Category: Mental Health

Why Depression Treatments May Have Different Efficacy for Women

Woman with depression
Photo by Sydney Sims on Unsplash

It is not clear why women experience higher rates of depression than men, complicating treatments that are already prone to failure. Research exploring the reasons behind this found a difference in a part of the brain associated with motivation, social interactions and reward. The researchers’ findings were published in the journal Biological Psychiatry.

The study set out to understand how a specific part of the brain, the nucleus accumbens, is affected during depression. The nucleus accumbens is important for motivation, response to rewarding experiences and social interactions – all of which are affected by depression.

Brain drawing
The nucleus accumbens (represented in blue) is a part of the brain that controls motivation. Researchers from UC Davis compared samples of the nucleus accumbens in mice and humans to find clues to how this part of the brain is affected by stress and depression in males and females.

Previous analyses within the nucleus accumbens showed that different genes were turned on or off in women, but not in men diagnosed with depression. These changes could have caused symptoms of depression, or alternatively, the experience of being depressed could have changed the brain. To differentiate between these possibilities, the researchers studied mice that had experienced negative social interactions, which induce stronger depression-related behavior in females than males.

“These high-throughput analyses are very informative for understanding long-lasting effects of stress on the brain. In our rodent model, negative social interactions changed gene expression patterns in female mice that mirrored patterns observed in women with depression,” said study leader Alexia Williams, a doctoral researcher. “This is exciting because women are understudied in this field, and this finding allowed me to focus my attention on the relevance of these data for women’s health.”

After identifying similar molecular changes in the brains of mice and humans, researchers chose one gene, regulator of g protein signaling-2, or Rgs2, to manipulate. This gene controls the expression of a protein that regulates neurotransmitter receptors that are targeted by antidepressant medications such as Prozac and Zoloft. “In humans, less stable versions of the Rgs2 protein are associated with increased risk of depression, so we were curious to see whether increasing Rgs2 in the nucleus accumbens could reduce depression-related behaviorus,” said Professor Brian Trainor, senior author on the study.

When the researchers experimentally increased Rgs2 protein in the nucleus accumbens of the mice, they effectively reversed the effects of stress on these female mice, noting that social approach and preferences for preferred foods increased to levels observed in females that did not experience any stress.

“These results highlight a molecular mechanism contributing to the lack of motivation often observed in depressed patients. Reduced function of proteins like Rgs2 may contribute to symptoms that are difficult to treat in those struggling with mental illnesses,” Williams said.

Findings from basic science studies such as this one may guide the development of pharmacotherapies to effectively treat individuals suffering from depression, the researchers said.

“Our hope is that by doing studies such as these, which focus on elucidating mechanisms of specific symptoms of complex mental illnesses, we will bring science one step closer to developing new treatments for those in need,” said Williams.

Source: UC Davis

Migraine Drug Could be Beneficial for Weight Loss

Obesity
Image source: Pixabay CC0

The commonly prescribed triptans, a class of migraine drugs, may be useful in treating obesity, a new study published in Journal of Experimental Medicine suggests. In studies on obese mice, a daily dose of a triptan caused them to eat less food and lose weight over the course of a month.

“We’ve shown that there is real potential to repurpose these drugs, which are already known to be safe, for appetite suppression and weight loss,” said study leader Chen Liu, PhD.

Serotonin has long been known to play a key role in appetite. However, there are 15 different serotonin receptors. Researchers have struggled to understand the role of each serotonin receptor in appetite, and previous drugs, including fen-phen and lorcaserin, that targeted certain individual receptors have been withdrawn from the market due to side effects.

Triptans, which are used to treat acute migraines and cluster headaches, work by targeting a different receptor — the serotonin 1B receptor (Htr1b) — that had not previously been well studied in the context of appetite and weight loss, said Dr Liu.

For the new study, the researchers tested six prescription triptans in obese mice that were fed a high-fat diet for seven weeks. Mice fed two of these drugs ate about the same amount, but mice fed the other four ate less. After 24 days, mice given a daily dose of the drug frovatriptan lost, on average, 3.6% of their body weight, while mice not given a triptan gained an average of 5.1% of their body weight. The researchers saw similar results when they implanted devices into the animals that gave them a steady dose of frovatriptan for 24 days.

“We found that these drugs, and one in particular, can lower body weight and improve glucose metabolism in less than a month, which is pretty impressive,” said Dr Liu.

Since triptans are generally prescribed for short-term use during migraines, Dr Liu suspects that patients would not have noticed the longer-term impacts on appetite and weight in the past.

To determine exactly how frovatriptan impacts food intake and weight, the researchers engineered mice to lack either Htr1b or Htr2c, the serotonin receptor targeted by fen-phen and lorcaserin. In mice without Htr1b, frovatriptan no longer could decrease appetite or cause weight loss, while cutting out Htr2c had no effect. This confirmed that the drug worked by targeting the serotonin 1B receptor.

“This finding could be important for drug development,” said Dr Liu. “We not only shed light on the potential to repurpose existing triptans but also brought attention to Htr1b as a candidate to treat obesity and regulate food intake.”

Source: UT Southwestern Medical Center

Forced Retirement a Major Factor in Physician Suicides

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Forced retirement is a major factor when it comes to physician suicides, according to a study by Dr Kristin Kim and colleagues. Physicians also neglect to discuss physical health concerns as work stressors, the authors noted, but these are still detrimental to wellbeing – especially when it renders physicians unable to work.

The study was published in the journal Suicide and Life-Threatening Behavior.

“Medicine must dispel the myth of never-ill physicians who place the needs of their patients before their own to the detriment of their own health.”

Kim et al., 2022

While physicians are known to be more likely than non-physicians to experience work-related stressors prior to suicide, the specific nature of these stressors was not known. The present study therefore aimed to better characterise job-related problems prior to physician suicide.

Using a mixed methods approach, researchers combined thematic analysis and natural language processing to develop themes representing death investigation narratives of 200 physician suicides with implicated job problems in the National Violent Death Reporting System database between 2003 and 2018.

The thematic analysis identified six overarching themes: incapacity to work due to deterioration of physical health, substance use jeopardising employment, interaction between mental health and work-related issues, relationship conflict affecting work, legal problems leading to work-related stress, and increased financial stress. Natural language processing analysis confirmed five of these themes and elucidated important subthemes.

Clinicians often neglect physical health when identifying work stressors, but poor physical health affects work performance and increases work stress, the authors said, noting that legal and psychological supports, particularly during malpractice investigations and “fit for duty” evaluations, are sorely needed.

“Medicine must dispel the myth of never-ill physicians who place the needs of their patients before their own to the detriment of their own health,” the researchers wrote.

First author Kristen Kim, MD, told Medpage Today that she hopes that this research will help physicians “give ourselves permission to attend to those needs … to prevent the dire consequences that we may see.”

The findings highlight the importance of bolstering systemic support for physicians experiencing job problems associated with their physical and mental health, substance use, relationships, legal matters, and finances in suicide prevention efforts.

The Mental Health Benefits of Going on Holiday

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For better mental health, music and other forms of relaxation have been shown to have positive benefits. Now, researchers have identified a previously overlooked way to improve mental health – going on holiday, a luxury many have abandoned since COVID.

In a new cross-disciplinary paper, researchers from Edith Cowan University (ECU) propose that we view tourism, as not just as a recreational experience but as an industry that can provide real health benefits.

The interdisciplinary collaboration found that many aspects of going on holiday could have a positive impact on those with mental health issues or conditions.

Led by researcher Dr Jun Wen, a diverse team of tourism, public health and marketing experts investigated how tourism could benefit those living with dementia.

“Medical experts can recommend dementia treatments such as music therapy, exercise, cognitive stimulation, reminiscence therapy, sensory stimulation and adaptations to a patient’s mealtimes and environment,” Dr Wen said.

“These are all also often found when on holidays. This research is among the first to conceptually discuss how these tourism experiences could potentially work as dementia interventions.”

According to Dr Wen, the varied nature of tourism meant there were many opportunities to incorporate treatments for conditions such as dementia. Being in new environments and having new experiences could provide cognitive and sensory stimulation, for example.

“Exercise has been linked to mental wellbeing and travelling often involves enhanced physical activity, such as more walking,” Dr Wen said.

“Mealtimes are often different on holiday: they’re usually more social affairs with multiple people and family-style meals have been found to positively influence dementia patients’ eating behaviour.

“And then there’s the basics like fresh air and sunshine increasing vitamin D and serotonin levels. Everything that comes together to represent a holistic tourism experience, makes it easy to see how patients with dementia may benefit from tourism as an intervention.”

Dr Wen said COVID’s impact on travel in recent years had raised questions about tourism’s value beyond lifestyle and economic factors.

“Tourism has been found to boost physical and psychological wellbeing,” he said. So, after COVID, it’s a good time to identify tourism’s place in public health — and not just for healthy tourists, but vulnerable groups.”

Dr Wen said he hoped that new research could begin to examine how tourism can enhance the lives of people with various conditions.

“We’re trying to do something new in bridging tourism and health science,” he said. “There will have to be more empirical research and evidence to see if tourism can become one of the medical interventions for different diseases like dementia or depression.

“So, tourism is not just about travelling and having fun; we need to rethink the role tourism plays in modern society.”

The article ‘Tourism as a dementia treatment based on positive psychology’ was published in Tourism Management.

Source: Edith Cowan University

ECT Particularly Effective in Treating Severe Mania

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Most patients with mania responded to electroconvulsive therapy (ECT), according to a Swedish study published in JAMA Network Open. Patients with more severe illness were also far more likely to respond to treatment, the study’s researchers found.

The study recruited 571 individuals who were in a manic episode treated with ECT, 482 (84.4%) responded. Of these, 28% of these patients were able to achieve remission of mania, the researchers found. ECT treatments were mostly given three times a week.

The patient group was 63% female, with a median age of 46. Most had mania with psychotic symptoms, and roughly a quarter were voluntarily admitted to the hospital, while 60% were involuntarily committed. About 45% had been exposed to prior ECT.

“These findings suggest that ECT may be a highly effective option for treating mania, which is in line with the literature reporting response rates of 56% to 100%,” the authors noted.

The severity of illness was associated with an increased chance of responding to ECT; 83% for markedly ill, 84% for severely ill, and 92% for extremely ill patients. Illness severity was graded according to Clinical Global Impression Improvement scale (CGI-I) score.

Additionally, patients who underwent more ECT treatments in an index series were significantly more likely to have a clinical response, with the greatest odds of response being among patients who received more than 9 treatments.

Clinical factors reducing a patient’s odds of responding to ECT included comorbid anxiety and comorbid obsessive compulsive disorder.

Factors not associated with a clinical response to ECT were age of mania onset, as well as psychopharmacotherapy before index admission, including lithium, lamotrigine, a first or second generation antipsychotic, valproate, benzodiazepine, antidepressant, anxiolytic, or a central stimulant.

“It is worth highlighting that 63% of patients in our study were treated with 1 or more antimanic agents before admission, suggesting that these treatments may not have been sufficient in reducing symptoms of mania,” the group noted.

Source: MedPage Today

Changes in Brain Structures Found in Patients with Anorexia Nervosa

Anorexia photo created by freepik – www.freepik.com

A major study published in the journal Biological Psychiatry has revealed key differences in brain structure between people with and without anorexia nervosa.

Anorexia nervosa is an eating disorder defined by restriction of energy intake relative to requirements, leading to a significantly low body weight. Patients will have an intense fear of gaining weight and distorted body image and are unable to recognise the seriousness of their significantly low body weight.

Little is known about why some people develop anorexia whilst others do not, although biological factors are widely recognised. The findings from the study, which was coordinated by neuroscientists at the University of Bath with international partners, draws on extensive analyses of brain scans taken from patients around the world and goes some way to answering the question.

They reveal that people with anorexia demonstrate ‘sizeable reductions’ in three critical measures of the brain: cortical thickness, subcortical volumes and cortical surface area. Brain size reductions are significant due the implied loss of brain cells or the connections between them.

The results are some of the clearest yet to show links between structural changes in the brain and eating disorders. The team says that the effect sizes in their study for anorexia are in fact the largest of any psychiatric disorder investigated to date.

This means that people with anorexia showed reductions in brain size and shape two to four times greater than people with conditions such as depression, ADHD, or OCD. The changes observed in brain size for anorexia may be attributable to reductions in body mass index (BMI).

The team emphasised the importance of early treatment to help people with anorexia avoid long-term, structural brain changes. Existing treatment typically involves forms of cognitive behavioural therapy and, critically, weight gain. Many people with anorexia are successfully treated and these results show the positive impact such treatment has on brain structure.

Their study pooled nearly 2000 pre-existing brain scans for people with anorexia, including people in recovery and ‘healthy controls’ (people neither with anorexia nor in recovery). For people in recovery from anorexia, the study found that reductions in brain structure were less severe, suggesting that, with appropriate early treatment and support, brain self-repair is possible.

Lead researcher, Dr Esther Walton of the Department of Psychology at the University of Bath explained: “For this study, we worked intensively over several years with research teams across the world. Being able to combine thousands of brain scans from people with anorexia allowed us to study the brain changes that might characterise this disorder in much greater detail.

“We found that the large reductions in brain structure, which we observed in patients, were less noticeable in patients already on the path to recovery. This is a good sign, because it indicates that these changes might not be permanent. With the right treatment, the brain might be able to bounce back.”

“The international scale of this work is extraordinary,” said Paul Thompson, a professor of neurology and lead scientist for the ENIGMA Consortium, an international effort to understand the link between brain structure, function and mental health. “Scientists from 22 centres worldwide pooled their brain scans to create the most detailed picture to date of how anorexia affects the brain. The brain changes in anorexia were more severe than in other any psychiatric condition we have studied. Effects of treatments and interventions can now be evaluated, using these new brain maps as a reference.”

He added: “This study is novel in term of the thousands of brain scans analysed, revealing that anorexia affects the brain more profoundly than any other psychiatric condition. This really is a wake-up call, showing the need for early interventions for people with eating disorders.”

Source: University of Bath

Autoimmune Clue in Some Schizophrenia Cases

Mirror symbolising schizophrenia
Source: Vince Fleming on Unsplash

Schizophrenia, which affects how people interact with reality, is difficult to treat because it has many possible causes. In a study published in Cell Reports Medicine, Japanese researchers have identified an autoantibody – an antibody which attacks the body’s own tissues – in some patients with schizophrenia.

Notably, they also found that this autoantibody caused schizophrenia-like behaviours and changes in the brain when they injected it into mice.

When considering possible autoantibodies that might cause schizophrenia, researchers from Tokyo Medical and Dental University (TMDU) had a specific protein in mind. Previous research has suggested that neural cell adhesion molecule (NCAM1), which helps facilitate synaptic connections, may have a role in the development of schizophrenia.

“We decided to look for autoantibodies against NCAM1 in around 200 healthy controls and 200 patients with schizophrenia,” explained lead author of the study Hiroki Shiwaku. “We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in just a small subset of schizophrenia cases.”

The research went on to find out whether these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified autoantibodies from some of the patients and injected them into the brains of mice.

“The results were impressive,” said the study’s senior author, Hidehiko Takahashi. “Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behaviour and synapses that were similar to what is seen in humans with schizophrenia.”

The mice given the patient autoantibodies had cognitive impairment and changes in their regulation of the startle reflex, which are both seen in other animal models of schizophrenia. They also had fewer synapses and dendritic spines, which are structures that are important for the connections between brain cells, and are also affected in schizophrenia.

The study findings hold promise for the diagnosis and treatment of schizophrenia can present very differently among patients and is often resistant to treatment. If schizophrenia is indeed caused by autoantibodies against NCAM1 in some patients, this will lead to important improvements in their diagnosis and treatment.

Source: Tokyo Medical and Dental University

LSD Microdosing Trips up in Randomised Controlled Study

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A randomised controlled study of LSD microdosing in healthy adults found no evidence of improvements to mood or cognition, which are some of its purported benefits. Other benefits were found to steadily decrease with time. The research has been published in the journal Addiction Biology.

‘Microdosing’ involves taking small amounts of a psychedelic drug at regular intervals. Preliminary research has indicated that microdosing is associated with a range of psychological benefits, such as increased productivity and reduced stress, but the gold standard for proving causation – randomised placebo-controlled studies – had not yet been done.

“I saw how widespread the practice of microdosing is, and yet there are few well-controlled studies to document its apparent benefits,” said study author Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago. “My human psychopharmacology laboratory is well suited to test effects of drugs under double-blind conditions.”

In the study, four low doses of LSD (13 or 26 μg) or placebo were administered to 56 healthy adults at 3–4 day intervals. The participants were aged 18–35 and they all reported having used a psychedelic drug at least once in their lifetime, but were not experienced with microdosing. The doses were administered under double-blind conditions, meaning that neither the participants nor the researchers knew who was receiving an active dose and who was receiving an inactive placebo.

“We removed any expectations that this was a psychedelic drug,” Prof de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”

After ingesting their dose, the participants completed cardiovascular assessments and hourly mood questionnaires. During the first and last sessions, the participants also completed cognitive and behavioral tasks related to emotional processing, working memory, simulated social rejection, and general cognitive performance.

Participants received their dose during five-hour laboratory sessions. They remained in a comfortable room and were given access to movies and reading materials when no activities were scheduled.

The researchers found that the higher dose of LSD (26 μg) produced a small decrease in false alarm rates for recognising fearful emotions and a small decrease in feelings of social rejection. The higher dose of LSD also produced heightened feelings of vigor and some participants who received the higher dose reported feeling a modest “high” during the drug sessions.

But neither the lower or higher doses of LSD had a significant effect on other aspects of emotional processing, mood, working memory, or general cognitive performance. “Under these limited conditions, the effects did not differ from placebo. But, future studies are needed to assess the effects of repeated doses under different conditions,” de Wit told PsyPost.

The participants also appeared to build a tolerance to LSD over the course of the study, with the strongest “high” reported at the first session, and the perception of a drug effect diminishing at each subsequent session.

“We can’t say necessarily that microdosing doesn’t work,” Prof de Wit said in a news release. “All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn’t see a robust effect.”

There are more questions to explore in future research “Does microdosing have more pronounced effects in individuals with anxiety or depression, or pressing psychological problems?” Prof de Wit said. “Would the effects be detected if different outcome measures were used, or if dosing continued for more than 2 weeks?”

Source: PsyPost

IBD and Depression is a Two-way Street

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While irritable bowel disease (IBD) and depression are known to occur together, scientists report a clinical overlap of these conditions in the Journal of Gastroenterology and Hepatology, implying the existence of a two-way relationship. Patients diagnosed with IBD were nine times as likely to develop depression than the general population. Their siblings who did not suffer from IBD were almost two times as likely to develop depression.

Conversely, patients with depression were two times as likely to develop IBD, and their siblings without depression were more than one and a half times as likely to develop IBD.

“This research reveals a clinical overlap between both conditions, and is the first study to investigate the two-way association between IBD and depression in siblings,” said Bing Zhang, MD, a gastroenterologist with Keck Medicine and co-lead author of the study.

The researchers drew on the data of more than 20 million people from Taiwan’s National Health Insurance Research Database. For 11 years, they tracked patients with either IBD or depression and their siblings without either condition, comparing onset of depression or IBD with a control group of people without either condition, but with similar age, sex and socioeconomic status.

Zhang hypothesises that many factors may contribute to the bidirectional nature of the disorders, including environmental stressors, the gut microbiome and genetics.

“The finding that people with IBD are more prone to depression makes sense because IBD causes constant gastrointestinal symptoms that can be very disruptive to a patient’s life,” he said. “And the elevated depression risk among siblings of IBD patients may reflect caregiver fatigue if the siblings have a role in caring for the patient.”

What surprised researchers was that patients with depression were prone to IBD. Zhang speculates that this discovery may have to do with what is known as the gut-brain axis, a scientifically established connection between the gastrointestinal system and the central nervous system, which consists of the spinal cord and the brain.

For example, he said, inflammation of the brain, which plays a role in depression, may be linked to the inflammation of the gastrointestinal tract, a hallmark of IBD.

The researchers are not sure why siblings of patients with depression are more likely to be diagnosed with IBD. Zhang surmises that there may be a shared genetic susceptibility for either disease that presents differently in family members.

Zhang hopes that the study findings will encourage health care professionals to take both family history and the relationship between gastrointestinal and mood disorders into consideration when evaluating or treating patients with either IBD or depression.

Through more research and better understanding of the gut-brain axis, he envisions leveraging the newfound connection between the conditions to improve the prevention, diagnosis and treatment of IBD and mental disorders.

Source: University of Southern California – Health Sciences

Study Reveals Higher Suicide Rates among Pharmacists

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While the COVID pandemic put the spotlight on the issue of mental health and burnout among doctors and nurses, less was known about the mental health of pharmacists. Results of a longitudinal study published in the Journal of the American Pharmacists Association reveal a suicide rate among pharmacists nearly twice that of the general population.

The figures are based on data from 2003 through 2018, show a suicide rate of 20 per 100 000 pharmacists compared to 12 per 100 000 in the general population. Study authors expect numbers to be even higher in subsequent years due to the additional stressors of the pandemic, and are currently evaluating more recent data.

“If we learned anything from the pandemic, it’s that there is a breaking point for health professionals,” said corresponding author Kelly C. Lee, PharmD, professor at UC San Diego.

The study identified the most common means of suicide in this population, with 49.8% of cases involving firearms, 29.4% involving poisoning and 13% involving suffocation. The use of firearms was similar between pharmacists and the general population, but poisoning via benzodiazepines, antidepressants and opioids was more frequent among pharmacists.

The data also provide some insight into contributing factors, including a history of mental illness and a high prevalence of job problems. Job problems are the most common feature of suicides across health care professions.

For pharmacists, Lee said job problems reflect significant changes in the industry in recent years, with more pharmacists being employed by hospitals and chain retailers as opposed to the small, private pharmacies more common in the past. Pharmacist responsibilities have also grown considerably, with larger volumes of pharmaceuticals to dispense and increasing demands to administer vaccines and other health care services.

“Pharmacists have many more responsibilities now, but are expected to do them with the same resources and compensation they had 20 years ago,” said Prof Lee. “And with strict monitoring from state and federal regulatory boards, pharmacists are expected to perform in a fast-paced environment with perfect accuracy. It’s difficult for any human to keep up with that pressure.”

Future research will further evaluate which job problems have the biggest impact and how the field can better respond. In the meantime, Prof Lee advised pharmacists to encourage help-seeking behaviours amongst themselves and their colleagues.

“Mental health is still highly stigmatised, and often even more so among health professionals,” said Prof Lee. “Even though we should know better, there is such an expectation to appear strong, capable and reliable in our roles that we struggle to admit any vulnerabilities. It’s time to take a look at what our jobs are doing to us and how we can better support each other, or we are going to lose our best pharmacists.”

Source: University of California San Diego