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  • Antipsychotic use during pregnancy not linked to childhood neurodevelopmental disorders or learning difficulties

    Antipsychotic use during pregnancy not linked to childhood neurodevelopmental disorders or learning difficulties

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    The use of antipsychotics during pregnancy isn’t linked to childhood neurodevelopmental disorders or learning difficulties, UNSW Sydney-led study shows – giving assurance to those concerned about continuing their medications during pregnancy. 

    Antipsychotics – a branch of medication designed to treat schizophrenia and bipolar disorder – are important tools for mental health care management. They work by blocking the effect of dopamine, which can help reduce psychotic symptoms such as hallucinations or delusions. 

    These versatile medications are also widely used for other mental health conditions and developmental disorders, like anxiety, depression, autism spectrum disorder, and insomnia. 

    But many women and pregnant people using these medications may feel concerned about the potential risks they pose to their unborn baby. 

    A new international study led by UNSW Sydney, published today in eClinicalMedicine, tracked the long-term risk of a child developing neurodevelopmental disorders and learning difficulties after being exposed to antipsychotics in the womb. 

    The findings show there’s little to no increased risk of the exposure leading to intellectual disability, poor academic performance in maths and language, or learning, speech and language disorders. 

    The findings are really reassuring for both women managing these psychiatric conditions during pregnancy and their providers.”


    Dr. Claudia Bruno, pharmacoepidemiologist at UNSW’s School of Population Health and lead author of the study

    “There’s no increased risk when taking the medication during pregnancy, not only for the specific neurodevelopmental disorders that we looked at, but also ADHD and autism as shown in our team’s previous studies.” 

    This research is the most comprehensive study on antipsychotics and neurodevelopmental outcomes to date: it pulls together nationwide data from Denmark, Finland, Iceland, Norway, and Sweden into a large sample size of 213,302 children born to mothers with a diagnosed psychiatric condition, 5.5 per cent (11,626) of which were prenatally exposed to antipsychotics. 

    These five Nordic countries all have similar health and education systems and keep detailed data on birth records, filled prescriptions, and diagnoses from inpatient and outpatient specialist care, as well as antenatal care. The researchers teamed these data with results from the children’s first standardised national school test (similar to Australia’s NAPLAN tests), which happens between the ages of 8-10. 

    “It’s reassuring that everything points to the same ‘no major indication’ of increased risks overall,” says Scientia Associate Professor Helga Zoega, senior author of the study and pharmacoepidemiologist, also based at UNSW’s School of Population Health. 

    “The study builds on our team’s previous work that looked at birth outcomes, including serious congenital malformations, where we’ve seen similar null results. 

    “I think it’s important to get excited about null results because this is essential information for the management of serious mental health conditions in pregnancy. It’s as equally important as finding an increased risk of outcomes.” 

    A gap that big health data is trying to fix 

    While this study is part of a growing body of research about medication safety in pregnancy, there’s still a lot left in this field to discover, says A/Prof. Zoega. 

    “This is a hugely understudied area,” she says. “Unfortunately, we know way too little about medication safety during pregnancy.” 

    One of the reasons so little is known about medicines and pregnancy is that it’s simply not feasible – or in many cases, ethical – to conduct randomised clinical trials on pregnant women. The potential risks of testing or withholding treatment to the unborn child and mother or pregnant person is often too great. 

    That’s where harnessing big data can step in – although the research isn’t as simple as looking at the raw data alone. 

    For example, women treated with antipsychotics during pregnancy were more likely to smoke, have higher BMIs, lower education levels, to be older (35 years or more) and use other medications during pregnancy compared to women who didn’t take antipsychotics during pregnancy – all of which are risk factors that can potentially impact birth outcomes. 

    These circumstances – called ‘confounding factors’ – are accounted for in observational research using careful study design and complex adjusted risk models to make sure the results show the impact of the medication alone. 

    “These types of studies are methodologically tricky, and can take a long time to do,” says A/Prof. Zoega. “This study has been in the making for almost 10 years now. 

    “We already know these women are dealing with psychiatric conditions, and by genetic default, their children would be more likely to have psychiatric or neurodevelopmental outcomes. But we’re focused on the risks and benefits of the medication treatment in pregnancy, so we use methods to make the comparison groups as similar as possible.” 

    The researchers also strengthened their findings by slicing up the data to take a closer look at whether individual medications, trimesters of exposure, and siblings carried higher risk levels. 

    While one antipsychotic, chlorpromazine, showed potential increased links to language and speech delays, these findings were based on small sample sizes of 8-15 children, so more research is needed to investigate this potential link. 

    Other than this anomaly, the results supported the finding that there was little to no increased risk of children prenatally exposed to antipsychotics developing neurodevelopmental disorders or learning difficulties. 

    Looking ahead 

    Dr Bruno is currently involved in two related studies on prenatal medication use and pregnancy outcomes. One explores if there is a relationship between the use of antiseizure medications during pregnancy and child school performance, and the other examines whether taking ADHD medication use and discontinuation during pregnancy on child health outcomes. 

    But she sees many avenues for future research to build on this work, including harnessing more Australian big health data. 

    “There’s so much to learn about medication safety in pregnancy,” says Dr Bruno. “These women are typically excluded from clinical trials, so there’s a real lack of data or evidence. 

    “While these results are highly generalisable to women in Australia, we now have real-world linked Australian data that can start contributing to large-scale international studies like this one which we’re very excited for.” 

    A/Prof. Zoega co-leads an international research collaboration called International Pregnancy Drug Safety Study (InPreSS), which investigates the safety of medication in pregnancy. She says there’s plenty to do in this space. 

    “Antipsychotics are only one class of medications, and we already know that up to 80 per cent of women use at least one prescription medicine during pregnancy. Most often, there’s little or no guidance on safety. 

    “There are so many unanswered questions that there’s enough for a lifetime of research.” 

    Source:

    University of New South Wales

    Journal reference:

    Bruno, C., et al. (2024) Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study. eClinicalMedicine. doi.org/10.1016/j.eclinm.2024.102531.

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  • Middle-aged adults in the U.S. experience higher levels of loneliness than European counterparts

    Middle-aged adults in the U.S. experience higher levels of loneliness than European counterparts

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    Middle-aged adults in the U.S. tend to report significantly higher levels of loneliness than their European counterparts, possibly due in part to weaker family ties and greater income inequality, according to research published by the American Psychological Association. 

    Loneliness is gaining attention globally as a public health issue because elevated loneliness increases one’s risk for depression, compromised immunity, chronic illness and mortality. Our research illustrates that people feel lonelier in some countries than in others during middle age. It also sheds light on reasons this may be occurring and how governments can address it with better policies.”


    Frank Infurna, PhD, lead author, associate professor of psychology at Arizona State University

    The research was published in the journal American Psychologist.

    Considering the increased public health focus in the United States (as evidenced by the surgeon general’s 2023 advisory on the epidemic of loneliness and isolation) and abroad (countries such as the United Kingdom and Japan have appointed ministers to address the problem), the researchers explored how loneliness has historically changed over time and how it differs across countries. 

    Infurna and his colleagues examined data from ongoing, nationally representative longitudinal surveys from the United States and 13 European countries, with more than 53,000 participants from three different generations (the Silent Generation, baby boomers and Generation X). Data were collected from 2002 to 2020 and only included responses given when participants were between the ages of 45 and 65. 

    “We focused on middle-aged adults because they form the backbone of society and empirical evidence demonstrates that U.S. midlife health is lagging other industrialized nations,” said Infurna. “Middle-aged adults carry much of society’s load by constituting most of the workforce, while simultaneously supporting the needs of younger and older generations in the family.”

    Compared with European counterparts, adults in the U.S. reported significantly higher levels of loneliness. This “loneliness gap” widened with younger generations (late baby boomers and Generation X) reporting greater loneliness than older ones (early baby boomers and the Silent Generation).

    While the U.S. showed consistent historical increases in midlife loneliness during the period data were collected, some European nations displayed more varied patterns. For instance, England and Mediterranean Europe demonstrated similar increases in loneliness for later-born participants (late baby boomers and Generation X). Continental and Nordic Europe demonstrated stable or even slightly declining levels across generations.

    The study identified differences in cultural norms, socioeconomic influences and social safety nets between the U.S. and other European countries as potential explanations for the loneliness gap between the U.S. and Europe. Cultural norms in the U.S. are often characterized by individualism, increased social media use, declining social connections and increasing political polarization. The pressure faced by U.S. middle-aged adults is also further compounded by a higher residential mobility, weaker family ties, increasing job insecurity and income inequality. Additionally, social safety nets in the U.S. tend to be less comprehensive compared with some European nations regarding family leave, unemployment protection and childcare support.

    “The cross-national differences observed in midlife loneliness should alert researchers and policymakers to better understand potential root causes that can foster loneliness and policy levers that can change or reverse such trends,” said Infurna. 

    The study also found that loneliness is generally on the rise compared with previous generations across both the U.S. and Europe, with Europe’s numbers only slightly behind those of the United States.

    The researchers said that loneliness as a public health issue requires policy interventions tailored to national contexts and generational shifts, including promoting family and work benefits, and reducing income inequality. 

    Loneliness as a global public health issue has called attention to the importance of advancing social connections, according to Infurna. The study defends the promotion of social safety nets, through generous family and work policies, which may lessen midlife loneliness by reducing financial pressures and work-family conflict, in addition to strengthening job security and workplace flexibility. Infurna said such practices would also address health and gender inequities.

    “The U.S. surgeon general advisory report coupled with nations appointing ministers of loneliness have shined a bright light on loneliness being a global public health issue,” he said. “As opposed to being considered an epidemic – an outbreak that spreads rapidly and affects many individuals – our findings paint a picture akin to loneliness being endemic, regularly occurring within an area or community.”

    Source:

    American Psychological Association

    Journal reference:

    Infurna, F. J., et al. (2024). Loneliness in midlife: Historical increases and elevated levels in the United States compared with Europe. American Psychologist. doi.org/10.1037/amp0001322.

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  • Non-invasive brain stimulation can change specific brain mechanism linked to human behavior

    Non-invasive brain stimulation can change specific brain mechanism linked to human behavior

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    For the first time, researchers at the University of Minnesota Twin Cities showed that non-invasive brain stimulation can change a specific brain mechanism that is directly related to human behavior. This is a major step forward for discovering new therapies to treat brain disorders such as schizophrenia, depression, Alzheimer’s disease, and Parkinson’s disease.

    The study was recently published in Nature Communications, a peer-reviewed, open access, scientific journal. 

    Researchers used what is called “transcranial alternating current stimulation” to modulate brain activity. This technique is also known as neuromodulation. By applying a small electrical current to the brain, the timing of when brain cells are active is shifted. This modulation of neural timing is related to neuroplasticity, which is a change in the connections between brain cells that is needed for human behavior, learning, and cognition. 

    Previous research showed that brain activity was time-locked to stimulation. What we found in this new study is that this relationship slowly changed and the brain adapted over time as we added in external stimulation. This showed brain activity shifting in a way we didn’t expect.” 


    Alexander Opitz, Associate Professor, Department of Biomedical Engineering, University of Minnesota

    This result is called “neural phase precession.” This is when the brain activity gradually changes over time in relation to a repeating pattern, like an external event or in this case non-invasive stimulation. In this research, all three investigated methods (computational models, humans, and animals) showed that the external stimulation could shift brain activity over time.

    “The timing of this repeating pattern has a direct impact on brain processes, for example, how we navigate space, learn, and remember,” Opitz said.

    The discovery of this new technique shows how the brain adapts to external stimulation. This technique can increase or decrease brain activity, but is most powerful when it targets specific brain functions that affect behaviors. This way, long-term memory as well as learning can be improved. The long-term goal is to use this technique in the treatment of psychiatric and neurological disorders.

    Opitz hopes that this discovery will help bring improved knowledge and technology to clinical applications, which could lead to more personalized therapies for schizophrenia, depression, Alzheimer’s disease, and Parkinson’s disease.

    In addition to Opitz, the research team included co-first authors Miles Wischnewski and Harry Tran. Other team members from the University of Minnesota Biomedical Engineering Department include Zhihe Zhao, Zachary Haigh, Nipun Perera, Ivan Alekseichuk, Sina Shirinpour and Jonna Rotteveel. This study was in collaboration with Dr. Jan Zimmermann, associate professor in the University of Minnesota Medical School.

    This work was supported primarily by the National Institute of Health (NIH) along with the Behavior and Brain Research Foundation and the University of Minnesota’s Minnesota’s Discovery, Research, and InnoVation Economy (MnDRIVE) Initiative. Computational resources were provided by the Minnesota Supercomputing Institute (MSI).

    Source:

    Journal reference:

    Wischnewski, M., et al. (2024). Induced neural phase precession through exogenous electric fields. Nature Communications. doi.org/10.1038/s41467-024-45898-5.

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  • Anxiety therapy prior to COVID-19 pandemic shields against increased stress

    Anxiety therapy prior to COVID-19 pandemic shields against increased stress

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    The start of the COVID-19 pandemic led to unprecedented exposure to stressors driven by fears of a novel and deadly disease, intense uncertainty, and resulting isolation measures, which in turn resulted in increases in anxiety for many. According to new research however, individuals who were in therapy for anxiety prior to the start of the pandemic did not experience upticks in their symptoms throughout this exceptionally challenging time.

    The new research suggests that cognitive-behavioral therapy (CBT) and dialectical behavior therapy (DBT) provided tools to help individuals with anxiety to manage their symptoms in the face of these intense stressors, according to the study’s authors. The study, led by psychologists at McLean Hospital, a member of Mass General Brigham, and Touro University, published March 13th in PLOS One.

    Our research suggests that CBT and DBT can offer major benefits to protect individuals’ mental health amidst a major world catastrophe and period of upheaval. People who have been treated for anxiety know that fighting it is not helpful, and that there are tools to help accept the current realities of their situations,” he added. “In some ways, having a previous anxiety disorder before a crisis occurs can be a blessing.” 


    David H. Rosmarin, PhD, ABPP, lead study author, clinical psychologist at McLean Hospital, and associate professor of psychology at Harvard Medical School

    For the study, researchers compared the treatment trajectories of 764 individuals who participated in outpatient therapy and divided them into four groups based on when they initiated treatment: pre-pandemic (start date on or prior to 12/31/2019), pandemic-onset (from 01/01/2020 to 03/31/2020), during-pandemic (from 04/01/2020 through 12/31/2020), and post-pandemic once vaccines became available (on or after 01/01/2021).

    Anxiety was measured at intake and at each subsequent session using the GAD-7 questionnaire, which assesses for anxiety symptoms. Then, the researchers analyzed the trajectories of anxiety and compared the four groups. Therapy consisted of CBT and DBT.

    Their findings revealed that overall, patients presented with moderate anxiety when they began treatment, which rapidly decreased within 25 days of starting therapy, and gradually declined to mild anxiety over the remainder of their sessions. When comparing the four groups of patients, the researchers found no substantive differences between groups, suggesting that treatment effects were robust to environmental stressors related to the pandemic. Moreover, among patients who were in treatment at the start of the pandemic, the researchers did not detect an increase in anxiety during the initial acute phase of COVID-19 (March 20, 2020 through July 1, 2020).

    We were surprised. We thought that during the height of the pandemic and before vaccines were available, patients would show increased anxiety and that therapy would be less effective but that was not the case.”


    Steven Pirutinsky, PhD, study co-author, assistant professor at Graduate School of Social Work at Touro University

    Studies have shown that the COVID-19 pandemic adversely impacted mental health, with measurable increases in anxiety from the pandemic’s onset in early 2020 through the fist availability of vaccinations in early 2021. One report from the World Health Organization found global prevalence of anxiety and depression increased by 25 percent in the first year of the pandemic.

    “There is a widespread misperception that anxiety is a risk factor for people crumbling and not being able to function,” says Rosmarin. “However, when people receive evidence-based psychotherapy and learn skills to cope, they can become more resilient than those who have never had anxiety at all.”

    Limitations of the study include that the participant pool, while demographically and clinically diverse, consisted primarily of highly educated individuals geographically specific to the northeastern United States. The pandemic-onset group was also smaller than the others, which may be attributed to limited availability of in-person therapy around that time. The study also did not look at other mental health measures, including depression and substance use. More research is needed to gain insights into how these findings may be impacted in other regions of the country, and conditions aside from anxiety disorders.

    Source:

    Journal reference:

    Rosmarin, D. H., et al. (2024) Response to anxiety treatment before, during, and after the COVID-19 pandemic. PLOS ONE. doi.org/10.1371/journal.pone.0296949.

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  • What coping strategies are most effective?

    What coping strategies are most effective?

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    In a recent review article published in the Journal of Clinical Medicine, researchers summarized the results of a systematic review that explored the impact of different coping strategies for people living with inflammatory bowel disease (IBD).

    Study: Coping Strategies and Inflammatory Bowel Disease: A Narrative Review. Image Credit: PeopleImages.com - Yuri A/Shutterstock.comStudy: Coping Strategies and Inflammatory Bowel Disease: A Narrative Review. Image Credit: PeopleImages.com – Yuri A/Shutterstock.com

    Background

    Through keyword searches, they identified 57 articles published in English in medical databases such as the Cochrane Library, PubMed, EBSCOhost, and EMBASE, concluding that personalized interventions can help diverse populations with IBD rehabilitation and management.

    Challenges treating IBD

    The two forms of IBD, namely ulcerative colitis (UC) and Crohn’s disease (CD), are thought to occur as a result of mucosal barrier dysfunctions, gastrointestinal microbiome disturbances, immune response dysregulation, genetic background, and environmental risk factors including smoking, air pollution, diet, and stress.

    As many as four in 10 IBD patients show no response to biological therapy, though patient education regarding risk factors can improve the management of the disease.

    Since IBD can be chronic, it has significant psychosocial effects and can affect work and quality of life.

    Patients may cope with these stresses through adaptive strategies that could mitigate their psychological burden, while maladaptive strategies like denial or avoidance could lead to worsening symptoms.

    Effects of coping mechanisms

    Researchers identified active coping strategies in which individuals act directly to solve problems and address stressors, known as problem-focused coping.

    This could include actively monitoring the disease and its symptoms to identify triggers, changes, and patterns. However, becoming overly focused on monitoring can increase stress.

    Another form of emotion-focused coping involves reframing thoughts, regulating emotions, and seeking support systems. While these strategies can improve mental well-being, they can also reduce adherence to treatment and lead to individuals delaying seeking medical care.

    Disease severity, complications, and activity influence the health-related quality of life (HRQoL) of people living with IBD. However, effectively managing stress, seeking support, being physically active, and adhering to medicine can improve their symptomology and overall well-being.

    Adaptive coping mechanisms can lead to perceiving the illness more positively and reduce distress. People with IBD often show resilience by adapting to the side effects of treatments, psychosocial stressors, and symptom flares with problem-solving skills and psychological flexibility.

    Individuals may experience reduced psychological resilience after being diagnosed with IBD, but mindfulness can be an effective form of therapy.

    Maladaptive coping strategies that are negatively associated with HRQoL include negative religious coping, acceptance-resignation, catastrophizing, low acceptance, passive coping, decreased cognitive flexibility, emotion-focused coping, and perceived control.

    Some strategies are also correlated with higher levels of anxiety and depression and lower work productivity.

    Researchers have found differences in coping strategies between people with UC and CD. People with CD may experience higher levels of psychological distress and neuroticism while being more likely to adopt maladaptive coping strategies.

    In another study, people with UC were more likely to cope by modifying meal content, sleeping more, and seeking medical care.

    People with CD, however, adopted strategies like skipping meals or switching to elemental diets as they perceived these as more useful.

    Interventions for IBD patients

    Educational programs can reduce disease-related anxiety and depression while improving knowledge and the use of adaptive coping strategies. Notably, these improvements have been observed despite disease activity remaining similar.

    This suggests that uncertainty around IBD can lead to worse outcomes and that individuals who know more about their condition benefit from this understanding.

    Cognitive behavioral therapy (CBT) has also been shown to improve symptoms of depression and anxiety, while interventions focusing on mind-body relaxation additionally improved symptoms and reduced expression of genes directly linked to inflammatory processes.

    Another study found that transcranial direct current stimulation reduced pain in the short term, but the effects faded after one week.

    People with inactive IBD show a higher inclination to participate in treatment; they also experience lower depression and a higher quality of life.

    Some patients with IBD may also experience joint and back pain; they show greater adaptability and flexibility but are less likely to perceive medical interventions as effective.

    Conclusions

    Individuals living with IBD experience severe challenges to their health and quality of life. As the prevalence of this condition increases, effective coping strategies must be identified to improve the treatment and management of this disease.

    The review indicates that patients adopt a multitude of coping mechanisms, some adaptive and some maladaptive.

    Their experience of the disease in terms of duration and severity modifies their coping strategies, and these strategies may also affect their condition.

    Understanding these complex interplays can help health professionals tailor interventions to groups of people who have specific needs, providing the necessary level of social support and promoting resilience and treatment adherence.

    Journal reference:

    • Popa, S.L., Stanculete, M.F., Grad, S., Brata, V.D., Duse, T., Badulescu, A., Dragan, R., Bottalico, P., Pop, C., Ismaiel, A., Turtoi, D., Dumitrascu, D.I., Pojoga, C., Gherman, C., David, L. (2024) Coping strategies and inflammatory bowel disease: a narrative review. Journal of Clinical Medicine. doi: https://doi.org/10.3390/jcm13061630. https://www.mdpi.com/2077-0383/13/6/1630

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  • Short-term, self-regulating therapies may help alleviate long COVID symptoms

    Short-term, self-regulating therapies may help alleviate long COVID symptoms

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    A new UCLA-led study suggests that some people living with long COVID may be able to alleviate certain symptoms by using short-term, self-regulating therapies.

    The small-scale study, published in the Journal of Psychosomatic Research, recruited a group of 20 long COVID patients, many of whom had been experiencing symptoms for more than a year. Each participant underwent six sessions of biofeedback therapy, which involves the practice of breathwork and relaxation techniques paired with visual feedback to teach self-regulation of autonomic functions such as heart rate and temperature.

    Clinical psychologist Dr. Natacha Emerson, the study’s lead author and assistant clinical professor in the UCLA Department of Psychiatry and Biobehavioral Sciences, said her study sought to test whether biofeedback would improve both the physical symptoms associated with long COVID and the psychological distress that often accompanies untreated chronic symptoms. While biofeedback has been established for chronic somatic symptoms, this is the first study to explore its effects in long COVID.

    Immediately following the six-weeks of treatment, participants self-reported significant improvements in physical, depression and anxiety symptoms as well as in sleep and quality of life. The benefits were also sustained three months later without further intervention.

    Study participants also reported fewer visits to their medical providers and reduced use of prescribed medications at this three-month time point.

    Our biggest hope is that we’ve identified a way to alleviate chronic physical symptoms that are not successfully treated by standard biomedical approaches, and that we did so with a short-term, non-pharmacological model that is easily scalable.”


    Dr. Natacha Emerson, study’s lead author and assistant clinical professor in the UCLA Department of Psychiatry and Biobehavioral Sciences

    An estimated 65 million people worldwide are reported to have long COVID, which causes a constellation of physical and mental health symptoms including brain fog, dizziness, heart palpitations, depression, anxiety and sleep issues. A patient is considered to have long COVID if they have persistent symptoms for at least three months, though many patients report ongoing symptoms lasting more than a year.

    “It is important to underscore that while this behavioral intervention may help symptoms, patients with long COVID are not in control of their symptoms and are not faking or exaggerating what they report to their doctors,” Emerson said. “Whether it is a racing heart rate, chronic cough, or fatigue, these are real symptoms, just not rooted in a disease process. Instead, we think the autonomic nervous system is off balance and signaling fight or flight mechanisms, similarly to what we see in panic attacks.”

    Emerson adds: “What is exciting is that we are restoring hope in people who feared they would be disabled long-term. And if this tool works, it is one they can practice long term and might apply to future periods of stress.”

    The authors said the study has several limitations including a small sample size and lack of a control group for comparison. Additionally, some patients were co-enrolled in other treatments such as acupuncture or psychotherapy, which may have contributed to overall improvements.

    Emerson and colleagues hope to replicate findings through a randomized control trial, including comparing biofeedback to other treatments such as psychotherapy or pulmonary rehabilitation. Other areas of study could include the addition of brain imaging techniques or inflammation-based biomarkers such as cortisol.

    Source:

    University of California – Los Angeles Health Sciences

    Journal reference:

    Emerson, N. D., et al. (2024). An open trial of biofeedback for long COVID. Journal of Psychosomatic Research. doi.org/10.1016/j.jpsychores.2024.111625.

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  • More women experience cardiovascular disease following a depression diagnosis than men

    More women experience cardiovascular disease following a depression diagnosis than men

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    People with depression face an increased risk of cardiovascular disease (CVD); however, more women experience CVD following a depression diagnosis than men, according to a new study published today in JACC: Asia. The study investigates the connection between depression and CVD, shedding light on potential mechanisms that contribute to its sex-based differences and underscoring the importance of tailoring CVD prevention and management strategies according to sex-specific factors. 

    Depression is the third leading cause of morbidity worldwide. Prior research shows that it is associated with a heightened risk of cardiovascular events, including myocardial infarction (MI), angina, stroke and CV mortality. Women with depression are at greater relative risk of developing heart-related negative health outcomes than men, but there is still controversy over the evidence on sex differences in the impact of depression on heart health and the mechanisms underlying this are not well understood. 

    The identification of sex-specific factors in the adverse effects of depression on cardiovascular outcomes may help in the development of targeted prevention and treatment strategies that address the specific CVD risks faced by depressed patients. A better understanding will allow healthcare providers to optimize care for both men and women with depression, leading to improved CVD outcomes for these populations.” 


    Hidehiro Kaneko, MD, assistant professor at the University of Tokyo in Japan and a corresponding author of the study

    Researchers in this study evaluated the association between depression and subsequent CVD events by conducting an observational cohort study using the JMDC Claims Database between 2005 and 2022. They identified 4,125,720 participants who met the study’s criteria. The median age was 44 (36-52) years, and 2,370,986 participants were men. Depression was defined as those clinically diagnosed before their initial health checkup. 

    Using standardized protocols, the study collected participant’s body mass index (BMI), blood pressure and fasting laboratory values at their initial health checkup. The primary outcome was a composite endpoint including MI, angina pectoris, stroke, heart failure (HF) and atrial fibrillation (AF). 

    Researchers analyzed the statistical significance of differences in clinical characteristics between participants with and without depression. Results indicate that the hazard ratio of depression for CVD was 1.39 in men and 1.64 in women compared with participants without depression. Models also indicate that hazard ratios of depression for MI, angina pectoris, stroke, HF, and AF were higher for women than for men. 

    Study authors highlight an important discussion regarding the potential mechanisms that may contribute to why depression impacts women’s heart health more than men’s. One explanation is that women may experience more severe and persistent symptoms of depression compared to men, and they may be more likely to have depression during critical periods of hormonal changes, such as pregnancy or menopause. 

    Other mechanisms include women’s greater susceptibility to traditional risk factors when depressed, such as hypertension, diabetes and obesity, which may contribute to the development of CVD. Differences in healthcare utilization and treatment between men and women and sex-specific differences in biological factors, such as genetics and hormonal profiles, may also increase women’s CVD risk. 

    “Our study found that the impact of sex differences on the association between depression and cardiovascular outcomes was consistent,” Kaneko said. “Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management. Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.” 

    Limitations of the study include the inability to establish direct causality between depression and cardiovascular events and the inability to accurately reflect the severity or duration of depressive symptoms. Potential confounding factors that may influence the association between depression and CVD were not accounted for, such as socioeconomic status. Researchers also acknowledge that COVID-19 may have been a confounder. 

    Source:

    American College of Cardiology

    Journal reference:

    Senoo, K., et al. (2024) Sex Differences in the Association Between Depression and Incident Cardiovascular Disease. JACC: Asia. doi.org/10.1016/j.jacasi.2023.11.015.

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  • Is there a higher risk of depression among specific populations of patients with rheumatoid arthritis?

    Is there a higher risk of depression among specific populations of patients with rheumatoid arthritis?

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    In a recent study published in JAMA Network Open, researchers assessed the risk of depression following the diagnosis of rheumatoid arthritis (RA).

    Study: Rheumatoid Arthritis and Risk of Depression in South Korea. Image Credit: Africa Studio/Shutterstock.com
    Study: Rheumatoid Arthritis and Risk of Depression in South Korea. Image Credit: Africa Studio/Shutterstock.com

    RA, a prevalent autoimmune disease, is characterized by systemic inflammation. The chronic nature of the disease necessitates lifelong treatment, often leading to comorbidities, including depression. Depression is highly prevalent among RA patients compared to the general population and has been associated with increased disease activity, pain exacerbation, elevated risk of myocardial infarction, less frequent remission, poor health-related quality of life, and higher health care utilization. Therefore, depression management and prevention are essential to improving the health and quality of life of RA patients.

    About the study

    In the present study, researchers examined associations of RA with subsequent depression risk in South Korea. They included subjects diagnosed with RA during 2010-17. Seropositive RA (SPRA) was defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes and enrolment in the Rare and Intractable Diseases (RID) program.

    RID program enrollment for SPRA required a positive test result for anticyclic citrullinated peptide antibodies or rheumatoid factors and a physician report indicating the fulfillment of RA classification criteria. Seronegative RA (SNRA) was defined using ICD-10 codes and prescription of disease-modifying anti-rheumatic drugs (DMARDs) for ≥ 270 days.

    The team excluded subjects if they were aged under 20, had prior depression, missing data, or developed depression within a year post-index date. RA patients were matched to individuals without RA (controls) by sex, age, and index date. The study endpoint was a new diagnosis of depression. Participants were followed up from one year post-RA diagnosis until the diagnosis of depression, death, or December 31, 2019.

    The Kaplan-Meier method was used to estimate the cumulative incidence of depression. Differences between groups were evaluated using log-rank tests. Cox regression analyses estimated adjusted hazard ratios and 95% confidence intervals for the risk of depression. The association between depression risk and the type of DMARDs used was also evaluated.

    Analyses were adjusted for sex, age, smoking/alcohol status, income, body mass index, physical activity, diabetes, chronic kidney disease, hyperlipidemia, and hypertension. Besides, stratified analyses were conducted by sex, age, comorbidities, and health behaviors. Restricted mean survival time (RMST) differences were analyzed between groups by sex and age.

    Findings

    Overall, 230,922 participants aged 54.6, on average, were included for analysis. There were 38,487 RA patients and 192,435 controls; most participants were female (71%). Among RA patients, 11,645 were seronegative, and 26,842 were seropositive. RA patients were more likely to be non-drinkers and less likely to be obese. SPRA patients were more likely to be female, older, non-drinkers, and less likely to be obese than SNRA patients.

    The median follow-up duration was 4.1 years, during which 6,422 RA patients and 20,641 had newly developed depression. RA patients had a higher risk of depression than controls. Moreover, SPRA and SNRA groups had elevated depression risk compared to controls. Among RA patients with depression, 402 were prescribed biological or targeted synthetic DMARDs, and 6,020 were prescribed only conventional synthetic DMARDs.

    Notably, the incidence of depression among RA patients was consistently lower among recipients of targeted synthetic or biological DMARDs than non-recipients. Stratified analyses yielded findings consistent with the primary analysis. RMST differences were variable across age groups, with a higher difference in the ≥ 60-year age group.

    Conclusions

    In sum, the researchers observed a 1.66-fold increased depression risk among RA patients relative to those without RA. There was no significant difference in depression risk by the serologic status of RA, with both SNRA and SPRA groups exhibiting an increased risk. RA patients receiving targeted synthetic or biological DMARDs had lower risks than those who did not. Nevertheless, the study has a few limitations. Notably, disease activity was inaccessible, resulting in limited evaluation of RA severity.

    Moreover, information on depression levels at the index date was not available. Besides, because participation was limited to those undergoing health screening, participants might have been healthier or engaged more in healthy behaviors than the general population.

    Taken together, the findings suggest an increased depression risk among RA patients, irrespective of RA serologic status, age, sex, and behavioral factors, warranting consistent screening of RA patients and comprehensive healthcare to address their physical and mental well-being.

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  • Nutrients like vitamin B12 and vitamin D potentially play a role in risk of multimorbidity

    Nutrients like vitamin B12 and vitamin D potentially play a role in risk of multimorbidity

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    In a recent study published in BMC Public Health, researchers explored potential associations between nutrient intake and multimorbidities.

    Study: Nutrient intake and risk of multimorbidity: a prospective cohort study of 25,389 women. Image Credit: Saowanee K/Shutterstock.com
    Study: Nutrient intake and risk of multimorbidity: a prospective cohort study of 25,389 women. Image Credit: Saowanee K/Shutterstock.com

    Background

    Multimorbidity, or the presence of many chronic illnesses, is a worldwide health concern, particularly among older individuals. It raises the risk of early mortality, hospitalization, loss of physical function, depression, polypharmacy, and a decline in quality of life, inflicting a considerable cost load on healthcare systems.

    Nutritional variables have a vital role in multimorbidity prevention. Unhealthy dietary habits like binge eating and excessive drinking might raise the risk. In the Netherlands, individuals with cardiometabolic multimorbidity eat more meat and snacks. Consuming fruits, vegetables, and whole grains can help reduce the risk. Mediterranean diets and increasing calcium and potassium intake are associated with decreased cardiometabolic multimorbidity. Lutein and zeaxanthin are potentially helpful nutrients. However, further study is needed to discover dietary therapies that reduce the multimorbidity burden.  

    About the study

    In the present prospective cohort study, researchers investigated the influence of dietary intake on multimorbidity risk.

    The researchers analyzed the United Kingdom Women’s Cohort Study (UKWCS) data from 25,389 females aged between 35 and 69 years. The UKWCS dataset included food intake, anthropometric parameters, socioeconomic status, lifestyle habits, and health outcomes. The participants self-reported baseline chronic diseases such as hypertension, angina, coronary artery disease, stroke, diabetes, hyperlipidemia, gallstones, large intestinal polyps, and cancer.

    The team excluded non-residents of England with multiple chronic diseases at baseline and missing covariate data. They used food frequency questionnaires (FFQs) from the UK for the European Prospective Investigation into Cancer and Nutrition (EPIC) study to estimate daily energy and nutrient intakes. They assessed multimorbidity using Charlson comorbidity index (CCI) scores electronically linked to the Hospital Episode Statistics (HES) database through March 2019, using the International Classification of Diseases, tenth edition, Australian modification (ICD-10-AM) codes. 

    The researchers assessed dietary intake using McCance & Widdowson Food Composition (fifth edition) and Food Standards Agency guidelines, adjusting for total calorie intake by nutrient density. They performed Cox proportional hazards modeling to estimate hazard ratios (HRs) for the relationships between regular nutrient intake and multimorbidity risk. They used multinomial logistic regressions to evaluate the association in the sensitivity analysis and performed a stratified assessment, considering 60 years as the threshold for age. Study covariates included age, body mass index (BMI), educational level, marital status, ethnicity, socioeconomic status (SES), and physical activity.

    Results

    The mean participant age was 51 years, among whom 31% (n=7,799) developed multimorbidities over a 22-year follow-up (median). Individuals with multimorbidity had a higher BMI, lower educational levels, and higher SES status and showed an increased likelihood of being single or widowed compared to their counterparts.

    Compared to the lowermost quintile, the uppermost quintile of regular calorie and protein intakes was related to 8.0% and 12% higher multimorbidity risks, respectively (hazard ratio, 1.1). Compared to the lowermost quintile, higher statistical quintiles of regular vitamin C consumption had a 10% lowered multimorbidity risk, while regular vitamin D consumption had a 10% increased multimorbidity risk. In comparison to the lowermost quintile of vitamin B12 consumption, multimorbidity risk was significantly higher in the topmost quintile (HR, 1.1). Compared with the lowermost quintile, higher quintiles of iron intake had marginally lowered multimorbidity risks.

    In the sensitivity analysis, the significantly higher multimorbidity risks linearly related to higher statistical quintiles of B12 and D vitamin intakes were non-significant using multinomial logistic regressions. The team found evidence of age-modifying effects on vitamin B1 and iron intakes associated with multimorbidity risk. For iron intake, the team found an 11% to 13% lower multimorbidity risk among individuals below 60 years compared to those aged above 60 years.

    Conclusions

    The study findings highlighted a relationship between nutrient consumption and the risk of multimorbidity for developing preventive, diagnostic, treatment, and prognostic methods. The findings indicated that higher intakes of vitamin B12, vitamin D, protein, and energy may raise the risk of multimorbidity, but higher intakes of vitamin C may reduce it. Iron consumption was adversely linked with multimorbidity risk in women aged <60 years, while there was no such association in women aged >60 years.

    The study reveals that specific nutrients, notably vitamin B12, vitamin D, protein, and energy, may influence the likelihood of multimorbidity. Researchers must further investigate the optimal nutritional consumption levels for individuals with multimorbidity, and policymakers and clinical practitioners should address individualized nutrition. Additional clinical studies are necessary to determine whether dietary treatments help improve multimorbidity. More studies are needed to draw definitive conclusions.

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  • Diabetes drug dulaglutide may reduce symptoms of depression

    Diabetes drug dulaglutide may reduce symptoms of depression

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    A recent Brain and Behavior study investigated the antidepressant effect of dulaglutide and the mechanism that underlies this effect.

    Study: Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress. Image Credit: luchschenF/Shutterstock.com
    Study: Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress. Image Credit: luchschenF/Shutterstock.com

    Background

    Depression is a chronic mood disorder that is associated with low mood, insomnia, weight loss, a state of unhappiness, aversion to activity, fatigue, and low self-esteem. According to the World Health Organization, depression has become one of the major health burdens across the world.

    This mental health condition is commonly treated with an antidepressant that takes around a month to alleviate the symptoms. However, several side effects are associated with the use of antidepressant drugs and could be toxic at high doses.

    A combination of psychological, genetic, and neurological factors contributes to the manifestations of depression. Even though the exact etiology of this mental health issue is not fully understood, research has shown chronic stress to be an inducer of depression. 

    The hippocampus is a region of the brain that is associated with depression and modifies functionally and morphologically in response to stress. Animal model studies have shown that a decrease in neuronal and glial size, reduction in synaptic markers, loss of dendrites, and increase in apoptosis in the hippocampus leads to depression.

    Many studies have uncovered the metabolic aspects of depression. For instance, diabetes and obesity are two common metabolic disorders that increase the risk of depression. Considering its high prevalence, novel therapies with high efficacy and fewer side effects are required to combat depression. The chronic mild stress (CMS) model has been recognized as a reliable rodent model to study depression. 

    Glucagon-like peptide-1 (GLP-1) and its receptor agonists are involved with anti-inflammatory effects and neuroprotective activities and can improve mental disorders, particularly depression and cognition. GLP-1 is a peptide hormone that stimulates the secretion of insulin and restricts the synthesis of glucagon in the pancreas in a glucose-dependent manner. Liraglutide is a GLP-1 analog that exhibited a positive effect in reducing anxiety and depression symptoms.

    Dulaglutide is a novel long-acting GLP-1 receptor agonist that improves cognitive dysfunction and neuronal damage in rats with vascular dementia. Although many studies highlighted the efficacy of dulaglutide in preventing depression-like behavior triggered by chronic social defeat stress (CSDS), the underlying mechanism of this effect is not clearly understood.

    About the study

    The current study used a metabolomics strategy to evaluate the effect of dulaglutide in a CMS model. Furthermore, the underlying mechanism of this effect was also assessed. Adult male ICR mice, which is a strain of albino mice, were selected for this study. All test mice were around seven weeks old.

    After one week of acclimatization, 60 mice were randomly assigned in four groups, namely, control (CON), the CMS and Vehicle group (CMS+Veh), the CMS and 0.3 mg/kg dulaglutide group (Low Dula), and the CMS and 0.6 mg/kg dulaglutide group (High Dula). Except for the CON group, all other groups were exposed to stressors.

    To establish the CMS model of depression, selected mice were exposed to two or three different stressors for 28 days continuously. For stress induction, mice were deprived of water and food for 12 hours, kept in wet bedding for 24 hours, kept in a tilted cage for 24 hours, pintail for 1 minute, and cold water treatment for five minutes. The body weight of each test mouse was measured weekly, and behavioral tests, such as the tail suspension test (TST), open field test (OFT), and forced swimming test (FST), were performed.

    Study findings

    The mice subjected to CMS for four weeks exhibited depressive- and anxiety-like symptoms. An LC-MS/MS metabolomics study was performed to understand the potential pathophysiological mechanisms and investigate the efficacy of drugs to alleviate depression-like symptoms.

    A distinct difference between the CON group, CMS+Veh group, and High Dula group was observed in accordance with the metabolic disorders induced by chronic stress, which was altered through dulaglutide treatment. Many potential biomarkers were identified that are associated with purine metabolism, arginine and proline metabolism, glycerophospholipid metabolism, glutamate metabolism, sphingolipid metabolism, and bile secretion.

    Lipid metabolism pathways could be potential targets through which dulaglutide alleviates depression. Lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), phosphatidylinositol (PI), sphingolipids, and phosphatidylcholine (PC), are involved with the therapeutic effect of dulaglutide in alleviating depression. Consistent with previous studies findings, this study highlighted the association between lipid metabolism and the antidepressant effect of dulaglutide.

    The current study indicated the downregulation of N-acetyl-L-aspartic acid (NAA) in the CMS model group. NAA, which is one of the most important metabolites of the vertebrate nervous system, was found in decreased levels in rats with chronic, unpredictable, mild stress. However, the current study indicated that dulaglutide therapy increased the levels of NAA through its upregulation in the hippocampus.

    In the CMS model group, an upregulation in L-glutamic acid and L-arginine was observed. Dulaglutide treatment caused a decrease in arginine and proline, thereby indirectly exhibiting a neuroprotective effect.

    Conclusions

    The current study highlighted the antidepressant effects of dulaglutide using the CMS depression model. Notably, the potential metabolisms that underlie the antidepressant effect of dulaglutide have been elucidated in this study. 

    Journal reference:

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