Pathophysiology of Unipolar Depression Flashcards
Bipolar defined
Drastic mood swings from extreme highs to extreme lows
Depression defined
Disorder of inner emotions
Affective disorder or mood disorder
Inappropriate exaggeration of mood
Major depression occurs when:
Sadness, grief and other negative emotions interfere with the ability to function in everyday normal life
S&S of Major Depression
Persistent sad, anxious, or empty mood
Loss of interest or pleasure in normal activities
Restlessness, excessive crying
Feelings of guilt, worhtlessness, helplessness, hopelessness
Disruptiono f sleep patterns
Changes in appetite and weight
Decreased energy, fatigue, feeling run down
Thoughts of death or suicide
Difficulty concentrating
Headache, digestive problems, chronic pain
Stop caring for themselves
MDD involves
Cognitive
Behavioral
Social disruption
Risk Factors for Depression
FH Stress Rural Unemployment Drug side effects Ethnicity/Culture Early Childhood Trauma Alcohol Divorced/separated/alone Illness Sex/gender Age (mid-20s)
Triggers + Depression
Results from underlying medical conditions, from drug treatments and from stress
Combination of genetic, psychological and environmental factors
Comorbidities + Depression
Associated with others (hypothyroidism, nutritional deficiences, neurological/psychiatric disorders
Psychotic Depression Defined
The condition also presents with psychotic behaviors such as hallucination and disturbed sense of reality
Define Dysthymia depression
Less severe, less disabling
Shows a prolong time course
Predisposes you to MDD
Define Seasonal Affective Disorder
Winter = depressed
Spring = remission
Light therapy might be an option
Sleep + Depression
Sleep deprivation can result in mood elevation but the depression return after a night of recovery sleep
Define Postpartum depression
Depression following delivery
Substantial hormone and physical changes + mental stress of having a baby
Depression is what type of disorder?
Heterogeneous
Risk ratio for 1st degree family members is:
2-3
Monoxygotic twins vs dizygotic twins
54% vs 19%
Heritability number is?
.35, which means 65% of the time the phenotypic effects are due to environment and random events
Define Common Variant hypothesis
Polygenic disorder and the genes involved are common alleles with a low risk ration
5HT involvement?
A polymorphism was IDed in the promotoer of SERT that is a 44 bp insertion/deletion –> short allele produce less SERT
S/S homozygotes are at greater risk of developing MDD
- Primarily in ppl with rough childhood
Trp ydroxylase 2 (TPH2) involvement?
Hypomorphic allele in the enzyme that catalyzes the rate-limiting step in 5HT synthesis in the brain
Brain-derived Neuronotrophic Factor (BDNF)
Regulates synaptic plasticity and neuronal survival/differentiation
Reduced by stress
Missense mutation affects synthesis and stability
- Typically in bipolar
Define Monoamine Hypothesis
Depression is due to serotonergic and noradrenergic hypofunctions
Monamine hypothesis explained
NE: attention and vigilance, hunger and satiety
5HT: eating behaviors, sleep libido, body temp, melatonin conversion (low 5HT = aggression and impulsive behaviors)
Diffuse Neuromodulatory Systems
NT just send their signals down neurons
The fact that it takes so long for antidepressant drug to work means:
Gene changes must be involved /changes in gene regulation alter the pattern of receptors and ion channels in the affected neurons
Could also mean there is a structural change
What regions of the brain are involved in the disruption of inner emotions?
Limbic system and prefrontal cortex
Prefrontal cortex and limbic system are a part of?
Part of the Default Mode Network (active during times of engagement)
Prefrontal cortex function
Planning, motivation and working memory
“elaboration of thoughts” which includes ability to predict and plan for the future, analyze consequences of planned actions
Control over steroeotyped actions
Disfunction in the Prefrontal cortex leads to?
Inability to solve complex problems Lack of motivation Lack of focus Impulsivity Inappropriate social interactions
Limbic System Function
Interconnected structures that function together in emotion and behavior
Includes: hypothalamus, amygdala, hippocampus, accumbens, cingulate cortex
Hypothalamus Function
Regulates autonomic function, endocrine function, basic behaviors (eating/sleeping)
Activation of PS: pleasure/warm fuzzy
Activation of S: anxiety, fear, anger
Controls display of emotional behavior
Dexamethasone Suppression Test used
Test hypothalamic function in MDD
Treatment with Dexamethasone leads to
Reduced ACTH and cortisol levels
50% of pts have
Elevated cortisol levels
Amygdala Function
Inner emotions (joy, anger, hope, fear, anxiety) Receives input from PFC and applies emotions to cortical info
Hippocampus function
Memory consolidation
Positional memory, timing mechanisms, inhibitiono f hypothalamic function
Accumbens function
“Reward center” which is activated by DA neurons
Responds to novelty and applies positive reinforcements to thoughts and actions
Cingulate Cortex Function
Emotional awareness
How does the limbic system function together?
Cingulate gyrus receives sensory info from thalamus, PFC and association cortex
Then sends axons to the hippocampal formation
Hippocampus innervates cortical regions and hypothalamus
- Link outcomes to memory, motivation and behavioral responses
Pathology + Depression
Reduced volume of hippocampus and areas in PFC
Atrophy + Depression
None is seen although one study shows dendritic spine reduction
Depression + Dentate Gyrus
Neurogenesis occurs here and is important for hippocampal function to form new memories
Elevated cortisol levels can cause:
Hippocampal atrophy (Cushing’s disease) and impaired hippocampal neurogenesis
Exercise + Antidepressant + Depression
Enhances neurogenesis and elevate BDNF levels (important regulator of hippocampal function)
Ketamine + Depression
Antidepressant
Rapid effects
Dissociative analgesic and psychotomimetic action
Supposed to rapidly reverese dendritic atrophy with BDNF
