan, C., Murray, R. M., & Pariante, C. M. (2011b). Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis. Psychological Medicine, 41(3), 463–476. https://doi.org/10.1017/S0033291710001170

    Article  PubMed  Google Scholar 

  • Aas, M., Djurovic, S., Athanasiu, L., Steen, N., Agartz, I., Lorentzen, S., et al. (2012). Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders. Schizophrenia Bulletin, 38(1), 15–22.

    Article  Google Scholar 

  • Aas, M., Haukvik, U., Djurovic, S., Bergmann, O., Athanasiu, L., et al. (2013). BDNF Valmet66 modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 46, 181–188.

    Article  Google Scholar 

  • Agnew-Blais, J., & Danese, A. (2016). Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: A systematic review and meta-analysis. Lancet Psychiatry, 3(4), 342–349.

    Article  Google Scholar 

  • Agrawal, A., Nelson, E. C., Littlefield, A. K., Bucholz, K. K., Degenhardt, L., Henders, A. K., et al. (2012). Cannabinoid receptor genotype moderation of the effects of child- hood physical abuse on anhedonia and depression. Archives of General Psychiatry, 69(7), 732–740. https://doi.org/10.1001/archgenpsychiatry.2011.2273

    Article  PubMed  PubMed Central  Google Scholar 

  • Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., et al. (2009). Early adversity and 5-HTT/BDNF genes: New evidence of gene-environment inter- actions on depressive symptoms in a general population. Psychological Medicine, 39(9), 1425–1432. https://doi.org/10.1017/S0033291709005248

    Article  PubMed  Google Scholar 

  • Appel, K., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., et al. (2011). Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology, 36(10), 1982–1991. https://doi.org/10.1038/npp.2011.81

    Article  PubMed  PubMed Central  Google Scholar 

  • Belvederi, M., Prestia, D., Mondelli, V., Pariante, C., Patti, S., Olivieri, B., Arzani, C., Masotti, M., Respino, M., Antonioli, M., Vassallo, L., Serafini, G., Perna, G., Pompili, M., & Amore, M. (2016). The HPA axis in bipolar disorder: Systematic review and meta-analysis. Psychoneuroendocrinology, 63, 327–342. https://doi.org/10.1016/j.psyneuen.2015.10.014

    Article  Google Scholar 

  • Berrios, G. (2001). Hacia una nueva epistemología de la Psiquiatría (1st ed.). Polemos.

    Google Scholar 

  • Bora, E., & Pantelis, C. (2016). Social cognition in schizophrenia in comparison to bipolar disorder: a meta-analysis. Schizophrenia Research, 175, 72–78.

    Article  Google Scholar 

  • Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., et al. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin- releasing hormone receptor gene. Archives of General Psychiatry, 65(2), 190–200. https://doi.org/10.1001/archgenpsychiatry.2007.26

    Article  PubMed  PubMed Central  Google Scholar 

  • Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389. https://doi.org/10.1126/science.1083968

    Article  PubMed  Google Scholar 

  • Cichon, S., Craddock, N., Daly, M., Faraone, S. V., Gejman, P. V., Kelsoe, J., Lehner, T., Levinson, D. F., Moran, A., Sklar, P., Sullivan, P. F., Anney, R., Gill, M., Corvin, A., Buitelaar, J., Franke, B., Elia, J., Hakonarson, H., Kent, L., et al. (2009). Genomewide association studies: History, rationale, and prospects for psychiatric disorders. The American Journal of Psychiatry, 166, 540–556.

    Google Scholar 

  • Cuthbert, B. N. (2015). Research domain criteria: Toward future psychiatric nosologies. Dialogues in Clinical Neuroscience, 17, 89–97.

    Article  Google Scholar 

  • Danese, A., & Baldwin, J. (2017). Hidden wounds? Inflammatory links between childhood trauma and psychopathology. Annual Review of Psychology, 68, 517–544.

    Article  Google Scholar 

  • El-Hage, W., Leman, S., Camus, V., & Belzung, C. (2013). Mechanisms of antidepressant resistance. Frontiers in Pharmacology, 4, 146.

    Article  Google Scholar 

  • Frodl, T., Reinhold, E., Koutsouleris, N., Donohoe, G., Bondy, B., Reiser, M., et al. (2010). Childhood stress, serotonin transporter gene and brain structures in major depression. Neuropsychopharmacology, 35(6), 1383–1390. https://doi.org/10.1038/npp.2010.8

    Article  PubMed  PubMed Central  Google Scholar 

  • Garno, J., Goldberg, J., Ramirez, P., & Ritzler, B. (2005). Impact of childhood abuse on the clinical course of bipolar disorder. The British Journal of Psychiatry, 186, 121–125. https://doi.org/10.1192/bjp.186.2.121

    Article  PubMed  Google Scholar 

  • Gatt, J. M., Nemeroff, C. B., Dobson-Stone, C., Paul, R. H., Bryant, R. A., Schofield, P. R., et al. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14(7), 681–695. https://doi.org/10.1038/mp.2008.143

    Article  PubMed  Google Scholar 

  • Gotlib, I. H., Joormann, J., Minor, K. L., & Hallmayer, J. (2008). HPA axis reactivity: A mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biological Psychiatry, 63(9), 847–851. https://doi.org/10.1016/j.biopsych.2007.10.008

    Article  PubMed  Google Scholar 

  • Hackman, D., & Farrah, M. (2009). Socioeconomic status and the developing brain. Trends in Cognitive Sciences, 13, 65–73.

    Article  Google Scholar 

  • Haeffel, G. J., Getchell, M., Koposov, R. A., Yrigollen, C. M., Deyoung, C. G., Klinteberg, B. A., et al. (2008). Association between polymorphisms in the dopamine transporter gene and depression: Evidence for a gene-environment interaction in a sample of juvenile detainees. Psychological Science, 19(1), 62–69. https://doi.org/10.1111/j.1467-9280.2008.02047.x

    Article  PubMed  Google Scholar 

  • Heim, C., Newport, J., Heit, S., Graham, Y., Wilcox, B., Bonsall, R., … Nemeroff, C. (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284, 592–597. https://doi.org/10.1001/jama.284.5.592

    Article  PubMed  Google Scholar 

  • Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33(6), 693–710. https://doi.org/10.1016/j.psyneuen.2008.03.008

    Article  PubMed  Google Scholar 

  • Hornung, O. P., & Heim, C. M. (2014). Gene–environment interactions and intermediate phenotypes: Early trauma and depression. Frontiers in Endocrinology, 5, 14. https://doi.org/10.3389/fendo.2014.00014

    Article  PubMed  PubMed Central  Google Scholar 

  • Hsu, D. T., Mickey, B. J., Langenecker, S. A., Heitzeg, M. M., Love, T. M., Wang, H., et al. (2012). Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing. The Journal of Neuroscience, 32(9), 3253–3260. https://doi.org/10.1523/JNEUROSCI.5533-11.2012

    Article  PubMed  PubMed Central  Google Scholar 

  • Insel, T. R. (2014). The NIMH Research Domain Criteria (RDoC) project: Precision medicine for psychiatry. The American Journal of Psychiatry, 171, 395–397.

    Article  Google Scholar 

  • Kauer-Sant’Anna, M., Tramontina, J., Andreazza, A. C., Cereser, K., da Costa, S., Santin, A., Yatham, L. N., & Kapczinski, F. (2007). Traumatic life events in bipolar disorder: Impact on BDNF levels and psychopathology. Bipolar Disorders, 9(1), 128–135.

    Article  Google Scholar 

  • Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J., Pariante, C., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., Nemeroff, C. B., Holsboer, F., Heim, C. M., Ressler, K. J., Rein, T., & Binder, E. B. (2013). Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions. Nature Neuroscience, 16(1), 33–41.

    Article  Google Scholar 

  • Krishnan, V., & Nestler, E. J. (2010). Linking molecules to mood: New insight into the biology of depression. The American Journal of Psychiatry, 167, 1305–1320.

    Article  Google Scholar 

  • Leuchter, A., Hunter, A., Krantz, D., & Cook, I. (2014). Intermediate phenotypes and biomarkers of treatment outcome in major depressive. Dialogues in Clinical Neuroscience, 16(4), 525–537.

    Article  Google Scholar 

  • Lutz, A., Greischar, L., Rawlings, N., Ricard, M., & Davison, R. (2004). Long term meditators self-induce high amplitude gamma synchrony during mental practice. PNAS, 16(101), 16369–16373.

    Article  Google Scholar 

  • Meyer-Lindenberg, A., & Weinberger, D. R. (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews. Neuroscience, 7, 818–827.

    Article  Google Scholar 

  • Modelli, V., Dazzan, P., Gabilondo, A., Tournikioti, K., Walshe, M., Marshall, N., Schulze, K. K., Murray, R. M., McDonald, C., & Pariante, C. M. (2008). Pituitary volume in unaffected relatives of patients with schizophrenia and bipolar disorder. Psychoneuroendocrinology, 33, 1004–1012.

    Article  Google Scholar 

  • Mondelli, V., Dazzan, P., Hepgul, N., Di Forti, M., Aas, M., D’Albenzio, A., Di Nicola, M., Fisher, H., Handley, R., Marques, T. R., Morgan, C., Navari, S., Taylor, H., Papadopoulos, A., Aitchison, K. J., Murray, R. M., & Pariante, C. M. (2010). Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment. Schizophrenia Research, 116(1–2), 234–242. https://doi.org/10.1016/j.schres.2009.08.013

    Article  PubMed  Google Scholar 

  • Nemeroff, C. B., Heim, C. M., Thase, M. E., Klein, D. N., Rush, A. J., Schatzberg, A. F., et al. (2003). Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 14293–14296. https://doi.org/10.1073/pnas.2336126100

    Article  PubMed  PubMed Central  Google Scholar 

  • Nestler, E. J., & Hyman, S. E. (2010). Animal models of neuropsychiatric disorders. Nature Neuroscience, 13, 1161–1169.

    Article  Google Scholar 

  • Perez, C., & Spatz, C. (1994). Childhood victimization and long-term intellectual and academic outcomes. Child Abuse & Neglect, 18(8), 617–633.

    Article  Google Scholar 

  • Rasetti, R., & Weinberger, D. R. (2011). Intermediate phenotypes in psychiatric disorders. Current Opinion in Genetics & Development, 21(3), 340–348. https://doi.org/10.1016/j.gde.2011.02.003

    Article  Google Scholar 

  • Read, J., Sampson, M., & Critchley, C. (2016). Are mental health services getting better at responding to abuse, assault and neglect? Acta Psychiatrica Scandinavica, 134, 287–294.

    Article  Google Scholar 

  • Ríos, U. (2019). ‘Evaluación de un modelo de interacción gen ambiente en pacientes con Trastorno Bipolar tipo I en eutimia. Asociación entre maltrato infantil y cognición social, y moderación de polimorfismos genéticos’ Tesis doctoral. Pontificia Universidad Católica de Chile.

    Google Scholar 

  • Rodriguez. (2008). Ciencias de la Mente. Aproximaciones desde Latinoamérica. Santiago: JC Saez-Editor.

    Google Scholar 

  • Samame, C. (2013). Social cognition throughout the three phases of bipolar disorder: A state-of-the-art overview. Psychiatry Research, 210, 1275–1286.

    Article  Google Scholar 

  • Savitz, J., Van der Merwe, L., Stein, D., Solms, M., & Ramesa, R. (2007). Genotype and childhood sexual trauma moderate neurocognitive performance: A possible role for brain-derived neurotrophic factor and apolipoprotein E variants. Biological Psychiatry, 62, 391–399.

    Article  Google Scholar 

  • Tanti, A., & Belzung, C. (2010). Open questions in current models of antidepressant action. British Journal of Pharmacology, 159, 1187–1200.

    Article  Google Scholar 

  • Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience and Biobehavioral Reviews, 27(1–2), 33–44.

    Article  Google Scholar 

  • Thomason, M. E., Henry, M. L., Paul Hamilton, J., Joormann, J., Pine, D. S., Ernst, M., et al. (2010). Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene. Biological Psychology, 85(1), 38–44. https://doi.org/10.1016/j.biopsycho.2010.04.009

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson, E., & Varela, F. (2001). Radical embodiment: Neural dynamics and consciousness. Trend on cognitive Science, 5, 418–425.

    Article  Google Scholar 

  • Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., & Gotlib, I. H. (2011). Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology, 36(1), 144–147. https://doi.org/10.1016/j.psyneuen.2010.07.003

    Article  PubMed  Google Scholar 

  • Tyrka, A. R., Price, L. H., Gelernter, J., Schepker, C., Anderson, G. M., & Carpenter, L. L. (2009). Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: Effects on hypothalamic-pituitary-adrenal axis reactivity. Biological Psychiatry, 66(7), 681–685. https://doi.org/10.1016/j.biopsych.2009.05.012

    Article  PubMed  PubMed Central  Google Scholar 

  • Varela, F. (1995). Resonant cells assemblies: A new approach to cognitive functions and neuronal synchrony. Biological Research, 28, 81–95.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Valparaiso, Mood Disorders Unit, Hospital Psiquiátrico del Salvador, Valparaíso, Valparaíso, Chile

    Ulises Ríos

Authors
  1. Ulises Ríos
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Psychiatry and Mental Health East, Faculty of Medicine, University of Chile, Millennium Institute for Research in Depression and Personality (MIDAP), Santiago, RM, Chile

    Juan Pablo Jiménez

  2. Department of Psychiatry and Mental Health East, Faculty of Medicine, University of Chile, Millennium Institute for Research in Depression and Personality (MIDAP), Santiago, RM, Chile

    Alberto Botto

  3. Research Department of Clinical Educational and Health Psychology, University College London, London, UK

    Peter Fonagy

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ríos, U. (2021). A Dimensional and Dynamic Approach to the Neurobiology of Mood Disorders: On Intermediate Phenotypes and Their Interaction with Early Stress. In: Jiménez, J.P., Botto, A., Fonagy, P. (eds) Etiopathogenic Theories and Models in Depression. Depression and Personality. Springer, Cham. https://doi.org/10.1007/978-3-030-77329-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation