Prof Alessandro Serretti, University of Bologna, Italy, gave us a picture of a brain affected by depression. Emotion and reward processing in the limbic system malfunction and the frontal cortex, including the voluntary and automatic regulation of emotion, is not able to control this overactivity. He described depression in terms of negative automatic thoughts with biases in attention, memory and interpretation. These contribute to the cognitive basis of depression.
Rumination and motivation impact a patient’s attention, which in turn influences executive function and memory. Patients struggle with preferential recall of negative versus positive material, due to elaboration bias and overgeneralisation. Interpretation bias is due to selective attention to negative stimuli. Difficulty disengaging from negative stimuli causes working memory to decline. Positive memories and stimuli are ineffective.
Prof Serretti proposed that cognitive symptoms may be an independent trait in MDD, and that cognitive impairment can persist, even in patients who have responded to treatment. The problem of residual deficits was highlighted by Prof John Harrison, King’s College, London. He reminded us of how patients describe their experiences - brain is cloudy, forgetful, can’t multi-task - and how these map onto the domains of cognition. Patients feel confused, inadequate, overwhelmed. And this doesn’t always go away, even when mood has lifted.
Cognitive impairment can persist
In one study, patients experienced cognitive symptoms 94% of the time during depressive episodes. But crucially, residual cognitive symptoms remained in remission, with patients reporting cognitive symptoms 44% of the time between depressive episodes. This highlights that cognitive deficits are enduring, clinically significant and represent an unmet need.
Prof Josep Maria Haro, University of Barcelona, presented the latest unpublished results from the Perform study. This is a 2-year prospective, non-interventional, cohort study that included adult outpatients from France, UK, Spain, Germany and Sweden. The objective of Perform was to better understand the course of a depressive episode and its impact on patient functioning. Depression symptoms were assessed using the PHQ-9, while functioning and work productivity were measured with SDS and WPAI-SHP, and cognitive complaints were assessed with PDQ-5. 1140 patients were included in the study (35 to 55 years of age).
They looked at which patient-related factors are associated with functional impairment. Using structural equation modelling, they found that cognitive symptoms independently predict and influence long-term functioning.
Cognitive symptoms independently predict and influence long-term functioning
Prof Tracy Greer, University of Texas Southwestern Medical Center, USA, emphasised that incorporating functional assessments to evaluate treatment response can greatly improve outcomes and should become a routine aspect of clinical care.
We now appreciate that MDD causes impairment in a wide range of domains and significant impairments in productivity. Over three-quarters of those depressed report some loss in productivity. Reduced work productivity accounts for approximately 80% of financial costs of depression.
Prof Greer showed evidence that cognitive symptoms mediate workplace outcomes to a greater extent than total depression severity.
Cognitive symptoms mediate workplace outcomes to a greater extent than total depression severity
We see that cognition is a critical determinant of health outcome.
As highlighted by many of the speakers, over the past decade, there has been increasing awareness of the importance of functional outcomes over mere symptomatic improvement. Prof Eduard Vieta, University of Barcelona, summed this up perfectly: going beyond the MADRS from feeling well, to doing well and being well.
Going beyond the MADRS from feeling well, to doing well and being well
Over 77% of patients consider presence of positive mental health - such as optimism, vigour and self-confidence - as very important in determining remission. Patients want to 'be well', which includes emotional and cognitive functioning.
Prof Vieta outlined a few key limitations of MADRS and HAM-D, neither of which adequately measure cognitive dysfunction in MDD. Cognitive and functional outcomes are needed to estimate the clinical trajectory of patients with depression. In addition, both objective and subjective (patient-reported) outcomes are relevant and provide complementary pictures.
Screening for cognitive impairment is warranted; however, there were no validated evaluation instruments. Danielle Cha, University of Queensland, Australia, presented the THINC-it® tool as the first screener that aligns with aspects of implementation principles.
THINC-it® is the first freely available, self-administered, computerised screening tool for cognitive dysfunction in MDD. It incorporates several tests into one simple program: DSST, Choice Reaction Time task, TMT-B, n-back memory task and PDQ-D5. The tool brings two worlds together - both objective and subjective assessments.
THINC-it® has recently been validated in a non-interventional, cross-sectional study that evaluated cognitive function in adults with MDD compared to healthy control individuals. It is the first digital tool to be validated as a composite of objective and subjective scales in a young population with MDD.
The first digital tool to be validated as a composite of objective and subjective scales in a young population with MDD
The study included 100 patients with DSM-5-defined MDD, aged 18 to 65 years and 100 age-, sex- and education-matched controls. 97.8% of healthy controls performed better than patients with MDD. 44.4% and 32.2% of patients with MDD performed at least 1 SD below or between 0.5 and 1 SD below the mean for healthy controls, respectively.
THINC-it® accounts for significant variability in perceived psychosocial function as measured by the SDS total and subscores. Similar findings were reported for workplace performance and QoL assessed using the EWPS and WHO-5 Well-Being Index, respectively.
This expert science exchange was organised by H. Lundbeck A/S.