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The problem starts with what we mean by remission, Professor Kamilla Miskowiak (Copenhagen, Denmark) told the symposium Focus on Depression. Conventionally, we define it as reaching a cut-off score on MADRS or HAM-D17. But many patients in remission by this criterion continue to have significant symptoms and half still consider themselves to be depressed.
The standard symptom rating scales pay little attention to patient functioning. True, there is no official definition of functional recovery. But it would have to include quality of life and capacity to undertake work and a social life, Dr. Miskowiak said.
Crucially, the presence of residual symptoms predicts rapid relapse. So we need to focus on them more.
Common residual symptoms in depression are those relating to sleep, energy and cognition. A problem with studying persisting cognitive deficits in depression is that we lack a consensus on terminology and means of assessment. Should we use patient self-rating measures, clinician-rated scales, or performance measures? This is not an idle question since subjective and objective measures correlate poorly, if at all.
Until recently, we have had no tools to use in systematic screening for cognitive deficits in depression. Happily, this situation is now changing. The SCRIP (Screening for Cognitive Improvement in Psychiatry) tool is being validated in several countries and the subjective rating scale COBRA (Cognitive Complaints in Bipolar Disorder Rating Assessment) is not far behind. Both are being validated in depressed patients. The appropriately named THINC® tool (which combines four objective performance measures with the PDQ rating scale) should have been validated by the autumn.
The good news is that 60-90% of depressed adolescents with first episode depression recover within a year. The bad news is that 50-70% of them will have a recurrence over the next five years. And of those in remission, many continue to suffer from functional deficits, said Professor Bernhard Baune (Adelaide, Australia).
Among the cognitive deficits are those in emotion-laden processing (“hot” cognition); those in memory, executive function, speed of thought and attention (“cold cognition”); and those in social cognition.
Problems with emotional processing are evident, for example, in negative affective bias. Depressed patients respond more quickly than controls to sad content (such as sad faces) and less fast to happy content. Functional magnetic resonance imaging shows that these differences are reflected in neural activity. This phenomenon seems specific to depression since it is not seen in Parkinson’s disease or schizophrenia. Also specific to depression is patients’ abnormally strong response to negative feedback.
Recent work from Adelaide shows that patients with abnormal negative affect function less well than others in everyday life.
Problems with cold cognition are evident in the 25-40% of patients with depression whose performance scores fall more than one standard deviation below the population mean. This difference is independent of other psychiatric or medical comorbidity. A high proportion of patients in remission recognise that they suffer such problems and rate them as “quite a bit” or “very much” of a problem.
Social processing involves both hot and cold spheres. Deficits are reflected in social isolation and an impaired understanding of others – evident, for example, in difficulty matching emotions to faces.
Overall, cognitive dysfunction in depression is strongly associated with unemployment and disability in life functioning six months after discharge from hospital.
Full resolution of depressive symptoms, embracing physical, behavioural and cognitive domains, is a major unmet need.
Given the multi-dimensional nature of these problems, it may be that multimodal intervention will make a difference, said Göran Hajak, when summing up the meeting.
Much needs to be done if we are to deal more adequately with residual symptoms in depression.
People with schizophrenia aged 55 years and above are about to become 25% of the total population with the disease. Yet only 1% of the schizophrenia research budget relates to older adults. So it is not surprising that much about the natural history of schizophrenia in this group remains unclear. To what extent is it really a quiescent disease at this stage in life? How does cognitive function change with time?
Data from New York City, presented by Carl Cohen (SUNY Downstate Medical Center, Brooklyn, New York, USA) casts light on what is happening in people with schizophrenia in mid to late life (55 years plus) and living in the community.
The starting point was a group of 250 who had developed schizophrenia before the age of 45. They were outpatients and did not have moderate or severe cognitive deficits or complicating factors such as a history of head trauma at baseline. Those living independently represented 39% of the sample: the others were in some form of supported residence. They were matched at baseline with 113 controls matched for age and income.
The cognition situation in older people is dynamic: some improve, others decline
At the start of the study, people with schizophrenia had a mean Dementia Rating Scale (DRS) score of 128, not far below the score of 138 among controls, but perhaps indicative of mild cognitive impairment.
As expected, there was considerable loss to follow-up, not least because of death. But those lost were similar to those who could be re-contacted. After a median follow-up of 4.5 years, the mean score of 127 among 104 people with schizophrenia showed no change. But this did not mean that no px had changed. While 59% showed essentially the same score at follow-up, 21% had experienced a decline in cognition – defined as a fall of 0.5 SD per year – and 19% had shown improvement -- defined as an increase in score of 0.5 SD per year. So the cognition the situation is actually quite dynamic.
On multivariate analysis, those whose cognition scores improved had had poorer scores at baseline. So there may be some regression to the mean. Though pxs living independently had better cognition at baseline, those living in supported housing were less likely to show decline over the period of follow-up, perhaps because of greater access to services.
Although an estimated 8% of the human genome is of retroviral origin, acquired during millions of years of primate evolution, most of it is now junk. It has been inactivated by mutation or epigenetic processes such as methylation. But what if some of it is capable of re-activation, perhaps by infections during embryonic development?
Though he repeatedly acknowledged that the idea is highly speculative, Awais Aftab (Case Western Reserve University, Cleveland, Ohio, USA) presented the argument that Human Endogenous Retroviruses (HERVS), particularly the HERV-W family, may play a malign role in the causation of schizophrenia.
There is evidence that HERV-W nucleotide sequences are more common in those affected with schizophrenia than in controls. The HERV-W envelope protein seems to activate production of inflammatory cytokines, which might contribute to the inflammation story in schizophrenia. And infections linked to schizophrenia can activate HERV-W elements, perhaps through demethylation of relevant genes.
In combination with genetic predisposition and environmental factors, archaeological remnants of millennia-old viral RNA could set the developing brain on the path towards schizophrenia and so provide a missing link in causation, at least in some patients. It is a suggestion worth considering.