̽��ֱ�� of Cambridge - Annemieke Apergis-Schoute

̽��ֱ��OCD Brain: how animal research helps us understand a devastating condition

cjb250 — Tue, 28 Mar 2017 10:36:15 +0000

When David Adam was just 18, a teasing comment from a university friend triggered a series of thoughts that he had contracted HIV and would die of AIDS. This was around the time of peak hysteria about this new disease, but even so, his thoughts represented more than the worries of a naïve, newly-sexually active young man: the fear was unshakeable and the thoughts consumed him, dominating his life.

For a long time, David remained silent about his obsession, afraid to tell anyone what he was going through. It was only a couple of decades later, when the thoughts began to affect his relationship with his young daughter, to whom he was sure he would transmit his ‘infection’, that he sought help. He was subsequently diagnosed with obsessive compulsive disorder (OCD).

OCD is sometimes viewed as a personality quirk – “I’m a little bit OCD,” people will say as they carefully arrange the books on their shelf. ̽��ֱ��truth is far more devastating. People living with OCD will scrub their hands compulsively, often with bleach, till they are bleeding. Others will check that they have locked the back door thirty, forty times – otherwise, they are sure a family member will come to harm - making going out almost impossible.

David, a journalist and science writer, has written and spoken extensively about his condition. He considers himself fortunate: his condition is under control, thanks to a combination of ‘talking therapies’ and medication. Others are not so fortunate: despite intensive therapy and medication, they are still unable to hold down a job or a relationship, so dominant are their OCD behaviours.

Now, in a series of short films for the ̽��ֱ�� of Cambridge, David has visited leading researchers who study OCD and asks what we know about the underlying biology that leads to the condition: just what is going on in the brain?

In the films, Professor Trevor Robbins, Head of Psychology at Cambridge, introduces David to scientists who use a combination of studies to explore the inner workings of the brain. These include studies involving rats and marmosets (small monkeys), as well as people.

One of the studies is a so-called ‘reversal learning’ test. In this test, the marmoset learns that pressing one button gives it a juice reward, while it gets no reward if it presses a second button. But then, unexpectedly, the buttons swap: how good is the marmoset at changing its thinking to adjust to this new information? A common trait in people with OCD is a tendency to have rigid, obsessive thinking that dominates their behaviour.

By manipulating localised regions of the animals’ brains, either permanently or via temporary drug infusions, scientists are able to understand better the exact pathways within the brain that malfunction in OCD and cause this rigid behaviour. As Professor Robbins explains, this would not be possible in human studies. But this knowledge will help underpin the development of new, more effective treatments – and this is crucial, as around 60% of patients with OCD do not respond to existing treatments.

̽��ֱ��films have been produced as part of the ̽��ֱ�� of Cambridge’s commitment to openness on animal research. In 2014, the ̽��ֱ�� announced that it had signed the Concordat on Openness on Animal Research. ̽��ֱ��following year, it launched its first film on the subject, Fighting Cancer: Animal research at Cambridge.

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OCD can be a devastating condition: therapy and medication often doesn’t work, leaving many people unable to hold down a job or a relationship – or even to leave their house. In our series of films, science writer David Adam looks at how research at Cambridge using animals helps us understand what is happening in the brain – and may lead to better treatments.

Understanding the OCD Brain: OCD and me

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Patients with OCD have difficulty learning when a stimulus is safe

cjb250 — Mon, 06 Mar 2017 20:00:45 +0000

OCD is a disorder characterised by intrusive thoughts and repetitive, irrational behaviours, for example an obsession with cleanliness leading to repetitive hand washing, or a fear that something terrible will happen if they don’t check the door dozens of times, making leaving the house extremely difficult.

A common way of helping treat OCD is to expose people to something they consider threatening – for example, if their obsession is around cleanliness, they may be made to touch a toilet seat but then prevented from washing their hands. However, so-called ‘exposure therapy’ often only has limited success and compulsions can return in times of stress. This new research, published today in the Proceedings of the National Academy of Sciences, may explain why memories about safety don’t stick.

In this study, researchers at Cambridge’s Behavioural and Clinical Neuroscience Institute tested 43 OCD patients and 35 matched healthy volunteers to see how well those people with OCD were able to reverse their thinking when a previously threatening stimulus became safe and vice versa, to examine safety versus threat learning as well as cognitive flexibility, which is thought to be significantly compromised in patients with OCD.

Volunteers lay in a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, while successively being shown one of two faces: when shown the red face, nothing happened, but when shown the green face, the volunteer would sometimes receive a mild electric shock. By measuring changes in skin conductance caused by tiny amounts of sweat, the researchers were able to see whether the volunteers learned which stimulus was safe and which threatening.

After a period of time, the researchers swapped the stimuli – now, the red face was paired with an electric shock while the green face was safe.

̽��ֱ��researchers found that while OCD patients were able to learn initially which stimulus was threatening, they never learned that the second stimulus was safe – in fact, they seemed to pay little attention to this safe stimulus. When the stimuli were reversed, participants were unable to differentiate between the previously threatening stimulus and the newly threatening stimulus. This was also reflected in their brain activity – OCD patients showed a lack of activity in an area at the front of the brain known as the ventromedial prefrontal cortex when viewing the safe stimulus.

“Our study suggests that something is going wrong in the brains of people with OCD when they are learning what is safe, and this in turn affects how they perceive threats under updated circumstances,” explains Dr Annemieke Apergis-Schoute, the study’s first author. “This needs to be taken into consideration when we’re developing future therapies to tackle the disorder. Current exposure therapies may help the patient take control over their compulsions, but our work suggests that they might never learn that their compulsions are unnecessary and they may return in times of stress.”

In a second study, published recently in Biological Psychiatry, Cambridge researchers showed that this cognitive inflexibility might be in part a result of a lack of ‘chatter’ between specific brain areas.

̽��ֱ��research, led by PhD student Matilde Vaghi, found that poor connectivity within some of the brain’s key networks as measured in an fMRI scanner while the patient was at rest may account for this inflexibility. It also may account for OCD patients’ poor goal-directed abilities (where we consciously act with a goal in mind – for example, when driving home and our route is disrupted, forcing us to take an unfamiliar route). Both are related to common symptoms of OCD.

̽��ֱ��researchers found disrupted connectivity within discrete frontostriatal circuits – neural pathways that connect the front of the brain with the basal ganglia (responsible for important functions such as the control of movement and ‘executive functions’ such as decision-making, learning and habit formation). They believe these may underlie the repetitive behaviours seen in OCD.

Professor Trevor Robbins, Head of Psychology at Cambridge, senior author on both studies, says: “When we look at this two studies together, we can see that there is a clear imbalance between key regions at the front of the brain in people with OCD. These may underlie some of the symptoms of inflexibility that we commonly see in patients with this condition.”

̽��ֱ��research was funded by the Wellcome Trust.

References

Apergis-Schoute, AM et al.Neural basis of impaired safety signaling in Obsessive Compulsive Disorder. PNAS; 6 Mar 2017; DOI: 10.1073/pnas.1609194114
Vaghi, MM et al. Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity. Biological Psychiatry; Aug 2016; DOI: 10.1016/j.biopsych.2016.08.009

People who suffer from obsessive compulsive disorder (OCD) are poorer at learning about the safety of a stimulus than healthy volunteers, which may contribute to their struggles to overcome compulsive behaviour, according to new research from the ̽��ֱ�� of Cambridge.

Current exposure therapies may help the patient take control over their compulsions, but our work suggests that they might never learn that their compulsions are unnecessary

Annemieke Apergis-Schoute

www.amenclinics.com

OCD Letter Blocks

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