Barcelona snapshots

Prof. Catherine J. Harmer

Catherine J. Harmer psiquiatra Controversias Psiquiatría Barcelona
University of Oxford, Reino Unido
Ponencia Antidepresivos: refinando las aproximaciones terapéuticas de futuro
Fecha Sábado, 21 de Abril 2018
Hora 9:00 a 9:45
Mesa redonda Complejidades en Psiquiatría: trastornos afectivos

BIOGRAFÍA

Catherine Harmer is a Professor of Cognitive Neuroscience at the University Department of Psychiatry in Oxford. She directs a multidisciplinary team of researchers in the Psychopharmacology and Emotion Research Lab (PERL) using a variety of techniques such as fMRI, MEG, TMS, psychopharmacological challenge techniques and neuropsychological assessments. Her work has led to the novel idea that antidepressants may work by rapidly resolving negative affective bias in depression which leads to gradual improvements in mood, social dysfunction and other key symptoms of depression over time. This concept has stimulated new research approaches for the treatment of depression with implications for stratification of treatment, early prediction of therapeutic response and identification of novel therapeutic targets. Catherine Harmer has been awarded prizes from the British Association for Psychopharmacology and the Royal College of Psychiatrists for this research and is the 2013 recipient of the AE Bennett award from the Society of Biological Psychiatry. She is on the executive committee of the European College for Neuropsychopharmacology and the British Neuroscience Association.

RESUMEN

Experimental medicine models offer the potential for screening and selecting novel candidate treatments for depression in humans prior to the initiation of randomised controlled trials. This approach may improve decision making about the development of a compound prior to incurring large costs and time delay. To be effective, the experimental medicine model needs to tap into a core mechanism involved in the disorder, to be sensitive to a range of pharmacological treatments that are effective in that disorder and to be able to predict eventual efficacy for that compound when tested in the clinic.

Negative affective bias is commonly reported in depression, where patients are more likely to focus on, interpret and remember negative vs positive emotional information. Early effects of conventional antidepressant drug treatments on negative affective bias have been reported in both behavioural and neuroimaging measures of emotional facial expression recognition and emotional memory with single and repeated dosing regimes. These early effects on emotional processing are predictive of later changes in clinical ratings of depression. Such findings raise the intriguing possibility that early remediation of negative bias may be a mechanism of antidepressant drug action and could be harnessed to screen and assess effects of novel candidate treatments for depression. This approach has been used to screen and understand novel treatments affecting the glutamate and opiate systems.

Dysfunction in the reward system has also been reported in depression yet the effects of treatment on reinforcement learning are still relatively unknown. Our recent work suggests that unlike negative affective bias, antidepressants can have early detrimental effects on reward learning which reverse with repeated administration. For example, patients with major depressive disorder were impaired at reward learning in a probabilistic learning task but this deficit was exaggerated after 2 weeks treatment with the noradrenaline and dopamine reuptake inhibitor, bupropion. After 6 weeks of bupropion, performance was returned to the same level as healthy volunteers i.e. was fully normalised. These findings together suggest that drugs useful in the treatment of depression have early effects on emotional processing but the effects on reward are delayed. As such these processes may rely on separable underlying processes.

Compared to clinical rating scores, objective measurement of emotional and cognitive function with behavioural assessment and neuroimaging may provide more information about the early effects of antidepressants. These early effects may help understand mechanisms and profiles of established and novel treatments for depression.

REFERENCIAS

[web] Lewis G et al (2017). Variation in the recall of socially rewarding information and depressive symptom severity: a prospective cohort study. Acta Psychiatr Scand. 2017 May;135(5):489-498. doi: 10.1111/acps.12729. Epub 2017 Apr 4. PubMed PMID:28374430; PubMed Central PMCID: PMC5763395.

[web] Walsh AEL, Browning M, Drevets WC, Furey M, Harmer CJ (2018). Dissociable temporal effects of bupropion on behavioural measures of emotional and reward processing in depression. Philos Trans R Soc Lond B Biol Sci. 2018 Mar 19;373(1742). pii: 20170030. doi: 10.1098/rstb.2017.0030. PubMed PMID: 29352029; PubMed Central PMCID: PMC5790828.

[web] Post A et al (2016). Selective Nociceptin Receptor Antagonist to Treat Depression: Evidence from Preclinical and Clinical Studies. Neuropsychopharmacology. 2016 Jun;41(7):1803-12. doi: 10.1038/npp.2015.348. Epub 2015 Nov 20. PubMed PMID:26585287; PubMed Central PMCID: PMC4869049.

[web] Harmer CJ et al (2009). Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry. 2009 Oct;166(10):1178-84. doi: 10.1176/appi.ajp.2009.09020149. Epub 2009 Sep 15. PubMed PMID: 19755572.