Tag: depression

Categories : Ageing Mental HealthTags :

SA Retirement Home Study Reveals the Mental Health Benefits for Residents Interacting with Children

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A small South African study published in the open-access journal PLOS ONE suggests that programmes promoting interaction between retirement home residents and children may provide quality of life improvements and could help manage residents’ anxiety and depression.

Among retirement home residents, previous research has shown that common mental health conditions often go undetected and untreated. These conditions, which include anxiety and depression, are typically treated with a combination of drugs and non-pharmacological interventions.

One intervention is the Eden Alternative, which identifies loneliness, helplessness and boredom as key challenges to overcome provide a higher quality of life. Evidence suggests that programmes that enable older adults to regularly interact with children may improve mental health, but these have mostly been done outside of retirement homes and few have looked at such programmes in South Africa.

To deepen the understanding of potential benefits of intergenerational interactions, Elizabeth Jane Earl and Debbie Marais of Stellenbosch University, South Africa, conducted a study at a retirement home in South Africa. Residents were able to regularly interact with children who attend an onsite preschool. Activities include playing games, doing puzzles, reading, or singing with the children.

Ten female residents were recruited and invited to complete a questionnaire evaluating their anxiety and depression levels, as well as asking them to describe their experiences with the children. Four of the participants were screened as possible having anxiety, depression, or both. The participants all took part in the same interactions, though to varying degrees of participation.

Generally, the participants reported positive experiences with the children. Analysing their responses, the researchers found that the interactions fostered a sense of purpose and belonging, fond reminiscences of their own childhood and a positive influence on mood and emotions. Recollections of childhood also sparked a sense of playfulness and positive self-evaluation. They noted that the participants differed in their preconceptions of children, which might have affected their experiences.

The authors wrote that, “Interactions with children promote a sense of belonging and purpose, evoke reminiscence, and positively influence the mental well-being of older persons.”

Based on their findings, Earl and Marais concluded that intergenerational interaction programmes may help manage the mental health conditions that are common for retirement home residents. They suggest that trained staff facilitate the interaction, preparing the children and residents, and should be voluntary, which helps preserve the residents’ agency. Running the interaction as a regular programme should help build bonds and give the residents something to look forward to. Additionally, there should be an educational aspect for the children, giving the residents a sense of purpose.

Looking to the future, they wrote that larger studies would be able to better outline the benefits of such programmes.

Categories : Mental Health NeurologyTags :

Neuroscientists Identify a New Subtype of Depression that Resists SSRIs

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In a new study, scientists at Stanford Medicine have described a new category of depression, the cognitive biotype, which accounts for 27% of depressed patients and is not effectively treated by commonly prescribed antidepressants. The findings were reported in JAMA Network.

For these patients, cognitive tasks showed difficulty in planning ahead, self-control, sustaining focus despite distractions and suppressing inappropriate behaviour; imaging showed decreased activity in two brain regions responsible for those tasks.

Because depression has traditionally been defined as a mood disorder, doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs), but these are less effective for patients with cognitive dysfunction. Researchers said that targeting these cognitive dysfunctions with less commonly used antidepressants or other treatments may alleviate symptoms and help restore social and occupational abilities.

The study is part of a broader effort by neuroscientists to find treatments that target depression biotypes, according to the study’s senior author, Leanne Williams, PhD, professor of psychiatry and behavioural sciences.

“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” Williams said. “Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”

Finding the biotype

In the study, 1008 adults with previously unmedicated major depressive disorder were randomly given one of three widely prescribed typical antidepressants: escitalopram (Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. Seven hundred and twelve of the participants completed the eight-week regimen.

Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured using two surveys – one, clinician-administered, and the other, a self-assessment, which included questions related to changes in sleep and eating. Measures on social and occupational functioning, as well as quality of life, were tracked as well.

The participants also completed a series of cognitive tests, before and after treatment, measuring verbal memory, working memory, decision speed and sustained attention, among other tasks.

Before treatment, scientists scanned 96 of the participants using functional magnetic resonance imaging as they engaged in a task called the “GoNoGo” that requires participants to press a button as quickly as possible when they see “Go” in green and to not press when they see “NoGo” in red. The fMRI tracked neuronal activity by measuring changes in blood oxygen levels, which showed levels of activity in different brain regions corresponding to Go or NoGo responses. Researchers then compared the participants’ images with those of individuals without depression.

The researchers found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioural tests, as well as reduced activity in certain frontal brain regions – a profile they labelled the ‘cognitive biotype’.

“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions,” said Laura Hack, MD, PhD, the lead author of the study and an assistant professor of psychiatry and behavioural sciences. “It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”

Pre-treatment fMRI showed those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared with the activity levels in participants who did not have the cognitive biotype. Together, the two regions form the cognitive control circuit, which is responsible for limiting unwanted or irrelevant thoughts and responses and improving goal selection, among other tasks.

After treatment, the researchers found that for the three antidepressants administered, the overall remission rates were 38.8% for participants with the newly discovered biotype and 47.7% for those without it. This difference was most prominent for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.

“Depression presents in different ways in different people, but finding commonalities – like similar profiles of brain function – helps medical professionals effectively treat participants by individualising care,” Williams said.

Depression isn’t one size fits all

Williams and Hack propose that behaviour measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient could complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they might be referred to imaging for confirmation before undergoing treatment.

Researchers under Williams and Hack are studying another drug, guanfacine, that specifically targets the dorsolateral prefrontal cortex region. They believe this treatment could be more effective for patients with the cognitive subtype.

Williams and Hack hope to conduct studies with participants who have the cognitive biotype, comparing different types of medication with treatments such as transcranial magnetic stimulation (TMS) and cognitive behavioural therapy.

“I regularly witness the suffering, the loss of hope and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”

Source: Stanford Medicine

Categories : Mental Health NeurologyTags :

Brain Transmission Speeds Increase Until Middle Age

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It has been believed speed of information transmitted among regions of the brain stabilised during early adolescence. A study in Nature Neuroscience has instead found that transmission speeds continue to increase into early adulthood, which may explain the emergence of mental health problems over this period. In fact, transmission speeds increase until around age 40, reaching a speed twice that of a 4-year old child.

As mental health problems such as anxiety, depression and bipolar disorders can emerge in late adolescence and early adulthood, a better understanding of brain development may lead to new treatments.

“A fundamental understanding of the developmental trajectory of brain circuitry may help identify sensitive periods of development when doctors could offer therapies to their patients,” says senior author Dora Hermes, PhD, a biomedical engineer at Mayo Clinic.

Called the human connectome, the structural system of neural pathways in the brain or nervous system develops as people age. But how structural changes affect the speed of neuronal signalling has not been well described.

“Just as transit time for a truck would depend on the structure of the road, so does the transmission speed of signals among brain areas depend on the structure of neural pathways,” Dr Hermes explains. “The human connectome matures during development and aging, and can be affected by disease. All these processes may affect the speed of information flow in the brain.” In the study, Dr Hermes and colleagues stimulated pairs of electrodes with a brief electrical pulse to measure the time it took signals to travel among brain regions in 74 research participants between the ages of 4 and 51. The intracranial measurements were done in a small population of patients who had electrodes implanted for epilepsy monitoring at University Medical Center Utrecht, Netherlands.

The response delays in connected brain regions showed that transmission speeds in the human brain increase throughout childhood and even into early adulthood. They plateau around 30 to 40 years of age.

The team’s data indicate that adult transmission speeds were about two times faster compared to those typically found in children. Transmission speeds also were typically faster in 30- or 40-year-old subjects compared to teenagers.

Brain transmission speed is measured in milliseconds, a unit of time equal to one-thousandth of a second. For example, the researchers measured the neuronal speed of a 4-year-old patient at 45 milliseconds for a signal to travel from the frontal to parietal regions of the brain. In a 38-year-old patient, the same pathway was measured at 20 milliseconds. For comparison, the blink of an eye takes about 100 to 400 milliseconds.

The researchers are working to characterise electrical stimulation-driven connectivity in the human brain. One of the next steps is to better understand how transmission speeds change with neurological diseases. They are collaborating with paediatric neurosurgeons and neurologists to understand how diseases change transmission speeds compared to what would be considered within the normal range for a certain age group.

Source: Mayo Clinic

Categories : Mental Health New Compounds and TreatmentsTags :

Scientists Create Antidepressant Drug Candidates from Traditional African Plant Medicine

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Scientists have developed two new drug candidates for potentially treating addiction and depression, modelled on the pharmacology of a traditional African psychedelic plant medicine called ibogaine. At very low doses, these new compounds were able to blunt symptoms of both conditions in mice.

The study, published in Cell, took inspiration from ibogaine’s impact on the serotonin transporter (SERT), which is also the target of selective serotonin reuptake inhibitor (SSRI) drugs, such as fluoxetine. A team of scientists from UC San Francisco and Yale and Duke universities virtually screened 200 million molecular structures to find ones that blocked SERT in the same way as ibogaine.

“Some people swear by ibogaine for treating addiction, but it isn’t a very good drug. It has bad side effects, and it’s not approved for use in the US,” said Brian Shoichet, PhD, co-senior author and professor in the UCSF School of Pharmacy. “Our compounds mimic just one of ibogaine’s many pharmacological effects, and still replicate its most desirable effects on behaviour, at least in mice.”

Dozens of scientists from the laboratories of Shoichet, Allan Basbaum, PhD, and Aashish Manglik, MD, PhD, (UCSF); Gary Rudnick, PhD, (Yale); and Bill Wetsel, PhD, (Duke) helped demonstrate the real-world promise of these novel molecules, which were initially identified using Shoichet’s computational docking methods.

Docking involves systematically testing virtual chemical structures for binding with a protein, enabling scientists to identify new drug leads without having to synthesise them in the lab. “This kind of project begins with visualizing what kinds of molecules will fit into a protein, docking the library, optimising and then relying on a team to show the molecules work,” said Isha Singh, PhD, a co-first author of the paper who did the work as a postdoc in Shoichet’s lab. “Now we know there’s a lot of untapped therapeutic potential in targeting SERT.”

Optimising a shaman’s cure

Ibogaine is found in the roots of the iboga plant, which is native to central Africa, and has been used for millennia during shamanistic rituals. In the 19th and 20th centuries, doctors in Europe and the US experimented with its use in treating a variety of ailments, but the drug never gained widespread acceptance and was ultimately made illegal in many countries.

Part of the problem, Shoichet explained, is that ibogaine interferes with many aspects of human biology.

“Ibogaine binds to hERG, which can cause heart arrhythmias, and from a scientific standpoint, it’s a ‘dirty’ drug, binding to lots of targets beyond SERT,” Shoichet said. “Before this experiment, we didn’t even know if the benefits of ibogaine came from its binding to SERT.”

Shoichet, who has used docking on brain receptors to identify drugs to treat depression and pain, became interested in SERT and ibogaine after Rudnick, an expert on SERT at Yale, spent a sabbatical in his lab. Singh picked up the project in 2018, hoping to turn the buzz around ibogaine into a better understanding of SERT.

It was the Shoichet lab’s first docking experiment on a transporter – a protein that moves molecules into and out of cells – rather than a receptor. One round of docking whittled the virtual library from 200 million to just 49 molecules, 36 of which could be synthesised. Rudnick’s lab tested them and found that 13 inhibited SERT.

The team then held virtual-reality-guided “docking parties,” to help Singh prioritise five molecules for optimization. The two most potent SERT inhibitors were shared with Basbaum and Wetsel’s teams for rigorous testing on animal models of addiction, depression and anxiety.

“All of a sudden, they popped – that’s when these drugs looked a lot more potent than even paroxetine [Paxil],” Shoichet said.

Manglik, an expert with cryo-electron microscopy (cryo-EM), confirmed that one of the two drugs, dubbed ‘8090,’ fit into SERT at the atomic level in a way that closely resembled Singh and Shoichet’s computational predictions. The drugs inhibited SERT in a similar way to ibogaine, but unlike the psychedelic, their effect was potent and selective, with no spillover impacts on a panel of hundreds of other receptors and transporters.

“With this sort of potency, we hope to have a better therapeutic window without side effects,” Basbaum said. “Dropping the dose almost 200-fold could make a big difference for patients.”

Source: University of California – San Francisco

Categories : Mental Health NeurologyTags :

Improper ‘Pruning’ of Brain Connections may Cause Teen Mental Health Disorders

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Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published in Nature Medicine.

The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.

One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.

Many mental health problems emerge during adolescence, such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”

In the study, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.

The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity – in other words, how different regions of the brain communicate with each other.

Adolescents who experienced mental health problems – regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders – showed similar patterns of brain activity. These patterns – the NP factor – were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.

The researchers confirmed their findings by replicating them in 1799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.

When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections – synapses – are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.

Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.

“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”

The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.

Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”

Source: University of Cambridge

Categories : Gender Mental HealthTags :

Researchers Tie Sex-specific Genes to Depression

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Depression is widely reported to be more common in women than in men, with women twice as likely to receive a diagnosis than men. A new study published in Nature has found that there are differences between male and female genes and how they relate to depression.

In a genome-wide association(GWA} study, the McGill University researchers analysed the genomes of more than 270 000 individuals. They found that sex-specific prediction methods were more accurate in forecasting an individual’s genetic risk of developing depression than prediction methods that did not specify sex. The researchers found 11 areas of DNA that were linked to depression in females, and only one area in males.

In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies; however, correlations with educational attainment and metabolic features including body fat, waist circumference, waist-to-hip ratio and triglycerides were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in the males.

Despite the biological processes involved in depression being similar in males and females, researchers found that different genes were involved for each sex. This information can be useful to identify future sex-specific treatments for depression.  “This is the first study to describe sex-specific genetic variants associated with depression, which is a very prevalent disease in both males and females. These findings are important to inform the development of specific therapies that will benefit both men and women while accounting for their differences,” says Dr Patricia Pelufo Silveira, lead author and Associate Professor in the Department of Psychiatry. “In the clinic, the presentation of depression is very different for men and women, as well as their response to treatment, but we have very little understanding of why this happens at the moment.”

Source: McGill University

Categories : Mental HealthTags :

Exercise for Managing Depression has Greater Efficacy than Meds or Counselling

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University of South Australia researchers are calling for exercise to be a mainstay approach for managing depression as a new study shows that physical activity is 1.5 times more effective than counselling or the leading medications.

Published in the British Journal of Sports Medicine, the review is the most comprehensive to date, encompassing 97 reviews, 1039 trials and 128 119 participants. It shows that physical activity is extremely beneficial for improving symptoms of depression, anxiety, and distress.

Specifically, the review showed that exercise interventions that were 12 weeks or shorter were the most effective at reducing mental health symptoms, highlighting the speed at which physical activity can make a change.

The largest benefits were seen among people with depression, pregnant and postpartum women, healthy individuals, and people diagnosed with HIV or kidney disease.

According to the World Health Organization, one in every eight people worldwide (970 million people) live with a mental disorder. 

Lead UniSA researcher, Dr Ben Singh, says physical activity must be prioritised to better manage the growing cases of mental health conditions.

“Physical activity is known to help improve mental health. Yet despite the evidence, it has not been widely adopted as a first-choice treatment,” Dr Singh says.

“Our review shows that physical activity interventions can significantly reduce symptoms of depression and anxiety in all clinical populations, with some groups showing even greater signs of improvement.

“Higher intensity exercise had greater improvements for depression and anxiety, while longer durations had smaller effects when compared to short and mid-duration bursts.

“We also found that all types of physical activity and exercise were beneficial, including aerobic exercise such as walking, resistance training, Pilates, and yoga.

“Importantly, the research shows that it doesn’t take much for exercise to make a positive change to your mental health.”

Senior researcher, UniSA’s Prof Carol Maher, says the study is the first to evaluate the effects of all types of physical activity on depression, anxiety, and psychological distress in all adult populations.

“Examining these studies as a whole is an effective way for clinicians to easily understand the body of evidence that supports physical activity in managing mental health disorders.

“We hope this review will underscore the need for physical activity, including structured exercise interventions, as a mainstay approach for managing depression and anxiety.”

Source: University of South Australia

Categories : Mental Health Obstetrics & GynaecologyTags :

During Pregnancy, Experiencing Racism Worsens Depression

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In a recent study published in The Journal of Advanced Nursing that included pregnant Black women from multiple US states, feeling upset by experiences of racism in the 12 months prior to delivery was associated with significantly higher odds of depression during pregnancy.

Perinatal depression is defined as major or minor depressive episodes that occur during pregnancy or in the first 12 months after birth. Mothers with perinatal depression often report symptoms including depressed mood; loss of interest or pleasure in daily activities; changes in weight, appetite and sleep; poor concentration; feelings of hopelessness; and suicidal ideations. Non-Hispanic Black women are twice as likely to experience symptoms of depression and suicidal ideations during the perinatal period than White women.

For this study, 7328 women answered survey questions. The findings showed that 11.4% of respondents reported feeling upset due to experiences of racism, and 11.4% reported experiencing depression during pregnancy. After adjusting for confounding factors, respondents who reported feeling upset due to the experience of racism had over two-fold higher odds of experiencing depression during pregnancy compared with respondents who did not report feeling upset due to the experience of racism.

“Our findings reinforce the importance of respectful maternity care, given the mental health impacts of experiences of racism during the perinatal period,” the authors wrote. “Racism is a powerful structural determinant of health with roots in a historical system of oppression that persists today in health care practices and policies. Perinatal health care providers, in collaboration with public health and other health disciplines, are ideally positioned to address inequities in maternal and child health that are rooted in racism.”

Source: Wiley

Categories : Mental Health NeurologyTags :

Why do People Remember Emotional Events Better?

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Most people remember emotional events, like their wedding day, very clearly, but researchers are not sure how the human brain prioritises emotional events in memory. In a study published in Nature Human Behaviour, Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, and his team identified a specific neural mechanism in the human brain that tags information with emotional associations for enhanced memory.

The team demonstrated that high-frequency brain waves in the amygdala, a hub for emotional processes, and the hippocampus, a hub for memory processes, are critical to enhancing memory for emotional stimuli. Disruptions to this neural mechanism, brought on either by electrical brain stimulation or depression, impair memory specifically for emotional stimuli.

Rising prevalence of memory disorders

The rising prevalence of memory disorders such as dementia has highlighted the damaging effects that memory loss has on individuals and society. Disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD) can also feature imbalanced memory processes, especially with the COVID pandemic. Understanding how the brain naturally regulates what information gets prioritised for storage and what fades away could provide critical insight for developing new therapeutic approaches to strengthening memory for those at risk of memory loss, or for normalising memory processes in those at risk of dysregulation.

“It’s easier to remember emotional events, like the birth of your child, than other events from around the same time,” says Salman E. Qasim, lead author of the study, who started this project during his PhD in Jacobs’ lab at Columbia Engineering. “The brain clearly has a natural mechanism for strengthening certain memories, and we wanted to identify it.”

The difficulty of studying neural mechanisms in humans

Most investigations into neural mechanisms take place in animals such as rats, because such studies require direct access to the brain to record brain activity and perform experiments that demonstrate causality, such as careful disruption of neural circuits. But it is difficult to observe or characterise a complex cognitive phenomenon like emotional memory enhancement in animal studies.

To study this process directly in humans. Qasim and Jacobs analysed data from memory experiments conducted with epilepsy patients undergoing direct, intracranial brain recording for seizure localisation and treatment. During these recordings, epilepsy patients memorised lists of words while the electrodes placed in their hippocampus and amygdala recorded the brain’s electrical activity.

Studying brain-wave patterns of emotional words

Qasim found that participants remembered more emotionally rated words, such as “dog” or “knife,” better than more neutral words, such as “chair.” Whenever participants successfully remembered emotional words, high-frequency neural activity (30-128 Hz) would become more prevalent in the amygdala-hippocampal circuit, a pattern which was absent when participants remembered more neutral words, or failed to remember a word altogether. Analysing 147 participant, they found a clear link between participants’ enhanced memory for emotional words and the prevalence in their brains of high-frequency brain waves across the amygdala-hippocampal circuit.

“Finding this pattern of brain activity linking emotions and memory was very exciting to us, because prior research has shown how important high-frequency activity in the hippocampus is to non-emotional memory,” said Jacobs. “It immediately cued us to think about the more general, causal implications – if we elicit high-frequency activity in this circuit, using therapeutic interventions, will we be able to strengthen memories at will?”

Electrical stimulation disrupts memory for emotional words

In order to establish whether this high-frequency activity actually reflected a causal mechanism, Jacobs and his team formulated a unique approach to replicate the kind of experimental disruptions typically reserved for animal research. First, they analysed a subset of these patients who had performed the memory task while direct electrical stimulation was applied to the hippocampus for half of the words that participants had to memorise. They found that electrical stimulation, which has a mixed history of either benefiting or diminishing memory depending on its usage, clearly and consistently impaired memory specifically for emotional words.

Uma Mohan, another PhD student in Jacobs’ lab at the time and co-author on the paper, noted that this stimulation also diminished high-frequency activity in the hippocampus. This provided causal evidence that, by knocking out the brain activity pattern correlating with emotional memory, stimulation was also selectively diminishing emotional memory.

Depression acts similarly to brain stimulation

Qasim further hypothesized that depression, which can involve dysregulated emotional memory, might act similarly to brain stimulation. He analyzed patients’ emotional memory in parallel with mood assessments the patients took to characterize their psychiatric state. And, in fact, in the subset of patients with depression, the team observed a concurrent decrease in emotion-mediated memory and high-frequency activity in the hippocampus and amygdala.

“By combining stimulation, recording, and psychometric assessment, they were able to demonstrate causality to a degree that you don’t always see in studies with human brain recordings,” said Bradley Lega, a neurosurgeon and scientist at the University of Texas Southwestern Medical Center and not an author on the paper. “We know high-frequency activity is associated with neuronal firing, so these findings open new avenues of research in humans and animals about how certain stimuli engage neurons in memory circuits.”

Next steps

Qasim is now investigating how individual neurons in the human brain fire during emotional memory processes. Qasim and Jacobs hope that their work might also inspire animal research exploring how this high-frequency activity is linked to norepinephrine, a neurotransmitter linked to attentional processes that they theorise might be behind the enhanced memory for emotional stimuli. They also hope that future research will target high-frequency activity in the amygdala-hippocampal circuit to protect memory.

“Our emotional memories are one of the most critical aspects of the human experience, informing everything from our decisions to our entire personality,” Qasim added. “Any steps we can take to mitigate their loss in memory disorders or prevent their hijacking in psychiatric disorders is hugely exciting.”

Source: Columbia University School of Engineering and Applied Science.

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