Tag: depression

Categories : Mental Health Obstetrics & GynaecologyTags :

Genetic Study Points to Oxytocin as Possible Treatment for Obesity and Postnatal Depression

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Source: University of Cambridge.

The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Categories : Diseases, Syndromes and Conditions Mental HealthTags :

Dengue Linked to Heightened Short- and Long-term Risk of Depression in Taiwan

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New study also uncovers short-term links with sleep disorders

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Analysis of the medical records of nearly 50 000 people who experienced dengue fever in Taiwan suggests that this disease is associated with elevated short- and long-term risk of depression. Hsin-I Shih and colleagues of National Cheng Kung University and National Health Research Institutes, Taiwan present these findings in the open-access journal PLOS Neglected Tropical Diseases.

People may develop dengue fever after being bitten by a mosquito carrying the dengue virus. Dengue fever can be mild, but it can also progress to life-threatening severity, and some people may have long-term health effects. Prior research has uncovered links between active dengue fever and psychiatric disorders, such as depression and anxiety. However, few studies have examined the long-term risk of such disorders after a dengue infection.

To address this knowledge gap, Shih and colleagues analysed the medical records of 45 334 dengue patients in Taiwan and, for comparison, 226 670 patients who did not experience dengue. Covering the years 2002 to 2015, the researchers examined whether dengue patients were more likely to develop anxiety, depressive disorders, and sleep disorders at various time points after infection. To help account for other factors that could influence mental health, the dengue patients were grouped with demographically similar non-dengue patients for statistical analysis.

The researchers found that the dengue patients had a greater likelihood of developing a depressive order across all timeframes, including less than three months, three to 12 months, and more than 12 months after their infection. Sleep disorders were only elevated within three to 12 months post-infection, and there was no observable elevated risk of anxiety.

Taking a closer look at patients whose dengue was severe enough for them to be hospitalized, the researchers found an elevated risk of anxiety disorders within the first three months of infection, as well as elevated risk of sleep disorders in the first 12 months. This subgroup also had elevated risk of depression across timeframes.

These findings suggest a potential link between dengue fever and subsequent depressive disorder. However, further research is needed to determine whether dengue contributes directly to development of depression, or if the association is due to some indirect mechanism.

The authors add: “This study highlights a significant association between dengue fever and an elevated risk of depression in both the short and long term, underscoring the need for further research into the mental health impacts of dengue infection.”

Provided by PLOS

Categories : Mental HealthTags :

A Ketamine Depression Treatment in a Safer Oral Tablet Form

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A University of Otago-led clinical trial has tested an oral form of ketamine therapy for treatment-resistant depression that has fewer side effects whilst also reducing the risk of abusing the powerful, tightly-regulated anaesthetic.

Working in collaboration with New Zealand’s Douglas Pharmaceuticals, researchers have conducted a trial of ketamine in an extended-release tablet form. The study, published in Nature Medicine, involved 168 adults for whom regular anti-depressant therapy repeatedly failed. They either took a range of oral doses of ketamine or a placebo for 12 weeks.

Professor Paul Glue, Otago’s Hazel Buckland Chair in Psychological Medicine, says the highest dose of ketamine – 180mg – showed significant improvement in depressive symptoms, compared with patients who received placebo.

“Ketamine can be given by injection or nasal spray, but these methods can leave people feeling spaced out, sedated, and increases their blood pressure. This study shows the extended-release ketamine tablets are safe and effective, and overall, tolerability was good, with participants reporting minimal side effects,” he says.

Douglas Pharmaceuticals is now seeking the interest of partners to complete registrational clinical trials and prepare for commercialisation of the tablets.

“We have found there are many people, here in New Zealand and around the world, who have treatment-resistant depression, and who have no or very little chance of accessing ketamine. Because most doses of this tablet formulation can be taken at home, this is potentially a much cheaper and convenient option for these patients compared with weekly clinic visits for ketamine injections or nasal sprays.”

Ketamine has been used legally by doctors in New Zealand since the 1970s for sedation and pain relief, but it has been classified as an illegal drug for recreational use since the 1980s.

Professor Glue says having the drug in a tablet form reduces the risk of abuse as the manufacturing process makes them difficult to manipulate.

Source: University of Otago

Categories : NeurologyTags :

New Non-invasive Brain Stimulation may One Day Treat Addiction, Depression and OCD

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Source: CC0

Neurological disorders, such as addiction, depression, and obsessive-compulsive disorder (OCD), affect millions of people worldwide and are often characterised by complex pathologies involving multiple brain regions and circuits. These conditions are notoriously difficult to treat due to the intricate and poorly understood nature of brain functions and the challenge of delivering therapies to deep brain structures without invasive procedures.

In the rapidly evolving field of neuroscience, non-invasive brain stimulation enables the understanding and treating a myriad of neurological and psychiatric conditions, free of surgery or implants. Researchers, led by Friedhelm Hummel, who holds the Defitchech Chair of Clinical Neuroengineering at EPFL’s School of Life Sciences, and postdoc Pierre Vassiliadis, are pioneering a new approach in the field.

Their research, which is described in Nature Human Behaviour, makes use of transcranial Temporal Interference Electric Stimulation (tTIS). The approach specifically targets deep brain regions serving as control centres of several important cognitive functions and involved in different neurological and psychiatric pathologies.

“Invasive deep brain stimulation (DBS) has already successfully been applied to the deeply seated neural control centers in order to curb addiction and treat Parkinson, OCD or depression,” says Hummel. “The key difference with our approach is that it is non-invasive, meaning that we use low-level electrical stimulation on the scalp to target these regions.”

The innovative technique is based on the concept of temporal interference, initially explored in rodent models, and now successfully translated to human applications by the EPFL team. In this experiment, one pair of electrodes is set to a frequency of 2000Hz, while another is set to 2080Hz. Thanks to detailed computational models of the brain structure, the electrodes are specifically positioned on the scalp to ensure that their signals intersect in the target region.

It is at this juncture that the magic of interference occurs: the slight frequency disparity of 80Hz between the two currents becomes the effective stimulation frequency within the target zone. The brilliance of this method lies in its selectivity; the high base frequencies (eg, 2000Hz) do not stimulate neural activity directly, leaving the intervening brain tissue unaffected and focusing the effect solely on the targeted region.

The focus of this latest research is the human striatum, a key player in reward and reinforcement mechanisms. “We’re examining how reinforcement learning, essentially how we learn through rewards, can be influenced by targeting specific brain frequencies,” says Vassiliadis. By applying stimulation of the striatum at 80Hz, the team found they could disrupt its normal functioning, directly affecting the learning process.

The therapeutic potential of their work is immense, particularly for conditions like addiction, apathy and depression, where reward mechanisms play a crucial role. “In addiction, for example, people tend to over-approach rewards. Our method could help reduce this pathological overemphasis,” Vassiliadis, who is also a researcher at UCLouvain’s Institute of Neuroscience, points out.

Vassiliadis, lead author of the paper, a medical doctor with a joint PhD, describes tTIS as using two pairs of electrodes attached to the scalp to apply weak electrical fields inside the brain. “Up until now, we couldn’t specifically target these regions with non-invasive techniques, as the low-level electrical fields would stimulate all the regions between the skull and the deeper zones – rendering any treatments ineffective. This approach allows us to selectively stimulate deep brain regions that are important in neuropsychiatric disorders,” he explains.

Furthermore, the team is exploring how different stimulation patterns can not only disrupt but also potentially enhance brain functions. “This first step was to prove the hypothesis of 80Hz affecting the striatum, and we did it by disrupting it’s functioning. Our research also shows promise in improving motor behaviour and increasing striatum activity, particularly in older adults with reduced learning abilities,” Vassiliadis adds.

Hummel, a trained neurologist, sees this technology as the beginning of a new chapter in brain stimulation, offering personalised treatment with less invasive methods. “We’re looking at a non-invasive approach that allows us to experiment and personalise treatment for deep brain stimulation in the early stages,” he says. Another key advantage of tTIS is its minimal side effects. Most participants in their studies reported only mild sensations on the skin, making it a highly tolerable and patient-friendly approach.

Hummel and Vassiliadis are optimistic about the impact of their research. They envision a future where non-invasive neuromodulation therapies could be readily available in hospitals, offering a cost-effective and expansive treatment scope.

Original written by Michael David Mitchell. The original text of this story is licensed under Creative Commons CC BY-SA 4.0. Edited for style and length.

Source: Ecole Polytechnique Fédérale de Lausanne

Categories : Mental HealthTags :

DNA from Ancient Viral Infections Implicated in Some Psychiatric Disorders

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New research led by King’s College London has found that thousands of DNA sequences originating from ancient viral infections are expressed in the brain, with some contributing to susceptibility for psychiatric disorders such as schizophrenia, bipolar disorder, and depression.

Around 8% of the human genome is made up of sequences called Human Endogenous Retroviruses (HERVs), which are products of ancient viral infections that occurred hundreds of thousands of years ago. Until recently, it was assumed that these ‘fossil viruses’ were simply junk DNA, with no important function in the body. However, due to advances in genomics research, scientists have now discovered where in our DNA these fossil viruses are located, enabling us to better understand when they are expressed and what functions they may have.

This new study, published in Nature Communications, builds upon these advances and is the first to show that a set of specific HERVs expressed in the human brain contribute to psychiatric disorder susceptibility, marking a step forward in understanding the complex genetic components that contribute to these conditions.

Dr Timothy Powell, co-senior author on the study and Senior Lecturer at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said: “This study uses a novel and robust approach to assess how genetic susceptibility for psychiatric disorders imparts its effects on the expression of ancient viral sequences present in the modern human genome. Our results suggest that these viral sequences probably play a more important role in the human brain than originally thought, with specific HERV expression profiles being associated with an increased susceptibility for some psychiatric disorders.”

The study analysed data from large genetic studies involving tens of thousands of people, both with and without mental health conditions, as well as information from autopsy brain samples from 800 individuals, to explore how DNA variations linked to psychiatric disorders affect the expression of HERVs.

Although most genetic risk variants linked to psychiatric diagnoses impacted genes with well-known biological functions, the researchers found that some genetic risk variants preferentially affected the expression of HERVs. The researchers reported five robust HERV expression signatures associated with psychiatric disorders, including two HERVs that are associated with risk for schizophrenia, one associated with risk for both bipolar disorder and schizophrenia, and one associated with risk for depression.

Dr Rodrigo Duarte, first author and Research Fellow at the IoPPN, King’s College London, said: “We know that psychiatric disorders have a substantial genetic component, with many parts of the genome incrementally contributing to susceptibility. In our study, we were able to investigate parts of the genome corresponding to HERVs, which led to the identification of five sequences that are relevant to psychiatric disorders. Whilst it is not clear yet how these HERVs affect brain cells to confer this increase in risk, our findings suggest that their expression regulation is important for brain function.”

Dr Douglas Nixon, co-senior author on the study and and researcher at the Feinstein Institutes for Medical Research at Northwell Health, in the US, said: “Further research is needed to understand the exact function of most HERVs, including those identified in our study. We think that a better understanding of these ancient viruses, and the known genes implicated in psychiatric disorders, have the potential to revolutionise mental health research and lead to novel ways to treat or diagnose these conditions.”

Source: King’s College London

Categories : Mental HealthTags :

Magnetic Device may Offer a New Way to Treat Depression

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Credit: Nagoya University

A head-mounted device that generates an ultra-low frequency ultralow magnetic field has been found to improve the symptoms of four male patients diagnosed with major depressive disorder. Future trials using the device may offer a safe and noninvasive way of treating depression. The results were published in the Asian Journal of Psychiatry.

The presence of a magnetic field with frequencies typically ranging from 0 to 300 Hz is known as an Extremely Low Frequency Magnetic Environment (ELF-ELME). Although the interaction between magnetic fields and biological systems is complex and not well understood, this frequency is believed to stimulate mitochondria and induce their renewal. Since mitochondria generate energy, they offer a potential way to treat many of the symptoms associated with depression such as lethargy.

For this study, the research team led by Professor Toshiya Inada at Nagoya University Graduate School of Medicine and Masako Tachibana of Nagoya University Hospital in Japan enrolled four male Japanese participants diagnosed with depression and receiving treatment between the ages of 18 and 75 years in a clinical trial known as an exploratory first-in human study.

In exploratory studies such as this, both participants and researchers are aware of the treatment being administered. Although the sample size is small and there is no control group, researchers can focus on gathering preliminary data to explore the safety, dosage, and potential efficacy of a new intervention.

Throughout the trial, participants wore a head-mounted magnetic field device that exposed them to ELF-ELME for two hours per day for eight weeks. As predicted, the researchers found that all patients reported a drop in their level of depression.

Although the experiment was an exploratory trial with a limited number of participants and no control group, the findings suggest that larger scale clinical trials are feasible. If such trials prove to be effective, their research could lead to a groundbreaking change in the current clinical practice of depression treatment.

Inada believes that the device has great potential to treat depression more effectively in a patient-centred way. “The magnetic field generated by the device is non-invasive, being 1/4.5 of the Japanese geomagnetic field and less than 1/60 of the International Commission on Non-Ionizing Radiation Protection’s general public exposure standard,” he said, “We anticipate that patients will be able to receive daily home treatment without even being aware of being in a low magnetic field environment.”

He continued: “Compared to current depression treatments, such as long-term antidepressant medications, electroconvulsive therapy, and repetitive transcranial magnetic stimulation, this therapy is superior in terms of convenience and lack of anticipated side effects. We could see our device being used for patients who prefer not to take medication or safely in combination with other treatments.”

Source: Nagoya University

Categories : Cardiovascular Disease Environmental EffectsTags :

Air Pollution and Depression Linked with Cardiovascular Deaths in Middle Age

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A study in more than 3000 US counties, with 315 million residents, has suggested that air pollution is linked with stress and depression, putting under-65-year-olds at increased risk of dying from cardiovascular disease. The research was presented at ESC Preventive Cardiology 2024, a scientific congress of the European Society of Cardiology (ESC).1

“Our study indicates that the air we breathe affects our mental well-being, which in turn impacts heart health,” said study lead author Dr Shady Abohashemof Harvard Medical School, Boston, US.

According to the World Health Organization, air pollution is estimated to have caused 4.2 million premature deaths worldwide in 2019.2 Mental illness has also been linked with premature death.3 This study examined whether air pollution and poor mental health are interrelated and have a joint impact on death from cardiovascular disease.

The study focused on particles less than 2.5 micrometres in diameter, also referred to as fine particles or PM2.5. They come from vehicle exhaust fumes, power plant combustion, and burning wood, and present the highest health risk. To conduct the study, county-level data on annual PM2.5 levels were obtained from the Centers for Disease Control and Prevention (CDC).4 PM2.5 exposure was categorised as high or low according to World Health Organization (WHO) standards. The researchers gathered data on the average number of days (age-standardised) that county residents experienced mental health issues – including stress, depression, and emotional problems – from the CDC.5 Each county was then categorised into three groups based on these numbers. Counties in the top third reported the most days of poor mental health (PMH).4 Age-adjusted premature cardiovascular mortality rates (under 65 years of age) per county, were obtained from the CDC.6 County characteristics were sourced from the County Health Rankings project.

The study included 3047 US counties, representing 315 720 938 residents (with over 207 million aged 20 to 64 years and 50% females) in 2013. Between 2013 and 2019, some 1 079 656 (0.34%) participants died from cardiovascular disease before the age of 65 years. The researchers analysed the associations between pollution, mental health, and premature cardiovascular mortality after adjusting for factors that could influence the relationships.7

Counties with dirty air (high PM2.5 concentrations) were 10% more likely to report high levels of PMH days compared to counties with clean air (low PM2.5 concentrations). That risk was markedly greater in counties with a high prevalence of minority groups or poverty. The link between PMH and premature cardiovascular mortality was strongest in counties with higher levels (above WHO recommended levels: ≥10 µm2) of air pollution. In these counties, higher levels of PMH were associated with a three-fold increase in premature cardiovascular mortality compared to lower PMH levels. Further, one-third of the pollution-related risk of premature cardiovascular deaths was explained by increased burden of PMH.

Dr Abohashem said: “Our results reveal a dual threat from air pollution: it not only worsens mental health but also significantly amplifies the risk of heart-related deaths associated with poor mental health. Public health strategies are urgently needed to address both air quality and mental wellbeing in order to preserve cardiovascular health.”

The levels of pollution across ESC countries can be viewed in the ESC Atlas of Cardiology.

Source: European Society of Cardiology

References and notes

1The abstract ‘Air pollution associates with poor mental health and amplifies the premature cardiovascular death in the United States: longitudinal nationwide analysis’ will be presented during the session ‘Young Investigators Award – Population Science and Public Health’ which takes place on 26 April 2024.

2World Health Organization: Ambient (outdoor) air pollution.

3Byrne P. Meeting the challenges of rising premature mortality in people with severe mental illness. Future Healthc J. 2023;10(2):98-102.

4CDC PLACES databases.

5CDC Behavioral Risk Factor Surveillance System.

6CDC WONDER databases.

7The analyses were adjusted for calendar year and county characteristics such as demographics, median household income, unemployment rates, violent crime rates, education level, food environment index, rates of health insurance, level of mental health provision, level of primary care provision.

Categories : Exercise Mental HealthTags :

Even a Little Light Exercise can Combat Depression, Study Shows

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New research has found a significant association between participating in low to moderate intensity exercise and reduced rates of depression. Researchers carried out an umbrella review of studies carried out across the world to examine the potential of physical activity as a mental health intervention.

The analysis, published in the journal Neuroscience and Biobehavioural Reviews, found that physical activity reduced the risk of depression by 23% and anxiety by 26%. A particularly strong association was found between low and moderate physical activity, which included activities such as gardening, golf and walking, and reduced risk of depression. But this was not strongly observed for high intensity exercise.

Physical activity was also significantly associated with reduced risk of severe mental health conditions, including a reduction in psychosis/schizophrenia by 27%. The results were consistent in both men and women, and across different age groups and across the world.

Lead author Lee Smith, Professor of Public Health at Anglia Ruskin University (ARU), said: “Preventing mental health complications effectively has emerged as a major challenge, and an area of paramount importance in the realm of public health. These conditions can be complex and necessitate a multi-pronged approach to treatment, which may encompass pharmacological interventions, psychotherapy, and lifestyle changes.

“These effects of physical activity intensity on depression highlight the need for precise exercise guidelines. Moderate exercise can improve mental health through biochemical reactions, whereas high-intensity exercise may worsen stress-related responses in some individuals.

“Acknowledging differences in people’s response to exercise is vital for effective mental health strategies, suggesting any activity recommendations should be tailored for the individual.

“The fact that even low to moderate levels of physical activity can be beneficial for mental health is particularly important, given that these levels of activity may be more achievable for people who can make smaller lifestyle changes without feeling they need to commit to a high-intensity exercise programme.”

Source: Anglia Ruskin University

Categories : Cardiovascular Disease Mental HealthTags :

Inflammation may Link Depression and Cardiomyopathy

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Coronary artery disease and major depression may be genetically linked via inflammatory pathways to an increased risk for cardiomyopathy, a degenerative heart muscle disease, researchers at Vanderbilt University Medical Center and Massachusetts General Hospital have found.

Their report, published in Nature Mental Health, suggests that drugs prescribed for coronary artery disease and depression, when used in combination, potentially may reduce inflammation and prevent the development of cardiomyopathy.

“This work suggests that chronic low-level inflammation may be a significant contributor to both depression and cardiovascular disease,” said the paper’s corresponding author, Lea Davis, PhD, associate professor of Medicine in the Division of Genetic Medicine and Vanderbilt Genetics Institute.

The connection between depression and other serious health conditions is well known. As many as 44% of patients with coronary artery disease (CAD), the most common form of cardiovascular disease, also have a diagnosis of major depression. Yet the biological relationship between the two conditions remains poorly understood.

A possible connection is inflammation. Changes in the levels of inflammatory markers have been observed in both conditions, suggesting that there may be a common biological pathway linking neuroinflammation in depression with atherosclerotic inflammation in CAD.

In the current study, the researchers used a technique called transcriptome-wide association scans to map single nucleotide polymorphisms (genetic variations) involved in regulating the expression of genes associated with both CAD and depression.

The technique identified 185 genes that were significantly associated with both depression and CAD, and which were “enriched” for biological roles in inflammation and cardiomyopathy.

This suggests that predisposition to both depression and CAD, which the researchers called (major) depressive CAD, or (m)dCAD, may further predispose individuals to cardiomyopathy.

However, when the researchers scanned large electronic health record databases at VUMC, Mass General, and the National Institutes of Health’s All of Us Research Program, they found the actual incidence of cardiomyopathy in patients with the enriched genes for (m)dCAD was lower than in patients with CAD alone.

One possible explanation is that medications prescribed for CAD and depression, such as statins and antidepressants, may prevent development of cardiomyopathy by reducing inflammation, the researchers concluded.

“More research is needed to investigate optimal treatment mechanisms,” Davis added, “but at a minimum this work suggests that patient heart and brain health should be considered together when developing management plans to treat depression or cardiovascular disease.”

Source: Vanderbilt University Medical Center

Categories : NeurologyTags :

Wide-ranging Animal Studies Link pH Changes to Cognitive and Psychiatric Disorders

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A global collaborative research group has identified brain energy metabolism dysfunction leading to altered pH and lactate levels as common hallmarks in numerous animal models of neuropsychiatric and neurodegenerative disorders. These include models of intellectual disability, autism spectrum disorders, schizophrenia, bipolar disorder, depressive disorders, and Alzheimer’s disease. The findings were published in eLife.

The research group, comprising 131 researchers from 105 laboratories across seven countries, sheds light on altered energy metabolism as a key factor in various neuropsychiatric and neurodegenerative disorders. While considered controversial, an elevated lactate level and the resulting decrease in pH is now also proposed as a potential primary component of these diseases. Unlike previous assumptions associating these changes with external factors like medicationa, the research group’s previous findings suggest that they may be intrinsic to the disorders. This conclusion was drawn from five animal models of schizophrenia/developmental disorders, bipolar disorder, and autism, which are exempt from such confounding factorsb. However, research on brain pH and lactate levels in animal models of other neuropsychiatric and neurological disorders has been limited. Until now, it was unclear whether such changes in the brain were a common phenomenon. Additionally, the relationship between alterations in brain pH and lactate levels and specific behavioural abnormalities had not been clearly established.

This study, encompassing 109 strains/conditions of mice, rats, and chicks, including animal models related to neuropsychiatric conditions, reveals that changes in brain pH and lactate levels are a common feature in a diverse range of animal models of conditions, including schizophrenia/developmental disorders, bipolar disorder, autism, as well as models of depression, epilepsy, and Alzheimer’s disease. This study’s significant insights include:

I. Common Phenomenon Across Disorders: About 30% of the 109 types of animal models exhibited significant changes in brain pH and lactate levels, emphasising the widespread occurrence of energy metabolism changes in the brain across various neuropsychiatric conditions.

II. Environmental Factors as a Cause: Models simulating depression through psychological stress, and those induced to develop diabetes or colitis, which have a high comorbidity risk for depression, showed decreased brain pH and increased lactate levels. Various acquired environmental factors could contribute to these changes.

III. Cognitive Impairment Link: A comprehensive analysis integrating behavioural test data revealed a predominant association between increased brain lactate levels and impaired working memory, illuminating an aspect of cognitive dysfunction.

IV. Confirmation in Independent Cohort: These associations, particularly between higher brain lactate levels and poor working memory performance, were validated in an independent cohort of animal models, reinforcing the initial findings.

V. Autism Spectrum Complexity: Variable responses were noted in autism models, with some showing increased pH and decreased lactate levels, suggesting subpopulations within the autism spectrum with diverse metabolic patterns.

“This is the first and largest systematic study evaluating brain pH and lactate levels across a range of animal models for neuropsychiatric and neurodegenerative disorders. Our findings may lay the groundwork for new approaches to develop the transdiagnostic characterisation of different disorders involving cognitive impairment,” states Dr Hideo Hagihara, the study’s lead author.

Professor Tsuyoshi Miyakawa, the corresponding author, explains, “This research could be a stepping stone towards identifying shared therapeutic targets in various neuropsychiatric disorders. Future studies will centre on uncovering treatment strategies that are effective across diverse animal models with brain pH changes. This could significantly contribute to developing tailored treatments for patient subgroups characterized by specific alterations in brain energy metabolism.”

The exact mechanism behind the reduction in pH and the increase in lactate levels remains elusive. But the authors suggest that, since lactate production increases in response to neural hyperactivity to meet the energy demand, this might be the underlying reason.

Source: Fujita Health University