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Complexity in Mental Health Research: Theory, Method, and Empirical Contributions

Guest edited by Dr Eiko I. Fried and Dr Donald Robinaugh

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Mental disorders are dynamic, heterogeneous, and multicausal phenomena. Despite increasingly widespread recognition of this inherent complexity, progress in understanding mental disorders as complex biopsychosocial systems has been limited.


To advance our understanding of the etiology, prevention, and treatment of mental disorders, it is critical that both our theories and our research methods reflect the complex reality of psychopathology. In this collection, BMC Medicine will present a series of theoretical, methodological, and empirical papers that embrace complexity and chart a path forward for investigating mental disorders as complex systems.

We are seeking submissions in three domains:

  1. Empirical research. Example topics include causal relations among features of psychopathology, vicious cycles, emergence, attractor states of health and illness, phase transitions, early warning signals, resilience, adaptation, and bridging the gap between biological, psychological and social levels of analysis.
  2. Methodological contributions that either introduce newly developed methods for investigating mental disorders as complex systems; or that describe applications of methods drawn from other fields (network science, dynamic systems theory) to mental health research.
  3. Theoretical contributions that adopt a complex systems perspective, especially theories formalized as mathematical or computational models.

Importantly, while the subject of this collection is complexity, we are principally interested in contributions that can be readily understood by a broad audience, with implications not only for researchers, but also clinical practitioners, policy makers, and public health.

We welcome direct submission of original research within the article collection's scope. Please submit directly to BMC Medicine, indicating in your cover letter that you are targeting this collection. Alternatively, you can email a pre-submission query to the editorial team at bmcmedicineeditorial@biomedcentral.com. The collection will remain open and accept submissions until July 2021.

Guest Editors provided guidance on the scope of this collection and advised on commissioned content. However, they are not involved in editorial decision-making on papers submitted to this collection. All final editorial decisions are with the Editor-in-Chief, Dr. Lin Lee.​

  1. In 2013, a few years after the launch of the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative, Cuthbert and Insel published a paper titled “Toward the future of psychiatric diag...

    Authors: Sarah E. Morris, Charles A. Sanislow, Jenni Pacheco, Uma Vaidyanathan, Joshua A. Gordon and Bruce N. Cuthbert
    Citation: BMC Medicine 2022 20:220
  2. Chronic stress increases chronic disease risk and may underlie the association between exposure to adverse socioeconomic conditions and adverse health outcomes. The relationship between exposure to such condit...

    Authors: Loes Crielaard, Mary Nicolaou, Alexia Sawyer, Rick Quax and Karien Stronks
    Citation: BMC Medicine 2021 19:242
  3. Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comor...

    Authors: C. O’Driscoll, J. E. J. Buckman, E. I. Fried, R. Saunders, Z. D. Cohen, G. Ambler, R. J. DeRubeis, S. Gilbody, S. D. Hollon, T. Kendrick, D. Kessler, G. Lewis, E. Watkins, N. Wiles and S. Pilling
    Citation: BMC Medicine 2021 19:109
  4. Reducing suicidal behaviour (SB) is a critical public health issue globally. The complex interplay of social determinants, service system factors, population demographics, and behavioural dynamics makes it ext...

    Authors: Jo-An Occhipinti, Adam Skinner, Frank Iorfino, Kenny Lawson, Julie Sturgess, Warren Burgess, Tracey Davenport, Danica Hudson and Ian Hickie
    Citation: BMC Medicine 2021 19:61
  5. Major depressive disorder (MDD) shows large heterogeneity of symptoms between patients, but within patients, particular symptom clusters may show similar trajectories. While symptom clusters and networks have ...

    Authors: K. Hebbrecht, M. Stuivenga, T. Birkenhäger, M. Morrens, E. I. Fried, B. Sabbe and E. J. Giltay
    Citation: BMC Medicine 2020 18:400
  6. The complexity of psychopathology is evident from its multifactorial etiology and diversity of symptom profiles and hampers effective treatment. In psychotherapy, therapists approach this complexity by using c...

    Authors: Lino von Klipstein, Harriëtte Riese, Date C. van der Veen, Michelle N. Servaas and Robert A. Schoevers
    Citation: BMC Medicine 2020 18:345

    The Commentary to this article has been published in BMC Medicine 2020 18:365

  7. Many studies detect associations between parent behaviour and child symptoms of anxiety and depression. Despite knowledge that anxiety and depression are influenced by a complex interplay of genetic and enviro...

    Authors: Rosa Cheesman, Espen Moen Eilertsen, Yasmin I. Ahmadzadeh, Line C. Gjerde, Laurie J. Hannigan, Alexandra Havdahl, Alexander I. Young, Thalia C. Eley, Pål R. Njølstad, Per Magnus, Ole A. Andreassen, Eivind Ystrom and Tom A. McAdams
    Citation: BMC Medicine 2020 18:284
  8. Despite the increasing understanding of factors that might underlie psychiatric disorders, prospectively detecting shifts from a healthy towards a symptomatic state has remained unattainable. A complex systems...

    Authors: Marieke J. Schreuder, Catharina A. Hartman, Sandip V. George, Claudia Menne-Lothmann, Jeroen Decoster, Ruud van Winkel, Philippe Delespaul, Marc De Hert, Catherine Derom, Evert Thiery, Bart P. F. Rutten, Nele Jacobs, Jim van Os, Johanna T. W. Wigman and Marieke Wichers
    Citation: BMC Medicine 2020 18:269
  9. In the network approach to psychopathology, psychiatric disorders are considered networks of causally active symptoms (nodes), with node centrality hypothesized to reflect symptoms’ causal influence within a n...

    Authors: Tobias R. Spiller, Ofir Levi, Yuval Neria, Benjamin Suarez-Jimenez, Yair Bar-Haim and Amit Lazarov
    Citation: BMC Medicine 2020 18:297
  10. Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms shared by both disorders, ...

    Authors: Robin N. Groen, Oisín Ryan, Johanna T. W. Wigman, Harriëtte Riese, Brenda W. J. H. Penninx, Erik J. Giltay, Marieke Wichers and Catharina A. Hartman
    Citation: BMC Medicine 2020 18:308
  11. The past decades of research have seen an increase in statistical tools to explore the complex dynamics of mental health from patient data, yet the application of these tools in clinical practice remains uncom...

    Authors: Julian Burger, Date C. van der Veen, Donald J. Robinaugh, Rick Quax, Harriëtte Riese, Robert A. Schoevers and Sacha Epskamp
    Citation: BMC Medicine 2020 18:99
  12. Transdiagnostic processes confer risk for multiple types of psychopathology and explain the co-occurrence of different disorders. For this reason, transdiagnostic processes provide ideal targets for early inte...

    Authors: Katie A. McLaughlin, Natalie L. Colich, Alexandra M. Rodman and David G. Weissman
    Citation: BMC Medicine 2020 18:96
  13. There is growing evidence that mental disorders behave like complex dynamic systems. Complex dynamic systems theory states that a slower recovery from small perturbations indicates a loss of resilience of a sy...

    Authors: Anna Kuranova, Sanne H. Booij, Claudia Menne-Lothmann, Jeroen Decoster, Ruud van Winkel, Philippe Delespaul, Marc De Hert, Catherine Derom, Evert Thiery, Bart P. F. Rutten, Nele Jacobs, Jim van Os, Johanna T. W. Wigman and Marieke Wichers
    Citation: BMC Medicine 2020 18:36
  14. Childhood maltreatment has been associated with significant impairment in social, emotional and behavioural functioning later in life. Nevertheless, some individuals who have experienced childhood maltreatment...

    Authors: Konstantinos Ioannidis, Adrian Dahl Askelund, Rogier A. Kievit and Anne-Laura van Harmelen
    Citation: BMC Medicine 2020 18:32

    The Correction to this article has been published in BMC Medicine 2020 18:202

  15. The human brain is complex and interconnected structurally. Brain connectome change is associated with Alzheimer’s disease (AD) and other neurodegenerative diseases. Genetics and genomics studies have identifi...

    Authors: Young Jae Woo, Panos Roussos, Vahram Haroutunian, Pavel Katsel, Samuel Gandy, Eric E. Schadt and Jun Zhu
    Citation: BMC Medicine 2020 18:23
  16. Childhood adversity (CA) is strongly associated with mental health problems. Resilience factors (RFs) reduce mental health problems following CA. Yet, knowledge on the nature of RFs is scarce. Therefore, we ex...

    Authors: J. Fritz, J. Stochl, E. I. Fried, I. M. Goodyer, C. D. van Borkulo, P. O. Wilkinson and A.-L. van Harmelen
    Citation: BMC Medicine 2019 17:203