Behavioural Brain Research 256 (2013) 368–376 Contents lists available at ScienceDirect Behavioural Brain Research j ourna l h o mepa ge: www.elsevier.com/locate/bbr Review Differences in neurobiological pathways of four “clinical content” subtypes of depression Christopher F. Sharpley a,∗ , Vicki Bitsika b a Brain-Behaviour Research Group, University of New England, Armidale, New South Wales 2351, Australia b Brain-Behaviour Research Group, Bond University, Gold Coast 4229, Australia h i g h l i g h t s • Depressive behavior is heterogenous. • Four “subtypes” of depression were identified from symptoms. • Each subtype has different behaviors and neurological pathways. • Effective individualized treatment requires attention to these differences. a r t i c l e i n f o Article history: Received 17 July 2013 Received in revised form 16 August 2013 Accepted 19 August 2013 Available online 28 August 2013 Keywords: Depression Symptoms Subtypes a b s t r a c t Although often considered as a mental disorder, depression is best described as a behavioral- neurobiological phenomenon. In addition, although usually reported as a unitary diagnosis, major depressive episode is composed of a range of different symptoms that can occur in nearly 1500 pos- sible combinations to fulfill the required diagnostic criterion. To investigate and describe the underlying behavioral and neurobiological substrates of these symptoms, they were clustered into “clinical content” subtypes of depression according to their predominant common behavioral characteristics. These sub- types were then found to possess different neurobiological pathways that argue for different treatment approaches. © 2013 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 2. “Clinical content” subtypes of depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 2.1. Clinical content subtype 1: depressed mood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 2.2. Clinical content subtype 2: anhedonic depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370 2.3. Clinical content subtype 3: cognitive depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 2.4. Clinical content subtype 4: somatic depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 1. Introduction Depression is a relatively common behavioral-neurobiological phenomenon, with approximately one in seven individuals being affected by it during their lives [1]. Clinical and subsyndromal depression adversely affect physical health, relationships and cog- ∗ Corresponding author at: PO Box 378, Coolangatta, Queensland 4225, Australia. Tel.: +61 7 5536 8386. E-mail address: csharpley@onthenet.com.au (C.F. Sharpley). nitive performance [2–4], and about 15% of depressed patients proceed to suicide [5]. When compared to chronic physical dis- eases such as angina, arthritis, asthma and diabetes, depression produces the greatest decrement in personal health [6] and the highest cost of care [7], perhaps reflecting the high rate of nonre- covery and recurrence (chronicity is estimated to be 20%) [8]. As a result, depression has been described as the major contributor to the total disease burden [9], and predicted to become the second leading cause of mental illness by 2020 [10,11]. Some data suggest that depression poses a similar risk as does smoking for mortal- ity from all causes, even when related health factors such as blood 0166-4328/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2013.08.030