Depression affects more than 150 million people around the world and is a leading cause of disability across the globe. The main focus of treatment has been on mood symptoms. However, cognitive functions affected in depression represent an important, yet under recognized aspect of the disorder. The efforts to acknowledge cognition as a core element in depression was addressed in the recent workshop in the USA at the National Academy of Sciences, Washington, DC.
Assessment of cognitive dysfunction was one of the key topics discussed. Subjective reports of cognitive problems are valuable but not sufficient to evaluate new treatments as they lack consistent findings across studies. It was emphasized that any potential treatment should be assessed with tests which can detect cognitive change, such as neuropsychological tests that are objective and can measure with consistency processes such as memory, attention, and planning.
Another important topic of discussion was on the assessment of treatments on day-to-day living. Regulators such as the Food and Drug Administration (USA) expect to see interventions that can help people get back to their work and social life. In line with the technological advances, mobile applications and wearable technologies can be the next direction for a more comprehensive assessment of cognition at different levels. It was further argued that the new tools could be used to screen people at a stage when they do not have clinical depression. This could then involve frequent but brief monitoring via mobile devices. On the other hand, people with clinical depression could take part in more detailed assessment of cognition with computerised and other laboratory tests.
Based on the current research, some promising pharmacological interventions like vortioxetine, modafinil, and ketamine received special mention regarding their positive effects on cognition. Non-invasive neuromodulation (tDCS, rTMS) and novel psychological treatments were also mentioned as having the potential to improve cognition.
However one major challenge for research into new interventions is the need to refine our ways of assessing treatments as successful. This is important given that depression is highly heterogeneous, meaning not all individual patients present clinically with the same symptomatology. Therefore the report commented that trial designs, addressing heterogeneity, might help develop treatments specifically focusing on cognitive symptoms/measures. Experimental medicine models, for example the dot-probe task which tests attentional bias and the n-back task which tests working memory, are already in use for early stage drug development.
Lastly, the experts discussed how we can learn from a similar approach already examined in the field of schizophrenia research. The efforts to define cognitive dysfunction in schizophrenia has led to a major initiative MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) which used a neuropsychological test battery to develop treatments to address cognitive dysfunction. It was then followed by CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) with a view that EEG and/or MRI neurobiological markers might be more useful in defining treatment targets. Interestingly, these initiatives have not led to a consistent biomarker for schizophrenia drug development. The main reason was that the measurements used were not sensitive enough to detect meaningful changes in responses. The report warned we must take heed of this work and avoid adopting the same non-refined approaches into the depression field.
Overall, the report provides comprehensive information on the challenges and future directions regarding cognitive dysfunction in depression. All the sections include distilled knowledge from the experts in the field. The workshop stands out as a great example of how to address a crucial clinical problem by proffering different viewpoints which in turn can lead to the establishment of guidelines for future research.
- Cognitive dysfunction is an important feature of depression leading to poorer outcomes; it could be a key treatment target.
- Candidate treatments should demonstrate clinically meaningful changes, especially on patients day-to-day living.
- Technological advances open up new directions for comprehensive assessment of cognition and could help guide treatment options.
- Refinement of research studies is warranted to account for individual differences in patients cognitive functions as well as other clinical factors.