Category: Mental Health

Categories : Mental Health New Compounds and TreatmentsTags :

Neurocrine’s Anticipated Schizophrenia Drug Flops in Clinical Trial

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Pharmaeceutical company Neurocrine’s anticipated schizophrenia drug, luvadaxistat, failed to have an impact on negative symptoms in a key clinical trial, but still showed promising cognitive benefits.

Neurocrine Biosciences had licensed seven of Takeda’s psychiatry drugs last year for over $2 billion. Luvadaxistat was the furthest along, having entered Phase 2 testing in 2017.

The experimental drug is supposed to help schizophrenia patients cope with “negative symptoms”—a range of difficult-to-treat conditions such as lack of motivation, trouble communicating and limited emotion. The drug is designed to block an enzyme that degrades a certain kind of amino acid important for brain function.

However, according to results from a mid-stage study, in comparison to placebo, patients treated with the drug didn’t perform significantly better, as measured by a scale that assesses the severity of negative symptoms.

While there was excitement around the science behind luvadaxistat, Wall Street analysts lost much of their optimism in the programme last month, after Concert Pharmaceuticals halted development of CTP-692, an experimental drug based on the same mechanism, after trials also saw disappointing results. 

Nevertheless, there remains a path ahead for luvadaxistat as Neurocrine is setting up to analyse the drug’s efficacy for cognitive benefits, as it appears that these results at least were in line with scientific predictions.

Source: BioPharma Dive

Categories : Mental HealthTags :

Benefits from ‘Microdosing’ Could Just Be Placebo

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People who claim they derived benefits from ‘microdosing‘, very small quantities of psychedelic drugs may simply be explained by the placebo effect, a new study has found.

The illegal nature of the drugs used for microdosing posed a problem for the study: not only did it make it unethical for researchers to obtain the drugs themselves and distribute them, but also participants knew what they were taking because they had obtained the drugs themselves. so participants mixed their own supplies of pills with a number of placebo pills, thereby blinding themselves to the trial.

Those participants taking the real psychoactive drugs and those unknowingly taking the placebos reported similar psychological benefits. “Our results are mixed: on the one hand, we observed microdosing’s benefits in a wide range of psychological measures; on the other hand, equal benefits were seen among participants taking placebos,” explained study lead author and Balázs Szigeti, Research Associate at Imperial College London.

“These findings suggest that the benefits are not due to the drug, but rather due to the placebo-like expectation effects. Many participants who reported that they experienced positive effects while taking the placebo were shocked to learn after the study that they hadn’t been taking the real drug.”

Although the results are not as reliable as a placebo-controlled study due to the black market origin of the drugs, the team cautioned, it nevertheless reflected ‘real world’ microdosing and was inexpensive.

“The successful execution of this study could inspire similar studies in a broad range of scientific or medical contexts,” said senior author David Erritzoe, Clinical Senior Lecturer in Psychiatry at Imperial College London. “Accounting for the placebo effect is important when assessing trends such as the use of cannabidiol oils, fad diets or supplements where social pressure or users’ expectations can lead to a strong placebo response. Self-blinding citizen science initiatives could be used as an inexpensive, initial screening tool before launching expensive clinical studies.”

Source: News-Medical.Net

Journal information: Szigeti, B., et al. (2021) Self-blinding citizen science to explore psychedelic microdosing. eLife. doi.org/10.7554/eLife.62878

Categories : Mental Health NeurologyTags :

Repurposed Drug Exploits Ion Channel in The Brain To Treat Depression

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Researchers from the Icahn School of Medicine at Mount Sinai Hospital have repurposed a drug to treat depression by using an ion channel that is a completely different mechanism than regular antidepressants.

A study demonstrated that a drug called ezogabine, which opens KCNQ2/3 type of potassium channels in the brain, is linked to significant improvements in depressive symptoms and anhedonia (a lack of ability to feel pleasure) in patients with depression. Anhedonia is a complex, core symptom of depression and is associated with poor outcomes such as increased risk of suicide and reduced responsiveness to antidepressants.
Ezogabine is an anticonvulsant for epilepsy treatment; this novel application in treating depression opens up the investigation of the KCNQ2/3 channel as a potential drug target.

“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment,” said Professor James Murrough, MD, PhD, at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.

The KCNQ2/3 channel belongs to the KCNQ (or Kv7) family of ion channels which are important controllers of brain cell excitability and function in the central nervous system, affecting brain cell function by controlling electrical charge flow across the cell membrane in the form of potassium (K+) ions. Previous research in mice also showed involvement of KCNQ2/3 in depression. Mice that were more resilient to stress had increased KCNQ2/3 channels in their brains.

“We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression,” said Ming-Hu-Han, PhD, who also discovered that by increasing the activity of this channel, such as by administering ezogabine, to depressed mice, the drug acted as an antidepressant.

A trial with adult human patients showed that, compared to placebo, those treated with ezogabine showed a large reduction in a number of key measures of depression severity, anhedonia, and overall illness severity.
“The fundamental insight by Dr Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Dr Murrough.

In collaboration with Dr Han, Dr Murrough carried out a series of human studies, with an initial open-label (no placebo) study in patients with depression providing initial evidence that ezogabine could improve symptoms of depression and anhedonia.

“I think it’s fair to say that most of us on the study team were quite surprised at the large size of the beneficial effect of ezogabine on clinical symptoms across multiple measures related to depression. We are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders. New treatments are urgently needed given that more than one-third of people suffering from depression are inadequately treated with currently approved therapeutics.”

Source: Eureka Alert

Categories : Mental HealthTags :

Researchers Describe Extremist ‘Psychological Signature’

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Researchers at Cambridge University have laid out a ‘psychological signature’ for extremist behaviour.
These extremist behaviours  support violence in the name of ideology, and encompass social, political or religious attitudes. The researchers say that particular behavioural traits and unconscious cognition in the brain make certain individuals more susceptible to extremist behaviour.

These mental factors include poorer working memory and slower “perceptual strategies” (the unconscious processing of changing stimuli, eg shape and colour), and also tendencies towards impulsivity and sensation seeking.

The researchers found that social conservatism is linked to slower but more accurate unconscious decision-making, whereas liberal thinking is linked to faster but less accurate ‘perceptual strategies’.
More dogmatic people are prone to impulsivity but are slower in processing perceptual evidence.
Previous approaches to identifying radicalisation and extremism involved screening individuals by age and gender. 
“I’m interested in the role that hidden cognitive functions play in sculpting ideological thinking,” said lead author Dr Leor Zmigrod, from Cambridge’s Department of Psychology.

“Many people will know those in their communities who have become radicalised or adopted increasingly extreme political views, whether on the left or right. We want to know why particular individuals are more susceptible.”
“By examining ‘hot’ emotional cognition alongside the ‘cold’ unconscious cognition of basic information processing we can see a psychological signature for those at risk of engaging with an ideology in an extreme way,” Zmigrod said.

“Subtle difficulties with complex mental processing may subconsciously push people towards extreme doctrines that provide clearer, more defined explanations of the world, making them susceptible to toxic forms of dogmatic and authoritarian ideologies.”

 Added Zmigrod: “There appear to be hidden similarities in the minds of those most willing to take extreme measures to support their ideological doctrines. Understanding this could help us to support those individuals vulnerable to extremism, and foster social understanding across ideological divides.”
This research revisited 334 participants from a previous study where participants performed 37 cognitive tasks and were assessed on 22 personality traits. They added a further 16 tests
Demographics only weakly predicted extremist behaviour. For example, dogmatism was associated with slower perceptual ‘evidence accumulation’, and lower social risk-taking and agreeableness but greater impulsivity and ethical risk-taking. Adding the psychological signatures to demographics increased the predictive power for dogmatism from 1.53% to 23.6%. 
Political conservatism and nationalism was linked to ‘caution’ in unconscious decision-making, as well as when rewards are less valuable later, and slightly reduced strategic information processing. Personality traits for conservatism and nationalism included greater goal-directedness, impulsivity and reward sensitivity, and lower social risk-taking. For these ideologies, demographics only had a predictive power of less than 8%, but including the psychological signature boosted it to 32.5%.

In all of the ideologies examined, ‘extreme pro-group action’, including violence against others, had a similar psychological signature.

Source: Medical Xpress

Journal information:Philosophical Transactions of the Royal Society B (2021). DOI: 10.1098/rstb.2020.0424

Categories : Mental HealthTags :

Video Gamers Self-report Feelings of Wellbeing

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Volunteers playing video games reported feelings of wellbeing, and video games did not appear to negatively impact players’ wellbeing, a study by the University of Oxford has found.

The researchers sought to investigate the validity of a widespread perception that playing video games may result in addiction and poor mental health. There has been extensive prior research establishing the varying cognitive benefits of playing different types of video games.

The researchers obtained online gameplay statistics from game producers Electronic Arts and Nintendo, then surveyed over 3000 players of two popular games: Animal Crossing: New Horizons and Plants vs Zombies: Battle for Neighborville. These popular games are more ‘relaxed’ than the type of intense action-themed games that often come up in discussions about video games and mental health. 

The surveys queried players on their wellbeing, their motivations and need satisfaction as they played their video games. Each of the volunteers had their gameplay time recorded by the respective game producers. On analysis, the researchers found that players reported slightly more positive responses than expected, with a slight positive correlation between gameplay time and wellbeing.

The researchers stated that the game producers’ only involvement was providing anonymised telemetry data. They also noted that they did not suggest a causal relationship between subjective wellbeing and how much time a person plays video games, only that playing video games does not seem to negatively impact the wellbeing of players.

Instead of considering the amount of time playing, the researchers suggest that the focus should be on why people play games to begin with. The researchers suggest that people who monitor the playing time of others should rather consider if the game is meeting their needs.

A recent, separate study revealed that boys with low physical activity who regularly played video games at 11 had fewer depressive symptoms three years later.

Source: Medical Xpress

Journal information: Niklas Johannes et al. Video game play is positively correlated with well-being, Royal Society Open Science (2021). DOI: 10.1098/rsos.202049

Categories : Mental Health Metabolic DisordersTags :

Why Antipsychotic Drugs Cause Weight Gain

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A University of Pittsburgh study has discovered that the reason antipsychotic medications have weight gain as side effects is because the pancreas also produces and responds to dopamine.

Dopamine is a neurotransmitter involved in mood regulation, pleasure and reward signalling. Many psychological disorders are thought to involve dopamine imbalances and are treated by medications designed to this end.
“There are dopamine theories of schizophrenia, drug addiction, depression and neurodegenerative disorders, and we are presenting a dopamine theory of metabolism,” said lead author Despoina Aslanoglou, PhD, at the University of Pittsburgh. “We’re seeing now that it is not only interesting to study dopamine in the brain, but it is equally interesting and important to study it in the periphery.”

Senior author Zachary Freyberg, MD, PhD, assistant professor of psychiatry and cell biology at Pitt, observed that the dopamine theory is not as simple or as well understood as we would like to think.

“We still don’t really understand how dopamine signals biologically,” said Dr Freyberg. “Even decades after dopamine receptors have been discovered and cloned, we still deploy this ‘magical thinking’ approach: something happens that’s good enough. We use drugs that work on dopamine receptors, but how they intersect with this ‘magical system’ is even less understood.”

The researchers found that dopamine is not only produced in the brain but also in the alpha and beta cells of the pancreas, which secrete glucagon and insulin, respectively.

Alpha cells can produce their own dopamine with no precursors in response to glucose levels, while beta cells require an L-DOPA precursor. It may be possible that alpha cells secrete dopamine for their own receptors, while also supplying it to beta cells to suppress the release of insulin.

Surprisingly, the researchers also discovered that pancreatic dopamine can affect other receptors, such as noradrenaline and adrenaline.
At low concentrations, dopamine binds to D2-like dopamine receptors, blocking the release of glucagon or insulin. At high concentrations, dopamine binds to beta-adrenergic receptors, becoming stimulatory and pushing up glucagon levels while inhibiting insulin levels by blocking alpha-adrenergic receptors.

The study revealed how blocking inhibitory dopamine receptors causes an unchecked release of insulin and glucagon, leading to metabolic disorders and eventually, obesity and diabetes. This finding will help to formulate better drugs that target the dopamine system, reducing the effect on the pancreas.

Source: News-Medical.Net

Categories : Gender Mental Health NeurologyTags :

Women are Better ‘Mind Readers’ Than Men, Study Finds

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Women are better at ‘reading minds’ than men, finds a new study aimed at better understanding social interaction and the challenges faced by people with autism. 

Sometimes known in the field of psychology as ‘mentalising‘, the process is when people try to ascertain what others are really thinking, for example when they are sarcastic or even lying. Mind-reading has some basis in neuroscience: for example, some research indicates that sensitivity to social interactions is associated with the posterior superior temporal sulcus, an area of the brain which is also known to process biological motion. Everybody has some proficiency with mind reading, and some are inherently better than others. However, some lack the ability to a point where it becomes difficult to function in society, for example in autism.

The study made use of a self-report questionnaire asking participants to rate how well, for example, they could relate to others. It used four questions, each with ratings from one to four, giving a maximum total score of 16. The researchers determined that women scored higher than men on the questionnaire, and also confirmed the challenges reported by those with autism. 

Senior author Dr Punit Shah, at the University of Bath’s Department of Psychology explained: “We will all undoubtedly have had experiences where we have felt we have not connected with other people we are talking to, where we’ve perceived that they have failed to understand us, or where things we’ve said have been taken the wrong way. Much of how we communicate relies on our understanding of what others are thinking, yet this is a surprisingly complex process that not everyone can do.”

Dr Shah emphasised that there is a different between mind-reading and empathy, saying: “Mind-reading refers to understanding what other people are thinking, whereas empathy is all about understanding what others are feeling. The difference might seem subtle but is critically important and involves very different brain networks. By focussing carefully on measuring mind-reading, without confusing it with empathy, we are confident that we have just measured mind-reading. And, when doing this, we consistently find that females reported greater mind-reading abilities than their male counterparts.”

Lead researcher, Rachel Clutterbuck, emphasised the clinical importance of the questionnaire. She said: “This new test, which takes under a minute to complete, has important utility in clinical settings. It is not always obvious if someone is experiencing difficulties understanding and responding to others—and many people have learnt techniques which can reduce the appearance of social difficulties, even though these remain.

“This work has great potential to better understand the lived experience of people with mind-reading difficulties, such as those with autism, whilst producing a precise quantitative score that may be used by clinicians to identify individuals who may benefit from interventions.”

Dr Shah added that this study was about helping to understand mind-reading capabilities, and had created a freely available questionnaire for other efforts in this regard.

Source: Medical Xpress

Journal information: Rachel A. Clutterbuck et al, Development and validation of the Four-Item Mentalising Index., Psychological Assessment (2021). DOI: 10.1037/pas0001004

Categories : Gender Mental HealthTags :

Protein ‘Flavours’ Cause Gender Difference in Psychiatric Drug Responses

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A new study has shown that different isoforms or ‘flavours’ of key proteins have different effects in males and females, causing psychiatric drugs to function well in one gender and in others to be ineffective or a have host of side effects.

“The ultimate goal is to find the kink in the armor of mental illness—the proteins in the brain that we can specifically target without impacting other organs and causing side effects,” explained Charles Hoeffer, an assistant professor of integrative physiology at the Institute for Behavioral Genetics. “Personalisation is also key. We need to stop hitting every mental illness with the same hammer.

AKT was discovered in the 1970s and known as a gene which resulted in cancer when mutation was present. It is now known to play a role in “synaptic plasticity”, where synaptic connections between neurons are strengthened to encode memories.

“Let’s say you see a shark and you’re scared and your brain wants to form a memory. You have to make new proteins to encode that memory,” explained Hoeffer.

Different isoforms have different functions in the brain; AKT1 together with AKT2 in the prefrontal cortex is important for making new memories.
“These subtle differences could be really important if you wanted to personalise treatments for people,” explained Marissa Ehringer, an associate professor of integrative physiology who partnered with Hoeffer on some of the research.

The researchers spent six years examining the brains of male and female animals, and the role the loss of AKT played. For example, male mice with functioning AKT1 were much better than those without AKT1 when it came to “extinction learning”—replacing an old memory, or association that is no longer needed. However, in female mice, not having AKT1 did not make much difference.

“We found the difference between males and females to be so great it became the focus of our work,” Hoeffer said. “It was like night and day.”

Although there is much still to be learned, Hoeffer suspects that there are many other such key proteins having different effects or purposes in males and females.  

“To help more people suffering from mental illness we need much more knowledge about the difference between male and female brains and how they could be treated differently,” Hoeffer said. “This study is an important step in that direction.”

Source:Medical Xpress
Journal information: Helen Wong et al. Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders, eLife (2020). DOI: 10.7554/eLife.56630

Categories : Mental HealthTags :

LSD Shown to Heighten Sociability in Mice

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Scientists at McGill University have discovered that mice micro-dosed with LSD have an increased level of sociability, pointing to a mechanism by which the drug can influence behaviour at these low concentrations.

Lysergic acid diethylamide (LSD) was discovered by accident while developing stimulants, and was first used to study psychotic states. There was initially great interest in and use of LSD for psychiatric treatment, but the harmful and lasting side-effects resulted in it steadily being outlawed. However, recent anecdotal evidence of individuals self-administering micro-doses of LSD to improve cognitive functioning have helped spur renewed interest in the famous drug.To investigate the ways LSD might be working on the brain, the McGill University researchers dosed mice with low levels of LSD over seven days, and observed a measurable increase in sociability.

This is useful as a main outcome of the study is a mechanism that describes the increased feelings of empathy and awareness that users of LSD describe.

Co-lead author Prof Nahum Sonenberg at McGill University, world renowned expert in the molecular biology of diseases, explained: “The fact that LSD binds the 5-HT2A receptor was previously known. The novelty of this research is to have identified that the prosocial effects of LSD activate the 5-HT2 receptors, which in-turn activate the excitatory synapses of the AMPA receptor as well as the protein complex mTORC1, which has been demonstrated to be dysregulated in diseases with social deficits such as autism spectrum disorder.

“Their next research goal is treating mutant mice with behavioural deficits mimicking human psychological pathologies, and to find out if micro-dosed LSD or some derivative could be a safe and effective therapeutic option.

“Social interaction is a fundamental characteristic of human behaviour,” noted co-lead author Dr Gabriella Gobbi, Professor in the Department of Psychiatry at McGill and psychiatrist at the McGill University Health Centre. “These hallucinogenic compounds, which, at low doses, are able to increase sociability may help to better understand the pharmacology and neurobiology of social behavior and, ultimately, to develop and discover novel and safer drugs for mental disorders.”

Source: Medical Xpress

Journal information: Danilo De Gregorio et al, Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2020705118

Categories : Addiction Mental HealthTags :

Happier Memories in Teens Linked to Less Alcohol and Marijuana Use

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A study of teenage American students has found that happy childhood memories, along with a positive view of the present and outlook for the future are associated with reduced alcohol use, binge drinking and marijuana use. 

Researchers say that action is needed because COVID restrictions have left teenagers isolated and vulnerable. Quarantining results in anxiety, stress and feelings of loneliness in children and adolescents, and the closure of schools has also taken away mental health support systems which some teenagers may rely on.

John Mark Froiland of Purdue University said: “School often seems a source of stress and anxiety to students. This puts them at greater risk of not participating in lessons, getting lower grades and of substance misuse. Many teenagers also aren’t engaging with online learning during Covid or have lower engagement levels.

“But they’re more likely to be enthusiastic learners and not use drink and drugs if teachers take time to build more positive relationships with them. They can help students see that everything they’re learning is truly valuable. Parents have a role to play too.”

The study was based on questionnaires completed by 1961 student participants in San Francisco, of which 53% were female. The researchers examined how happy the students believed their childhood was, how happy they were currently and how optimistic they were about their futures.

In addition, they looked at alcohol and marijuana use over the past 30 days and binge use, as well as academic grades, behaviour during lessons and motivation.

Positive attitudes towards the past, present and future was associated with lower alcohol use, binge drinking and marijuana use, while the reverse was true for negative attitudes.

An optimistic outlook increased the likelihood that they would be motivated and focus on learning. Other findings included drinking being associated with marijuana use, and that girls had better behavioural engagement than boys.

Source: News-Medical.Net

Journal information: Froiland, J.M., et al. (2020) Positive and negative time attitudes, intrinsic motivation, behavioral engagement and substance use among urban adolescents. Addiction Research & Theory. doi.org/10.1080/16066359.2020.1857740.