Mood Disorders - Summarize notes from lecture and PowerPoint PDF

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Mood Disorders

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Objectives

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Given a history of mood episodes, list the mood disorders that a patient may have. Given a case, recognize the signs and symptoms of manic and depressive episodes. Name and interpret the most commonly used screening test for depression. List alterations in the functioning of the hypothalamic-pituitary axis that may be present in those with mood disorders. Identify drugs and disease states that are associated with the development of signs and symptoms of mood disorders. List the major hypotheses (covered in class) for the development of mood disorders and identify the chemical alterations associated with each hypothesis. Describe the impact of depression, mania or bipolar disorder on a patient. Given a case, recognize potential complications of mood disorders.

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Definitions (DSM-5) •

major depressive episode o an episode of significant distress or impairment in social, occupational or other important areas of function lasting at least two weeks o characterized by markedly diminished pleasure or interest or a depressed mood.

Signs & Symptoms -- Major Depressive Episode • • • • • •

depressed mood loss of pleasure or interest significant weight loss (5%) Insomnia or hypersomnia* psychomotor agitation or retardation* Fatigue or loss of energy*

One italicized symptom must be present Must have 5 or more symptoms * indicates must occur nearly every day

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feelings of worthlessness or inappropriate guilt* diminished ability to think, concentrate or indecisiveness* recurrent thoughts of death or recurrent suicidal ideation or suicide attempt

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The US Preventative Services Task Force recommends routine screening for depression in adults with a variety of scales 9 item PHQ-9 is first choice in primary care Screening is appropriate annually or at time of regular “health checks”

What two problems do you want to ask about to screen for depression? 

Over the past 2 weeks, how often have you been bothered by the following problems? o Little interest or pleasure in doing things. o Feeling down, depressed or hopeless. Signs and Symptoms of Depression

Categories (not DSM-5) • • • •

Emotional Somatic Vegetative Intellectual

Emotional • • •

depressed mood anhedonia (loss of pleasure) irritability

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loss of interes social withdrawal guilt worthlessness self pity fear helplessness hopelessness psychosis suicidal ideation

Somatic • • • • • •

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Usually have no physiologic basis Headache Backache Gastrointestinal complaints Pain Other

Intellectual

Vegetative • • • •

Other GI complaints Weight gain Psychomotor retardation Fatigue Psychomotor agitation Menstrual irregularities Impotence

Lack of energy Insomnia Constipation Weight loss

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Decreased concentrating ability Memory lapses Diminished ability to calculate Trouble making decision

Depression  50% of those patients having a single episode of depression will have a second episode • 2:1 ratio greater in women than men • lifetime expectancy o men = 10%; women = 20% Which disease state is most similar to depression? • • • •

Diabetes mellitus Hypertension Hypothyroidism Hyperthyroidism

Hormonal Abnormalities in Depression • • • • •

Abnormal DST – failure to suppress cortisol release (dexamethasone) Reduced ACTH response to CRF Reduced TSH response to TRH Low T3 Distinguish depression from hypothyroidism

Complications of Depression • • • • • • •

Suicidal ideation Hallucinations, delusions Self-neglect Need for institutionalization Disruption of family, employment, etc. Substance abuse Association with inflammation, diabetes, cardiovascular disease, reduced immune response

Hypotheses - Depression • • • •

Biogenic Amine Serotonin Dopamine Neurotrophic/Neuroplasticity

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Epigenic Inflammatory Gut bacteria

Biogenic Amine Hypothesis of Depression • • • • •

Reserpine associated suicides Decreased biogenic amines lead to depression Most treatments reduce sensitivity of post synaptic beta adrenergic receptors TCAs inhibit reuptake, increase monoamines in synapse High norepinephrine in mania

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30% increase in brain MAO in subgroup of patients with depression

Serotonin Hypothesis of Depression • • • •

Low serotonin levels in suicide victims Low 5-HIAA metabolite levels in depressed individuals Variants in the gene that regulates 5-HT availability are associated with increased stress sensitivity Low serotonin results in: o Depression - males and females o Aggression - males o Alcoholism - males and females

Dopamine Hypothesis of Depression • • • • •

Dopaminergic agents induce mania; parkinsons associated with depression Anhedonia and amotivation similar to negative symptoms of schizophrenia Mesoaccumbens portion of mesolimbic pathway mediates goal directed behavior Decreased volume of nucleus accumbens associated with anhedonia Some antidepressants increase dopamine activity to alleviate these symptoms

Neurotrophic Hypothesis of Depression • • •

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Brain needs to alter structure in response to stress Stress  increase glucocorticoids and decrease in hippocampal BDNF This results in: o Atrophy / death of hippocampal neurons (decrease hippocampal volume) o Dysfunction in glucocorticoid receptors (perhaps why feedback loop broken) Experimental increases in hippocampal BDNF  antidepressant effects Negative effects of ↑BDNF o Lower seizure threshold, increase malignancies, changes in memory

Inflammatory Hypothesis of Depression • • • •

Sustained activation of immune system or chronic inflammation may lead to depression Stress elevates levels of inflammatory elements such as pro-inflammatory cytokines (IL-6, IL10, TNF-alpha, interferon-gamma, CRP) Pro-inflammatory cytokines affect neuroendocrine system, neuroplasticity and neurotransmitter metabolism Serotonin and stress hormones are downstream manifestations with inflammation the primary driver

Epigenic Hypotheses of Depression •

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Epigenic o Heritable changes in gene expression caused by mechanisms other than changes in underlying DNA sequence Factors that can cause noncoding changes in RNAs regulating gene expression

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o Low level of maternal grooming (rodents) o Artificially induced stress o Early life trauma Help address the results of twin studies and the heredity vs. acquired debate

Gut Bacteria • • • •

Certain gut bacteria associated with greater quality of life They happen to produce metabolites of dopamine Alteration in gut flora under exploration Stay tuned!

Depression is a State • • •

Most likely multiple causes and or vulnerabilities All causes manifest as depression Perhaps we can come up with cause specific treatments rather than broad spectrum antidepressants

Is there a curable cause of depression? Disease States/Conditions Associated with Depression • • • • • • • •

congestive heart failure myocardial infarction stroke brain tumors Parkinson's Disease Alzheimer's Disease other CNS diseases postpartum/peripartum

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hypothyroidism hyperparathyroidism Addison's Disease Cushing's Disease diabetes mellitus rheumatoid arthritis neoplastic disease pernicious anemia

Selected Drugs Associated with Depression • • • • • • • • • • •

Reserpine Methyldopa Beta blockers o Propranolol, Atenolol, Metoprolol Guanethidine Clonidine Anticonvulsants o Gabapentin, Topiramate Prazosin Guanabenz Stimulant withdrawal Antimalarials Acyclovir

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Omeprazole Corticosteroids Cyclobenzaprine Oral contraceptives/estrogen Benzodiazepines Antipsychotics Barbiturates Alcohol NSAIDs Cyclosporine Statins Varenicline Opioids

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Interferon (30% alpha)

Drug Associated • • • •

Using >2 drugs with depression as a listed adverse effect associated with increase in rate of depression 4.7% for patients taking no depression associated medication 6.9% for patients taking one depression associated medication 15.3% for patients taking > 2 depression associated medications

Postpartum Depression (PPD) • • • • • • •

In DSM-5 called peripartum specifier May begin before delivery Depressive episode with onset within 4 weeks postpartum Or during pregnancy or postpartum year 10-15% of births during pregnancy or postpartum Prior history a risk factor Recurrence rate 30- 50%

Perinatal Depression Risk Factors • • • • • • • • • • • •

History of depression Family History of depression Physical or sexual abuse Unplanned pregnancy Unwanted pregnancy Stressful life events Gestational diabetes Pregnancy complications Preterm delivery Lower socioeconomic status Lack of social support Lack of financial support

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Adolescent parenthood Poor partner relationship Single Psychiatric disorders o Prior history of PPD o Depression o Depressive or anxiety sx o Bipolar o Those who stop meds Infant health concerns Difficulty breastfeeding

Postpartum Depression • • • • • • •

Adding to postpartum issues Sleep Stress Changes in thyroid function Pituitary changes Initial presentation may be anxiety Symptoms may include: o mood swings, excessive fears about parenting, anger, indifference to newborn, uncontrollable weeping, changes in eating/sleeping

Why now for depressive episodes? • • • • • • • •

Postpartum Medical illness Inflammation Drugs Drug withdrawal Hormonal fluctuation Stress o Loss, unhappy relationships, TBI, failure, actions resulting in guilt Psychological factors

Definitions – DSM-5 manic episode •

a distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day . . . marked impairment in functioning, hospitalization necessary to reduce harm

hypomania •

a distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day . . . without marked impairment

Signs & Symptoms Mania/Hypomania • • • • • • •

Inflated self-esteem o Grandiosity Decreased need for sleep Talkative o Pressure to keep talking Flight of ideas o Racing thoughts Distractibility Increase in goal-directed activity or Psychomotor agitation Pleasurable, risky activity o Excessive involvement

Signs and Symptoms of Mania Categories • •

• Mood Hyperactivity

Mood

Speech • Grandiosity

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elevated (euphoric) expansive (enthusiasm, seeking to recruit others) irritable (especially when thwarted)

Hyperactivity • • • •

Decreased need for sleep Participates in multiple activities Elaborate planning Increased energy level

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Increased sociability Sexual behavior Risk taking behavior Buying sprees Flamboyant appearance

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loud, rapid flight of ideas jokes, puns, plays on words

Speech

Which drugs could you administer that might result in something resembling a manic state? Complications of Mania • • • • • • • • •

risk taking behavior somatic condition irritable - violence suicidal ideation hallucinations, delusions self-neglect need for institutionalization disruption of family, employment, etc. substance abuse

Pathophysiology • •

A different type of neurodegenerative disease Inflammation and stress o Different pro-inflammatory markers than in depression are elevated in mania

Kindling • • • • • • •

Repeated subthreshold stimuli produce no perceptible physiological or behavioral effect Finally, one breaks through and produces major physiological and behavioral effects Thus, increased and often more intense response to a given stimulus is manifest After a sufficient number of kindled responses, spontaneous physiologic/behavioral response occurs without the presence of a stimulus Relates to why repeated episodes occur with increasing frequency Kindling ... initial periods of cycling may begin with an environmental stressor, but if the cycles continue or occur unchecked, the brain becomes kindled or sensitized - pathways inside the central nervous system are reinforced so to speak - and future episodes of depression, hypomania, or mania will occur by themselves (independently of an outside stimulus), with greater and greater frequency.

Selected Disease States Associated with Mania • • • • •

Hyperthyroidism Sleep deprivation Head trauma Stroke Brain tumor

Sleep deprivation is a significant why now for a bipolar episode Selected Drugs Associated with Mania • • • • • • • •

Stimulants o Phenylpropanolamine, amphetamine, cocaine Corticosteroids Levodopa Androgens Thyroid Folate Antidepressants Amantadine

Episodes and Disorders  

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Bipolar I Disorder  Has had a manic episode Bipolar II Disorder  Has had a hypomanic episode, and  Has had a major depressive episode Cyclothymic Disorder  Has had numerous hypomanic episodes and depressive symptoms that do not meet criteria for a depressive episode

Episodes and Disorders 

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Disruptive Mood Dysregulation Disorder  A depressive disorder  Characterized by age inappropriate temper outbursts in at least 2 settings  Onset before age 10 Major Depressive Disorder  Has had a depressive episode

Episodes and Disorders 

Persistent Depressive Disorder  Also called dysthymia

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Depressed mood most days for at least 2 years At least 2 symptoms of a major depressive episode

Episodes and Disorders 

Premenstrual Dysphoric Disorder  In most cycles, multiple symptoms in week before onset of menses  Symptoms improve within a few days of onset and are absent in the week after  Affective lability, mood swings, irritability, anger, depressed mood, anxiety, tension, on edge, decreased interest, difficulty concentrating, lethargy, fatigue, change in appetite, sleep changes, overwhelmed feeling, physical symptoms (bloating, muscle pain, weigh gain, breast tenderness)

Seasonal Affective Disorder     

Winter/fall depressive episodes Eat more and sleep more (hibernation prep?) A course pattern specifier (“with seasonal pattern”) Seen more in higher latitudes May need light therapy, sleep cycle changes and medication  First hour awake, 20-30 minutes, eyes open  Filter out UV, 20 inches from face

Cycles in Mood Disorders • • • •

Comprised of individual episodes Episodes characterized by severity and duration Period of euthymic (normal) mood between episodes may or may not be present The frequency of the cycle tends to shorten with each recurrent episode (usually due to reduction in the length of the euthymic interval)

Conclusion • • • •

Numerous discoveries have been made regarding the pathophysiology of depression at the molecular, neurophysiological and anatomical levels But we have not yet elucidated defined mechanisms by which these disorders occur The mood disorders are common and are defined by individual episodes and a tendency towards recurrence. The impact of mood disorders can be profound and can result in considerable morbidity and mortality....