A Systematic Review of Childhood Trauma and Cognitive Functioning in Individuals with Major Depressive Disorder (MDD) or Bipolar Disorder (BD)
Keywords:
Childhood trauma, cognitive functioning, major depressive disorder, bipolar disorder, systematic reviewAbstract
Purpose: This study aims to systematically investigate the relationship between childhood trauma and cognitive functioning in individuals diagnosed with Major Depressive Disorder (MDD) or Bipolar Disorder (BD).
Methods and Materials: This study employed a systematic review approach, analyzing peer-reviewed English-language articles published between 2020 and 2025. A three-stage screening protocol was used: removal of duplicate records, evaluation of relevance to the research domain, and inclusion based on direct response to the research question. Comprehensive database searches were conducted using a combination of keywords related to childhood trauma, cognitive function, and mood disorders. Inclusion criteria required that studies involve participants aged 18 or older with a confirmed diagnosis of MDD or BD, assess objective cognitive outcomes, and establish a relationship with childhood trauma. Fifteen eligible studies were identified and analyzed based on variables such as study design, population characteristics, assessment tools, and outcomes.
Findings: The included studies provided consistent evidence of significant associations between adverse childhood experiences (ACEs)—particularly emotional abuse and neglect—and structural and functional brain changes, including reduced gray matter, disrupted white matter integrity, and altered connectivity in regions involved in emotional regulation. These neural alterations were linked to impairments in memory, attention, executive functioning, and processing speed. Biological findings highlighted elevated levels of inflammatory markers (e.g., IL-6, TNF-α, CRP) and immune system dysregulation in individuals with childhood trauma histories. The cognitive effects and inflammatory responses varied across diagnostic groups, with some findings more pronounced in BD. Moderating factors such as family functioning, education, and medication type also influenced cognitive outcomes.
Conclusion: This review underscores the critical role of childhood trauma in shaping cognitive deficits in mood disorders and calls for trauma-informed, multidisciplinary treatment strategies.
Downloads
References
Agnew-Blais, J., & Danese, A. (2016). Childhood maltreatment and unfavorable clinical outcomes in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry, 3(4), 342-349. https://doi.org/10.1016/S2215-0366(15)00544-1
Barczyk, Z., Foulds, J. A., Porter, R. J., & Douglas, K. M. (2023). Childhood trauma and cognitive functioning in mood disorders: A systematic review. Bipolar Disorder, 25(4), 263-277
Epub - 2023 Mar 2029. https://doi.org/10.1111/bdi.13321
Bektaş, N. (2025). Investigating Sociodemographic Features, Childhood Trauma, Personality and Psychological Symptoms as Predictors of Emotional Eating. Ayna Klinik Psikoloji Dergisi, 12(1), 1-25. https://doi.org/10.31682/ayna.1407214
Congia, A. C., Ragassi Urbano, M., Zoega Soares, M., & Odebrecht Vargas Nunes, S. (2022). Cognitive impairment, childhood trauma, sedentary behaviour, and elevated C-reactive protein levels in major affective disorders. Journal of psychiatric research, 155, 1-9. https://doi.org/10.1016/j.jpsychires.2022.07.052
Douglas, K. M., Gallagher, P., Robinson, L. J., Carter, J. D., McIntosh, V. V. W., Frampton, C. M. A., Watson, S., Young, A. H., Ferrier, I. N., & Porter, R. J. (2018). Prevalence of cognitive impairment in major depression and bipolar disorder. Bipolar Disorder, 20(3), 260-274. https://doi.org/10.1111/bdi.12602
Douglas, K. M., & Porter, R. J. (2012). The effect of childhood trauma on pharmacological treatment response in depressed inpatients. Psychiatry research, 200(2-3), 1058-1061. https://doi.org/10.1016/j.psychres.2012.06.015
Du, Y., Liu, J., Lin, R., Chattun, M. R., Gong, W., Hua, L., Tang, H., Han, Y., Lu, Q., & Yao, Z. (2024). The mediating role of family functioning between childhood trauma and depression severity in major depressive disorder and bipolar disorder. Journal of affective disorders, 365, 443-450. https://doi.org/10.1016/j.jad.2024.08.155
Goodman, J. B., Freeman, E. E., & Chalmers, K. A. (2019). The relationship between early life stress and working memory in adulthood: A systematic review and meta-analysis. Memory, 27(6), 868-880. https://doi.org/10.1080/09658211.2018.1561897
Harb, F., Wart, A. G., Brzezinski, J., deRoon‐Cassini, T. A., & Larson, C. L. (2025). Subtypes of Childhood Maltreatment and Posttraumatic Stress Disorder Symptoms in an Adult Trauma Sample: The Mechanistic Role of Sleep. Psychological Trauma Theory Research Practice and Policy, 17(2), 353-362. https://doi.org/10.1037/tra0001716
Humphreys, K. L., LeMoult, J., Wear, J. G., Piersiak, H. A., Lee, A., & Gotlib, I. H. (2020). Child maltreatment and depression: A meta-analysis of studies using the childhood trauma questionnaire. Child abuse & neglect, 102, 104361. https://doi.org/10.1016/j.chiabu.2020.104361
Jiaa, H., & Lubetkin, E. I. (2020). Impact of adverse childhood experiences on quality-adjusted life expectancy in the U.S. population. Child abuse & neglect, 102, 104418. https://doi.org/10.1016/j.chiabu.2020.104418
Jørgensen, J. L., Macoveanu, J., Petersen, J. Z., Knudsen, G. M., Kessing, L. V., Balslev Jørgensen, M., & Woznica Miskowi, K. (2023). Association of childhood trauma with cognitive impairment and structural brain alterations in remitted patients with bipolar disorder. Journal of affective disorders, 337, 75-85. https://doi.org/10.1016/j.jad.2023.05.078
Kalmakis, K. A., & Chandler, G. E. (2015). Health consequences of adverse childhood experiences: A systematic review. J Am Assoc Nurse Pract, 27(8), 457-465. https://doi.org/10.1002/2327-6924.12215
Lai, W., Zhang, H., Jiang, Y., Huang, X., Liao, Y., Hao, J., Liu, Y., Chen, Y., Wang, W., Guo, L., Zhang, W. H., Teopiz, K. M., McIntyre, R. S., Han, X., & Lu, C. (2025). Trauma exposure as a risk factor of major depressive disorder: A matched case-control study. Journal of psychiatric research, 182, 204-211. https://doi.org/10.1016/j.jpsychires.2025.01.028
Lu, S., Pan, F., Gao, W., Wei, Z., Wang, D., Hu, S., Huang, M., Xu, Y., & Li, L. (2017). Neural correlates of childhood trauma with executive function in young healthy adults. Oncotarget, 8(45), 79843-79853. https://doi.org/10.18632/oncotarget.20051
Maed, M., Zhou, B., Razhayon, M., Jirakran, K., Sughondhabirom, A., Sodsai, P., & Almulla, A. F. (2024). T cell activation and lowered T regulatory cell numbers are key processes in severe major depressive disorder: Effects of recurrence of illness and adverse childhood experiences. Journal of affective disorders, 362, 62-74. https://doi.org/10.1016/j.jad.2024.06.097
Majer, M., Ising, M., Künzel, H., Binder, E. B., Holsboer, F., Modell, S., & Zihl, J. (2004). Impaired divided attention predicts delayed response and risk to relapse in subjects with depressive disorders. Psychol Med, 34(8), 1453-1463. https://doi.org/10.1017/S0033291704002697
Masson, M., Bussières, E. L., East-Richard, C., Mercier, A. R., & Cellard, C. (2015). Neuropsychological profile of children, adolescents and adults experiencing maltreatment: A meta-analysis. Clin Neuropsychol, 29(5), 573-594. https://doi.org/10.1080/13854046.2015.1061057
Miao, H., Zhong, S., Liu, X., Lai, S., Zhu, Y., Song, Z., Wang, Y., & Jia, Y. (2022). Childhood trauma history is linked to abnormal brain metabolism of non-medicated adult patients with major depressive disorder. Journal of affective disorders, 302, 101-109. https://doi.org/10.1016/j.jad.2021.12.103
Nguyen, K. T., & Shaw, L. (2020). The aetiology of non-clinical narcissism: Clarifying the role of adverse childhood experiences and parental overvaluation. Personality and individual differences, 154, 109615. https://doi.org/10.1016/j.paid.2019.109615
Palomo, A. G., Andreu, H., Olivier, L., Ochandiano, I., de Juan, O., Fernández-Plaza, T., Salmerón, S., Bracco, L., Colomer, L., Mena, J. I., Vieta, E., & Pacchiarotti, I. (2024). Clinical, sociodemographic and environmental predicting factors for relapse in bipolar disorder: A systematic review. Journal of affective disorders, 360, 276-296. https://doi.org/10.1016/j.jad.2024.05.064
Poletti, S., Paolini, M., Ernst, J., Bollettini, I., Melloni, E., Vai, B., Harrington, Y., Bravi, B., Calesella, F., Lorenzi, C., Zanardi, R., & Benedetti, F. (2022). Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders. Brain, Behavior, & Immunity - Health, 26, 100529. https://doi.org/10.1016/j.bbih.2022.100529
Porcu, M., Ragassi Urbano, M., Verri, W. A., Machado, R. C. R., Vargas, H. O., & Nunes, S. O. V. (2022). Comparison of the severity of depressive and anxiety symptoms, biomarkers, and childhood trauma among bipolar smokers and non-smokers, and controls. Journal of Affective Disorders Reports, 8, 100336. https://doi.org/10.1016/j.jadr.2022.100336
Riemann, G., Chrispijn, M., Kupka, R. W., Penninx, B. W. J., & Giltay, H. E. J. (2024). Borderline personality features in relationship to childhood trauma in unipolar depressive and bipolar disorders. Journal of affective disorders, 363, 358-364. https://doi.org/10.1016/j.jad.2024.07.101
Rock, P., Roiser, J., Riedel, W., & Blackwell, A. (2014). Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med, 44(10), 2029-2040. https://doi.org/10.1017/S0033291713002535
Schmid, M. T., & Hammar, Å. (2013). A follow-up study of first episode major depressive disorder: Impairment in inhibition and semantic fluency – potential predictors for relapse? Front Psychol, 4, 633. https://doi.org/10.3389/fpsyg.2013.00633
Taylor, S. E., Way, B. M., & Seeman, T. E. (2011). Early adversity and adult health outcomes. Dev Psychopathol, 23(3), 939-954. https://doi.org/10.1017/S0954579411000411
Yang, L. (2025). Childhood Maltreatment and Non-Suicidal Self-Injury: The Mediating Role of Mentalization and Depression. European Journal of Psychotraumatology, 16(1). https://doi.org/10.1080/20008066.2025.2466279
Yoon Park, J., Woo Lee, C., Jang, Y., Lee, W., Yoon, J., Oh, S., Park, Y. S., Ryoo, H. A., Lee, J., Cho, N., Lee, C. H., Lee, Y. C., Won, H. H., Kang, H. S., Ha, T. H., & Myung, W. (2023). Relationship between childhood trauma and resilience in patients with mood disorders. Journal of affective disorders, 323, 162-170. https://doi.org/10.1016/j.jad.2022.11.003
Zhang, H. (2025). The Relationship Between Childhood Trauma and Social Anxiety in College Students: The Mediating Role of Evaluation Fear. BMC psychiatry, 25(1). https://doi.org/10.1186/s12888-025-06668-9
Zhang, Z. H., Zhou, C. H., Mao, Z. h., Sun, L., Li, T., Wang, C. h., & Bo, Q. (2025). Impact of childhood trauma on cognitive function in patients with bipolar disorder. Front Psychiatry, 16, 1513021. https://doi.org/10.3389/fpsyt.2025.1513021
Zuckerman, H., Pan, Z., Park, C., Brietzke, E., Musial, N., Shariq, A. S., Iacobucci, M., Yim, S. J., Lui, L. M. W., Rong, C., & McIntyre, R. S. (2018). Recognition and treatment of cognitive dysfunction in major depressive disorder. Front Psych, 9, 655. https://doi.org/10.3389/fpsyt.2018.00655
Downloads
Publication Timeline
- Submitted
- Revised
- Accepted
Issue
Section
License
Copyright (c) 2025 Mobina Poormolaie , Saeedeh Zomorodi (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.