A dose by any other name: neuroscience-based drug classification gains ground
Interview with Professor José Alberto Del Porto, Sao Paulo, Brazil
Different ways of thinking – Criticality and dual disorders
Give elders their due
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
No mean change does not mean no change
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.
Does pro-schizophrenia RNA hide deep in the genome?
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.
Cognition in older people with schizophrenia, and retroviruses in the young: diverse ideas in “further topics” session
Targeted training addresses cognitive deficits and brain dysfunction in schizophrenia
An interview with Stephen McLeod-Bryant, University of Miami Miller School of Medicine
Cormorbid and complex: achieving good outcome with the “difficult” patient
Neurobiology of depression – examining resilience to stress
Hot on the heels of a study showing that at least 8.4 million Americans provide care to an adult with an emotional or mental health issue, comes further information highlighting caregiver burden. We report from an APA Scientific and Clinical Reports session which featured findings of a survey of schizophrenia caregivers.
Imagine if one working week every month your work performance was limited or compromised. That’s the situation faced by many schizophrenia caregivers who also hold down paid jobs, according to the findings of a large-scale caregiver survey presented by Dr Debra Lerner of the Tufts Medical Center, Boston, at the 2016 APA congress.
Dr Lerner said that over 18% of adults in the US act as unpaid caregivers, and she cited the findings from On Pins and Needles study which showed that three quarters of caregivers looking after someone with mental health issues find the task emotionally stressful.
Holding down a job
Many caregivers to people with schizophrenia and schizoaffective disorder work, and Dr Lerner therefore said it was important to try to understand the impact that their caregiving had on work function and productivity. To this end, Dr Lerner got involved in conducting a survey of caregivers who also worked, asking about their paid work commitments and employment.
She described the anonymous on-line survey, which included a number of validated tools such as the work limitations questionnaire (WLQ), designed to assess time lost from work (absenteeism), presenteeism and impact of caregiving on work productivity.
Results from over 1000 caregiver questionnaires were available for analysis, and showed that the average age of caregivers was 55 years, with the average age of the care-recipient 40 years. Most caregivers were women and most were the parent of the person with schizophrenia or schizoaffective disorder.
Heavy work commitments
Over 60% of caregiver respondents were in current work and of those, 69% reported being in full time work. Dr Lerner said that these statistics showing high rates of full time work among carers, emphasized the need to make things easier for caregivers, particularly as the survey showed that most worked outside of the home and many had lengthy commutes to their place of work.
Work losses common
Over a quarter of caregivers in work said they often had to take time off work but more than half said it was difficult to take time away from work for personal matters. Missing an average of 0.6 days per week from work and associated with work productivity losses of around 8%, Dr Lerner said that caregivers had work losses that are equivalent to those experienced by patients with MDD.
The survey highlights that being a caregiver to a person with schizophrenia spills over into work – with a negative impact on productivity. More research is needed to understand and quantify the burdens on those who care for people with serious mental illness.
New insights on schizophrenia caregiver burden: impact on work and productivity
Dual disorders – confusion and neglect
Mood disorders are a leading cause of disability, yet many are highly treatable. To choose the best possible management plan for patients and to plan service provision effectively, it is important to know which patients are at risk of hospitalization and understand the factors that may affect length of stay (LOS) and readmission.
Back for more
Speaking at an APA session in May 2016, Dr John Goethe of Hartford Hospital in Connecticut, reported the findings of a study of over 12,500 hospitalized patients with mood disorders discharged between 2000 and 2013, which looked at predictors of prolonged LOS and later readmissions. Two thirds of the sample had MDD and readmission was assessed at various time-points after the index admission – 1, 3, 6 and 12 months post-discharge.
A number of potential predictors of long LOS (greater than 9 days) and readmission were examined: presence of psychotic features; being on more than 2 psychotropic drugs; and co-occurrence of other psychiatric conditions, namely bipolar disorder, substance use disorder (drugs and alcohol) and PTSD.
More than 1 in 5 returns
Dr Goethe reported that at the 12-month time-point, 22% of patients with MDD and 24% with bipolar had been readmitted. In terms of LOS for these mood disorders, stays were longer for bipolar disorder than for MDD. He said that having psychotic features with MDD increased the 30-day readmission rate to 11% compared with 7% in patients without psychotic features. Similarly, patients receiving more than 2 drugs for their condition, or having co-occurrent PTSD were more likely to be readmitted at any time during follow-up. In MDD, alcohol use appear to have a protective effect at the 1 month time-point in MDD, reducing readmission rates, but this effect was lost with continued follow-up.
In terms of LOS, psychotic features with MDD and multiple therapies increased LOS, while co-occurrent PTSD reduced LOS.
Real-world patient complexities
In the same APA session, delegates heard the findings of two meta-analyses that assessed the types of patients with mood disorders included in randomized, placebo controlled trials (RCTs) in the past 20 years. Professor Mark Zimmerman, Professor of Psychiatry at Brown Medical School, Rhode Island said that a review of antidepressant trials in patients with MDD, which included 170 different studies published in the past 15 years, shows that most of the MDD patients seen in routine practice would be very unlikely to meet the entry criteria. For example, patients with MDD were typically excluded from RCTs for having depression diagnosed for more than 2 years, multiple episodes, for having co-occurrent axis I diagnoses and for suicidality.
According to Professor Zimmerman, this means that at least 40% of the MDD patients seen in routine practice would not be eligible to take part in an RCT of an antidepressant therapy.
The same exercise looking at RCTs in bipolar disorder, also highlighted that patient cohorts are restricted and unrepresentative of real-world patient populations.
Professor Zimmerman conceded that the nature of regulatory studies requires assessment in homogeneous patient populations but he lamented that there is consequently a dearth of real-world data on the effectiveness of treatments in the highly heterogeneous and complex patients actually encountered in everyday practice.
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Mood disorders in the real world
A highly heterogeneous group of patients come under the umbrella of mood disorders.