Category: Mental Health

Categories : Genetics Mental HealthTags :

Serious Eating Disorder ARFID is Highly Heritable

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A twin study of the relatively newly described eating disorder ARFID has found that it is strongly influenced by genetic factors. The study, perfomed by researchers at Karolinska Institutet, has been published in the journal JAMA Psychiatry.

An estimated 1 to 5% of people suffer from an eating disorder that few are even aware exists. Avoidant/restrictive food intake disorder (ARFID) is a serious eating disorder that leads to malnutrition and nutritional deficiencies, and is a relatively new diagnosis only introduced to the World Health Organization’s ICD-11 this year.

Unlike anorexia, ARFID is not about the patient’s experience of their own body and fear of gaining weight. Instead, the disease is characterised by the avoidance of certain types of food due to a sensory discomfort because of the characteristics or appearance of food, or for example, the fear of choking, a food poisoning phobia or lack of appetite.

17 000 twin pairs involved in the study 

Researchers at Karolinska Institutet have now investigated the importance of genetic factors for developing ARFID. A cohort of almost 17 000 pairs of twins in Sweden born between 1992 and 2010 participated in the study. A total of 682 children with ARFID between the ages of six and 12 years could be identified.  

The researchers used the twin method to determine the influence of genes and the environment on the onset of the disease.

“We know that identical twins share all genes and that fraternal twins share about half of their genes that make people different. When we then see that a certain trait is more common in both members of identical twin pairs than in fraternal twin pairs, it is an indication that there is a genetic influence. We can then estimate the degree to which a trait is influenced by genetic factors,” says Lisa Dinkler, a postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. 

The genetic component for developing ARFID was high, 79%.

“This study suggests that ARFID is highly heritable. The genetic component is higher than that of other eating disorders and on par with that of neuropsychiatric disorders such as autism and ADHD,” says Lisa Dinkler. 

The findings are important, says Lisa Dinkler, because an increased understanding of what causes the disease can make it easier for those affected and their relatives. 
 
“I hope that the results can reduce stigma and guilt, which is a big problem with eating disorders. A child does not choose to develop ARFID, nor can a parent cause it in a child. That is important to remember.”, says Lisa Dinkler.

Possible connections with other conditions 

The next step in Lisa Dinkler’s research is to study the extent to which ARFID is associated with other psychiatric diagnoses, such as anxiety and depression, neurodevelopmental disorders, and gastrointestinal problems.

“We will use twin studies to test the extent to which ARFID shares underlying genetic and environmental factors with these conditions,” says Lisa Dinkler.

ARFID is a relatively new diagnosis. In 2013, the disorder was included in the Diagnostic and Statistical Manual of Mental Disorders, DSM-5, and this year it was included in the World Health Organization’s diagnostic manual ICD. The latest edition, ICD-11, will be introduced to the Swedish healthcare system in a couple of years, consequently, the diagnosis is not an official part of Swedish health and medical care yet.

Source: Karolinska Institutet

Categories : Mental HealthTags :

In Anorexia, Brain Scans Show that Mindfulness Exercises Reduce Anxiety

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A team of researchers at Kyoto University’s Graduate School of Medicine has now found that mindfulness meditation does reduce anxieties associated with anorexia nervosa. Results from the study, published in BHPsych Open, show changes in the activity of brain regions involved in anxiety.

Anorexia nervosa (AN) is a severe psychiatric illness associated with intense anxieties concerning weight, shape, and self-esteem. AN is characterised by food restriction, voluntary vomiting, and extreme emaciation. Mindfulness meditation has already become a globally recognised method for addressing AN but its effectiveness in clinically treating neurogenic emaciation has not been studied yet.

The team’s mindfulness meditation program has seen a significant decrease in obsessive thoughts about test subject’s self-image and brain activity associated with related emotions.

“Our results suggest that the participants in the study became better at accepting their anxiety as it is,” says lead author Tomomi Noda.

Mindfulness and meditation work hand-in-hand. The former teaches practitioners to hone their awareness of their present experience and their ability to not judge and rather accept their circumstances. The latter is the medium by which mindfulness can be approached.

“We focused on the possibility that patients with AN try to avoid their crippling anxiety about weight gain and self-image by restricting food or vomiting,” adds co-author Masanori Isobe.

A 4-week mindfulness intervention program examined neural changes using tasks designed to induce weight-related anxiety. The researchers then regulated this anxiety by helping patients accept their current situations and experiences at face value, instead of avoiding them.

The researchers used functional magnetic resonance imaging (fMRI) to analyse attention regulation in relation to eating disorders. The study’s results support the subjective experiences of the researchers, although it was unexpected to them that several global events, such as the COVID pandemic and the Russo-Ukrainian war, were significant factors in patients’ anxieties.

“We anticipate practical implications of our results in clinical psychiatry and psychology and broader research into mitigating suffering through mindfulness, using the strategy of self-acceptance to regulate attention,” concludes group leader Toshiya Murai.

Source: Kyoto University

Categories : Mental Health PaediatricsTags :

Boys can Also be at Risk for Eating Disorders

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Depression, young man
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In the public mind, eating disorders are associated mainly with girls from wealthy backgrounds. Now, a new study on twins published in the Journal of Psychopathology and Clinical Science has found that boys living in disadvantaged circumstances are at an increased risk for disordered eating – particularly if they have underlying genetic risk factors.

“This is critical information for health care providers who might not otherwise screen for or recognize disordered eating in this population,” said Megan Mikhail, lead author of the study and Ph.D. candidate in the MSU Clinical Psychology program. “It is also important for the public to recognize that eating disorders can affect everyone, including people who do not fit the historical stereotypes.”

The study from Michigan State University, is the first to look at associations between multiple forms of disadvantage and risk for disordered eating in boys, as well as how disadvantage may interact with biological risks to impact disordered eating in boys.

Using a large population-based sample of male twins from the Michigan State University Twin Registry, the researchers found that boys from more disadvantaged backgrounds reported greater disordered eating symptoms and had earlier activation of genetic influences on disordered eating, which could lead to increased long-term risk.

By using population-based sample, the researchers could avoid overlooking those unable to afford mental health care. They examined factors such as parental income, education and neighbourhood disadvantage to see how those factors related to disordered eating symptoms in the boys. Since all the participants were twins, researchers were also able to study genetic influences on disordered eating.

“This research is particularly relevant following the COVID pandemic when many families experienced financial hardship,” said Kelly Klump, MSU Foundation Professor of Psychology and co-author of the study. “Those financial stressors are putting many young people at risk for an eating disorder, so it’s vital that there be increased screening and access to care for these young people.”

Source: Michigan State University

Categories : Mental Health PaediatricsTags :

UK Study Reveals Doubling in Antipsychotics Prescriptions for Under-18s

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A cohort study on the prescription of antipsychotics to children and adolescents in the UK has found that they have doubled over the past two decades. The findings, published in The Lancet Psychiatry, depict a concerning tendency for more, longer prescriptions of antipsychotics for a wider array of indications, many of them off-label, and which may be influenced by US and European approvals.

Studies around the world have reported an increase in the prescription of antipsychotics for children and adolescents. While this may reflect actual changing clinical needs, most antipsychotics are not approved for use in under-18s due to lacking safety data, especially in the long term. There is also little evidence on indications for, and doses of, antipsychotic prescribing in children and adolescents.

The study used a cohort of over 7 million children and adolescents (age 3–18 years) assembled from a large English primary care database, and found a doubling in the proportion of prescribed antipsychotics between 2000 and 2019.

This increase resulted from the accumulation of repeated prescriptions to the same individuals combined with an increase in new prescriptions. The researchers found that antipsychotic prescribing was more frequent for children in more deprived areas, which reflected a previous UK study on adults.

The study also revealed multiple clinical indications for antipsychotics beyond their initial approvals, most commonly for anxiety and depression. Risperidone was the most prescribed antipsychotic for all indications apart from depression, for which the most prescribed antipsychotic was quetiapine, and eating disorders, for which it was olanzapine.

Prescribing trends for certain disorders could be though to reflect prevalence. The authors noted however that “the most common indications for antipsychotics were ASD, ADHD, anxiety, and depression. It could be the increasing prevalence of these disorders that causes higher prescribing rates. However, increasing ASD prevalence results primarily from patients with less severe ASD, who are unlikely to receive antipsychotics.”

They also observed that increases in prescribing appeared to be linked to new US and European approvals.

Limitations included the database not identifying whether a prescription was for a first time, and not tying indications directly to prescriptions. Dosage regimen information was also only available for a third of prescriptions. The database was also not necessarily nationally representative, and only reflected prescriptions issued in secondary care – referral to primary care means that the rate of prescribing may be underestimated.

Categories : Mental Health NeurologyTags :

Schizophrenia Associated with 12-hour Gene Cycles in the Brain

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In the open-access journal PLOS Biology, researchers present the first evidence of 12-hour cycles of gene activity in the human brain. Led by Madeline R. Scott, the study also reveals that some of those 12-hour rhythms are missing or altered in the postmortem brains of patients with schizophrenia.

Schizophrenia patients are known to have disturbances in several types of 24-hour bodily rhythms, including sleep/wake cycles, hormone levels, and gene activity in the prefrontal cortex of the brain. However, virtually nothing is known about gene activity in the brain for cycles that are shorter than the usual 24-hour circadian rhythm. A few years ago, researchers discovered that certain genes in the body were associated with 12-hour bodily rhythms, which may have an origin in the 12-hour cycle of ocean tides.

As it is not possible to measure gene transcript levels in living brains, the new study instead used a time-of-death analysis to search for 12-hour rhythms in gene activity within postmortem brains. They focused on the dorsolateral prefrontal cortex as it is associated with cognitive symptoms and other abnormalities in gene expression rhythms that have been observed in schizophrenia.

Numerous genes in the normal dorsolateral prefrontal cortex were found to have 12-hour rhythms in activity. Among them, gene activity levels related to building connections between neurons peaked in the afternoon/night, while those related to mitochondrial function (and therefore cellular energy supply) peaked in the morning/evening.

In contrast, postmortem brains from patients with schizophrenia contained fewer genes with 12-hour activity cycles, and those related to neural connections were missing entirely. Additionally, although the mitochondria-related genes did maintain a 12-hour rhythm, their activity did not peak at the normal times. Whether these abnormal rhythms underlie the behavioural abnormalities in schizophrenia, or whether they result from medications, nicotine use, or sleep disturbances should be examined in future studies.

Co-author Colleen A. McClung adds: “We find that the human brain has not only circadian (24 hour) rhythms in gene expression but also 12-hour rhythms in a number of genes that are important for cellular function and neuronal maintenance. Many of these gene expression rhythms are lost in people with schizophrenia, and there is a dramatic shift in the timing of rhythms in mitochondrial-related transcripts which could lead to suboptimal mitochondrial function at the times of day when cellular energy is needed the most.”

Source: ScienceDaily

Categories : Mental HealthTags :

Study Explains Emotional ‘Blunting’ from SSRI Use

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Scientists have worked out why selective serotonin reuptake inhibitors (SSRIs), a common antidepressant class, cause around a half of users to feel emotionally ‘blunted’. In a study published in Neuropsychopharmacology, they show that the drugs interfere with reinforcement learning, which allows humans to adapt to their environment.

As their name implies, SSRIs target the neurotransmitter serotonin, and are commonly used to treat more resistant depression and anxiety. One of their widely-reported side effects 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. Researchers sought to address this by recruiting healthy volunteers and administering one of the best tolerated SSRIs, escitalopram, 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.

No differences were found in ‘cold’ cognition – such as attention and memory, nor any differences found 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.

The team found that the escitalopram group was less likely to use the positive and negative feedback to guide their learning of the task compared to the placebo group. This suggests that the drug affected their sensitivity to the rewards and their ability to respond accordingly.

The 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 University 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.”

Source: University of Cambridge

Categories : Mental Health Metabolic DisordersTags :

Great SCOT! Repurposing Old Antipsychotics as Diabetes Treatments

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Researchers have found that a class of older antipsychotic drugs could be a promising new therapeutic option for people with type 2 diabetes, helping fill a need among patients who aren’t able to take other currently available treatments. The drugs interact with the metabolic enzyme succinyl CoA:3-ketoacid CoA transferase (SCOT), preventing the muscles from using ketones for fuel.

“There is a growing need to find new therapies for type 2 diabetes,” says John Ussher, professor in the Faculty of Pharmacy & Pharmaceutical Sciences and lead author of the recent study published in the journal Diabetes.

Metformin is one of the most common therapeutics for type 2 diabetes, but about 15% of patients aren’t able to take it. Iinsulin secretagogues, another commonly used drug class, isn’t as effective for later-stage patients.

“For the patients who can’t take metformin, patients with late-stage diabetes where their beta cells aren’t working as well, when you’re trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms so then you have more options to try and lower blood sugar in those individuals,” Ussher explains.

The mechanism Ussher and his team turned their attention to is SCOT, which is an enzyme involved in the body’s process of making energy from ketones. Using computer modelling to find drugs that could potentially interact with SCOT, they landed on an older generation of antipsychotic drugs, a drug class called diphenylbutylpiperidines, or DPBP for short.

Ussher and his team had previously found that a specific drug within this class called pimozide could be repurposed to help treat diabetes, but they’ve since expanded their focus to see whether more of the DPBP class could also be useful for treating the disease.

“We’ve tested three drugs now, and they all interact with this enzyme,” says Ussher. “They all improve blood sugar control by preventing the muscle from burning ketones as a fuel source.”

“We believe this SCOT inhibition is the reason these antipsychotics might actually have a second life for repurposing as an anti-diabetic agent,” he adds.

Developing a drug is a complicated, time-consuming and expensive process. It involves clinical trials to test the safety and efficacy of the drug, and can easily cost hundreds of millions of dollars. Not to mention, it can take years to go from development in the laboratory to use in the clinic or hospital. Repurposing an existing drug may help fast-track the process, Ussher notes.

“With something that’s an older drug which we used historically in humans that we no longer use, we know what the adverse effects are, we know in general that it’s safe,” he says.

Though clinical trials are still needed, repurposing a drug allows researchers to focus specifically on the efficacy and safety of the new intended use, offering a quicker and cheaper path to a new therapy.

“As you already have safety data, it somewhat accelerates the process,” says Ussher. “And from an economic standpoint, often because a lot of these drugs being pursued for repurposing are older, they’re off patent and cheaper.”

Repurposing is effective because it capitalises on a main characteristic of most drugs, ie not being restricted to just one target in the body. As Ussher explains, most drugs actually have numerous targets they can influence.

“That’s where repurposing comes in,” he says. “Can we identify the other targets that a drug may interact with, and by identifying those other targets, can this drug serve a purpose for a different disease?”

This is what Ussher’s lab did in recognising the DPBP drug class could target SCOT activity as well as the dopamine receptors it targets in its original intended use to treat psychosis.

Knowledge of these original targets can also provide valuable context when refining and improving the repurposed drug. Since DPBP drugs were originally antipsychotics, many of their potential side-effects such as drowsiness, dizziness or fatigue arise from their effects on their original target: the dopamine receptors in the brain. Ussher’s lab is planning to try creating a modified version of the drug class that doesn’t reach the brain and has fewer potential adverse effects.

“For us, the excitement is that it looks like the entire family of these compounds interacts with this protein [SCOT] and can improve blood sugar control in type 2 diabetes.”

Source: University of Alberta

Categories : Mental Health NeurologyTags :

Neuroimaging can’t Identify Psychiatric Disorders – Yet

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Neuroimaging technologies hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new study published in the American Journal of Psychiatry shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).

Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.

“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.

For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at US emergency departments following traumatic events. Specifically, when researchers measured patients’ brain activity during the performance of simple tasks such as mapping responses to threats and rewards, they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.

However, when Yale researchers analysed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.

“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalise across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.

In fact, Yale researchers are currently working with the investigators of the original study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.

“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”

Source: Yale University

Categories : Mental HealthTags :

Walking the Tightrope of Prescribing Benzodiazepines

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Antidepressants and psychotherapy typically are the preferred treatment options for anxiety and depression, although benzodiazepines can be helpful in treating acute or persistent anxiety that does not respond to first-line therapy. In “Walking the Benzodiazepine High Wire,” published in Psychiatric Services, two experts advocate advocate a multipronged strategy for the cautious prescribing of this class of anxiety medications rather than a stringent and exclusively regulatory approach to their use.

Kurt Kroenke, MD, of the Regenstrief Institute and Indiana University School of Medicine, and Matthew E. Hirschtritt, MD, MPH, of Kaiser Permanente Northern California and University of California, San Francisco,

Noting that the number of benzodiazepine prescriptions in the US has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose, Dr Kroenke and Dr Hirschtritt counsel that to stem this disquieting tide, provider and patient education, coupled with prescribing surveillance, may be preferable to overly strict governmental regulation of benzodiazepines.

“Benzodiazepines should not be tried first or probably even second, but as with opiates which can be appropriate for acute pain at end of life or following a severe injury or major surgery, there are appropriate reasons for prescribing benzodiazepines for severe anxiety,” said Dr Kroenke.

He is a pioneer in the field of medical symptomology and international leader in the interpretation and treatment of psychological and physical symptoms. He has co-developed brief survey measures in worldwide clinical use to track symptoms of anxiety (GAD-7); depression (PHQ-9); suicide risk (P-4); and other conditions. These tools have been translated into more than 100 languages and assist clinicians around the world in selecting treatments and evaluating their effectiveness.

The authors conclude: “The tightrope between the benefits and risks of prescribing a medication that may be useful for some patients and harmful for others exists not only for controlled drugs but also for treatments such as antibiotics, which continue to be overprescribed, leading to antibiotic resistance. A multipronged strategy for BZD [benzodiazepine] use that includes ongoing education of providers, patients, and the general population; surveillance to optimise selective and appropriate use; and closer oversight of outlier prescribing patterns is preferable to a stringent and exclusively regulatory approach.”

Source: Regenstrief Institute

Categories : Mental HealthTags :

Even Placebos Given Openly can Reduce Feelings of Guilt

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While guilt is usually an appropriate emotional reaction, usually in response to doing something negative or hurtful, sometimes it can be unwarranted and persistent. Researchers at the University of Basel have shown that placebos can help assuage feelings of guilt, even when the placebo is administered openly, ie the participants are aware of the treatment being a placebo.

Guilt is considered an important moral emotion, as long as it is adaptive – in other words, appropriate and in proportion to the situation. “It can improve interpersonal relationships and is therefore valuable for social cohesion,” says Dilan Sezer, researcher at the Division of Clinical Psychology and Psychotherapy at the University of Basel. Previous research had demonstrated that placebos – even given openly – can still be effective in provoking a beneficial response.

In order to arouse feelings of guilt, healthy participants were recruited and asked to write about a time when they had disregarded important rules of conduct, or treated someone close to them unfairly, hurt or even harmed them. The idea was that the study participants should still feel bad about the chosen situation.

Participants were then randomised to three conditions: Participants in one group received placebo pills with being deceptively told that this was a real medication while participants in another group were told that they are given a placebo. Both groups were told that what they had been given will be effective against feelings of guilt. The control group received no treatment at all. The results, published in Scientific Reports, showed that feelings of guilt were significantly reduced in both placebo groups compared with those without medication.

This was also the case when the subjects knew they had been given a placebo.  “Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” states the study’s lead author, Dilan Sezer.

Where feelings of guilt are irrational and continue for longer periods of time, they are considered maladaptive – in other words, disproportionate. These emotions can affect people’s health and are also, among other things, a common symptom of depression.

Scientific studies have shown that placebo effects can be powerful in treating depression. But the finding that open-label placebos can also be useful for such strong emotions as guilt is new. It stands to reason, says Dilan Sezer, that we should try to harness these effects to help those affected. “The administering of open-label placebos, in particular, is a promising approach, as it preserves patient autonomy by allowing patients to be fully aware of how the intervention works.” The results of the study are an initial promising step in the direction of symptom-specific and more ethical treatments for psychological complaints using open-label placebos, Sezer continues.

Further research will need to be done into whether it is possible to treat maladaptive guilt with placebos. And it is still not known whether similar effects are also possible with other feeling states. For Dilan Sezer, one thing is certain: “Using open-label placebos would be an inexpensive and straightforward treatment option for many psychological and physical complaints.”

Source: University of Basel