̽��ֱ�� of Cambridge - obsessive compulsive disorder

Chemical imbalance in the forebrain underpins compulsive behaviour and OCD

fpjl2 — Tue, 27 Jun 2023 15:47:51 +0000

Scientists at the ̽��ֱ�� of Cambridge have used powerful new brain imaging techniques to reveal a neurochemical imbalance within regions of the frontal lobes in patients with obsessive-compulsive disorder (OCD).

̽��ֱ��study shows that the balance between glutamate and GABA – two major neurotransmitter chemicals – is “disrupted” in OCD patients in two frontal regions of the brain.

Researchers also found that people who do not have OCD but are prone to habitual and compulsive behaviour have increased glutamate levels in one of these brain regions.

Neuroscientists behind the study say the findings will open up new avenues for treating OCD, a psychiatric disorder that affects up to 3% of Western populations and can be deeply disabling.

Using magnetic resonance spectroscopy, the researchers measured levels of glutamate and GABA in regions of the cerebral cortex, the outermost and most highly developed part of the human brain.

Glutamate is an 'excitatory' neurochemical: it facilitates electrical impulses that fire neurons to send information around brain networks. GABA is an 'inhibitory' neurotransmitter that works in opposition to glutamate by dampening neural excitability, creating a balance.

OCD sufferers had higher levels of glutamate and lower levels of GABA in the anterior cingulate cortex, compared to people without OCD.

Additionally, the severity of OCD symptoms, along with the inclination towards habitual and compulsive behaviour, was related to higher glutamate levels in the supplementary motor region. This was found to be the case in OCD patients as well as in healthy participants with milder compulsive tendencies.

̽��ֱ��anterior cingulate cortex and the supplementary motor area are both centrally involved in deciding the balance between our conscious goals and more automatic habits. ̽��ֱ��research suggests that “compulsions arise from a dysregulated brain system for controlling habits” say scientists.

̽��ֱ��research is funded by the Wellcome Trust, and the latest findings are published today in the journal Nature Communications.

“Understanding obsessive-compulsive disorder is a central question for psychiatry. We have now shown definitive changes in these key neurotransmitters in OCD sufferers,” said senior author Prof Trevor Robbins from Cambridge’s Department of Psychology. “Excess glutamate and reduced GABA is disrupting the neural circuitry in key regions of the OCD brain.”

“Our findings are a major piece of the puzzle for understanding the mechanisms behind OCD. ̽��ֱ��results suggest new strategies for medication in OCD based on available drugs that regulate glutamate. In particular, drugs that inhibit presynaptic glutamate receptors,” said Robbins. A presynaptic receptor is the part of a nerve cell that controls release of neurotransmitter chemicals.

Severe OCD is a mental health disorder that causes untold misery for some sufferers. It can lead to loss of work and relationships, and social isolation. “Symptoms of intrusive thoughts and repetitive rituals can confine patients to their homes for months on end,” said Robbins. In extreme cases, the lack of control and sense of hopelessness caused by OCD can result in thoughts of suicide .

Current treatments for OCD are limited. While people with milder symptoms can benefit from some anti-depressants, for those with severe symptoms there are few options – often extreme – such as deep-brain stimulation and even neurosurgery to remove the anterior cingulate cortex entirely.

“Some treatments already target glutamate imbalance in a roundabout way,” said Dr Marjan Biria, study lead author, who conducted the work in Robbins’ Cambridge lab. “Now we have the evidence for why certain approaches seem to have some beneficial effects.”

̽��ֱ��Wolfson Brain Imaging Centre at Cambridge is home to one of only seven ultra-powerful 7-Tesla Magnetic Resonance Spectroscopy (MRS) scanners in the UK. For the latest study, researchers scanned 31 clinically-diagnosed OCD sufferers, and 30 healthy volunteers as a control group.

“Standard MRS scanners can be quite crude, not picking up the glutamate signal very accurately. ̽��ֱ��7-Tesla machine allows us to separate the overlapping signals and measure glutamate and GABA more precisely,” said Biria.

In addition to scans, researchers conducted tests and questionnaires with all participants to gauge obsessive-compulsive and habitual tendencies. ̽��ֱ��test used a computer-based task to establish a link between an action and reward. ̽��ֱ��scientists then uncoupled this link and observed whether participants continued to respond as a measure of habit.

“We tested whether people were more prone to repeating the same responses, like a habit, or adapting their behaviour to better pursue goals,” said Robbins. “Compulsions and habits are not the same, but impaired regulation of habits can be the basis of compulsions and shift people away from their goal-directed behaviour."

“In the supplementary motor area, which is a likely controller of the habit system, even the more mildly repetitive behaviour of healthy volunteers was related to the glutamate-GABA ratio.”

However, only clinical OCD sufferers showed excess glutamate and reduced GABA in their anterior cingulate cortex.

̽��ֱ��researchers say that raised glutamate levels may prove to be a “biomarker” for OCD. This could guide new therapies, including medication but also non-invasive use of magnetic stimulation through the scalp, an approach which is showing some promise for treatment of OCD.

Reference: Biria, M et al. (2023) Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls. Nature Communications. DOI: 10.1038/s41467-023-38695-z.

Neuroscientists say that the findings are a “major piece of the puzzle” in understanding OCD, and could open up new lines of treatment.

̽��ֱ��results suggest new strategies for medication in OCD based on available drugs that regulate glutamate

Trevor Robbins

Marjan Biria

Imaging of the Supplementary Motor Area (left) and the Anterior Cingulate Cortex (right) from the study

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Contaminating a fake rubber hand could help people overcome OCD, study suggests

cjb250 — Thu, 09 Jan 2020 08:48:07 +0000

Obsessive compulsive disorder (OCD) affects as many as one in 50 people worldwide. One of the most common types of the condition, affecting almost a half of OCD patients, is characterised by severe contamination fears – even from touching something as commonplace as a door knob – leading to excessive washing behaviour. ̽��ֱ��condition can have a serious impact on people’s lives, their mental health, their relationships and their ability to hold down jobs.

OCD is treated using a combination of medication such as Prozac and a form of cognitive behavioural therapy (‘talking therapy’) termed ‘exposure and response prevention’. This exposure therapy often involves instructing OCD patients to touch contaminated surfaces, such as a toilet, but to refrain from then washing their hands; however, this experience can be so stressful that many patients cannot take part.

“OCD can be an extremely debilitating condition for many people, but the treatments are not always straightforward,” explained Baland Jalal, a neuroscientist based in the Department of Psychiatry at the ̽��ֱ�� of Cambridge. “In fact, exposure therapy can be very stressful and so is not always effective or even feasible for many patients.”

To overcome this challenge, a team of researchers from the UK and USA tested whether, rather than asking patients to contaminate their own hands, it might be possible to help them overcome their fears by contaminating a fake hand instead – a procedure they call ‘multisensory stimulation therapy’.

̽��ֱ��technique builds on a famous trick known as the ‘rubber hand illusion’. In this illusion, an individual places both hands in front of them on a table, either side of a partition such that they cannot see their right hand. Instead, to the left of the partition they see a fake right hand. ̽��ֱ��illusionist – in this case, the experimenter – strokes both the fake hand and hidden right hand using a paintbrush. After several minutes of stroking the individual often reports ‘feeling’ touch arising from the fake hand as though it was their own.

In the majority of cases, the rubber hand illusion only works if both hands are stroked in synchrony; if they are stroked asynchronously, the illusion is diminished or disappears entirely. However, in a number of psychiatric conditions such as schizophrenia and body dysmorphic disorder, the illusion appears to work in both cases, suggesting that the body image held in the minds of these patients is more malleable than in healthy individuals.

In a previous study, carried out by Jalal and neuroscientist VS Ramachandran using healthy volunteers, once the illusion had begun to work, the researchers contaminated the dummy hand with fake faeces. ̽��ֱ��participants reported disgust sensations as if it were their own hand that had been contaminated.

In a new study published today in Frontiers in Human Neuroscience, Jalal and Ramachandran teamed up with researchers at Harvard ̽��ֱ�� – Richard J McNally, Director of Clinical Training in Department Psychology and Jason A Elias and Sriramya Potluri in the Department Psychiatry.

̽��ֱ��team recruited 29 OCD patients from the McLean Hospital Obsessive Compulsive Disorder Institute, an intensive residential treatment programme affiliated with Harvard Medical School. Sixteen of these patients had their hidden and dummy hands stroked at the same time, while the remaining 13 patients (the control group) had their hands stroked out of synch.

After 5 minutes of stroking, the participant was asked to rate how much the rubber hand felt like their own. ̽��ֱ��experimenter then used a tissue to smear the fake faeces on the rubber hand while simultaneously dabbing a damp paper towel on the participant’s real right hand (to create the sensation of having the contaminant smeared on their real hand). ̽��ֱ��participant was then asked to rate their disgust, anxiety and handwashing urge levels, and the experimenter rated the participant’s facial expression of disgust.

̽��ֱ��researchers found that patients in both the experimental and control groups felt an equally strong rubber hand illusion. In other words, even when their real and fake hands were being stroked asynchronously, they had still begun to sense the fake hand as their own. Unsurprisingly, therefore, patients in both groups initially reported similar levels of contamination.

̽��ֱ��experimenter then removed the clean paper towel and the tissue that had been used to contaminate the rubber hand, leaving fake faeces on the rubber hand. ̽��ֱ��experimenter continued to stroke the rubber hand and the participant’s real hand for an additional 5 minutes, after which the participant again provided contamination ratings and the experimenter rated their facial expression.

Now, the patients in the experimental condition were more disgusted: 65% of participants in the experimental condition had a disgust facial expression compared to 35% in the control. This supports previous studies that show that the rubber hand illusion becomes stronger the longer the hand is stroked.

Next, the experimenter stopped the stroking and placed the fake faeces on the patient’s real, right hand and asked the participant once again to provide contamination ratings. Now the differences were much more pronounced in the experimental condition. While those in the control group had average disgust, anxiety and washing urge levels at nearly 7, the experimental group had levels of nearly 9 – that is, an overall 23% difference in contamination ratings.

“Over time, stroking the real and fake hands in synchrony appears to create a stronger and stronger and stronger illusion to the extent that it eventually felt very much like their own hand,” said Jalal. “This meant that after ten minutes, the reaction to contamination was more extreme. Although this was the point our experiment ended, research has shown that continued exposure leads to a decline in contamination feelings – which is the basis of traditional exposure therapy.”

Jalal says it can be safely assumed that the fake hand contamination procedure would lead to similar fall in levels of disgust and contamination ratings, possibly after 30 minutes.

Jalal says the rubber hand illusion may offer a way of treating OCD patients without the high stress levels that exposure therapy can cause. “If you can provide an indirect treatment that is reasonably realistic, where you contaminate a rubber hand instead of a real hand, this might provide a bridge that will allow more people to tolerate exposure therapy or even to replace exposure therapy altogether.”

Jalal has previously worked on other indirect treatments for treating patients with OCD, including a smartphone app. He says that unlike other indirect treatments, this new approach creates a compelling illusion that a part of the patient’s body is being exposed to contamination and so could be even more immersive. It also has additional benefits: “Whereas traditional exposure therapy can be stressful, the rubber hand illusion often makes people laugh at first, helping put them at ease. It is also straightforward and cheap compared to virtual reality, and so can easily reach patients in distress no matter where they are, such as poorly resourced and emergency settings.”

Jalal says the next step is to do randomised clinical trials and compare this technique to existing treatments. Ramachandran agrees, adding: “These results are compelling but not conclusive. We need larger samples and to iron out some methodological wrinkles.”

Other applications of multisensory stimulation therapy might include therapy for people afraid of needles. Exposure therapy would mean repeated needle injections into a real arm and could result in punctured veins. Using a fake hand could provide a clever and convenient alternative.

Reference
“Fake it till You Make it”! Contaminating Rubber Hands (“Multisensory Stimulation Therapy”) to Treat Obsessive-Compulsive Disorder. Frontiers in Neuroscience; 9 Jan 2020; DOI: 10.3389/fnhum.2019.00414

̽��ֱ��famous, but bizarre, ‘rubber hand illusion’ could help people who suffer from obsessive compulsive disorder overcome their condition without the often unbearable stress of exposure therapy, suggests new research.

Whereas traditional exposure therapy can be stressful, the rubber hand illusion often makes people laugh at first, helping put them at ease

Baland Jalal

Divya Kumar

Rubber hand illusion

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Deep brain stimulation may significantly improve OCD symptoms, study suggests

cjb250 — Thu, 07 Mar 2019 13:00:59 +0000

OCD is characterised by unwanted intrusive thoughts and repetitive rituals and causes pronounced impairment in everyday life. In very severe cases, OCD patients are unable to leave their house or flat due to fears of contamination. This repetitive and compulsive behavior is associated with cognitive rigidity or an impairment in cognitive flexibility – an inability to adapt to new situations or new rules.

One treatment for this type of OCD is a form of cognitive behavior therapy called "exposure and response prevention", which involves instructing OCD patients to touch contaminated surfaces, such as a toilet, but to refrain from then washing their hands. OCD is also treated with medicines known as selective serotonin reuptake inhibitors, or SSRIs, such as Prozac. But as many as 40% of OCD patients fail to respond to treatment.

Deep brain stimulation (DBS) is an emerging treatment for severe OCD when all other treatments fail. In a study by researchers at ̽��ֱ�� College London and the ̽��ֱ�� of Cambridge, together with several other UK-based centres, six patients with treatment-resistant OCD entered a controlled double-blind trial of DBS.

̽��ֱ��study directly compared effects at two different brain locations – the subthalamic nucleus (STN) and ventral capsule (VC) – in the same patients. ̽��ֱ��two sites had both previously been identified as being important in OCD, but it had been unclear whether they were simply parts of the same brain network and if they worked on the same type of symptoms.

In an article published today in Biological Psychiatry, the researchers show that both sites were remarkably effective in reducing OCD symptoms, but on different aspects: VC stimulation improved mood, while STN stimulation improved cognitive flexibility.

These findings suggest that DBS at these two sites works on different brain circuits, one involving the medial prefrontal cortex and the other the lateral prefrontal cortex. This was also confirmed using brain imaging.

Lead author Professor Eileen Joyce from the UCL Queen Square Institute of Neurology says: “This is the first study to compare directly the effects of deep brain stimulation at two brain sites and has discovered important information about how the brain changes in severe OCD responsible for obsessions and compulsions, depressed mood and cognitive inflexibility might be alleviated.”

̽��ֱ��researchers assessed OCD symptoms and mood using standardised scales. Cognitive flexibility was assessed with the CANTAB IED test, invented by Professors Barbara Sahakian and Trevor Robbins from the ̽��ֱ�� of Cambridge. This test has been used previously by the Cambridge team to show that cognitive flexibility is a major deficit in patients with OCD and is related to the the lateral prefrontal cortex. ̽��ֱ��new research shows that OCD is also linked to medial prefrontal cortex abnormality.

"To our knowledge this is the first study with two sites which demonstrates that one site improves mood, while the other site improves cognitive flexibility, and that both sites reduce OCD symptoms,” says Professor Robbins.

"While DBS is only used when medication and specific psychological treatments have been tried and failed, for some patients it may provide them with the opportunity to regain well-being and quality of life,” adds Professor Sahakian.

One of the trial participants was first diagnosed at the age of 26 years with OCD but had symptoms since the age of seven. Prior to the trial, the participant had been ‘profoundly debilitated’ by OCD for 10 years and had been living continuously in psychiatric units for 6 years, receiving treatment from numerous specialist OCD services and specialists.

Following surgery, the patient said: “I didn’t feel anything for a few days but then… I felt inexplicably excited and happy with the great sense of looking forward to life. I recognised the feeling from 20 years before when I had been completely well.

“ ̽��ֱ��surgery has transformed my life. I am living completely independently and doing volunteer work.”

̽��ֱ��study was funded by the Medical Research Council, Wellcome and the NIHR Biomedical Research Centre.

Reference
Tyagi, H et al. A randomised trial directly comparing ventral capsule and anteromedial sub thalamic nucleus stimulation in obsessive compulsive disorder: Clinical and Imaging evidence for dissociable effects. Biological Psychiatry; 7 March 2019; DOI: 10.1016/j.biopsych.2019.01.017

̽��ֱ��debilitating behaviours and all-consuming thoughts, which affect people with severe obsessive compulsive disorder (OCD), could be significantly improved with targeted deep brain stimulation, according to new research published today.

Gentle07

Washing hands

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Brain training app helps reduce OCD symptoms, study finds

cjb250 — Tue, 23 Oct 2018 09:00:00 +0000

In a study published in the journal Scientific Reports, Baland Jalal and Professor Barbara Sahakian from the Department of Psychiatry, show how just one week of training can lead to significant improvements.

One of the most common types of OCD, affecting up to 46% of OCD patients, is characterised by severe contamination fears and excessive washing behaviour. Excessive washing can be harmful as sometimes OCD patients use spirits, surface cleansers or even bleach to clean their hands. ̽��ֱ��behaviours can have a serious impact on people’s lives, their mental health, their relationships and their ability to hold down jobs.

This repetitive and compulsive behaviour is also associated with ‘cognitive rigidity’ – in other words, an inability to adapt to new situations or new rules. Breaking out of compulsive habits, such as handwashing, requires cognitive flexibility so that the OCD patient can switch to new activities instead.

OCD is treated using a combination of medication such as Prozac and a form of cognitive behavioural therapy (‘talking therapy’) termed ‘exposure and response prevention’. This latter therapy often involves instructing OCD patients to touch contaminated surfaces, such as a toilet, but to refrain from then washing their hands.

These treatments are not particularly effective, however – as many as 40% of patients fail to show a good response to either treatment. This may be in part because often people with OCD have suffered for years prior to receiving a diagnosis and treatment. Another difficulty is that patients may fail to attend exposure and response prevention therapy as they find it too stressful to undertake.

For these reasons, Cambridge researchers developed a new treatment to help people with contamination fears and excessive washing. ̽��ֱ��intervention, which can be delivered through a smartphone app, involves patients watching videos of themselves washing their hands or touching fake contaminated surfaces.

Ninety-three healthy people who had indicated strong contamination fears as measured by high scores on the ‘Padua Inventory Contamination Fear Subscale’ participated in the study. ̽��ֱ��researchers used healthy volunteers rather than OCD patients in their study to ensure that the intervention did not potentially worsen symptoms.

̽��ֱ��participants were divided into three groups: the first group watched videos on their smartphones of themselves washing their hands; the second group watched similar videos but of themselves touching fake contaminated surfaces; and the third, control group watched themselves making neutral hand movements on their smartphones.

After only one week of viewing their brief 30 second videos four times a day, participants from both of the first two groups – that is, those who had watched the hand washing video and those with the exposure and response prevention video – improved in terms of reductions in OCD symptoms and showed greater cognitive flexibility compared with the neutral control group. On average, participants in the first two groups saw their Yale-Brown Obsessive Compulsive Scale (YBOCS) scores improve by around 21%. YBOCS scores are the most widely used clinical assessments for assessing the severity of OCD.

Importantly, completion rates for the study were excellent – all participants completed the one-week intervention, with participants viewing their video an average (mean) of 25 out of 28 times.

Mr Jalal said: “Participants told us that the smartphone washing app allowed them to easily engage in their daily activities. For example, one participant said ‘if I am commuting on the bus and touch something contaminated and can’t wash my hands for the next two hours, the app would be a sufficient substitute’.”

Professor Sahakian said: “This technology will allow people to gain help at any time within the environment where they live or work, rather than having to wait for appointments. ̽��ֱ��use of smartphone videos allows the treatment to be personalised to the individual.

“These results while very exciting and encouraging, require further research, examining the use of these smartphone interventions in people with a diagnosis of OCD.”

̽��ֱ��smartphone app is not currently available for public use. Further research is required before the researchers can show conclusively that it is effective at helping patients with OCD.

̽��ֱ��research was funded by the Wellcome Trust, NIHR Cambridge Biomedical Research Centre, the Medical Research Council and the Wallitt Foundation.

Reference
Baland Jalal, Annette Bruhl, Claire O’Callaghan, Thomas Piercy, Rudolf N. Cardinal, Vilayanur S. Ramachandran and Barbara J. Sahakian. Novel smartphone interventions improve cognitive flexibility and obsessive-compulsive disorder symptoms in individuals with contamination fears. Scientific Reports; 23 Oct 2018; DOI: 10.1038/s41598-018-33142-2

A ‘brain training’ app developed at the ̽��ֱ�� of Cambridge could help people who suffer from obsessive compulsive disorder (OCD) manage their symptoms, which may typically include excessive handwashing and contamination fears.

This technology will allow people to gain help at any time within the environment where they live or work, rather than having to wait for appointments

Barbara Sahakian

Thomas Piercy

Images from app

Researcher profile: Baland Jalal

“Cambridge is the perfect place for the ‘idealistic scholar’ – those who believe they can re-write the science textbooks. ̽��ֱ��culture—like no other—embraces novel ideas, even if outlandish and far-fetched on the surface,” says Baland Jalal, a neuroscientist at the Behavioural and Clinical Neuroscience Institute and PhD candidate at Trinity College.

“It is no coincidence that the foremost scientists in history have stepped foot here, including my scientific hero Newton. One cannot help but feel inspired, as if part of a lineage of greatness—‘standing on the shoulder of giants’.”

Jalal considers himself fortunate to have been able to stand on the shoulders of proverbial giants throughout his research career. He received his initial training at the ̽��ֱ�� of California in the laboratory of legendary neuroscientist VS Ramachandran.

“California was an enchanting experience. Rama and I would often go for long strolls on San Diego’s beaches where he would tell mesmerizing stories about the good-old-days when he was a Cambridge student and how he later invented his famous ‘mirror box’ for phantom limb pain. He was like a second father – a mentor who instilled in me a genuine love of science.”

Jalal now works with husband-and-wife team Professors Barbara Sahakian and Trevor Robbins, who he describes as embodying “the ‘Cambridge spirit’ of innovation”. His work is ultimately about developed new psychiatric treatments. “This often involves taking an unorthodox and somewhat radical approach—thinking ‘outside the box’ so to speak,” he says. Ideas include the above treatment for OCD and a second treatment based on the ‘rubber hand illusion’, making a fake hand feel like it is your own.

His other area of interest is in sleep paralysis—being paralyzed from head to toe while seeing ghosts and space aliens when waking up from sleep. He has studied this peculiar phenomenon around the world and recently invented a novel meditation-relaxation therapy for this condition, called MR Therapy.

“I hope my research will lead to new therapies that can help people in distress around the world - especially folks in low-income countries who don’t have adequate access to health care. ̽��ֱ��feeling I have when someone tells me that my work has helped alleviate their anguish is – simply – indescribable.”

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Study of learning and memory problems in OCD helps young people unlock their potential at school

cjb250 — Mon, 22 Jan 2018 12:00:14 +0000

OCD in children and adolescents is a distressing condition, which is often chronic and persists into adulthood. Almost 90% of these young patients have problems at school, home, or socially; with difficulties doing homework and concentrating at school being the two most common problems. Children and adolescents are well set up for learning and, indeed, can quickly pick up new foreign languages, computing skills or motor tasks, such as riding a bike, much quicker than older adults. But if an adolescent is not learning well in school, they are likely to become stressed and anxious.

Researchers at the ̽��ֱ�� of Cambridge have previously shown that there are core problems of cognitive inflexibility in adults with OCD. Since flexibility in problem-solving is an important skill for performance in school, they wanted to study whether adolescents with OCD had difficulty in this area. Cognitive flexibility becomes important when trying to find the correct solutions to a problem, particularly when your first attempt at solving that problem does not work. To reach the correct solution, you have to switch to a new approach from the one you have previously been using.

In healthy individuals, there is a balance between goal-directed control and habit control, and this balance is crucial for daily functioning. For example, when learning to drive, we focus on specific goals, such as travelling at the right speed, staying within the traffic lines and following safety rules. We often have strategies to perform these tasks optimally. However, once we are an experienced driver, we frequently find that driving becomes habitual. In new situations, healthy people tend to use goal-directed control; however, under conditions of stress, they frequently select habitual learning.

In a new study published in the journal Psychological Medicine, researchers looked at whether cognitive flexibility for learning tasks and goal-directed control was impaired early in the development of OCD. ̽��ֱ��study was led by Dr Julia Gottwald and Professor Barbara Sahakian from the Department of Psychiatry.

Thirty-six adolescents with OCD and 36 healthy young people completed learning and memory tasks. These computerised tests included recognition memory (remembering which of two objects they had seen before) and episodic memory (where in space they remember seeing an object). A subset of 30 participants in each group also carried out a task designed to assess the balance of goal-directed and habitual behavioural control.

̽��ֱ��researchers found that adolescent patients with OCD had impairments in all learning and memory tasks. ̽��ֱ��study also demonstrated for the first time impaired goal-directed control and lack of cognitive plasticity early in the development of OCD.

Dr Julia Gottwald, the study’s first author, comments: “While many studies have focused on adult OCD, we actually know very little about the condition in teenagers. Our study suggests that teens with OCD have problems with memory and the ability to flexibly adjust their actions when the environment changes.”

Professor Barbara Sahakian, senior author, says: “I was surprised and concerned to see such broad problems of learning and memory in these young people so early in the course of OCD. It will be important to follow this study up to examine these cognitive problems further and in particular to determine how they impact on clinical symptoms and school performance.”

Experiencing learning and memory problems at school could affect self-esteem. Furthermore, some symptoms seen in people with OCD, such as compulsive checking, may result from them having reduced confidence in their memory ability. ̽��ֱ��stress of having difficulty in learning may also start a negative influence and promote inflexible habit learning.

Dr Anna Conway Morris commented: “This study has been very useful in assisting adolescents with OCD with the help they needed at school in terms of structuring the environment to ensure that there was a level playing field. This allowed them to receive the help they needed to realise their potential.

“One person with OCD was able to obtain good A Levels and to be accepted by a good university where she could get the support that she needed in order to do well in that environment.”

Future studies will examine in more detail the nature of these impairments and how they might affect clinical symptoms and school performance.

̽��ֱ��research was funded by the Wellcome Trust and the Medical Research Council.

Reference
Gottwald, J, et al. Impaired cognitive plasticity and goal-directed control in adolescent obsessive-compulsive disorder. Psychological Medicine; 22 Jan 2018; DOI: 10.1017/S0033291717003464

Adolescents with obsessive-compulsive disorder (OCD) have widespread learning and memory problems, according to research published today. ̽��ֱ��findings have already been used to assist adolescents with OCD obtain the help they needed at school to realise their potential – including helping one individual go on to university.

I was surprised and concerned to see such broad problems of learning and memory in these young people so early in the course of OCD

Barbara Sahakian

Luci Correia

Carol

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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̽��ֱ��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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Women and people under the age of 35 at greatest risk of anxiety

cjb250 — Sun, 05 Jun 2016 23:01:09 +0000

̽��ֱ��review, published today in the journal Brain and Behavior, also highlighted how anxiety disorders often provide a double burden on people experiencing other health-related problems, such as heart disease, cancer and even pregnancy.

Anxiety disorders, which often manifest as excessive worry, fear and a tendency to avoid potentially stressful situations including social gatherings, are some of the most common mental health problems in the Western world. ̽��ֱ��annual cost related to the disorders in the United States is estimated to be $42.3 million. In the European Union, over 60 million people are affected by anxiety disorders in a given year.

There have been many studies looking at the number of people affected by anxiety disorders and the groups that are at highest risk, and in an attempt to synthesise the various studies, National Institute for Health Research (NIHR)-funded researchers from the ̽��ֱ�� of Cambridge’s Institute of Public Health carried out a global review of systematic reviews. Out of over 1,200 reviews, the researchers identified 48 reviews that matched their criteria for inclusion.

Between 1990 and 2010, the overall proportion of people affected remained largely unchanged, with around four out of every 100 experiencing anxiety. ̽��ֱ��highest proportion of people with anxiety is in North America, where almost eight out of every 100 people are affected; the proportion is lowest in East Asia, where less than three in 100 people have this mental health problem.

Women are almost twice as likely to be affected as men, and young individuals – both male and female – under 35 years of age are disproportionately affected.

̽��ֱ��researchers also found that people with other health conditions are often far more likely to also experience anxiety disorders. For example, around one in ten adults (10.9%) with cardiovascular disease and living in Western countries are affected by generalised anxiety disorder, with women showing higher anxiety levels than men. People living with multiple sclerosis are most affected – as many as one in three patients (32%) also have an anxiety disorder.

According to first author Olivia Remes from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge: “Anxiety disorders can make life extremely difficult for some people and it is important for our health services to understand how common they are and which groups of people are at greatest risk.

“By collecting all these data together, we see that these disorders are common across all groups, but women and young people are disproportionately affected. Also, people who have a chronic health condition are at a particular risk, adding a double burden on their lives.”

Obsessive compulsive disorder (OCD) – which is an anxiety disorder characterized by obsessions and compulsions – was found to be a problem in pregnant women and in the period immediately after birth. In the general population, only one in a hundred people are affected by OCD, but the proportion with the disorder was double in pregnant women and slightly higher in post-partum women.

However, the analysis also showed that data on some populations was lacking or of poor quality. This was particularly true for marginalised communities, such as indigenous cultures in North America, Australia and New Zealand, and drug users, street youth and sex workers. Anxiety disorders also represent an important issue among people identifying as lesbian, gay, and bisexual; however, there are not enough studies in these populations, and those that have looked at it are of variable quality.

Dr Louise Lafortune, Senior Research Associate at the Cambridge Institute of Public Health, explains: “Anxiety disorders affect a lot of people and can lead to impairment, disability, and risk of suicide. Although many groups have examined this important topic, significant gaps in research remain.”

Professor Carol Brayne, Director of the Cambridge Institute of Public Health, adds: “Even with a reasonably large number of studies of anxiety disorder, data about marginalised groups is hard to find, and these are people who are likely to be at an even greater risk than the general population. We hope that, by identifying these gaps, future research can be directed towards these groups and include greater understanding of how such evidence can help reduce individual and population burdens.”

Reference
Remes, O et al. A systematic review of reviews on the prevalence of anxiety disorders in adult populations. Brain and Behavior; 6 June 2016; DOI: 10.1002/brb3.497

Women are almost twice as likely to experience anxiety as men, according to a review of existing scientific literature, led by the ̽��ֱ�� of Cambridge. ̽��ֱ��study also found that people from Western Europe and North America are more likely to suffer from anxiety than people from other cultures.

Anxiety disorders can make life extremely difficult for some people and it is important for our health services to understand how common they are and which groups of people are at greatest risk

Olivia Remes

Flavia

Anxiety

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