BACKGROUND Despite the existence of several pathophysiological theories about bipolar disorder, it has so far been difficult to find diagnostic biomarkers and to develop new pharmacologic treatments based on the more novel theories. AIM To reflect on the causes and consequences of problems that beset pathophysiological research into psychiatric disorders in general and bipolar disorder in particular. METHOD In this essay we address the problems facing professionals engaged in research into bipolar disorder and we interpret these problem in the light of brain complexity. RESULTS The complexity of the brain can be divided into two types: spatial complexity, which reflects the various physiological levels of the central nervous system (genetic, molecular, cellular, neuronal circuits and phenomenological levels), and temporal complexity, i.e. neurodevelopment. We discuss the consequences of these two types of complexity and make suggestions relating to clinical practice and pathophysiological psychiatric research. CONCLUSION To achieve further progress in the field of brain research, we need to acquire a deeper understanding of the spatial and temporal complexity of the brain and consider the possible consequences of such knowledge for the pathophysiology and treatment of psychiatric illnesses such as bipolar disorder.

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Keywords Biomarker, Bipolar disorder, Brain complexity, Diagnostic system, Glia, Immune system
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Journal Tijdschrift voor Psychiatrie
Haarman, B.C.M, Riemersma-Van der Lek, R.F, Burger, H, Drexhage, H.A, & Nolen, W.A. (2018). Het ontregelde brein; consequenties van ruimtelijke en temporele complexiteit van het brein voor pathofysiologie en diagnostiek van de bipolaire stoornis. The dysregulated brain - Consequences of spatial and temporal brain complexity for bipolar disorder pathophysiology and diagnosis.. Tijdschrift voor Psychiatrie (Vol. 60, pp. 105–113). Retrieved from