̽��ֱ�� of Cambridge - depression

‘Teen-friendly’ mindfulness therapy aims to help combat depression

cjb250 — Mon, 18 Nov 2024 08:00:40 +0000

Researchers have developed a mindfulness therapy tailored specifically to appeal to teenagers to help them cope with increasing levels of depression and mental health problems.

Magnetic field applied to both sides of brain shows rapid improvement for depression

cjb250 — Mon, 28 Oct 2024 15:23:23 +0000

̽��ֱ��treatment – known as repetitive transcranial magnetic stimulation (TMS) – involves placing an electromagnetic coil against the scalp to relay a high-frequency magnetic field to the brain.

Around one in 20 adults is estimated to suffer from depression. Although treatments exist, such as anti-depressant medication and cognitive behavioural therapy (‘talking therapy’), they are ineffective for just under one in three patients.

One of the key characteristics of depression is under-activity of some regions (such as the dorsolateral prefrontal cortex) and over-activity of others (such as the orbitofrontal cortex (OFC)).

Repetitive transcranial magnetic stimulation applied to the left side of the dorsolateral prefrontal cortex (an area at the upper front area of the brain) is approved for treatment of depression in the UK by NICE and in the US by the FDA. It has previously been shown to lead to considerable improvements among patients after a course of 20 sessions, but because the sessions usually take place over 20-30 days, the treatment is not ideal for everyone, particularly in acute cases or where a person is suicidal.

In research published in Psychological Medicine, scientists from Cambridge, UK, and Guiyang, China, tested how effective an accelerated form of TMS is. In this approach, the treatment is given over 20 sessions, but with four sessions per day over a period of five consecutive days.

̽��ֱ��researchers also tested a ‘dual’ approach, whereby a magnetic field was additionally applied to the right-hand side of the OFC (which sits below the dorsolateral prefrontal cortex).

Seventy-five patients were recruited to the trial from the Second People’s Hospital of Guizhou Province in China. ̽��ֱ��severity of their depression was measured on a scale known as the Hamilton Rating Scale of Depression.

Participants were split randomly into three groups: a ‘dual’ group receiving TMS applied first to the right- and then to the left-hand sides of the brain; a ‘single’ group receiving sham TMS to the right-side followed by active TMS applied to the left-side; and a control group receiving a sham treatment to both sides. Each session lasted in total 22 minutes.

There was a significant improvement in scores assessed immediately after the final treatment in the dual treatment group compared to the other two groups. When the researchers looked for clinically-relevant responses – that is, where an individual’s score fell by at least 50% – they found that almost half (48%) of the patients in the dual treatment group saw such a reduction, compared to just under one in five (18%) in the single treatment group and fewer than one in 20 (4%) in the control group.

Four weeks later, around six in 10 participants in both the dual and single treatment groups (61% and 59% respectively) showed clinically relevant responses, compared to just over one in five (22%) in the control group.

Professor Valerie Voon from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, who led the UK side of the study, said: “Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression. This means it could be particularly useful in severe cases of depression, including when someone is experiencing suicidal thoughts. It may also help people be discharged from hospital more rapidly or even avoid admission in the first place.

“ ̽��ֱ��treatment works faster because, by targeting two areas of the brain implicated in depression, we’re effectively correcting imbalances in two import processes, getting brain regions ‘talking’ to each other correctly.”

̽��ֱ��treatment was most effective in those patients who at the start of the trial showed greater connectivity between the OFC and the thalamus (an area in the middle of the brain responsible for, among other things, regulation of consciousness, sleep, and alertness). ̽��ֱ��OFC is important for helping us make decisions, particularly in choosing rewards and avoiding punishment. Its over-activity in depression, particularly in relation to its role in anti-reward or punishment, might help explain why people with depression show a bias towards negative expectations and ruminations.

Dr Yanping Shu from the Guizhou Mental Health Centre, Guiyang, China, said: “This new treatment has demonstrated a more pronounced – and faster – improvement in response rates for patients with major depressive disorder. It represents a significant step forward in improving outcomes, enabling rapid discharge from hospitals for individuals with treatment-resistant depression, and we are hopeful it will lead to new possibilities in mental health care.”

Dr Hailun Cui from Fudan ̽��ֱ��, a PhD student in Professor Voon’s lab at the time of the study, added: “ ̽��ֱ��management of treatment-resistant depression remains one of the most challenging areas in mental health care. These patients often fail to respond to standard treatments, including medication and psychotherapy, leaving them in a prolonged state of severe distress, functional impairment, and increased risk of suicide.

“This new TMS approach offers a beacon of hope in this difficult landscape. Patients frequently reported experiencing ‘lighter and brighter’ feelings as early as the second day of treatment. ̽��ֱ��rapid improvements, coupled with a higher response rate that could benefit a broader depressed population, mark a significant breakthrough in the field.”

Just under a half (48%) of participants in the dual treatment group reported local pain where the dual treatment was applied, compared to just under one in 10 (9%) of participants in the single treatment group. However, despite this, there were no dropouts.

For some individuals, this treatment may be sufficient, but for others ‘maintenance therapy’ may be necessary, with an additional day session if their symptoms appear to be worsening over time. It may also be possible to re-administer standard therapy as patients can then become more able to engage in psychotherapy. Other options include using transcranial direct current stimulation, a non-invasive form of stimulation using weak electrical impulses that can be delivered at home.

̽��ֱ��researchers are now exploring exactly which part of the orbitofrontal cortex is most effective to target and for which types of depression.

̽��ֱ��research was supported by in the UK by the Medical Research Council and by the National Institute for Health and Care Research Cambridge Biomedical Research Centre.*

Reference
Cui, H, Ding, H & Hu, L et al. A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study. Psychological Medicine; 23 Oct 2024; DOI: 10.1017/S0033291724002289

*A full list of funders is available in the journal paper.

A type of therapy that involves applying a magnetic field to both sides of the brain has been shown to be effective at rapidly treating depression in patients for whom standard treatments have been ineffective.

Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression

Valerie Voon

TheDigitalArtist

Digital image of a brain

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Genetic study points to oxytocin as possible treatment for obesity and postnatal depression

cjb250 — Tue, 02 Jul 2024 15:00:18 +0000

Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high income countries. Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.

While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the ̽��ֱ�� of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits on the X chromosome.

Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. ̽��ֱ��mothers also had obesity, but in addition had experienced postnatal depression.

To test if it was the TRPC5 gene that was causing the problems in the boys and their mothers, the researchers turned to animal models, genetically-engineering mice with a defective version of the gene (Trpc5 in mice).

Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.

Dr Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, said: “What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours.”

TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.

When the researchers looked in more detail at this brain region, they discovered that TRPC5 acts on oxytocin neurons – nerve cells that produce the hormone oxytocin, often nicknamed the ‘love hormone’ because of its release in response to displays of affection, emotion and bonding.

Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.

In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have been known for some time to play an important role in regulating weight. Children in whom the POMC gene is not working properly often have an insatiable appetite and gain weight from an early age.

Professor Sadaf Farooqi from the Institute of Metabolic Science at the ̽��ֱ�� of Cambridge said: “There's a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, social interaction, the flight or fight response, and caring for their infants. Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts.”

While deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people – around three-quarters of whom were women – that carried variants of the gene and had a higher-than-average body mass index.

̽��ֱ��researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal depression.

Professor Farooqi said: “While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works. In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”

There is already evidence in animals that the oxytocin system is involved in both depression and in maternal care and there have been small trials into the use of oxytocin as a treatment. ̽��ֱ��team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials.

Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.”

This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.

Reference
Li, Y, Cacciottolo, TM & Yin, N. Loss of Transient Receptor Potential Channel 5 Causes Obesity and Postpartum Depression. Cell; 2 July 2024; DOI: 10.1016/j.cell.2024.06.001

Scientists have identified a gene which, when missing or impaired, can cause obesity, behavioural problems and, in mothers, postnatal depression. ̽��ֱ��discovery, reported on 2 July in Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.

This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology. We need to be more understanding and sympathetic towards people who suffer with these conditions

Sadaf Farooqi

Olli Turho (Getty Images)

Illustration of a tired African American mother crying

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Feeling depressed linked to short-term increase in bodyweight among people with overweight or obesity

cjb250 — Wed, 10 Jan 2024 19:00:05 +0000

̽��ֱ��study, published today in PLOS ONE, found that the increase was only seen among people with overweight or obesity, but found no link between generally having greater symptoms of depression and higher bodyweight.

Research has suggested a connection between weight and mental health – with each potentially influencing the other – but the relationship is complex and remains poorly understood, particularly in relation to how changes in an individual’s mental health influence their bodyweight over time.

To help answer this question, researchers at Cambridge’s Medical Research Council (MRC) Epidemiology Unit examined data from over 2,000 adults living in Cambridgeshire, UK, who had been recruited to the Fenland COVID-19 Study.

Participants completed digital questionnaires on mental wellbeing and bodyweight every month for up to nine months during the COVID-19 pandemic (August 2020 – April 2021) using a mobile app developed by Huma Therapeutics Limited.

Questions assessed an individual’s symptoms of depression, anxiety and perceived stress. A higher score indicated greater severity, with the maximum possible scores being 24 for depression, 21 for anxiety and 40 for stress. ̽��ֱ��team then used statistical modelling to explore whether having poorer mental wellbeing than usual was related to changes in bodyweight one month later.

̽��ֱ��researchers found that for every increment increase in an individual’s usual score for depressive symptoms, their subsequent weight one month later increased by 45g. This may seem small but would mean, for example, that in an individual whose depressive symptoms score rose from five to 10 (equal to an increase from ‘mild’ to ‘moderate’ depressive symptoms) it would relate to an average weight gain of 225g (0.225kg).

This effect was only observed in those individuals with overweight (defined as BMI 25-29.9kg/m2) or with obesity (BMI of over 30kg/m2). Individuals with overweight had on average an increase of 52g for each increment point increase from their usual depressive symptoms score and for those with obesity the comparable weight gain was 71g. ̽��ֱ��effect was not seen in those individuals with a healthy weight.

First author Dr Julia Mueller from the MRC Epidemiology Unit said: “Overall, this suggests that individuals with overweight or obesity are more vulnerable to weight gain in response to feeling more depressed. Although the weight gain was relatively small, even small weight changes occurring over short periods of time can lead to larger weight changes in the long-term, particularly among those with overweight and obesity.

“People with a high BMI are already at greater risk from other health conditions, so this could potentially lead to a further deterioration in their health. Monitoring and addressing depressive symptoms in individuals with overweight or obesity could help prevent further weight gain and be beneficial to both their mental and physical health.”

̽��ֱ��researchers found no evidence that perceived stress or anxiety were related to changes in weight.

Senior author Dr Kirsten Rennie from the MRC Epidemiology Unit said: “Apps on our phones make it possible for people to answer short questions at home more frequently and over extended periods of time, which provides much more information about their wellbeing. This technology could help us understand how changes in mental health influence behaviour among people with overweight or obesity and offer ways to develop timely interventions when needed.”

Although previous studies have suggested that poor mental health is both a cause and consequence of obesity, the research team found no evidence that weight predicted subsequent symptoms of depression.

̽��ֱ��research was supported by the Medical Research Council.

Reference
Mueller, J et al. ̽��ֱ��relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study. PLOS ONE; 10 Jan 2024; DOI: 10.1371/journal.pone.0295117

Increases in symptoms of depression are associated with a subsequent increase in bodyweight when measured one month later, new research from the ̽��ֱ�� of Cambridge has found.

i yunmai

Person standing on white digital bathroom scale

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Simple blood test can help diagnose bipolar disorder

sc604 — Wed, 25 Oct 2023 15:00:00 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, used a combination of an online psychiatric assessment and a blood test to diagnose patients with bipolar disorder, many of whom had been misdiagnosed with major depressive disorder.

̽��ֱ��researchers say the blood test on its own could diagnose up to 30% of patients with bipolar disorder, but that it is even more effective when combined with a digital mental health assessment.

Incorporating biomarker testing could help physicians differentiate between major depressive disorder and bipolar disorder, which have overlapping symptoms but require different pharmacological treatments.

Although the blood test is still a proof of concept, the researchers say it could be an effective complement to existing psychiatric diagnosis and could help researchers understand the biological origins of mental health conditions. ̽��ֱ��results are reported in the journal JAMA Psychiatry.

Bipolar disorder affects approximately one percent of the population – as many as 80 million people worldwide – but for nearly 40% of patients, it is misdiagnosed as major depressive disorder.

“People with bipolar disorder will experience periods of low mood and periods of very high mood or mania,” said first author Dr Jakub Tomasik, from Cambridge’s Department of Chemical Engineering and Biotechnology. “But patients will often only see a doctor when they’re experiencing low mood, which is why bipolar disorder frequently gets misdiagnosed as major depressive disorder.”

“When someone with bipolar disorder is experiencing a period of low mood, to a physician, it can look very similar to someone with major depressive disorder,” said Professor Sabine Bahn, who led the research. “However, the two conditions need to be treated differently: if someone with bipolar disorder is prescribed antidepressants without the addition of a mood stabiliser, it can trigger a manic episode.”

̽��ֱ��most effective way to get an accurate diagnosis of bipolar disorder is a full psychiatric assessment. However, patients often face long waits to get these assessments, and they take time to carry out.

“Psychiatric assessments are highly effective, but the ability to diagnose bipolar disorder with a simple blood test could ensure that patients get the right treatment the first time and alleviate some of the pressures on medical professionals,” said Tomasik.

̽��ֱ��researchers used samples and data from the Delta study, conducted in the UK between 2018 and 2020, to identify bipolar disorder in patients who had received a diagnosis of major depressive disorder within the previous five years and had current depressive symptoms. Participants were recruited online through voluntary response sampling.

More than 3000 participants were recruited, and they each completed an online mental health assessment of more than 600 questions. ̽��ֱ��assessment covered a range of topics that may be relevant to mental health disorders, including past or current depressive episodes, generalised anxiety, symptoms of mania, family history or substance abuse.

Of the participants who completed the online assessment, around 1000 were selected to send in a dried blood sample from a simple finger prick, which the researchers analysed for more than 600 different metabolites using mass spectrometry. After completing the Composite International Diagnostic Interview, a fully structured and validated diagnostic tool to establish mood disorder diagnoses, 241 participants were included in the study.

Analysis of the data showed a significant biomarker signal for bipolar disorder, even after accounting for confounding factors such as medication. ̽��ֱ��identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of major depressive disorder or bipolar disorder during the study’s one-year follow-up period.

̽��ֱ��researchers found that the combination of patient-reported information and the biomarker test significantly improved diagnostic outcomes for people with bipolar disorder, especially in those where the diagnosis was not obvious.

“ ̽��ֱ��online assessment was more effective overall, but the biomarker test performs well and is much faster,” said Bahn. “A combination of both approaches would be ideal, as they’re complementary.”

“We found that some patients preferred the biomarker test, because it was an objective result that they could see,” said Tomasik. “Mental illness has a biological basis, and it’s important for patients to know it’s not in their mind. It’s an illness that affects the body like any other.”

“In addition to the diagnostic capabilities of biomarkers, they could also be used to identify potential drug targets for mood disorders, which could lead to better treatments,” said Bahn. “It’s an exciting time to be in this area of research.”

A patent has been filed on the research by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. ̽��ֱ��research was supported by the Stanley Medical Research Institute and Psyomics, a ̽��ֱ�� spin-out company co-founded by Sabine Bahn.

Sabine Bahn is Professor of Neurotechnology at the Department of Chemical Engineering and Biotechnology and is a Fellow of Lucy Cavendish College, Cambridge.

Reference:
Jakub Tomasik et al. ‘Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression.’ JAMA Psychiatry (2023). DOI: 10.1001/jamapsychiatry.2023.4096

Researchers have developed a new way of improving diagnosis of bipolar disorder that uses a simple blood test to identify biomarkers associated with the condition.

̽��ֱ��ability to diagnose bipolar disorder with a simple blood test could ensure that patients get the right treatment the first time

Jakub Tomasik

Cambridge Centre for Neuropsychiatric Research

Providing a drop of blood for a test

̽��ֱ��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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Healthy lifestyle can help prevent depression – and new research may explain why

cjb250 — Mon, 11 Sep 2023 15:00:41 +0000

In research published today in Nature Mental Health, an international team of researchers, including from the ̽��ֱ�� of Cambridge and Fudan ̽��ֱ��, looked at a combination of factors including lifestyle factors, genetics, brain structure and our immune and metabolic systems to identify the underlying mechanisms that might explain this link.

According to the World Health Organization, around one in 20 adults experiences depression, and the condition poses a significant burden on public health worldwide. ̽��ֱ��factors that influence the onset of depression are complicated and include a mixture of biological and lifestyle factors.

To better understand the relationship between these factors and depression, the researchers turned to UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information about its participants.

By examining data from almost 290,000 people – of whom 13,000 had depression – followed over a nine-year period, the team was able to identify seven healthy lifestyle factors linked with a lower risk of depression. These were:

moderate alcohol consumption
healthy diet
regular physical activity
healthy sleep
never smoking
low-to-moderate sedentary behaviour
frequent social connection

Of all of these factors, having a good night’s sleep – between seven and nine hours a night – made the biggest difference, reducing the risk of depression, including single depressive episodes and treatment-resistant depression, by 22%.

Frequent social connection, which in general reduced the risk of depression by 18%, was the most protective against recurrent depressive disorder.

Moderate alcohol consumption decreased the risk of depression by 11%, healthy diet by 6%, regular physical activity by 14%, never smoking by 20%, and low-to-moderate sedentary behaviour by 13%.

Based on the number of healthy lifestyle factors an individual adhered to, they were assigned to one of three groups: unfavourable, intermediate, and favourable lifestyle. Individuals in the intermediate group were around 41% less likely to develop depression compared to those in the unfavourable lifestyle, while those in the favourable lifestyle group were 57% less likely.

̽��ֱ��team then examined the DNA of the participants, assigning each a genetic risk score. This score was based on the number of genetic variants an individual carried that have a known link to risk of depression. Those with the lowest genetic risk score were 25% less likely to develop depression when compared to those with the highest score – a much smaller impact than lifestyle.

In people at high, medium, and low genetic risk for depression, the team further found that a healthy lifestyle can cut the risk of depression. This research underlines the importance of living a healthy lifestyle for preventing depression, regardless of a person's genetic risk.

Professor Barbara Sahakian, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “Although our DNA – the genetic hand we’ve been dealt – can increase our risk of depression, we’ve shown that a healthy lifestyle is potentially more important.

“Some of these lifestyle factors are things we have a degree control over, so trying to find ways to improve them – making sure we have a good night’s sleep and getting out to see friends, for example – could make a real difference to people’s lives.”

To understand why a healthy lifestyle might reduce the risk of depression, the team studied a number of other factors.

First off, they examined MRI brain scans from just under 33,000 participants and found a number of regions of the brain where a larger volume – more neurons and connections – was linked to a healthy lifestyle. These included the pallidum, thalamus, amygdala and hippocampus.

Next, the team looked for markers in the blood that indicated problems with the immune system or metabolism (how we process food and produce energy). Among those markers found to be linked to lifestyle were the C-reactive protein, a molecule produced in the body in response to stress, and triglycerides, one of the primary forms of fat that the body uses to store energy for later.

These links are supported by a number of previous studies. For example, exposure to stress in life can affect how well we are able to regulate blood sugar, which may lead to a deterioration of immune function and accelerate age-related damage to cells and molecules in the body. Poor physical activity and lack of sleep can damage the body’s ability to respond to stress. Loneliness and lack of social support have been found to increase the risk of infection and increase markers of immune deficiency.

̽��ֱ��team found that the pathway from lifestyle to immune and metabolic functions was the most significant. In other words, a poorer lifestyle impacts on our immune system and metabolism, which in turn increases our risk of depression.

Dr Christelle Langley, also from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “We’re used to thinking of a healthy lifestyle as being important to our physical health, but it’s just as important for our mental health. It’s good for our brain health and cognition, but also indirectly by promoting a healthier immune system and better metabolism.”

Professor Jianfeng Feng, from Fudan ̽��ֱ�� and Warwick ̽��ֱ��, added: “We know that depression can start as early as in adolescence or young adulthood, so educating young people on the importance of a healthy lifestyle and its impact on mental health should begin in schools.”

This study was supported by grants from organisations including the National Natural Science Foundation of China and the Ministry of Science, China*.

Reference
Zhao, Y & Yang, L et al. ̽��ֱ��brain structure, immunometabolic and genetic mechanisms underlying the association between lifestyle and depression. Nature Mental Health; 11 Sept 2023; DOI: 10.1038/s44220-023-00120-1

*A full list of funders can be found in the paper.

A healthy lifestyle that involves moderate alcohol consumption, a healthy diet, regular physical activity, healthy sleep and frequent social connection, while avoiding smoking and too much sedentary behaviour, reduces the risk of depression, new research has found.

Although our DNA – the genetic hand we’ve been dealt – can increase our risk of depression, we’ve shown that a healthy lifestyle is potentially more important.

Barbara Sahakian

Sweet Life

A group of people standing around a table with plates of food

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Scientists explain emotional ‘blunting’ caused by common antidepressants

cjb250 — Mon, 23 Jan 2023 06:00:50 +0000

According to the NHS, more than 8.3 million patients in England received an antidepressant drug in 2021/22. A widely-used class of antidepressants, particularly for persistent or severe cases, is selective serotonin reuptake inhibitors (SSRIs). These drugs target serotonin, a chemical that carries messages between nerve cells in the brain and has been dubbed the ‘pleasure chemical’.

One of the widely-reported side effects of SSRIs is ‘blunting’, where patients report feeling emotionally dull and no longer finding things as pleasurable as they used to. Between 40-60% of patients taking SSRIs are believed to experience this side effect.

To date, most studies of SSRIs have only examined their short term use, but, for clinical use in depression these drugs are taken chronically, over a longer period of time. A team led by researchers at the ̽��ֱ�� of Cambridge, in collaboration with the ̽��ֱ�� of Copenhagen, sought to address this by recruiting healthy volunteers and administering escitalopram, an SSRI known to be one of the best-tolerated, over several weeks and assessing the impact the drug had on their performance on a suite of cognitive tests.

In total, 66 volunteers took part in the experiment, 32 of whom were given escitalopram while the other 34 were given a placebo. Volunteers took the drug or placebo for at least 21 days and completed a comprehensive set of self-report questionnaires and were given a series of tests to assess cognitive functions including learning, inhibition, executive function, reinforcement behaviour, and decision-making.

̽��ֱ��results of the study are published today in Neuropsychopharmacology.

̽��ֱ��team found no significant group differences when it came to ‘cold’ cognition – such as attention and memory. There were no differences in most tests of ‘hot’ cognition – cognitive functions that involve our emotions.

However, the key novel finding was that there was reduced reinforcement sensitivity on two tasks for the escitalopram group compared to those on placebo. Reinforcement learning is how we learn from feedback from our actions and environment.

In order to assess reinforcement sensitivity, the researchers used a ‘probabilistic reversal test’. In this task, a participant would typically be shown two stimuli, A and B. If they chose A, then four out of five times, they would receive a reward; if they chose B, they would only receive a reward one time out of five. Volunteers would not be told this rule, but would have to learn it themselves, and at some point in the experiment, the probabilities would switch and participants would need to learn the new rule.

̽��ֱ��team found that participants taking escitalopram were less likely to use the positive and negative feedback to guide their learning of the task compared with participants on placebo. This suggests that the drug affected their sensitivity to the rewards and their ability to respond accordingly.

̽��ֱ��finding may also explain the one difference the team found in the self-reported questionnaires, that volunteers taking escitalopram had more trouble reaching orgasm when having sex, a side effect often reported by patients.

Professor Barbara Sahakian, senior author, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and a Fellow at Clare Hall, said: “Emotional blunting is a common side effect of SSRI antidepressants. In a way, this may be in part how they work – they take away some of the emotional pain that people who experience depression feel, but, unfortunately, it seems that they also take away some of the enjoyment. From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”

Dr Christelle Langley, joint first author also from the Department of Psychiatry, added: “Our findings provide important evidence for the role of serotonin in reinforcement learning. We are following this work up with a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning.”

̽��ֱ��research was funded by the Lundbeck Foundation.

Reference
Langley, C, Armand, S, et al. Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: A double-blind, placebo-controlled semi-randomised study. Neuropsychopharmacology; 23 Jan 2023; DOI: 10.1038/s41386-022-01523-x

Scientists have worked out why common anti-depressants cause around a half of users to feel emotionally ‘blunted’. In a study published today, they show that the drugs affect reinforcement learning, an important behavioural process that allows us to learn from our environment.

Ethan Sykes

Man looking out of window

̽��ֱ��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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Pandemic restrictions aggravating known triggers for self-harm and poor mental health among children and young people

cjb250 — Wed, 10 Mar 2021 23:30:04 +0000

Writing in ̽��ֱ��BMJ, Professor Tamsin Ford at the ̽��ֱ�� of Cambridge and colleagues say deterioration in mental health is clearest among families already struggling and call for urgent action “to ensure that this generation is not disproportionately disadvantaged by COVID-19.”

They point to evidence that the mental health of the UK’s children and young people was deteriorating before the pandemic, while health, educational, and social outcomes for children with mental health conditions were worse in the 21st century than the late 20th century. For example, between 2004 and 2017 anxiety, depression, and self-harm increased, particularly among teenage girls.

Given that self-harm is an important risk factor for suicide, it is not surprising that rates of suicide among the UK’s children and young people also increased in recent years, they write, though numbers remain low compared with other age groups - about 100 people aged under 18 died by suicide each year in England between 2014 and 2016.

Studies carried out during the pandemic suggest that although some families are coping well, others are facing financial adversity, struggling to home school, and risk experiencing vicious cycles of increasing stress and distress.

Probable mental health conditions increased from 11% in 2017 to 16% in July 2020 across all age, sex, and ethnic groups according to England’s Mental Health of Children and Young People Survey (MHCYP). In addition, a sample of 2,673 parents recruited through social media reported deteriorating mental health and increased behavioural problems among children aged 4 to 11 years between March and May 2020 (during lockdown) but reduced emotional symptoms among 11-16 year olds.

̽��ֱ��more socioeconomically deprived respondents had consistently worse mental health in both surveys, note the authors - a stark warning given that economic recession is expected to increase the numbers of families under financial strain.

̽��ֱ��authors acknowledge that deteriorating mental health is by no means uniform. For example, a sizeable proportion of 19,000 8-18 year olds from 237 English schools surveyed during early summer 2020 reported feeling happier, while a quarter of young people in the MHCYP survey reported that lockdown had made their life better.

And while the incidence of self-harm recorded in primary care was substantially lower than expected for 10-17 year olds in April 2020, it returned to pre-pandemic levels by September 2020, with similar patterns detected for all mental health referrals in England.

Data also show a doubling in the number of urgent referrals for eating disorders in England during 2020, despite a smaller increase in non-urgent referrals.

Professor Tamsin Ford from the Department of Psychiatry at the ̽��ֱ�� of Cambridge said: “Even before the pandemic, we were seeing deteriorating mental health among children and young people, which was amplified by inadequate service provision to support their needs. ̽��ֱ��lockdown and other measures aimed at tackling the pandemic will only serve to exacerbate these problems – and even more so for some different age groups and socioeconomic circumstances.

“Young people’s lives have been turned upside down by the pandemic, as is the case for lots of people, but their education has also been disrupted and many young people now face an uncertain future. We’re calling on policymakers to recognise the importance of education to social and mental health outcomes alongside an appropriate focus on employment and economic prospects.”

Reference
Ford, T. et al. Mental health of children and young people during pandemic. BMJ; 11 Mar 2020; DOI: 10.1136/bmj.n614

Adapted from a press release by ̽��ֱ��BMJ

Experts have issued a stark warning about the effects of the pandemic on the mental health of children and young people.

Even before the pandemic, we were seeing deteriorating mental health among children and young people, which was amplified by inadequate service provision to support their needs

Tamsin Ford

Kelly Sikkema

Boy wearing face mask

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