Finals

• Major depressive disorder (MDD)


  Has significant potential morbidity and mortality, contributing to suicide, incidence and adverse outcomes of medical illness, disruption in interpersonal relationships, substance abuse, and lost work time
• Signs and symptoms of major depressive disorder

  • Normal appearance
  • Decline in grooming and hygiene
  • Change in weight
  • Psychomotor retardation
  • Flattening or loss of reactivity in the patient's affect (ie, emotional expression)
  • Psychomotor agitation or restlessness
  • Depressed mood (for children and adolescents, this can also be an irritable mood)
  • Diminished interest or loss of pleasure in almost all activities (anhedonia)
  • Significant weight change or appetite disturbance (for children, this can be failure to achieve expected weight gain)
  • Sleep disturbance (insomnia or hypersomnia)
  • Psychomotor agitation or retardation
  • Fatigue or loss of energy
  • Feelings of worthlessness
  • Diminished ability to think or concentrate; indecisiveness
  • Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or specific plan for committing suicide
• Monoamine hypothesis


  Suggests that depression is linked to a lack of or dysfunction in serotonin, norepinephrine, and dopamine (monoamines) in the brain regions involved in mood regulation (cortical and limbic)
• Evidence supporting the monoamine hypothesis

  • Reserpine can deplete monoamines and cause depression in some people
  • Depressed patients who respond well to specific antidepressants that target these monoamines are more likely to relapse if the monoamines are depleted again
  • Genetic variations that affect how monoamines are processed may influence vulnerability to depression and response to treatment
  • Studies of depressed patients have sometimes shown an alteration in monoamine function
  • Most antidepressants currently available work by affecting the monoamine system
• Neurotrophic hypothesis


  Proposes that a loss of neurotrophic support plays a key role in depression
• BDNF


  • A crucial nerve growth factor that supports neural plasticity (brain remodels and reorganizes after injury), resilience, and neurogenesis (creation of new neurons)
  • Evidence suggests depression is linked to a loss of BDNF support, potentially leading to atrophy (shrinkage) in the hippocampus, decreased volume in the anterior cingulate cortex, and reduced volume in the medial prefrontal cortex
• Studies show a possible 5-10% volume loss in the hippocampus of depressed individuals. Similar shrinkage is observed in the anterior cingulate cortex and medial orbital frontal cortex. The duration of untreated depression seems to be linked to the severity of volume loss
• Animal studies suggest direct BDNF infusion into specific brain regions has antidepressant-like effects. All major antidepressant classes appear to increase BDNF levels in animal models with chronic use (not immediate effects). This BDNF increase coincides with increased neurogenesis in the hippocampus of these animals. Effective treatments like electroconvulsive therapy also seem to stimulate BDNF and hippocampus neurogenesis in animals
• Lower BDNF levels in the cerebrospinal fluid and serum are observed in depressed individuals. Antidepressant use in humans can increase BDNF levels and may even be linked to increased hippocampus volume in some patients. However, while evidence is strong, some inconsistencies exist. BDNF knockout mice don't always show increased depression or anxiety as expected with BDNF deficiency. Animal studies sometimes even show increased BDNF after certain stressors and depressive behaviors with BDNF injections
• Variations (polymorphisms) in the BDNF gene might explain some of the conflicting findings. These variations can significantly impact how BDNF functions and potentially influence anxiety and depression risk
• Glutamate


  An excitatory neurotransmitter. Increased glutamate levels and changes in glutamate-related brain structures are observed in depression. Antidepressants seem to work partly by reducing glutamate activity. Chronic use lowers glutamate release in the hippocampus and other areas
• Ketamine


  An NMDA receptor antagonist that shows promise for rapid antidepressant effects, but has psychoactive side effects and is unsuitable for long-term use
• HPA axis


  A complex feedback system regulating stress response. MDD is associated with elevated cortisol levels, non suppression of ACTH release in a dexamethasone suppression test, and chronically elevated levels of corticotropin-releasing hormone (CRH)
• HPA axis abnormalities in MDD are linked more frequently to severe depression types than milder forms. Exogenous glucocorticoids and endogenous cortisol elevation can cause mood symptoms and cognitive deficits similar to MDD
• Thyroid dysregulation


  Up to 25% of depressed patients may have abnormal thyroid function, including blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) stimulation and elevated circulating thyroxine (T4) during depression. Clinical hypothyroidism often presents with depressive symptoms that improve with thyroid hormone replacement
• Sex steroids and depression

  Estrogen deficiency states (postpartum, postmenopausal) may contribute to depression in some women. Severe testosterone deficiency in men can be associated with depressive symptoms. Hormone replacement therapy in individuals with hypogonadism (reduced gonadal function) may improve mood and depression symptoms
• The different hypotheses (monoamine, neuroendocrine, neurotrophic) are not independent but interact in complex ways. HPA axis and sex steroid abnormalities may decrease the production of BDNF, a protein crucial for neuronal health. Antidepressants, by affecting monoamine receptors, have the opposite effect of stress: increase BDNF production and down-regulate the HPA axis
• The weakness of the monoamine hypothesis is the delayed antidepressant effects. Maximum benefit of antidepressants typically takes weeks to appear. Synthesis of neurotrophic factors like BDNF takes around 2 weeks and coincides with the typical timeline for improvement with antidepressants
• Types of anxiety disorders

  • Generalized Anxiety Disorder (GAD)
  • Panic Disorder
  • Obsessive-Compulsive Disorder (OCD)
  • Social Anxiety Disorder
  • Post-Traumatic Stress Disorder (PTSD)
• Generalized Anxiety Disorder (GAD)


  Chronic, free-floating anxiety and undue worry
• Panic Disorder


  Recurrent episodes of brief overwhelming anxiety, often without a precipitant, with fear of future attacks and avoidance behaviors
• Obsessive-Compulsive Disorder (OCD)


  Repetitive anxiety-provoking thoughts (obsessions) or repetitive behaviors (compulsions) aimed at reducing anxiety
• Social Anxiety Disorder


  Severe anxiety in social interactions, limiting ability to function adequately
• Post-traumatic Stress Disorder (PTSD)


  Intrusive anxiety-provoking thoughts or imagery, hypervigilance, nightmares, and avoidance of situations that remind the patient of the trauma
• Alterations in neurotransmitter activity, particularly serotonin and gamma-aminobutyric acid (GABA), contribute to heightened anxiety responses
• Types of pain disorders

  • Neuropathic pain
  • Chronic pain conditions, such as fibromyalgia
  • Joint pain, such as from osteoarthritis or rheumatoid arthritis
• Neuropathic pain


  Characterized by burning, tingling, or shooting sensations, often accompanied by sensory abnormalities
• Chronic pain conditions, such as fibromyalgia


  Involve widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive difficulties
• Psychological symptoms such as depression, anxiety, and reduced quality of life are common in patients with chronic pain. Chronic pain is comorbid with major depression, especially in cases of chronic pain, exacerbating overall symptom severity and impacting treatment outcomes
• Premenstrual Dysphoric Disorder


  Occurs in the late luteal phase of the menstrual cycle and includes symptoms such as anxiety, depressed mood, irritability, insomnia, and fatigue that are more severe than PMS and disruptive to daily life
• Pharmacological interventions, particularly selective serotonin reuptake inhibitors (SSRIs), are beneficial in reducing symptoms of Premenstrual Dysphoric Disorder
• Arthritis or rheumatoid arthritis


  Characterized by joint stiffness, swelling, and reduced range of motion
• Psychological symptoms


  Depression, anxiety, and reduced quality of life are common in patients with chronic pain
• Chronic pain


  Comorbid with major depression, exacerbating overall symptom severity and impacting treatment outcomes
• Premenstrual Dysphoric Disorder


  Occurs in the late luteal phase of the menstrual cycle
• Symptoms of Premenstrual Dysphoric Disorder

  • Anxiety
  • Depressed mood
  • Irritability
  • Insomnia
  • Fatigue, and other physical symptoms that are more severe than PMS and disruptive to daily life
• Pharmacological interventions for Premenstrual Dysphoric Disorder

  Particularly selective serotonin reuptake inhibitors (SSRIs), are beneficial in reducing symptoms
• Withdrawal symptoms from smoking cessation

  • Cravings
  • Irritability
  • Anxiety
  • Depression
• Nicotine dependency


  Leads to the urge to smoke, complicating cessation efforts
• Nicotine withdrawal


  May accompany mood symptoms and weight