BIOSCI 41 Midterm 2

• Mood disorders encompass various conditions like mania, hypomania, and depression.

Mania

• Extremely elevated, euphoric, or irritable mood is present.
• Excessively high energy levels are experienced, reducing the need for sleep.
• Symptoms include racing thoughts, grandiosity, distractibility, impulsivity, risk-taking, and hyperactivity.
• Psychosis (delusions, hallucinations) may occur.

Hypomania

• Less intense form of mania is present.
• Mood is elevated but less intense, with increased energy levels.
• Individuals remain functional with a decreased but present need for sleep.
• Fast thoughts are organized, with increased productivity and sociability.
• Psychosis is uncommon.

Mild Depression

• Low mood, sadness, and slight anhedonia are present.
• Energy levels are slightly lower than normal.
• Individuals struggle with falling or staying asleep.
• Negative thoughts and mild guilt, with less interest in activities.
• Psychosis is uncommon.

Severe Depression

• Characterized by persistent sadness, hopelessness, and despair.
• Fatigue and lack of energy are experienced.
• Insomnia or hypersomnia may be present.
• Thoughts of suicidal ideation and worthlessness, with withdrawal from social situations and inability to function normally.
• Psychosis is possible in severe cases.

Bipolar I

• Requires at least one full manic episode.
• Depression is often present but not required.
• More severe with possible psychosis.
• Impairs daily life functioning, and hospitalization is more common due to mania.

Bipolar II

• Does not show full mania, only hypomania.
• Depression is required for diagnosis.
• Less severe than Bipolar I but with recurrent depression.
• People may still function relatively well.
• Psychosis is less common but possible in severe depression.

Schizoaffective Disorder

• Combines symptoms of schizophrenia with mood disorder symptoms such as depression or mania.
• Symptoms include mood disturbances and schizophrenia-like symptoms (depression, mania, delusions, hallucinations).
• Psychosis can be present without mood symptoms.
• Mood episodes can be depressive, manic, or mixed.
• Treatment uses antipsychotics plus mood stabilizers.

Bipolar Disorder

• Symptoms include mood episodes (mania, hypomania, depression) without primary psychosis.
• Psychosis occurs only during mood episodes, if at all.
• Treatment includes mood stabilizers and antidepressants.

Behaviors Associated with Bipolar Mania

• Spending sprees and business ventures.
• Hypersexuality and unwanted pregnancy.
• Ill-considered marriages.
• Conflict with the law.
• Car accidents, fights and disputes, and poor relationships.

Altman Self Rating Scale (ASRM)

• A 5-item self-rating mania scale is used to assess the presence and/or severity of manic symptoms.
• Used in inpatient or outpatient settings to screen for manic symptoms for clinical or research.

Neurobiology of Bipolar Disorders - Physiologic Brain Changes

• Enlarged ventricles may indicate progressive brain volume loss.
• Decreased white matter correlates with bipolar disorder severity.
• The disruption of myelinated tracts affects the prefrontal cortex and limbic system.
• Decreased white matter is associated with suicidality, indicating neuroinflammation, ischemia, or demyelination.
• Grey matter loss in the right frontal cortex may impair emotional regulation and executive function.

Hyperintensity Signal

• Bright areas are visible in white matter on an MRI scan.
• Indicates small regions of cell death.
• Suggests myelin damage, which may contribute to cognitive dysfunction.
• Lesions may disrupt neural connectivity, especially between the prefrontal cortex and limbic system.

Amygdala and emotion

• Crucial for recognizing fear and processing emotional responses.
• Damage or dysfunction impairs emotional recognition and dysregulates mood.
• The parahippocampal gyrus supports contextual memory and integrates emotions with past experiences.
• Works alongside the amygdala to assign emotional meaning to memories.

Amygdala Activity in Bipolar Disorder

• Adolescents show increased right amygdala and parahippocampal gyrus activation in response to fearful faces.
• Younger people may show greater right amygdala hyperactivity, leading to increased emotional volatility. Older individuals may develop left amygdala hyperactivity, leading to persistent emotional dysregulation, especially in mania and depression.

Meta Data on Bipolar Disorder

• Meta-analysis reveals that the adult left amygdala and parahippocampal gyrus is hyperactive in Bipolar patients with right-sided gray matter decreases in the frontal cortex.
• This explains why people with bipolar disorder struggle with recognizing fearful and neutral facial expressions
• Right sided grey matter loss in the frontal cortex impairs top-down emotional control, allowing hyperactive limbic structures to dominate emotional responses.

Anterior Cingulate Cortex

• Acts as a bridge between the limbic system (emotion) and prefrontal cortex (rational control).
• Dysfunction in this area can lead to reduced matter, leading to weaker emotional regulation.
• Altered activity levels; decreased during depression leads to emotional blunting and lack of motivation, and increased during mania leads to impulsivity and excess emotional reactivity. FMRI concludes that repeated mood episodes are linked to progressive ACC atrophy, suggesting that bipolar disorder has a neurodegenerative component.

Sociocultural Aspects of Bipolar Disorders

• Worldwide lifetime prevalence of BP-I is 0.6%, BP-II is 0.4%, and subthreshold BP is 1.4%, yielding a total prevalence estimate of 2.4%.
• 12-month prevalence of BP-I is 0.4%, BP-II is 0.3%, and subthreshold BP is 0.8%.
• Lifetime rates of BP-I and subthreshold BP are greater in males.
• Females had higher cases of BP-II.
• Onset typically occurs between the ages of 20-30.

Comorbidity

• Comorbidity is the simultaneous presence of two or more diseases or medical conditions in a patient.
• 3/4 of those with BPS also met criteria for another lifetime disorder, more than half of whom had 3 or more disorders.
• Anxiety disorders, particularly panic attacks, were the most common comorbid conditions.

Bipolar Clinical Characteristics Over 12 Months

• The vast majority of 12-month BPS cases reported severe or moderate manic/hypomanic or major depressive episodes.
• Combined manic/hypomanic and depressive episodes were more severe among BP-I and BP-II compared to threshold BP.
• Younger individuals are more at risk for initial onset.
• Age-related changes can worsen symptoms over time.
• Women tend to have a later onset and more depressive symptoms.
• Men have an earlier onset and more manic symptoms.
• Poor sleep, substance use, stress, and lack of exercise can exacerbate symptoms, while healthy habits and good social support can help stabilize the disorder.

Bipolar Disorder and Metabolic Disorders

• Bipolar and metabolic disorders are often comorbid.
• Individuals with BP are at higher risk of developing metabolic issues such as obesity, diabetes, and cardiovascular problems.
• May be caused by: medications (antipsychotics), lifestyle factors (poor diet, lack of exercise), and the biological underpinnings of bipolar disorder itself.
• Individuals with BPD have elevated uric acid levels.

Bipolar Disorder and Gout

• Both are linked to high uric acid levels.
• Gout occurs when uric acid crystals build up in joints, causing pain and inflammation.
• Uric acid is typically elevated in individuals with bipolar disorder.
• Elevated uric acid levels are associated with purine metabolism, sugar consumption, and the body's inability to process uric acid effectively.
• Lithium may have an incidental benefit for managing elevated uric acid levels in individuals with bipolar disorder.

Lithium

• Lithium reduced uric acid levels by increasing its excretion.
• It regulates mood by modulating neurotransmitters, particularly glutamate and GABA, to stabilize mood and prevent manic episodes.

Gender, Sugar Consumption, and Bipolar Mania

• Sugar consumption, fructose may contribute to elevated uric acid levels.
• Since males generally have higher levels of uric acid than females, they may be more prone to the effects of sugar intake on their metabolic health.
• Elevated uric acid levels are associated with mood swings and the onset of manic episodes.

Lithium and Glutamate

• Glutamate is an excitatory neurotransmitter.
• In BPD, glutamate levels can fluctuate dramatically, leading to extreme mood states.
• Lithium stabilizes glutamate levels to prevent overstimulation of neurons that can trigger manic episodes.

First-Line treatments for bipolar disorder

• Manic Phase: Mood stabilizers (lithium or valproate) or antipsychotics (olanzapine or risperidone).
• Depressive Phase: Antidepressants with caution, or lamotrigine (a mood stabilizer).
• Maintenance Phase: Mood stabilizers (lithium, valproate) and sometimes antipsychotics.

Second-Line Treatments for bipolar disorder

• Manic Phase: Anticonvulsants (carbamazepine) or additional antipsychotic medications if first-line treatments are ineffective.
• Depressive Phase: Anticonvulsants, atypical antipsychotics, or the combination of lithium and antidepressants if antidepressants are ineffective or contraindicated.
• Maintenance Phase: A broader range of antipsychotics or anticonvulsants, sometimes in combination with a mood stabilizer.

Antipsychotics

• Action of antipsychotics: They work by altering the activity of neurotransmitters in the brain, particularly dopamine, which is involved in mood regulation and psychotic symptoms.
• Side effects of antipsychotics: Motor side effects, such as tremors, rigidity, bradykinesia, and dyskinesia, particularly with first-generation antipsychotics.

Mood Chart

• It is used by individuals with bipolar disorder to track mood, sleep patterns, and other symptoms.
• Recording daily moods on a scale from 1 (depressed) to 10 (manic), along with notes about activities, medication, and triggers.

Methylation

• A chemical group (methyl group, -CH3) attaches to a part of the DNA
• This can turn off or silence a gene, preventing it from being used to make proteins.
• Methylation silences gene expression by adding methyl groups to DNA, typically at CpG sites, which blocks transcription factors.

Epigenetics

• Changes in gene expression without altering the DNA sequence.
• Caused by environment, lifestyle, and experiences.
• Includes mechanisms like DNA methylation.
• Monozygotic twin studies are useful.

Promoter Hypermethylation

• Can lead to disorders like bipolar or schizophrenia.
• Excessive methylation in promoter regions silences gene expression.
• Silencing critical genes (5-HTT and BDNF) affects brain function, disrupting mood regulation, neural growth, and protection.

Epigenetic Modification Gene examples

• 5-HTT (serotonin transporter gene): Epigenetic changes, including methylation.
• BDNF (brain-derived neurotrophic factor): Methylation of BDNF.
• COX-2: Plays a key role in inflammation and pain.

BDNF and Bipolar

• Supports neural growth and neuroplasticity.
• In BPD, BDNF levels are altered with reduced expression seen in the depressed phase.
• Lower methylation leads to higher gene expression.
• Lithium treatment increases BDNF levels and promotes neuroplasticity, helping stabilize mood.