Depression overshadows the past as well as the present

Depressed people have a peculiar view of the past – rather than glorifying the ‘good old days’, they project their generally bleak outlook on to past events, according to new research.

It is known depression makes sufferers see the present and the future as sad, but this is the first time research has shown it also casts a long shadow over people’s memories of the past.

Psychologists at Germany’s Heinrich Heine Universität Düsseldorf and at the UK’s University of Portsmouth published their research in Clinical Psychological Science.

It establishes the first clear link between depression and hindsight bias, or a distorted view of the past.

Dr Hartmut Blank, in the University of Portsmouth’s Department of Psychology, is one of the authors.

He said: “Depression is not only associated with a negative view of the world, the self and the future, but we now know with a negative view of the past.”

Hindsight bias includes three core elements: exaggerated perceptions of foreseeability – we think we knew all along how events would turn out; inevitability – something ‘had’ to happen; and memory bias – misremembering what we once thought when we know the outcome of something.

Hindsight bias has been studied in various settings, including sports events, political elections, medical diagnoses or bankers’ investment strategies. Until now, it hasn’t been used to study depression.

Dr Blank said: “Everyone is susceptible to hindsight bias, but it takes on a very specific form in depression. While non-depressed people tend to show hindsight bias for positive events but not negative events, people with depression show the reverse pattern.

“Making things worse, depressed people also see negative event outcomes as both foreseeable and inevitable – a toxic combination, reinforcing feelings of helplessness and lack of control that already characterise the experience of people with depression.

“Everyone experiences disappointment and regret from time to time and doing so helps us adapt and grow and to make better decisions. But people with depression struggle to control negative feelings and hindsight bias appears to set up a cycle of misery.

“We have shown hindsight bias in people who are depressed is a further burden on their shoulders, ‘helping’ to sustain the condition in terms of learning the wrong lessons from the past.”

The researchers tested over 100 university students, about half of whom suffered from mild to severe depression. They were asked to imagine themselves in a variety of everyday scenarios with positive or negative outcomes (from different domains of everyday life, e.g. work, performance, family, leisure, social, romantic). For each scenario, the researchers then collected measures of hindsight bias (foreseeability, inevitability and distorted memory for initial expectations).

The results showed that with increasing severity of depression, a specific hindsight bias pattern emerged – exaggerated foreseeability and inevitability of negative (but not positive) event outcomes, as well as a tendency to misremember initial expectations in line with negative outcomes. Characteristically, this ‘depressive hindsight bias’ was strongly related to clinical measures of depressive thinking, suggesting that it is part of a general negative worldview in depression.

Dr Blank said: “This is only a first study to explore the crucial role of hindsight bias in depression; more work needs to be done in different experimental and real-life settings, and also using clinical samples, to further examine and establish the link between hindsight bias and depression.”

Study in mice may reveal insights into causes of miscarriages for some women

Researchers at St. Michael’s Hospital have identified how natural killer cells in the mouse placenta can cause a fetus to fail to grow in the womb or cause miscarriages.

They also identified several possible treatments in a paper published online today in the journal Nature Communications.

The researchers, led by Dr. Heyu Ni, a scientist in the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, are basic scientists whose ultimate goal is to prevent women who suffer from a disease known as FNAIT from giving birth to underdeveloped babies or miscarrying.

Fetal and neonatal alloimmune thrombocytopenia, or FNAIT, affects pregnant women and their unborn babies when the mother’s immune system sees some of her fetus’ cells as foreign and sends antibodies to attack and destroy those cells.

The researchers found that, in mice, the mother’s FNAIT immune response also triggers the activation of natural killer cells that target cells with the father’s proteins, including trophoblasts — cells responsible for the placenta’s development and growth.

Natural killer cells are a type of lymphocyte — one of the subtypes of white blood cells in the immune system. They play a major role in defending the fetus against cells carrying viruses and those that are growing abnormally, providing protection from disease and developmental issues in the early stages of pregnancy.

This immune attack can cause the placenta to deform and can disrupt the flow of nutrients to the fetus, both of which may limit the baby’s growth in the womb and increase the likelihood of miscarriage, said Dr. Ni, who is also a scientist at Canadian Blood Services Centre for Innovation.

“Natural killer cells are normal in pregnancy and necessary for early placental development in humans and other mammals, but their number in placenta should decrease in the late stage of pregnancy,” he said. “In our study, we found that natural killer cells were not decreased, but prevalent and active in cases of FNAIT.”

FNAIT occurs in around one in every 1,000 live births, but it is likely much more common, said Dr. Ni, because this number does not include women with FNAIT who have miscarriages.

Researchers estimate two to three per cent of the population is at risk for FNAIT, and some reports estimate up to 30 per cent of affected fetuses miscarry, the authors wrote.

This finding represents an important discovery about how abnormalities at the placenta may contribute to FNAIT, said Dr. Ni. It expands on his previous research that found another cause of miscarriage in FNAIT cases.

The same kind of blood-clotting in coronary arteries or blood vessels in the brain that causes heart attacks and strokes also happens in the placenta. The massive clotting can destroy the placenta, block blood flow to the fetus, which can lead to miscarriages.

Based on the findings of today’s study, the authors found there were several methods that might effectively prevent FNAIT-related miscarriages by targeting natural killer cells.

The first treatment option is to use intravenous immunoglobulin G (IVIG), a blood product prepared from pools of plasma from more than 1,000 healthy donors. IVIG blocks the sensors of natural killer cells, disorienting them and preventing them from targeting placental cells, according to the authors. IVIG also decreases maternal anti-fetal antibodies, they said.

IVIG has already been approved to treat several autoimmune diseases, but would need to be used in high doses to effectively treat FNAIT, making it very expensive, said Dr. Ni.

In the lab, the authors also tested other treatments including specifically targeting cell receptors to block the activation of natural killer cells. It will be less expensive because less of the protein is required for these treatments, said Dr. Ni, and may be more efficient than IVIG.

These new therapies reduced the risk of miscarriage and reduced growth in mice with FNAIT, the authors found. However, they have not yet been approved for clinical use in human FNAIT, said Dr. Ni.

Rates of reduced growth and miscarriage could also be decreased by removing natural killer cells from the body; however Dr. Ni said this is not a recommended treatment because of the essential role natural killer cells play in early placental development as well as in both the mother and fetus’ immune systems.

More research will be needed to determine whether these new anti-natural killer cell treatments would be effective in humans, said Dr. Ni.

“By understanding what causes reduced growth and miscarriages in FNAIT cases, we are one step closer to being able to identify FNAIT cases early and reduce the rates of the devastating outcomes of this disease,” he said.