Category: 8. Health

Oxytocin promotes social behaviors and helps maintain relationships. But clinical trials in patients with autism show variability in how consistently oxytocin improves these behaviors. Steve Chang, from Yale University, led a study to explore how oxytocin influences brain activity to shape social behavior in rhesus monkeys and why its effects are so variable. This work is featured in JNeurosci‘s Central Questions for Social Neuroscience Research Special Collection. 

The researchers focused on the basolateral amygdala (BLA) and the anterior cingulate cortex (ACC) because these brain areas process reward and integrate information during social decision-making. Delivering oxytocin directly into the BLA had state-dependent effects; when monkeys were socially motivated prior to oxytocin exposure, the hormone maintained socially beneficial decisions and social task behavior over a longer time period, but oxytocin didn’t influence the same monkeys when they were less motivated. Brain activity supported these results showing that oxytocin increased BLA and ACC activity only when monkeys were socially motivated. Activity in the BLA and ACC was also more coordinated during prolonged social states, suggesting that oxytocin may stabilize communication in this pathway to sustain social behavior. 

Says Chang, “We previously found that communication between these brain areas is important for social reward and behavior. So, the link between enhancement of this signal and prolonged social behavior was interesting to see.” Elaborating on clinical implications, Chang adds, “We have to be more careful and not just use a standardized approach. Even within individuals, there are variations in the effectiveness of oxytocin treatment! It may be important to individually tailor treatments.” 

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Physicians have long known there is a connection between mental health and physical health, but what was not recognized is that this anxiety can actually interfere with the outcome of certain cancer treatments. Most notably, emotional distress has a profound impact on the effectiveness of immunotherapy.

In a recent study published in Nature Medicine, researchers compared the outcomes of patients with non-small-cell lung cancer receiving immunotherapy to determine if emotional distress played a factor in their treatment outcome. They found patients without emotional distress had progression-free survival almost double that of patients suffering from emotional distress. Likewise, the objective response rate to immunotherapy was 46.8% for those with emotional distress, compared to 65% in those who did not suffer from this condition.

This data drives home the importance of early mental health screening and intervention to help improve patient outcomes.

For insight into this crucial mental/physical health connection, we turned to Shiyao Wang, MD, of the Cleveland Clinic Cancer Institute’s Department of Palliative and Supportive Medicine, who recently co-authored a paper in Translational Lung Cancer Research about this topic. A psychiatrist by training, Dr. Wang did his fellowship in consultation-liaison psychiatry at Thomas Jefferson University Hospital. He now works as a psychosocial oncologist at Cleveland Clinic Cancer Institute.

CQD: Thank you for taking the time to talk with us today. First, can you tell us a bit about what your team does?

SW: We offer comprehensive psychological and psychiatric mental health support for patients receiving cancer care at Cleveland Clinic. Our team includes two full-time psychosocial oncologists, three cancer psychologists as well as a psychologist in Florida. We also have a new psychologist starting at our site in Akron.

CQD: What sparked your interest in this study?

SW: The reason I got interested in this study is because we now know that cancer treatment outcomes will be negatively impacted if emotional distress is not properly recognized and treated. This opens the door for mental health professionals to talk with medical oncologists about the importance of treating mental health issues.

CQD: Can you explain specifically how emotional distress disrupts the effectiveness of immunotherapy?

SW: Yes, The whole point of immunotherapy is to make the immune system more robust to target cancer. When patients are going through distress, their HPA (hypothalamic-pituitary-adrenal) axis is dysregulated. Their CD-8 cells and NK cells, which are in charge of killing cancer cells, are less active.

People having chronic stress tend to have dysregulated sleep and decreased appetite and are less likely to follow recommended lifestyle modifications, which further impacts immune activity, so overall, their immunotherapy outcome appears less robust.

CQD: How do you define emotional distress? Wouldn’t most people with cancer have this?

SW: Yes, but it’s on a spectrum. Some people have milder emotional distress that is proportional to cancer diagnosis and treatment. They may have better coping skills and social supports and have learned ways to handle stress. In those cases, they may go through a shorter period of distress and then quickly focus on their care plan and how to move forward versus other people who feel more overwhelmed and have a hard time managing this in an effective way.

Cognitive functioning comes into this as well, because when we’re under duress, it’s harder to think clearly, be motivated to make your next recommended appointment or remember to take medications, for example. That makes the whole task of receiving cancer treatment more challenging.

CQD: Were there other findings in the study that stood out to you?

SW: Yes, the researchers found that poorer outcomes for those with emotional distress were universal across all subgroups, so no matter the patient’s age, gender, histology, smoking status or degree of metastases, we see a consistent negative outcome when patients are experiencing emotional distress. This data reinforces the point that this is something we need to screen for.

CQD: Your paper mentioned that there’s a mutually reinforcing relationship between cancer and emotional distress. Can you explain what that means?

SW: Getting a cancer diagnosis is inherently very overwhelming and stress inducing. When patients are going through this distress, it can sometimes get in the way of effectively engaging in their cancer treatment. If a person is too depressed or anxious to move forward and adhere to treatment recommendations, we tend to see worse outcomes and more suffering, which is likely to perpetuate anxiety and depression, so it’s a two-way street.

Coming to the hospital every single day for 35 days of radiation, for example, is very stressful and requires a lot of motivation, planning and coordination with the patient’s care team and family. That’s especially true for people who still have to work and take care of their family. Having all that stress can impact their ability to concentrate, impact their motivation and affect their desire to further engage with care.

In those cases, we talk about their values, identify their strengths and discuss how to support them and keep them going through this tough process.

CQD: What are the best ways to identify patients in emotional distress?

SW: I see more oncologists including mental health symptoms in their assessment, which is a very good sign. We have the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9), which are scoring tools to help identify patients who are more vulnerable and may suffer from mental health symptoms. From there, a comprehensive psychosocial assessment may be beneficial to identify the existence and severity of mental distress. The social work team at Cleveland Clinic Cancer Institute works closely with the oncology and mental health teams in this process.

CQD: Can you share how the Clinic helps patients with cancer in these situations?

SW: The mental health team at Cleveland Clinic Cancer Institute takes referrals from oncologists, palliative care providers and sometimes inpatient psychiatrists. We assess what the patient’s needs are and provide recommendations to manage symptoms and help the patient achieve their goals.

Not everyone who’s experiencing emotional distress needs to see a psychiatrist. For example, someone may be having existential questions like what’s the point of going through chemo when I feel worse every day? In those cases, potentially talking with a cancer psychologist will help them process and accept their cancer diagnosis, identify their coping styles and skills and understand what their goals and values are. In other cases, there are biological factors that precipitate and/or perpetuate patient’s mental health symptoms, which can be intervened with pharmacological treatment.

CQD: What other types of supports does Cleveland Clinic offer?

SW: Through a good assessment, we can find out what is most beneficial for each patient. In some cases, housing, financial burdens and/or employment disruption are adding emotional distress. For example, for patients who live outside the area and are at Cleveland Clinic Cancer Institute for treatment, our social workers can help them find temporary lodging or provide financial assistance.

The Palliative and Supportive Care Teams provide symptomatic management for patients going through cancer, including pain, constipation, fatigue, nausea and diarrhea, and facilitate goal-of-care discussions. Cleveland Clinic Cancer Institute also offers patients and caregivers supportive services such as yoga, meditation, massage therapy as well as art and music therapy. There are other supporting services in the community that we often refer patients to, such as the Gathering Place and 4^th Angel program. They provide additional services to patients and their family, such as group therapy for certain types of cancer and peer support via a mentorship program.

CQD: What role does your team play in educating patients about the importance of mental health in their cancer care?

SW: For many patients, we are the first contact they’ve ever had with a mental health professional. Being able to help patients understand emotions and feelings they are going through is common. Working with them from an oncology care standpoint can be very helpful to de-stigmatize mental health services overall. Getting our team involved as part of the treatment team can be very beneficial for patients’ quality of life, overall well-being and treatment outcome.

An international team, led by scientists from the Victor Chang Cardiac Research Institute has studied around 3000 people affected by the heart disease dilated cardiomyopathy (DCM) – a driver of heart failure and sudden cardiac arrest.

They discovered those who had a mutation in a particular gene called TTN were 21 times more likely to develop the disease than family members who did not carry a mutation.

For the first time, the team found that a person’s general health and lifestyle factors; such as being overweight or having high alcohol consumption, contributed to an earlier DCM diagnosis.

The study published in the European Heart Journal involving 1000 families affected by DCM also found men with the mutation were more likely to develop DCM at a younger age than women.

Our study reveals just how much mutations in this gene raise the risk of developing DCM. That’s a good thing for patients because it means doctors can keep a far closer eye on them, and ensure they have early access to medical treatments.

We have also crucially shown is that it’s not all down to your genes. Maintaining a healthy lifestyle and being on the right medications could help prevent or delay dilated cardiomyopathy for decades. We hope it will incentivise those at risk to exercise, eat well and drink less and better manage other risk factors too.”

Professor Fatkin, head of the Inherited Heart Diseases Laboratory, Victor Chang Cardiac Research Institute

DCM affects approximately one in 250 people worldwide – that’s around 32 million individuals.

Truncating mutations in the TTN gene are the most common genetic cause of DCM and can be tested for through a simple blood test but until now it was not known how much these mutations raised the risk of developing the disease, or how other risk factors, both clinical and lifestyle, contributed to the onset of the disease.

Clinical factors such as having high blood pressure or type 2 diabetes also increased the risk, whilst having a history of atrial fibrillation doubled the chance of getting DCM.

The findings highlight the need for more research and clinical trials to determine if people with TTN mutations would benefit from being given DCM medications before symptoms begin.

“There are still so many questions to be solved – for example should we be giving drug therapies to those at risk far earlier? Could that delay or prevent DCM from developing entirely, and if so when exactly should that therapy start?” adds Professor Fatkin.

About the study

The researchers recruited 3158 patients from 1043 families affected by TTN mutations. It was the largest study of its kind ever done and involved patients from Australia, North America, the UK, Europe and South Korea. Family members were assessed clinically and underwent genetic testing to see if they carried a TTN mutation.

The researchers first examined the link between the age of diagnosis and the type of mutation and then investigated the relationship between age at DCM diagnosis and cardiac risk factors (such as high blood pressure, coronary artery disease, obesity, diabetes, thyroid disease), and lifestyle factors (including alcohol intake and exercise patterns).

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A multi-center study has identified critical risk factors that increase the likelihood of death in children with a heart defect who are awaiting or have recently undergone heart transplantation, according to findings published in Circulation.

Fontan circulatory failure (FCF) is a long-term complication in children born with single-ventricle heart defects who have undergone a series of surgeries that culminates with the Fontan procedure. While this surgery helps reroute blood flow and extend life expectancy, it can lead to chronic health problems, including heart failure and damage to other organs. Many of these patients eventually require a heart transplant.

The new study, conducted across 20 U.S. medical centers, offers new insights into how specific health complications affect survival in children with the condition, said co-author Anna Joong, MD, cardiologist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

“We have a strong interest in understanding patients with Fontan circulatory failure: how we can better manage their heart failure, when the ideal time is to list them for a heart transplant, and what the risk factors are while waiting for a transplant,” Dr. Joong said.

In the study, investigators analyzed data from 409 patients who had undergone a Fontan procedure and were listed for heart transplant between 2008 and 2022. They tracked outcomes from the time of waitlisting through one year after transplant. They found that 5.9 percent died awaiting a transplant, and among those transplanted, 8.5 percent died within the first year.

The investigators also found that certain pre-existing conditions significantly increased the risk of death, including:

• Repeated hospitalizations in the year before being listed for transplant doubled the risk of death.
• Clinical cyanosis – a condition in which oxygen levels in the blood are dangerously low – was associated with a fivefold increase in mortality risk.
• Sleep apnea, mental health conditions requiring treatment, and anatomical complications like Fontan pathway obstruction were all linked with a higher risk of death.

Overall, survival has improved for patients who have single ventricle physiology and who had a Fontan. A really novel finding of this study was that patients with low oxygen levels were associated with poor outcomes. That’s an important thing for clinicians and families to know about, as an additional risk factor and when to refer to advanced heart failure therapies.”

Dr. Anna Joong, MD, cardiologist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine

The findings should guide clinicians in identifying high-risk patients earlier and considering more aggressive interventions, including earlier heart failure team and transplant referral, Dr. Joong said. Overall, the study lays the groundwork for improving transplant outcomes and tailoring care to the specific needs of children born with single-ventricle heart defects.

Moving forward, Joong and her collaborators will continue to study children post-heart transplant to understand their quality of life and address any functional limitations, she said.

The study was supported by a grant from the Additional Ventures and Enduring Hearts organizations and a gift from the Van Hooser family.

Organic light-emitting diodes (OLEDs) are at the forefront of modern display and lighting technologies, powering nearly everything from smartphone screens to large televisions and monitors. A key phenomenon that is actively being researched to enhance OLED efficiency is thermally activated delayed fluorescence (TADF). This process occurs when absorbed energy trapped in a non-light-emitting state (triplet state) is shifted into a light-emitting state (singlet state) using heat from the surroundings. In simple terms, materials exhibiting TADF can efficiently produce light from energy that would normally be lost, leading to brighter and more energy-efficient devices.

Beyond displays, the ability to capture sharp images of biological tissues while causing minimal harm is crucial for medical diagnostics and research. To this end, techniques leveraging two-photon absorption (2PA) have proven useful. In 2PA, instead of absorbing a single high-energy photon, a molecule absorbs two lower-energy photons simultaneously from a high-intensity laser to reach an excited state capable of emitting fluorescence. Light with lower-energy photons and longer wavelengths, like near infrared, is ideal for biomedical imaging, since it can penetrate much deeper into tissues without scattering. As a bonus, 2PA means that only a small portion of tissue at the laser’s focal point is excited, causing less damage to living cells.

Although TADF and 2PA are both desirable properties in organic materials—one for efficient light emission, and the other for superior imaging—combining both in a single molecule has been extremely challenging. This is because these mechanisms impose conflicting design requirements. Strong TADF calls for a twisted molecular structure that physically separates electron orbitals to facilitate energy conversion. In contrast, 2PA typically requires a more planar structure with significant orbital overlap to enable effective light absorption.

“Recognizing that these two functions have complementary advantages but conflicting molecular requirements, I was motivated to design a material that could harmonize both, ultimately aiming to create new multifunctional materials that could link the fields of electronics and life sciences,” says Dr. Youhei Chitose, Assistant Professor of the Graduate School of Engineering at Kyushu University, Japan, and the lead author of the study.

To fill this knowledge gap, the research team employed a clever molecular design strategy. They created a molecule called CzTRZCN that acts as a molecular switch, changing its structure and properties depending on whether it’s absorbing or emitting light. Their approach involved combining an electron-rich carbazole (Cz) compound with an electron-deficient triazine (TRZ) core. The researchers were able to finetune how the electrons grouped into orbitals within the structure by also adding cyano (CN) groups, which exert a strong pull onto electrons.

The end result meant that during light absorption, CzTRZCN maintains enough orbital overlap between its components to efficiently absorb two photons simultaneously. After excitation, the molecule undergoes structural changes that separate these components, enabling TADF.

Through a combination of theoretical calculations and experimental validation, the team demonstrated that their newly designed material achieved remarkable dual functionality. When integrated into an OLED device, CzTRZCN achieved an external quantum efficiency of 13.5%, establishing a new benchmark among triazine-based TADF materials. Moreover, it exhibited a high 2PA cross-section (a measure of 2PA efficiency) and high brightness, signifying its potential for medical imaging.

“The proposed molecule is a metal-free organic compound with low toxicity to cells and high biocompatibility. This makes it ideal for use in medical probes for precise cancer and neurological diagnostics, especially through time-resolved fluorescence microscopy,” highlights Chitose.

Overall, this study represents an important step toward developing versatile organic materials that bridge the fields of photoelectronics and bioimaging. Beyond medical use, the proposed molecular design strategy for achieving different orbital characteristics for absorption and emission can be widely applied to other multifunctional materials.

“Moving forward, we aim to expand this molecular design approach to cover a broader range of emission wavelengths. We also plan to collaborate with researchers in biomedical and device engineering fields to explore the implementation of these materials in practical applications such as in vivo imaging, wearable sensors, and OLEDs,” concludes Chitose.