Helpful Links

The California Coalition for Youth is a program implemented to prevent suicide in california’s youth. They offer a direct line at (800)843 5200. This organization for the last 34 years has made a significant difference in the lives of youth healing through trauma, identity questions, human trafficking, and teen-related struggles such as bullying. 

According to their website they specifically focus on family conflicts, depression, sexual assault, dating issues, dating violence, and youth homelessness. This also includes internal conflicts such as self-harm, suicide ideation. 

This organization is truly remarkable in their targeted approach to mental health support in California. If you would like to learn more or donate, please see the link: 

https://calyouth.org/donate/ 

Transcript for the Podcast

Transcript: Welcome to Mirroring Medicine with Kodi and Isabel! In this episode of Mirroring Medicine we will be highlighting Suicide Prevention. We will go over the statistics, U.S. trends, risk factors, molecular mechanisms of depression, and mechanisms of treatments. We hope that those experiencing suicide ideation are aware that treatment exists and there is a path to recovery.

Please note, if you or someone that you know is experiencing depression, suicidal thoughts there ia a national hotline available. This is National Hopeline Network, Suicide & Crisis Hotline which can be reached at 1-800-442-4673.  

First, let us define what suicide is and the key terms associated with this topic?

According to the National Institute of Mental health, Suicide is the death caused by self-directed injuries, with the intent to die. 

A suicide attempt is when an individual is self-directed, injurious behavior with the intent to die. However, suicide attempt does not result in death, but rather in most cases injury and hospitalization. 

Suicide ideation is when an individual is thicking about, considering or planning their suicide. 

When looking into the historal underpinnings of suicide, we see that it has occured in every culture, region and ethnic group according to the NIH article Two Mistaken Beliefs about Suicide. Noted as one of the first documented suicides being in 510 B.C. according to History Collection, 2017. 

What causes suicide?

According to Pridmore et al, there are many identified variables associated with suicide this includes mental disorders, being a male, being unmarried, alcohol use, health problems, and unemployment. When looking at meta-analysis of the documented suicides, “95% of those who are designated as high-risk do not die by suicide, and 50% of those who do die by suicide come from the group which would be classified as low-risk.” Meaning creating a preventative algorithm is especially challenging. 

In the U.S. Suicide is one of the leading causes of dealth according to the national institute of mental health they cite the Centers for Disease Control and Prevention (CDC) WISQARS Leading Causes of Death Reports. From 2022 the data concluded that: 

Suicide was the eleventh leading cause of death overall in the United States, claiming the lives of over 49,400 people.

Suicide was the second leading cause of death among individuals between the ages of 10-14 and 25-34, the third leading cause of death among individuals between the ages of 15-24, and the fourth leading cause of death among individuals between the ages of 35 and 44.

There were nearly two times as many suicides (49,476) in the United States as there were homicides (24,849). 

Male Suicide is often mentioned in regards to the contemporary male loneliness epidemic.

As of 2022, the suicide rate amoung males was 4 time higher than females, according to the Leading Causes of Death Reports mentioned earlier.

As a society how can we prevent suicide?

According to Schwartz-Lifshitz et al, the most effective ways in preventing suicide include responsible media coverage, public education on the subject, and screening for risk factors. 

Treatment for suicide prevention include pharmocotherapy and psychotherapy. Psychotherapy involves talking with a mental health professional to address and modify thought and behavior patterns, while pharmacotherapy involves using medication to alter brain chemistry and manage symptoms. 

According to the article, “The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis” by Kamenov et al, when looking at the efficacy of psychotherapy and pharmacotherapy across 153 articles, combined treatment shows the largest efficacy. In the literature reviewed, the most common psychotherapeutic interventions used with cognitive behavioral therapy and interpersonal therapy.

Non-profit: The California Coalition for Youth is a program implemented to prevent suicide in california’s youth. They offer a direct line at (800)843 5200. This organization for the last 34 years has made a significant difference in the lives of youth healing through trauma, identity questions, human trafficking, and teen-related struggles such as bullying. 

According to their website they specifically focus on family conflicts, depression, sexual assault, dating issues, dating violence, and youth homelessness. This also includes internal conflicts such as self-harm, suicide ideation. 

This organization is truly remarkable in their targeted approach to mental health support in California. If you would like to learn more or donate, please see the link in our show captions: https://calyouth.org/donate/ 

Kodi’s Part: 

Molecular Mechanisms of Depression that can lead to Suicide

So as Isabel has mentioned before on the history of Suicide and how depressive symptoms could at times to suicidal ideation or even suicide, I am going to talk about the molecular mechanisms of depression. So what do I mean by the molecular mechanisms of depression? I will be talking about on the small level what is happening on the cell level or even smaller with smaller molecules that can affect your emotions and the brain’s processing of it. 

So what are the molecular mechanisms of depression or major depressive disorder (also known as MDD)? According to the article in Nature Journals on Major depressive disorder: hypothesis, mechanism, prevention and treatment (Cui, L., Li, S., Wang, S. et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment. Sig Transduct Target Ther 9, 30 (2024). https://doi.org/10.1038/s41392-024-01738-y), major depressive disorder is characterized by anhedonia is a feature of MDD, which means the inability to feel the feelings of pleasure at things that used to feel or is commonly known as pleasurable. MDD is also accompanied by a lack of drive, sleep issues, cognitive challenges, and emotional symptoms such as guilt. This article discusses the numerous hypotheses that can contribute to the feeling of depression or the pathogenesis of MDD (major depressive disorder). This includes the monoamine hypothesis where neurotransmitters (also known as molecules that transport between neurons) become dysregulated specifically with molecules with one amine (a nitrogen containing group). According to the monoamine hypotheses of mood disorders by the journal of basic neurochemistry: molecular, cellular, and medical aspects. 6th edition, (Barchas JD, Altemus M. Monoamine Hypotheses of Mood Disorders. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28257/) they state that depression is caused by functional deficiencies like catecholamines like norepinephrine. And the decrease of activation of 5-HT (serotonin 5-hydroxytryptamine), norepinephrine, dopamine, and epinephrine. The other alternative hypotheses may include HPA (hypothalamus-pituitary-adrenal) axis dysfunction hypothesis, inflammatory hypothesis, genetic and epigenetic (meaning the environments’ effect on your gene regulation) anomaly hypothesis, structural and functional brain remodeling hypothesis, and the social psychological hypothesis. Since we are talking about the molecular mechanisms of depression, I will be focusing more on the monoamine hypothesis. So in order to answer this question of what monoamines are and how they affect our body, we need to know the function of these neurotransmitters, how they are degraded in the body, and the available treatment options for them. 

What are monoamines? 

According to science direct in the chapter on Pharmacological mechanisms and the modulation of Pain, monoamine neurotransmitters are a class of neurotransmitters containing one amino group connected to an aromatic ring by a carbon-carbon chain. The current monoamine neurotransmitters include dopamine, norepinephrine, and serotonin (5-hydroxytryptamine), and these are derived from your amino acids like phenylalanine, tyrosine, and tryptophan (also known as the bulky amino acids). 

What are the functions of these monoamines?

Dopamine - According to the cleveland clinic, “Dopamine is a neurotransmitter made in your brain. It plays a role as a “reward center” and in many body functions, including memory, movement, motivation, mood, attention and more. High or low dopamine levels are associated with diseases including Parkinson’s disease, restless legs syndrome and attention deficit hyperactivity disorder (ADHD). Including involvement in movement, memory, pleasurable reward and motivation, behavior and cognition, attention, sleep and arousal, mood, learning, and lactation. (https://my.clevelandclinic.org/health/articles/22581-dopamine)

Norepinephrine - According to StatPearls Journal for the article on Physiology, Noradrenergic Synapse, “Norepinephrine, also known as noradrenaline is a neurotransmitter of the brain and plays an essential role in the regulation of arousal, attention, cognitive function, and stress reactions, included in the sympathetic nervous system for the fight or flight response. (Hussain LS, Reddy V, Maani CV. Physiology, Noradrenergic Synapse. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540977/)

Serotonin - According to the Cleveland clinic, “Serotonin plays several roles in your body, including influencing learning, memory, happiness as well as regulating body temperature, sleep, sexual behavior and hunger. Lack of enough serotonin is thought to play a role in depression, anxiety, mania and other health conditions.” (https://my.clevelandclinic.org/health/articles/22572-serotonin)

What do they bind, how do they activate, and how does it translate to depression?

Monoamines bind to G-protein coupled receptors also known as GPCRs to trigger a molecular cascade that exhibits the reward or happiness feeling downstream. Or they can also bind to ligand-gated ion channels that depolarize or hyperpolarize due to their effect on the body as well. 

So the three primary fates of monoamines are reuptake into the presynaptic neuron or the neuron that releases these monoamines (kind of think of it as anything not used gets put back in place), enzymatic degradation which break down these monoamines to they are no longer functional, or diffusion away from the synapse to nearby glial cells which clear the area of the synapse. Of course, these are the other fates if they do not bind to the postsynaptic neuron. This can lead to depression due to lack of binding, leading to less happiness being felt or the anhedonia mentioned prior.

Molecular Mechanisms of Treatments of Depression

So what are treatments that people usually take to manage their depression or prevent symptoms of major depressive episodes? So mainly I am going to be talking about the medication side and the molecular mechanisms for these medications. According to the mayo clinic, here are antidepressants that are also known as SSRIs which are Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and atypical antidepressants. Some SSRIs include Prozac, Paxil, Zoloft, Celexa, and Lexapro. (https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046273) The mechanisms of action of SSRIs inhibit the first fate that I have talked about previously about the reuptake into the presynaptic neuron. By blocking this channel through medication, these monoamines cannot be taken up by the neuron that produced it as much and then have more of a chance for activation on the postsynaptic receptors for a more extended period according to StatPearl on SSRIs. This can prevent this lack of happiness by activation of these postsynaptic neurons by more chances of binding for these monoamines. (Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554406/)

Thank you for joining us on Mirroring Medicine. Today we explored the history, risk factors, and molecular mechanisms behind depression and suicide—and, most importantly, the hope that comes with effective prevention and treatment.

If you or someone you know is struggling with suicidal thoughts, help is available. In the U.S., you can call or text 988, or reach the National Hopeline Network at 1-800-442-4673 for immediate support.

Remember: recovery is possible and you are not alone. We encourage you to share these resources, start conversations about mental health, and continue learning.

Until next time, this is Isabel and Kodi wishing you care, compassion, and connection.

Citations

Citations:

1. “History of Suicide: 10 Historical Figures Who Ended Their Lives.” History Collection,⁠ https://historycollection.com/suicide-club-10-historical-figures-ended-lives/⁠.

2. “National Suicide Prevention Lifeline: 1-800-273-TALK (8255).” National Toolkit, Florida State University College of Social Work,⁠ https://nationaltoolkit.csw.fsu.edu/resource/national-suicide-prevention-lifeline-1-800-273-talk-8255/⁠.

3. “Suicide Statistics.” National Institute of Mental Health,⁠ https://www.nimh.nih.gov/health/statistics/suicide⁠.

4. Pridmore, Saxby, et al. “Two Mistaken Beliefs about Suicide.” Iranian Journal of Psychiatry, vol. 14, no. 2, Apr. 2019, pp. 182–83. PubMed Central, PMC6702281,⁠ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702281/⁠.

5. Schwartz-Lifshitz, Michal, et al. “Can We Really Prevent Suicide?” Current Psychiatry Reports, vol. 14, no. 6, Dec. 2012, pp. 624–33. https://doi.org/10.1007/s11920-012-0318-3.

6. Cui, L., et al. “Major Depressive Disorder: Hypothesis, Mechanism, Prevention and Treatment.” Signal Transduction and Targeted Therapy, vol. 9, no. 30, 2024,⁠ https://doi.org/10.1038/s41392-024-01738-y⁠.

7. Barchas, J. D., and M. Altemus. “Monoamine Hypotheses of Mood Disorders.” Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 6th ed., edited by G. J. Siegel et al., Lippincott-Raven, 1999,⁠ https://www.ncbi.nlm.nih.gov/books/NBK28257/⁠.

8. “Dopamine.” Cleveland Clinic,⁠ https://my.clevelandclinic.org/health/articles/22581-dopamine⁠.

9. “Antidepressants: Selecting One That’s Right for You.” Mayo Clinic,⁠ https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046273⁠.

10. Chu, A., and R. Wadhwa. “Selective Serotonin Reuptake Inhibitors.” StatPearls, updated 1 May 2023, StatPearls Publishing, 2025–,⁠ https://www.ncbi.nlm.nih.gov/books/NBK554406/⁠.