Introduction

In this section, Dr. Brett Sher introduces the podcast and his guest, Dr. Cindy Culkin, an associate professor in the department of Psychiatry and the department of medical neurosciences at Dalhousie University. They discuss how metabolic health and mental health are interconnected.

Transition to Psychiatry

• Dr. Culkin started off as a family physician but transitioned into psychiatry.

• She was drawn to treating the whole patient rather than just one body part.

• Half of her patients had underlying psychiatric illness that she recognized while working as a family physician.

• She worked alongside an endocrinologist who sent her diabetic patients with depression for treatment.

Interest in Bipolar Disorder

• After 10 years of practicing family medicine, Dr. Culkin wanted a new challenge and decided to specialize in psychiatry.

• She specifically wanted to treat patients with bipolar disorder because it fascinated her.

• Patients with bipolar disorder present differently when they are well, manic or depressed.

Conclusion

In this section, Dr. Brett Sher concludes the podcast by thanking his guest for sharing her insights on metabolic health and mental health.

Final Thoughts

• The connection between metabolic health and mental health is important for treating people living with mental illness.

• Research can impact clinical care significantly.

• Metabolic dysfunction can directly impact and improve the symptoms and lives of people living with mental illness such as bipolar disorder.

Psychiatry and Metabolic Disease

In this section, the speaker discusses the importance of studying psychiatry and treating patients with psychiatric illness. They also talk about the connection between metabolic disease and psychiatric illness.

Interest in Psychiatry

• The speaker was interested in studying psychiatry because they wanted to make a difference in treating the sickest of the sick patients.

• The medical community tends to focus on heart disease and cancer, but psychiatric conditions are actually the greatest cause of disability.

• Patients with psychiatric illness often have comorbid medical conditions such as metabolic syndrome, heart disease, stroke, and obesity.

Connection Between Metabolic Disease and Psychiatric Illness

• The speaker's research has focused on the connection between metabolic disease and psychiatric illness.

• The first study conducted by the speaker looked at obesity and outcomes in bipolar disorder. Patients who were overweight or obese had poor outcomes from a psychiatric standpoint.

• 54% of all patients with bipolar disorder have either type 2 diabetes or insulin resistance, which is found at three times the rates compared to the general population.

• Metabolic dysregulation is often missed in patients with psychiatric illness, even though it is a contributor to heart disease, brain disease, and poor response to mood stabilizing treatment.

Paradigm Shift

• The speaker was not confined by current paradigms when conducting their research.

• Insulin resistance was something that was right in front of them but often missed during diagnosis.

Insulin Resistance and Mental Health

In this section, the speaker discusses how insulin resistance is not only prevalent in bipolar disorder patients but also in other psychiatric illnesses. The speaker explains that treating metabolic conditions such as insulin resistance can help improve mental health.

Insulin Resistance and Psychiatric Illness

• The speaker connects the dots between increased prevalence of insulin resistance, type 2 diabetes, and psychiatric illnesses.

• Treating metabolic conditions like insulin resistance can help improve someone's mental health.

• There was pushback from people who thought treating insulin resistance wouldn't help with neurotransmitter or brain problems.

• The Stanley Medical Research Institute supported the idea of treating insulin resistance to see if it would get people better.

Insulin Resistance and Bipolar Disorder

• Insulin resistance modifies the course of bipolar disorder leading to a neural progressive form of bipolar disorder which causes cognitive impairment and functional impairment.

• People should be screened for insulin resistance from onset of diagnosis because there are still higher rates of insulin resistance especially if they're on typical antipsychotics.

• Antipsychotics can worsen insulin resistance so it's important to address it when seen regularly.

Trio BD Study

• Patients with bipolar 1 or bipolar 2 and treatment-resistant were studied for their response to treatment after being diagnosed with insulin resistance.

Metformin as a Mood Stabilizer

In this section, the speaker discusses why they chose metformin as a mood stabilizer and how it works.

Choosing Metformin

• Corwin is a safe and cheap drug that has been used for 50-60 years.

• The speaker wanted to use regulatory glue tide or other drugs but thought psychiatrists would not go for them.

• Metformin treats type 2 diabetes and only reverses insulin resistance 50% of the time.

• Other mood sensitizers like cementide and pioglitazone are used in conjunction with diet and exercise to get insulin resistance turned around.

Reaction to Trial Results

• Family doctors who referred patients were unwilling to prescribe new drugs despite current treatments not working.

• The speaker had to send family doctors a copy of the TRBD study to convince them that prescribing metformin was necessary.

Study Results

In this section, the speaker discusses the results of their study on using metformin as a mood stabilizer.

Reversing Insulin Resistance

• Of the 2010 patients, only half reversed their insulin resistance.

• Patients who converted improved by week six, including those who had been ill for an average of 25 years.

Treatment Resistant Population

• Patients had failed two to three drugs and eight or nine psychotropic drugs in their lifetime.

• The mean Madras score was 28, indicating moderate to markedly depressed patients.

Improvement

• Almost 90% of the patients had not had a remission in those 25 years.

• Patients improved within six weeks, with effect sizes for just about every measure being significant.

Metformin as a Treatment for Bipolar Disorder

In this section, the speaker discusses the use of metformin as a treatment for bipolar disorder and how it has shown to be effective in improving patients' quality of life.

Mechanism-Driven Treatment

• Metformin is a mechanism-driven treatment that corrects underlying aberrant mechanisms.

• It has been shown to be safe and effective in reducing suicide and preventing mania.

• Patients have reported significant improvements in their quality of life.

Challenges with Implementation

• The paradigm shift towards using metformin as a treatment for bipolar disorder has been slow to catch on among psychiatrists and doctors.

• Many physicians are unfamiliar with the drug and its indications, making it challenging to prescribe.

• The speaker emphasizes the importance of treating patients holistically and medically.

Patient Response

• Patients who have been treated with metformin are sold on its effectiveness due to their significant improvement in quality of life.

• The speaker notes that patients report experiencing a higher quality remission than they have experienced with other treatments.

Future Research

• There is potential for future research into other mechanisms that affect metabolic dysregulation in the body, such as blood-brain barrier leakage.

• Drugs like telmosartan and losartan may be used to repair the blood-brain barrier.

Importance of Mood Metabolism Program

In this section, the speaker talks about the importance of the mood metabolism program and how it can help in treating psychiatric illnesses.

Need for Mood Metabolism Program

• The speaker believes that more people should be convinced to take up the mood metabolism program.

• The program is not part of the core curriculum, but it is impactful in treating psychiatric illnesses.

• Residents who choose to work with the speaker for electives are taught how to test for insulin resistance and use different drugs to treat it.

Blood-Brain Barrier and Insulin Resistance

In this section, the speaker discusses blood-brain barrier leakage and its correlation with insulin resistance.

Blood-Brain Barrier Leakage

• The blood-brain barrier prevents toxins or inflammatory markers from going from your blood into your brain.

• Patients with bipolar disorder and extensive blood-brain barrier leakage were found to have worse metabolic parameters, higher depression and anxiety scores, poor overall functioning, chronic course that tended to be treatment-resistant.

• Blood-brain barrier leakage is a marker for more severe psychiatric illness that insulin resistance contributes to.

Correlation with Insulin Resistance

• Patients with normal blood-brain barrier permeability were a very heterogeneous group.

• Patients that had extensive leakage were all bipolar patients with insulin resistance.

• Severity of insulin resistance or duration may contribute to why some bipolar patients with insulin resistance didn't have extensive blood-brain barrier leakage.

Treatment using Metformin

In this section, the speaker talks about treating patients using metformin.

Case Studies

• A patient coming out of a trio study was imaged before and after treatment with metformin. His blood-brain bearer had completely healed after 12-14 weeks of treatment, and his depression remitted for the first time in five years.

• A colleague sent a treatment-resistant patient with PTSD to the speaker. The patient was insulin resistant, had extensive leakage, and high scores on PTSD rating scales. After 12-14 weeks of treatment with metformin, the blood-brain bearer healed, and he is well.

Off-label Treatment

• Treating patients with metformin is off-label like most things used in psychiatry.

• Patients should be informed about the risks and benefits of using metformin.

Unifying Psychiatric Illnesses

In this section, the speaker discusses how psychiatric illnesses are diagnosed and coded. They explain that while we think of them as separate conditions, they may actually be on the same spectrum.

Psychiatric Illnesses on the Same Spectrum

• Psychiatric illnesses are often thought of as separate conditions.

• However, they may actually be on the same spectrum.

• This could be due to factors such as the blood-brain barrier or insulin resistance.

Treating Insulin Resistance in Mental Illness

• One treatment for many different disorders is possible.

• Metformin is a common medication used to treat insulin resistance in mental illness.

• If patients do not respond to metformin, other medications such as semaglutide or pioglitazone can be used.

• Telmisartan can also be used if there is extensive blood-brain barrier leakage.

Lifestyle Changes for Treatment Resistant Patients

In this section, the speaker discusses lifestyle changes for patients who have not responded well to medication.

Ketogenic Diet and Exercise

• Patients with treatment-resistant seizures are frequently prescribed a ketogenic diet.

• Nutrition and lifestyle changes should not only be reserved for treatment failures or resistant patients.

• Diet and exercise should typically be the mainstay of initial approach but some patients are too sick for this initially.

Addressing Lifestyle Changes with Medication

• Metabolic drugs like metformin can help patients feel better and then lifestyle changes can be addressed.

• Adding a ketogenic diet may be beneficial for some patients.

• Lifestyle changes such as exercise and diet could potentially help patients stay well and even taper off metabolic drugs.

Long-Term Challenges

• Metabolic dysregulation tends to march on over time, which is often genetic.

• Some patients end up needing multiple medications or insulin for type 2 diabetes.

Nutritional Intervention for Mental Illness

Dr. Ellen Vora discusses the importance of support and being open to nutritional intervention for mental illness. She talks about the need for a structured program that provides support to implement a ketogenic diet.

Importance of Support and Structured Program

• Patients need support and structure to implement a ketogenic diet.

• A structured program is needed to provide the necessary support for people to implement something like the ketogenic diet.

• People need direction and structure when it comes to making lifestyle changes, such as adopting a new diet.

Ketogenic Diet and Symptom Improvement

• Dr. Vora has interviewed people who have had success with ketogenic diets for their mental illness.

• There is no specific ketogenic diet, but dietary interventions can parallel the effects of a ketogenic diet in terms of increasing protein and decreasing simple carbohydrates.

• While mood stabilizers may still be necessary, managing metabolic dysregulation through nutrition could potentially reduce medication doses.

Adoption of Nutritional Intervention

• Patient testimonials can help spread awareness about nutritional intervention.

• Dr. Vora hopes that more family doctors will inquire about nutritional intervention as an additional treatment option for psychiatric illnesses.

Replicating the Trio Study and Incorporating Metabolic Psychiatry into Medical Training

In this section, the speaker discusses the importance of replicating the Trio study and incorporating metabolic psychiatry into medical training.

Replication of Trio Study

• The speaker's colleagues are hoping to get funding to replicate the Trio study and add a few other tests to look at mechanisms more deeply.

• Replication would help in terms of people starting to realize that metabolic dysregulation has an impact on psychiatric clinical outcomes.

Incorporating Metabolic Psychiatry into Medical Training

• The speaker does talks with family doctors because she thought she could get them on board easier than psychiatrists outside.

• The speaker teaches R2s about metabolic psychiatry, and they are close enough to their medical training that they're more accepting of it. She hopes that as they graduate, they will incorporate it into their practice.

• However, it is not a core part of their program for residents to come through and learn about metabolic psychiatry yet. It's a massive new approach based on better understanding of mechanisms underlying severe psychiatric illness.

Moving Forward with Education

• Education is key in moving forward with incorporating metabolic psychiatry into medical training and treatment practices. It takes time for change to happen, but the speaker is doing fantastic work in helping move things forward.

• Patients can arm themselves with the Trio paper and take it with them when seeing their doctors as many doctors may not have seen it before due to being super busy. This can help change things slowly over time.