Affective Biases in Humans and Animals
Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.
KeywordsEmotion Reward Rodents Animal model Major depressive disorder Antidepressants
Acknowledgments and Disclosures
ESJR currently holds research funding from the MRC, BBSRC, Wellcome Trust, and Eli Lilly. Previous support which has contributed to the development of this work includes funding from RCUK and the British Pharmacological Society Integrative Pharmacology Fund. JPR is funded by the Wellcome Trust and previously received support from the Medical Research Council.
JPR is a consultant for Cambridge Cognition.
- Agid Y, Buzsaki G, Diamond DM, Frackowiak R, Giedd J, Girault JA, Grace A, Lambert JJ, Manji H, Mayberg H, Popoli M, Prochiantz A, Richter-Levin G, Somogyi P, Spedding M, Svenningsson P, Weinberger D (2007) How can drug discovery for psychiatric disorders be improved? Nat Rev Drug Discov 6:189–201PubMedCrossRefGoogle Scholar
- Amitai N, Young J, Higa K, Sharp R, Geyer M, Powell S (2013). Isolation rearing effects on probabilistic learning and cognitive flexibility in rats. Cogn Affect Behav Neurosci 1–19Google Scholar
- Beck AT (1967) Depression: clinical, experimental and theoretical aspects. Harper & Row, New YorkGoogle Scholar
- Enkel T, Gholizadeh D, von Bohlen Und Halbach O, Sanchis-Segura C, Hurlemann R, Spanagel R et al. (2010). Ambiguous-cue interpretation is biased under stress- and depression-like states in rats. Neuropsychopharmacology 35:1008–1015Google Scholar
- Geyer M, Markou A (1995) Animal models of psychiatric disorders. In: Bloom F, Kupfer D (eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York, pp 787–798Google Scholar
- Hollon SD, DeRubeis RJ, Fawcett J, Amsterdam JD, Shelton RC, Zajecka J, Young PR, Gallop R (2014) Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. JAMA Psychiatry 71:1157–1164PubMedPubMedCentralCrossRefGoogle Scholar
- Huys QJ, Daw ND, Dayan P (2015) Depression: a decision-theoretic analysis. Annu Rev NeurosciGoogle Scholar
- Ineichen C, Sigrist H, Spinelli S, Lesch KP, Sautter E, Seifritz E, Pryce CR (2012) Establishing a probabilistic reversal learning test in mice: evidence for the processes mediating reward-stay and punishment-shift behaviour and for their modulation by serotonin. Neuropharmacology 63(6):1012–1021PubMedCrossRefGoogle Scholar
- Riedel M, Moller HJ, Obermeier M, Adli M, Bauer M, Kronmuller K, Brieger P, Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Schennach-Wolff R, Henkel V, Seemuller F (2011) Clinical predictors of response and remission in inpatients with depressive syndromes. J Affect Disord 133:137–149PubMedCrossRefGoogle Scholar
- Robinson OJ, Cools R, Sahakian BJ (2011) Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience. Psychopharmacology (Berl) 2:599–605Google Scholar
- Rock PL, Roiser JP, Riedel WJ, Blackwell AD (2013) Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med 1–12Google Scholar
- Snyder HR (2012) Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull 139:81Google Scholar
- Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163:28–40PubMedCrossRefGoogle Scholar
- Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:655–679PubMedCrossRefGoogle Scholar