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Full Notes
Bipolar Disorder and Depression
- Bipolar disorder: massive shifts in energy, perception, and mood
- Maladaptive and can cause damage to the individual and those around them
- People with bipolar disorder are at 20–30 times greater risk of suicide
- Discussion also relevant for those with major depression
- Up to 20% of people will suffer from major depression at some point in their life
GLP‑1 and Appetite Suppression
- Glucagon-like peptide‑1 (GLP‑1): peptide that can suppress appetite
- Released in the gut and acts on intestinofugal enteric neurons
- Causes gut distension, making people feel full
- Activates neural pathways within the brain that trigger satiety
- Yerba mate: tea that promotes the release of GLP‑1
- Can provide mild appetite suppression and caffeine
- Avoid smoked varieties due to potential carcinogenic effects
- New prescription drugs for diabetes and obesity stimulate GLP‑1 release or are synthetic versions of GLP‑1
Parallel Pathways
- Parallel pathways: independent pathways that operate together to accomplish a common goal
- Example: GLP‑1 acting on the gut and brain for appetite suppression
- Example: Activation of epinephrine/adrenaline in response to stress or excitement
- Communication between brain and body is often bidirectional
-
Important theme in understanding biological organization
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Bipolar Disorder
- Affects 1% of the population
- Higher risk of suicide (20–30% greater incidence)
- Typical age of onset: 20–25 years old
- Two types: Bipolar I and Bipolar II
Bipolar I
- Characterized by extended periods of mania (elevated mood, energy, distractibility, impulsivity)
- Manic episodes last for 7 days or more
- Can be mistaken for other conditions (e.g., traumatic brain injury, drug use)
- Diagnosis requires at least three of the following symptoms:
- Distractibility
- Impulsivity
- Grandiosity
- Flight of ideas (rapid, disorganized thoughts)
- Increased goal-directed activity
- Decreased need for sleep
-
Excessive involvement in pleasurable activities with potential for negative consequences
Manic Bipolar Disorder -
Manic episodes: grandiosity, flight of ideas, agitation, no sleep, rapid pressured speech
- To be diagnosed with a manic episode, at least three symptoms must be present for at least seven days
- Psychiatrists must determine that these manic episodes are not due to something other than bipolar disorder (e.g., traumatic brain injury, seizures, medications, etc.)
Bipolar Disorder Types
Bipolar I
- Extended manic episodes (seven days or more)
- May or may not experience depressive episodes
- Can be diagnosed accurately even if only experiencing manic episodes and then dropping down to baseline
Bipolar II
- Characterized by the presence of both manic episodes (mania) and depressive episodes (hypomania)
- Hypomania: a somewhat suppressed level of mania, can be due to the duration or intensity of mania
- Often diagnosed on the basis of manic episodes lasting four days or less
- Associated with drops into depressive episodes
- People with bipolar I can also go from manic episodes to severe major depression
Variability in Presentation
- Bipolar disorder can vary tremendously between individuals
- Some may experience very high highs and very low lows, while others may rapidly cycle between mania and depression
-
It is important to erase the idea that manic bipolar disorder is a simple sine wave, cycling up and down between mania and depression
Bipolar Depression -
Bipolar disorder can be challenging to diagnose due to its varying forms
- Bipolar 1: manic episodes lasting 7 days or more
- Bipolar 2: hypomanic episodes lasting 4 days or less
- Manic episodes are the defining criteria of bipolar disorder
Bipolar 1 vs Bipolar 2
- Bipolar 1:
- 50% of time symptom-free
- 32% of time depressed
- 15% of time in manic or mixed manic state
- Bipolar 2:
- 50% of time in a depressed state
- 45% of time symptom-free
- 4–5% of time in hypomanic state
Global Burden of Bipolar Disorder
- Bipolar disorder is one of the highest risk factors for global burden (years lost in engaging in normal life due to disability)
- Proper treatment is crucial to reduce the impact of bipolar disorder on life trajectory
Heritability of Bipolar Disorder
- Interaction between genes and environment
- Identical twins: if one has major depression, there’s a 20–45% chance the other will also have major depressive disorder
-
This indicates that genes play a role, but environmental factors also contribute to the development of bipolar disorder
Genetics of Bipolar Disorder -
Heritability of bipolar disorder is 85%
- Higher genetic component than major depression
- No single gene or gene cluster identified for bipolar disorder
- Genetic susceptibility to environmental influences can trigger bipolar disorder
- If a family member has bipolar disorder, be on the lookout for symptoms in yourself and other family members
Distinguishing Bipolar Disorder from Borderline Personality Disorder
- Borderline Personality Disorder (BPD) can resemble bipolar disorder
- Key distinction: BPD episodes often have an environmental trigger, while bipolar disorder episodes can occur without a trigger
- BPD is characterized by “splitting” — sudden emotional shifts in response to external factors
- BPD is also a serious disorder, causing suffering for the individual and those around them
Treatments for Bipolar Disorder
-
Lithium is a successful treatment for many patients with bipolar disorder
- Discovered as a treatment before understanding the underlying biology of the disorder
- Naturally occurring substance, arrived on Earth through stardust
- For more information on the origins of lithium, refer to the linked YouTube talk in the show notes
Lithium and Bipolar Disorder
-
Discovery of lithium as a treatment for bipolar disorder
- Australian physician John Cade
- Observed mood vacillations in fellow prisoners of war during WWII
- Hypothesized a buildup of a chemical in the brain causing mania, which was then urinated out
- Cade’s experiments
- Collected urine from manic and non-manic patients
- Injected urine into guinea pigs
- Observed that urine from manic patients seemed more toxic
- Separated urea and uric acid, found urea was not the cause
- Used lithium to dilute uric acid, creating lithium urate
- Found lithium urate calmed guinea pigs and had a calming effect
- Tested lithium alone and found it also had a calming effect
- Cade’s paper: “Lithium Salts in the Treatment of Psychotic Excitement”
- Published in the Medical Journal of Australia in 1949
- Described case studies of patients with bipolar disorder treated with lithium
- Lithium treatment today
- Still used with success in many patients with bipolar disorder
- Requires careful monitoring of blood levels due to toxicity
- Not patentable, as it is a naturally occurring element
- FDA approved for use in the United States in 1970
-
Importance of understanding lithium’s mechanism
- Not all patients respond to lithium treatment
- Possibility for better treatments with fewer side effects
- Urgent need for new and better treatments for bipolar disorder
Lithium and Bipolar Disorder
-
Lithium: understanding its mechanisms can lead to new discoveries
- Thousands of scientific studies on lithium’s actions and mechanisms
- Increases BDNF (brain-derived neurotrophic factor)
- BDNF is permissive for neuroplasticity
- Allows neurons to change if proper environmental conditions are met
- Potent anti-inflammatory
- Suppresses inflammation in neural tissues and the brain
- Neuroprotective
- Prevents neurons from dying under certain conditions
- Protects against excitotoxicity (hyperactivity of certain brain areas killing off neurons)
- Increases BDNF (brain-derived neurotrophic factor)
Neural Circuits in Bipolar Disorder
- People with bipolar disorder have atrophy or removal of certain neural connections over time
- Leads to diminished interoception (registering one’s own internal state)
- Hyperactivity of certain neural circuits early in the disease
- Leads to excitotoxicity and atrophy of circuits responsible for interoception
- Lithium protects against atrophy of interoception circuits
- Through its anti-inflammatory, neuroprotective effects, and ability to increase BDNF
Treatment Challenges in Bipolar Disorder
- Different treatments or combinations of treatments for manic and depressive episodes
- Complexity of oscillations in mood and atrophy of interoception circuits
- Accurate understanding of bipolar disorder often depends on reports from people around the patient, not the patient themselves
Neural Circuits in Manic States
- Interoception is diminished in people with bipolar disorder
-
Further research needed to understand the neural circuits that lead to manic states
Neural Circuits in Bipolar Disorder -
Recent study: Longitudinal Changes in Structural Connectivity in Young People at High Genetic Risk for Bipolar Disorder
- Analyzed neural circuit connections (conectomics) in people with bipolar disorder
- Found deficits in connectivity between parietal brain regions and the limbic system
- Limbic system: collection of brain structures responsible for shifting overall states (e.g., calmness, alertness)
- Parietal lobe: exerts top-down control over the limbic system
- People with bipolar disorder have reduced internal awareness due to disrupted neural structures like the insula
- Top-down control over limbic system is also disrupted in bipolar disorder
Homeostatic Plasticity
- A form of neuroplasticity that balances neural circuit activity
- If a neural circuit is overactive, changes occur at the cellular level to reduce activity
- If a neural circuit is underactive, changes occur to increase activity
- Involves the addition or removal of receptors in the postsynaptic neuron
- Discovered in the visual system by Gina Turrigiano at Brandeis University
-
Important for understanding the treatment of psychiatric conditions, including bipolar disorder
Homeostatic Neuroplasticity in Bipolar Disorder -
Lithium and ketamine seem to exert their actions through effects on homeostatic neuroplasticity
- Lithium reduces excitability of neurons over time, making them less excitable
- Ketamine increases the number of receptors in postsynaptic neurons, leading to greater excitability and electrical activity within neural circuits
Ketamine and Lithium in Bipolar Disorder
- Ketamine: effective treatment for major depression and depressive episodes in bipolar disorder
- Effects are potent but transient, requiring repeated treatments
- Lithium: reduces manic episodes and intensity of manic symptoms in bipolar disorder
- Protects neural circuits from dying away due to overactivity and excitotoxicity
- Reduces the number of receptors in certain elements within circuits, leading to less excitability and preventing excitotoxicity
Talk Therapies in Bipolar Disorder
- Drug therapies are most effective when combined with talk therapies
- Talk therapy alone is rarely effective for bipolar disorder
- Cognitive Behavioral Therapy (CBT) is the most popular and effective talk therapy for bipolar disorder
- Progressive exposure to triggers or conditions that exacerbate bipolar disorder in a controlled clinical setting
- Family Focused Therapy
- Involves family members in the treatment process, helping patients navigate and predict conditions that can trigger bipolar episodes
-
Interpersonal and Social Rhythm Therapy
- Focuses on establishing and maintaining regular daily routines and social rhythms to stabilize mood and prevent relapse
Interpersonal and Social Rhythm Therapy
- Focuses on establishing and maintaining regular daily routines and social rhythms to stabilize mood and prevent relapse
-
Expansion on family-focused therapy
- Incorporates social and interpersonal aspects
- Recognizes the impact of relationships and financial situations on bipolar disorder
Electric Shock Therapy (ECT)
- Effective treatment for major depression
- Used for treatment-resistant depression
- Stimulates the release of serotonin, dopamine, acetylcholine, and BDNF
- Invasive, high cost, requires anesthesia, and may cause memory loss
Repetitive Transcranial Magnetic Stimulation (rTMS)
- Non-invasive technique to reduce activity in specific neural circuits
- Effective in increasing neuroplasticity and reducing depressive episodes
- Early technique with limited availability
Ketamine Therapy
- Primarily targets depressive aspects of bipolar disorder
Psilocybin
- Shows promise for treating major depression, OCD, and eating disorders
- No controlled clinical trials for treating mania in bipolar disorder
Cannabis
- Not effective for treating manic or depressive phases of bipolar disorder
- May help with sleep in some cases
Naturopathic Approaches
- Not recommended as the sole treatment for bipolar disorder
- Should be combined with appropriate prescription drug approaches from a board-certified psychiatrist
Lifestyle Interventions
-
Can support people with bipolar disorder alongside medical treatments
Lifestyle Factors and Bipolar Disorder -
Sleep, exercise, nutrition, social interactions, and sunlight can support the nervous system and psyche of someone with bipolar disorder
- These factors have a modulatory effect, indirectly shifting the likelihood or intensity of an episode
- However, most people with bipolar disorder will still need drug therapy intervention
- Lifestyle interventions alone are unlikely to prevent extreme forms of mania and depression in bipolar disorder
Inositol and Omega‑3 Fatty Acids
- Inositol and omega‑3 fatty acids have shown potential in adjusting symptoms of bipolar disorder
- Inositol:
- Related to second messenger pathways, which can affect cell membrane fluidity
- Can improve sleep, reduce anxiety, and help with symptoms of OCD
- Omega‑3 fatty acids:
- Found in fish oil and can change cell membrane fluidity
- Some studies show improvement in depressive symptoms and manic symptoms in bipolar disorder
- Should not be viewed as the only treatment approach for bipolar disorder
Importance of a Comprehensive Treatment Approach
- People with bipolar disorder should consider a combination of drug treatments, talk therapy, lifestyle interventions, and supplement-based treatments (such as omega‑3 supplementation) to manage their illness
-
Omega‑3 fatty acid supplementation is interesting for its potential effects on brain imaging and neural circuits in people with bipolar disorder, but it should not be relied upon as the sole treatment
Omega‑3 Fatty Acids and Bipolar Disorder -
Study published in the American Journal of Psychiatry
- Omega‑3 fatty acid treatment and T2 whole brain relaxation times in bipolar disorder
- MRI scans show how brain structures and neural activity can be evaluated
- Study shows that membranes of neurons in bipolar subjects treated with Omega‑3 fatty acids showed more fluidity and ability to move in and around the membranes
- Omega‑3 supplementation not the only intervention, but worth considering and discussing with a doctor
Creativity and Bipolar Disorder
- Certain aspects of mania are associated with creativity
- Occupations with higher incidence of bipolar depression: poetry, fiction writing, art, nonfiction writing, music composition, theater
- Important to distinguish between emotional states and full-blown bipolar disorder
- Bipolar disorder is extremely maladaptive and associated with high suicide risk
- Be cautious when labeling people as “bipolar” or “OCD” without understanding the severity of these psychiatric conditions
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