Q: How does vascular health impact the brain?

In late life depression, MRI studies have shown that vascular lesions lead to depression by disrupting networks called the frontal–subcortical–limbic networks. This is critical for mood regulation. Interestingly, there is some evidence that young adolescents with depression have impaired vascular functioning (arterial stiffness) so again, the relationship appears bidirectional and may well occur earlier than we expect or is clinically evident.

Q: What do you see as the best way to address the health burden of depression and heart disease in Australia?

Greater investment in medical research in this area to develop new treatments, early detection and monitor population trends is key. As mentioned in another response, some of the common risk factors for both conditions occur in early life (adversity, poverty, trauma) so investing in early years of life and focussing on the lifecourse is key socio-economic factors like education and employment are critical so the importance of providing a fair safety net for all members of society (universal health care, good minimum wage, policy to protect against homelessness, food accessibility and security, Indigenous Australians, new arrivals and migrants, incarcerated individuals) cannot be understated. It's more difficult to encourage and promote lifestyle behaviours in the absence of these things. There have also been sub populations almost entirely neglected from heart disease research in the past including women (especially pregnant women), Indigenous Australians, new arrivals and migrants and similarly men who have depression (especially elderly men who are at highest risk of suicide). Thus much of the policy and clinical guidelines are based on outdated data or data that is not fully representative of the Australian population.

Q: Are you seeing increases in children who are at risk of developing heart disease and depression as they get older?

Older age is one of the strongest risk factors for heart disease. Depression and other mood disorders tend to first occur in early life (before age 25). In fact anxiety commonly occurs anywhere from age 6 years according to US data.

Q: What is the proposed mechanism through which intermittent fasting can positively influence heart failure and mood? Could time restricted feeding (e.g., eating within an 8 hour window) potentially have the same effects?

Animal studies suggest that IF slows the accumulation of molecular damage causing cardiometabolic dysfunction that is observed in HF. Rat models showed that IF caused structural changes and improvements in maladaptive remodelling, increased cardiac functioning and improved left ventricular volumes and diameter. In other words, periods without eating (ever seton day) resulted in the generation of new blood vessels. This is the rationale for IF improving both cardiac functioning and mood. One study has been conducted in humans with a type of heart failure called preserved ejection fraction which showed good results for cardiac functioning and quality of life (Published by Kitzman in JAMA) but data are scarce beyond that. It stands to reason that Time Restricted Eating would have the same effects but we need human trials to answer that question. Refer to the work of Dr Sacchin Panda for more info on TRE.

Q: Is it possible that chronic inflammation explains the link between depression and heart disease? If so, what interventions would you recommend to target this?

Yes this is perhaps the most popular candidate mechanism and one for which there is the strongest evidence. This is the common pathway by which interventions that are ultimately anti-inflammatory in nature like diet, exercise, stress reduction, some medications, quitting smoking likely exert their influence on both conditions. In addition to lifestyle, we are especially interested in novel anti inflammatory therapies like statins and aspirin on psychiatric conditions for this reason.

Q: Are there RCTs showing that treating depression reduces the risk of future heart disease? What treatments for depression have these focused on e.g., pharmacotherapy or CBT?

Another million dollar question! There have been very few studies that have investigated the impact of treating depression on preventing the onset of a heart event. One that I am aware of is the IMPACT trial (a collaborative care model for managing depression which uses a stepped approach to treatment depending on severity). It showed that depression treatment delivered before the onset of clinical heart disease reduced the risk of a heart event over 8 years. However, a significant reduction was observed for men but not women. This is a common issue in these studies. When depression is treated after a heart attack, it can improve mood and behavioural outcomes and sometimes even risk of having another event but it does not appear to prolong survival. Studies using psychotherapy, SSRI (anti depressants) and combinations of both have not been very successful in improving MACE outcomes (major adverse cardiac events).

Q: Do behavioral factors such as poor diet, exercise, smoking and alcohol explain the association between depression and heart disease or are there other pathways that account for the relationship?

Yes as discussed in a previous response, lifestyle factors do explain some but not all of the relationship between the two. Each condition appears to exert an independent influence on the other through shared physiology. The evidence is now strong enough that the America Heart Association has stated that depression is now an independent risk factor for poor outcomes after a cardiac event.

Q: Has your research found any advantages for resistance training over cardio in the treatment of depression and promoting heart health?

As discussed in another response, there doesn't seem to be evidence of superiority for resistance training over cardio but it is likely that both are required for maximum health benefits. Having said that the guidelines states that any exercise is good exercise. 150min of mod to vig activity appears to have protective effects over depression risk. In addition it seems important to do what is enjoyable. Our team is studying the effects of surfing and mental health for example. For heart disease, it is largely dependent upon on the individual's baseline level and level of cardiac functioning. Supervised exercise is needed in the post-cardiac period (strength and cardio). Bed rest is certainly not best for the patient anymore as was thought in the 1960s but we know now how bad sedentary activity is in driving muscle wastage.

Q: What does your research suggest about keto or paleo diets or even just a reduction in carbohydrates and sugar and increase in protein consumption for mood and heart health?

One things that is not clear from our SMILES trial (Mediterranean diet for the management of depression) is that we simply don't know what drove the improvements in depression. We know that adherence to the diet was closely correlated with reductions in depressive symptoms. But whether this was because people cut out junk or whether there was something special about the macro/micronutrient profile of the diet remains unclear as the trial was not big enough to look at this. The diet provided ∼11 MJ of daily energy, and was high in fat (40% of energy; >50% from monounsaturated fats), low to moderate in carbohydrate (36% of energy), moderate in protein (18% of energy), and moderate in alcohol (2% of energy from red wine). It was high in fibre (50 g/d), folate (709 μg/d), and vitamin C (247 mg/d) consistent with large quantities of fruits (411 g/d) and vegetables (709 g/d). It met all Recommended Dietary Intakes (RDI) or Adequate Intake (AI) requirements for adult males and females. There are some animal data from psychiatric conditions like schizophrenia that suggest that elimination diets (eg. keto) may be beneficial. Indeed, it is likely that different people will need personalised dietary approaches based on their clinical profile and symptoms. With respect to cardio-protective diets, Mediterranean style diets have by far the strongest evidence. We have shown that a diet with high levels of pro-inflammatory properties (traditional Western diet) predicts onset of heart disease in Australian men over 5 years. I suspect that in the future, more personalised approaches to dietary interventions will benefit cardiac patients as well as psychiatric patients and indeed the general population as we get more sophisticated with personalised medicine.

Question 1

What sort of exercise is best for alleviating symptoms of depression and improving heart health?

Adrienne O'Neil · Accepted Answer

Completing 150 min/week of moderate-vigorous physical activity can be protective against developing both physical condition like heart disease as well as mental health conditions like depression. Even low doses (e.g.< 150 min per week of light-, or moderate-intensity) can reduce risk. It really does depend on the individuals' level of impairment (mental and/or physical; some individuals with heart failure find it difficult to walk around the block). Australian guidelines state that “doing any physical activity is better than doing none”.  Mixing up muscle-strengthening and aerobic exercise can reduce depressive symptoms but one doesn't appear superior over the other. Some psychological therapies encourage people to identify activities they enjoy; any activity that is physical that is also enjoyable will likely have added benefits (gardening, playing with grand children, surfing, horse riding, dancing).

Question 2

How does vascular health impact the brain?

Adrienne O'Neil · Accepted Answer

In late life depression, MRI studies have shown that vascular lesions lead to depression by disrupting networks called the frontal–subcortical–limbic networks. This is critical for mood regulation. Interestingly, there is some evidence that young adolescents with depression have impaired vascular functioning (arterial stiffness) so again, the relationship appears bidirectional and may well occur earlier than we expect or is clinically evident.

Question 3

What do you see as the best way to address the health burden of depression and heart disease in Australia?

Adrienne O'Neil · Accepted Answer

Greater investment in medical research in this area to develop new treatments, early detection and monitor population trends is key. As mentioned in another response, some of the common risk factors for both conditions occur in early life (adversity, poverty, trauma) so investing in early years of life and focussing on the lifecourse is key socio-economic factors like education and employment are critical so the importance of providing a fair safety net for all members of society (universal health care, good minimum wage, policy to protect against homelessness, food accessibility and security, Indigenous Australians, new arrivals and migrants, incarcerated individuals) cannot be understated. It's more difficult to encourage and promote lifestyle behaviours in the absence of these things. There have also been sub populations almost entirely neglected from heart disease research in the past including women (especially pregnant women), Indigenous Australians, new arrivals and migrants and similarly men who have depression (especially elderly men who are at highest risk of suicide). Thus much of the policy and clinical guidelines are based on outdated data or data that is not fully representative of the Australian population.

Question 4

Are you seeing increases in children who are at risk of developing heart disease and depression as they get older?

Adrienne O'Neil · Accepted Answer

Older age is one of the strongest risk factors for heart disease. Depression and other mood disorders tend to first occur in early life (before age 25). In fact anxiety commonly occurs anywhere from age 6 years according to US data.

Question 5

What is the proposed mechanism through which intermittent fasting can positively influence heart failure and mood? Could time restricted feeding (e.g., eating within an 8 hour window) potentially have the same effects?

Adrienne O'Neil · Accepted Answer

Animal studies suggest that IF slows the accumulation of molecular damage causing cardiometabolic dysfunction that is observed in HF. Rat models showed that IF caused structural changes and improvements in maladaptive remodelling, increased cardiac functioning and improved left ventricular volumes and diameter. In other words,  periods without eating (ever seton day) resulted in the generation of new blood vessels. This is the rationale for IF improving both cardiac functioning and mood. One study has been conducted in humans with a type of heart failure called preserved ejection fraction which showed good results for cardiac functioning and quality of life (Published by Kitzman in JAMA) but data are scarce beyond that. It stands to reason that Time Restricted Eating would have the same effects but we need human trials to answer that question.  Refer to the work of Dr Sacchin Panda for more info on TRE.

Question 6

Is it possible that chronic inflammation explains the link between depression and heart disease? If so, what interventions would you recommend to target this?

Adrienne O'Neil · Accepted Answer

Yes this is perhaps the most popular candidate mechanism and one for which there is the strongest evidence. This is the common pathway by which interventions that are ultimately anti-inflammatory in nature like diet, exercise, stress reduction, some medications, quitting smoking likely exert their influence on both conditions. In addition to lifestyle, we are especially interested in novel anti inflammatory therapies like statins and aspirin on psychiatric conditions for this reason.

Question 7

Are there RCTs showing that treating depression reduces the risk of future heart disease? What treatments for depression have these focused on e.g., pharmacotherapy or CBT?

Adrienne O'Neil · Accepted Answer

Another million dollar question! There have been very few studies that have investigated the impact of treating depression on preventing the onset of a heart event. One that I am aware of is the IMPACT trial (a collaborative care model for managing depression which uses a stepped approach to treatment depending on severity). It showed that depression treatment delivered before the onset of clinical heart disease reduced the risk of a heart event over 8 years. However, a significant reduction was observed for men but not women. This is a common issue in these studies. When depression is treated after a heart attack, it can improve mood and behavioural outcomes and sometimes even risk of having another event but it does not appear to prolong survival. Studies using psychotherapy, SSRI (anti depressants) and combinations of both have not been very successful in improving MACE outcomes (major adverse cardiac events).

Question 8

Do behavioral factors such as poor diet, exercise, smoking and alcohol explain the association between depression and heart disease or are there other pathways that account for the relationship?

Adrienne O'Neil · Accepted Answer

Yes as discussed in a previous response, lifestyle factors do explain some but not all of the relationship between the two. Each condition appears to exert an independent influence on the other through shared physiology. The evidence is now strong enough that the America Heart Association has stated that depression is now an independent risk factor for poor outcomes after a cardiac event.

Question 9

Has your research found any advantages for resistance training over cardio in the treatment of depression and promoting heart health?

Adrienne O'Neil · Accepted Answer

As discussed in another response, there doesn't seem to be evidence of superiority for resistance training over cardio but it is likely that both are required for maximum health benefits. Having said that the guidelines states that any exercise is good exercise. 150min of mod to vig activity appears to have protective effects over depression risk. In addition it seems important to do what is enjoyable. Our team is studying the effects of surfing and mental health for example.  For heart disease, it is largely dependent upon on the individual's baseline level and level of cardiac functioning. Supervised exercise is needed in the post-cardiac period (strength and cardio). Bed rest is certainly not best for the patient anymore as was thought in the 1960s but we know now how bad sedentary activity is in driving muscle wastage.

Question 10

What does your research suggest about keto or paleo diets or even just a reduction in carbohydrates and sugar and increase in protein consumption for mood and heart health?

Adrienne O'Neil · Accepted Answer

One things that is not clear from our SMILES trial (Mediterranean diet for the management of depression) is that we simply don't know what drove the improvements in depression. We know that adherence to the diet was closely correlated with reductions in depressive symptoms. But whether this was because people cut out junk or whether there was something special about the macro/micronutrient profile of the diet remains unclear as the trial was not big enough to look at this.  The diet provided ∼11 MJ of daily energy, and was high in fat (40% of energy; >50% from monounsaturated fats), low to moderate in carbohydrate (36% of energy), moderate in protein (18% of energy), and moderate in alcohol (2% of energy from red wine). It was high in fibre (50 g/d), folate (709 μg/d), and vitamin C (247 mg/d) consistent with large quantities of fruits (411 g/d) and vegetables (709 g/d). It met all Recommended Dietary Intakes (RDI) or Adequate Intake (AI) requirements for adult males and females. There are some animal data from psychiatric conditions like schizophrenia that suggest that elimination diets (eg. keto) may be beneficial. Indeed, it is likely that different people will need personalised dietary approaches based on their clinical profile and symptoms. With respect to cardio-protective diets, Mediterranean style diets have by far the strongest evidence. We have shown that a diet with high levels of pro-inflammatory properties (traditional Western diet) predicts onset of heart disease in Australian men over 5 years. I suspect that in the future, more personalised approaches to dietary interventions will benefit cardiac patients as well as psychiatric patients and indeed the general population as we get more sophisticated with personalised medicine.

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