Mood Disorders Lecture Notes PDF

MOOD DISORDERS Dr. Asmaa Elrakaybi gu.edu.eg Neurotransmitters and mood regulation Key neurotransmitters involved in mood regulation: Serotonin: Affects mood, anxiety, and happiness. Norepinephrine: Involved in stress response and alertness (fight or flight)....

MOOD DISORDERS Dr. Asmaa Elrakaybi gu.edu.eg Neurotransmitters and mood regulation Key neurotransmitters involved in mood regulation: Serotonin: Affects mood, anxiety, and happiness. Norepinephrine: Involved in stress response and alertness (fight or flight). Dopamine: Related to pleasure, reward, and motivation. GABA and Glutamate: Maintain the balance between excitation and inhibition, crucial for mood stability. Pathophysiology of mood disorders 1- The monoamine hypothesis The hypothesis suggests that mood disorders, particularly depression, are caused by a deficiency in the monoamine neurotransmitters: serotonin, norepinephrine, and dopamine. Mania is caused by excess of these neurotransmitters. Early antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs), work by increasing serotonin levels in the brain, supporting this hypothesis. However, not all patients respond to SSRIs, suggesting other factors may also be involved. 2- The Neurotrophic Hypothesis This hypothesis suggests that mood disorders are linked to reduced levels of Brain-Derived Neurotrophic Factor (BDNF), a protein that promotes the growth and survival of neurons. BDNF is crucial for neuroplasticity, the brain's ability to adapt and form new connections. Reduced levels are seen in mood disorders, leading to impaired synaptic connections and brain shrinkage, especially in the hippocampus. https://www.nature.com/articles/4002075 Antidepressants have been shown to increase BDNF levels, contributing to recovery. 3- The Neuroinflammation Hypothesis Patients with mood disorders often show elevated levels of pro-inflammatory cytokines such as IL-6 and CRP. Chronic inflammation can disrupt normal neurotransmitter activity and neuronal function, further contributing to symptoms of depression and anxiety. Anti-inflammatory treatments have shown potential https://www.nature.com/articles/s41380-024-02714-2 in improving mood in some studies. 4- Activation of hypothalamic-pituitary-adrenal (HPA) axis The HPA axis is the body’s central stress response system, involving interactions between the hypothalamus, pituitary gland, and adrenal glands. It regulates the release of cortisol, the primary stress hormone. Chronic Stress Hyperactivation of the HPA Increased cortisol release from adrenal glands axis Damage to hippocampal neurons Increased susceptibility to depression and mood (responsible for memory, learning, disorders and emotional regulation) Further dysregulation of the HPA Hippocampal atrophy axis 5- Circadian rhythm alterations Are the disruptions in the natural 24-hour cycle of biological processes that regulate various bodily functions, including sleep-wake cycles, hormone release, and metabolism. 1- The HPA axis, which regulates the stress response, is influenced by circadian rhythms. Alterations in these rhythms can lead to increased cortisol levels and increased risk of depression 2- Circadian rhythms influence the synthesis and release of neurotransmitters. Disruptions in circadian rhythms can lead to imbalances in these neurotransmitters. 3- Altered circadian rhythms can affect sleep patterns which might exacerbate depressive symptoms 6- The Neuroprogression Hypothesis The hypothesis suggests that untreated or chronic mood disorders lead to progressive structural and functional brain changes. The recurrence of mood episodes might contribute to: Cumulative damage in neural cells (e.g., neurons and glia), affecting the integrity of neural circuits and enhancing brain vulnerability to developing future illness episodes Persistent low-grade inflammation and oxidative stress. Further contributing to neuronal damage. Decreased neuroplasticity and brain atrophy. Chronic activation of HPA axis contributes to further hippocampal atrophy Major depressive disorders  Epidemiology and etiology: The lifetime prevalence estimates for MDD are 16.2%. Women are twice as likely as men to experience MDD. Theaverage age of onset is in the mid-twenties. Interestingly, MDD appears to occur earlier in life in people born in more recent decades. According to the WHO, depression is one of the leading cause of disability and the fourth leading cause of the global burden of disease. Some individuals have only a single episode with full return to premorbid functioning, 50%-85% have recurrences. CLINICAL PRESENTATION Patients typically present with a combination of emotional, physical, and cognitive symptoms Emotional: 1) Depressed mood most of the day almost every day, 2) Sadness Anhedonia Pessimism 3) Feeling of emptiness Irritability Anxiety Worthlessness Physical: 1. Disturbed sleep Change in appetite/weight 2. Decreased energy Fatigue 3. Bodily aches and pain Cognitive: 1. Impaired concentration 2. Indecisiveness Poor memory Occasionally, severely depressed patients also will present with psychotic symptoms: Hallucinations Delusions.  Diagnostic criteria The diagnosis of a major depressive episode (MDE) requires the presence of five depressive symptoms for a minimum of 2 weeks (nearly every day) that cause clinically significant effects. The diagnosis of MDD is based on the presence of one or more MDEs during a person’s lifetime One of the first 2 symptoms is a must in Depressed mood. addition to other symptoms Markedly diminished interest or pleasure in usual activities (anhedonia). Increase of decrease in appetite or weight. Increase or decrease in amount of sleep. The symptoms are not due to the direct Increase or decrease in psychomotor activity. physiologic effects Fatigue or loss of energy. of a substance or Feelings of worthlessness or guilt. medical condition. Diminished ability to think, concentrate, or make decisions. Recurrent thoughts of death, suicidal ideation, or suicide attempt. The symptoms must interfere with the patient’s everyday ability to function.  Patient assessment 2. Psychometric instruments used 1.Psychiatric history to assess severity of Athorough history of depression. symptoms is compared with the diagnostic criteria, and the diagnosis is made on the basis of Clinician rating Patient rating collected data. scales scales TheHamilton Rating Scale PHQ-9 for Depression Useful way of determining a patient’s level of depression before, during, and after treatment.  Patient assessment 3. Physical examination and 4. Medications and laboratory tests substance use They can induce depression as These are necessary to rule out adverse effect. physical causes: Interferons, Alcohol, CNS depressants e.g., thyroid disorders vitamin (benzodiazepines- barbiturates), β- deficiencies, anemia, cardiovascular blockers (propranolol, sotalol), Cocaine diseases, neurologic disorders, and amphetamines withdrawal, chronic pain , cancer corticosteroids, contraceptives Pharmacists should perform a drug and substance use review to identify possible causes  COURSEAND PROGNOSIS Symptoms of a major depressive episode usually develop gradually over days to weeks. Untreated, MDEslast 6 months or more. Approximately two-thirds of patients recover and return to normal mood, but one-third have only a partial remission. It is not uncommon for a patient to experience only a single MDE, but most patients with MDD experience multiple episodes. Time between episodes (isolated vs clusters) The number of prior episodes predicts the likelihood of developing subsequent episodes (>3 - - - 90%to have a 4th) MDD has a high mortality rate because approximately 15% of patients ultimately complete suicide. Bipolar disorders  Bipolar disorder is characterized by one or more episodes of mania or hypomania, often with a history of one or more major depressive episodes Mood episodes It is chronic, Occur with or can be manic, Increased risk with relapses without depressed, or of suicide and remissions psychosis mixed. Mania can be thought of as the affective opposite of depression. Mania: A manic episode is characterized by at least 1 week (or any duration, if hospitalization needed) of an abnormal and persistently elevated (expansive or irritable mood) The patient must also have three of the following symptoms (four if mood is irritable): ✓ Inflated self-esteem or grandiosity, ✓ Decreased need for sleep, ✓ Pressured speech, more talkative than usual ✓ Flight of ideas, ✓ Distractibility, ✓ Increased hyperactivity or psychomotor agitation, ✓ Involvement in high-risk activities without respect to the consequences. Hypomania: Hypomania is an abnormally and persistently elevated, expansive, or irritable mood but not of sufficient severity to cause significant impairment and does not require hospitalization: ✓ A hypomanic episode is a milder form of mania. ✓ This episode must exist for 4 days or longer and ✓ It is not severe enough to warrant hospitalization, ✓ It is not severe enough to cause marked social or occupational impairment, and ✓ It is not associated with psychosis Epidemiology: Bipolar I Bipolar II Characterized by one or more Characterized by one or more manic or mixed mood episodes. major depressive episodes and Affects men and women equally Major depressive episodes are at least one hypomanic not necessary for the diagnosis, episode. however, it is very common More common in women Cyclothymic disorder Periods of hypomanic episodes and Rapid cycling depressive episodes that do not meet At least four episodes of mania or all criteria for diagnosis of hypomania depression in 1 year and major depressive episode  Epidemiology: 78% to 85% of individuals with bipolar disorder report having another mental disorder during their lifetime. The most common comorbid conditions are anxiety, substance abuse, and impulse control disorders. The mean age of onset is 20 years (early childhood to the mid-40s). Bipolar disorder, particularly type II bipolar disorder, is often misdiagnosed as major depression (patients may not recall periods of hypomania, or may not interpret them as being pathological).  Epidemiology: Burden of illness; People living with BD experience substantial impairment. Patients are unable to maintain proper work approximately 30% or more of the time. Quality of life is reduced. Impairments are more pronounced in patients with depressive symptom. It is considered the sixth leading cause of disability‐adjusted life years among people aged 10‐24 years worldwide Epidemiology: Bipolar I patients spend about 32% of weeks with depressive symptoms Bipolar compared with 9% of weeks with manic disorder is often or hypomanic symptoms. misdiagnosed or Patients with bipolar II disorder spend underdiagnosed 50% of weeks symptomatic for depression and only 1% with hypomania. Clinical presentation: Clinical presentation and diagnosis: One must be present Clinical presentation and diagnosis: Increased talking (pressure of speech) Decreased need for sleep Clinical presentation and diagnosis: Distractible (poor attention) Clinical presentation and diagnosis: Exclude other causes Clinical presentation and diagnosis: If bipolar depression is mistaken for MDD and the patient is treated with antidepressants, it can precipitate a manic episode or induce rapid cycling. Depressive and bipolar disorders contribute to increased risk of suicidal attempts. Suicidality risk is increased in the presence of: Substance abuse. Prior suicide attempts and lethality of attempts. Access to a means of suicide. Command hallucinations or psychosis. Severe anxiety. Family history of attempted or completed suicide. Premenstrual dysphoric disorder Premenstrual dysphoric disorder PMDD is a severe form of premenstrual syndrome (PMS) characterized by significant emotional and physical symptoms occurring in the luteal phase of the menstrual cycle. Affects approximately 3-8% of women of reproductive age. More common in women with a history of mood disorders. Symptoms: Emotional: Severe depression, anxiety, irritability, mood swings. Physical: Fatigue, sleep disturbances, headaches, joint or muscle pain. Diagnostic Criteria (DSM-5) A- Symptoms must occur during the week prior to menstruation and resolve within a few days after the onset of menses. B- At least five symptoms must be present, including one or more of the following: - Marked affective lability (mood swings) - Irritability or anger - Depressed mood or feelings of hopelessness - Anxiety or tension One (or more) of the following symptoms must additionally be present to reach a total of 5 symptoms when combined with symptoms from criterion B above - Decreased interest in usual activities - Subjective difficulty in concentration - Lethargy, easy fatigability, or marked lack of energy - Marked change in appetite; overeating or specific food cravings - Hypersomnia or insomnia - A sense of being overwhelmed or out of control - Physical symptoms such as breast tenderness or swelling; joint or muscle pain, a sensation of “bloating” or weight gain Thank You gu.edu.eg