Mood Disorders (Pathology) - Block 3 Flashcards
What is the 2nd leading cause of diability worldwide?
Depression
Who is more affected by depression?
Females
What is depression?
Depressed mood and not being able to enjow normal activities that is maintained for at least 2 weeks
What is the chief complaint in depressed patients?
Physical sx
What are the clinical subtypes of depression?
MDD
Persistent Depressive Disorder
Depressive episode (most common)
Atypical
SAD
Bipolar
What is persistent depressive disorder?
Dysthymia: sx of depressed mood that occurs on most days, and persist for at least one year
How does dysthymia differ from MDD?
Less severe and moreschronic, symptoms are greater in:
1. Number
2. Severity
3. Duration
4. Interference with functioning
- Reflected in the DSM diagnostic criteria for depression and dysthymia
What is bipolar I?
Suffering from alternating depressive episodes that alternate with manic episodes
What are the characteristics of manic episodes?
- High moods
- Hyperactivity
- Restlessness
- Irritability
- Talkativeness
- Reduced need for sleep
- Delusions
How can mania have adverse outcomes?
- Traffic accidents
- Arrests
- Spending money
- Hypersexuality
- Psychiatric hospitalizations
What is hypomania?
Persistent mood disinhibition, increased creativity, and euphoria
* Less severe than full mania
* Associated with Bipolar II
How do patients switch from depressive to mania?
Using antidepressants
Describe the course of depression?
Self-limiting: episodes will resolve in 3-6 months
What is the underlying cause of depression?
We don’t really know
* Environmental: trauma
* Neurobiological: genetics
What are the risk factors of depression?
Genetics:
* monozygotic twins (50%)
* dizygotic twins (10-25%)
Vulnerabiltiy to developing depression and anxiety from stressors
What are the neurobiological influences that contribute to depression?
Emotional function:
* Abnormalities in the amygdala, hippocampus, cingulate cortex, and prefrontal cortex
* HPA axis dysregulation, variants in BDNF, altered neurotransmitter function
What areas of the brain are affected by depression?
What are the neurochemical theories of MDD?
- Biogenic (Monoamine) Amine theory
- Receptor Sensitivity theory
- Dysregulation hypothesis
- Neuroendocrine theories
What is the amine hypothesis?
Depression is often characterized by changes in monoamine neurotransmitters (NE, D, Serotonin)
How do medications support the amine hypothesis?
Antidepressants and amphetamines increase NT -> decrease depression
Reserpine: decrease NE and DA -> Increases depression
What metabolite in CSF/urine support the amine hypotheis?
NE -> major metabolite is 3-Methoxy-4-hydroxyphenylglycol (MHPG)
According to monoamine theory what drugs revealed to have an effects on mood?
Imipramine, iproniazid, reserpine
Imipramine/Deipramine
MOA
Blocks 5HT transporters and its active metabolite desipramine blocks NE transported -> Increases NTs in the synapse
Iproniazid
MOA?
Inhibits MAO prevetning the degradation of 4HT, NE, and DA in the neuron after reuptake
How does reserpine induce depression?
Depletes 5HT, NE, and DA by inhibitng the transport by irrevirsibly binding to VMAT
Depressed patients have shown to have decreased ____?
CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA), which is the major metabolite of serotonin (5-HT)
What is the problem with amine hypothesis?
Antidepressant medications block transmitter reuptake immediately, but there is a significantly delayed effect on the patient’s symptom improvement of about 4 weeks
What is the receptor sensitivity theory?
The reuptake blockade alters the sensitivity of pre and postsynaptic NE and 5HT receptors over time
What is the dysregulation hypothesis?
Depression is the failure to maintain homeostatic regulation of various neurotransmitter systems (not dependent on changeing levels of NT)
What are the the hypothalmic endocrine changes that occur with depression?
- Hypersecretion of cortisol
- Hyposecretion of TSH/TRH
- Reduced BDNF levels
What is the major target for depression therapies?
Dopamine
Overall, depression is a caused by an insuffiency in what NTs?
NE and 5-HT
What are the types of anxiety disorders?
- GAD
- Phobias
- PTSD
- Panic disorders
- OCD
Women are about 2x as likely as men to have anxiety disorders except for ___?
OCD
What is anxiety?
Diffuse Response About Impending Real or Imagined Threat or Danger
* excessive or the perceived threat is out of proportion with the actual threat
* Difficulty controlling the worry or anxiety process, so that it interferes with daily activities
What is the cause of anxiety disorders?
we really don’t know
If most mental illness causes are unknow, how would be define the neuropathophysiology of a disorder?
Pharm therapies
What are the NTs involved with anxiety?
- 5HT
- NE
- GABA
- CRH -> cortisol
How does GABA play a role in anxiety?
When nerve signals fire too quickly, carrying anxiety-inducing signals, GABA would normally act to slow the response, reducing the overwhelming feelings of anxiety
- Anxiety patients may have abnormalities in GABA
Where is the major source of NE?
Locus coerulus
What is the function of NE?
- NS activation
- Triggers fight or flight
What are seratonin producing neurons located?
Raphe nuclei
What med class has the strongest evidence of serotonergic system in the the tx for anxiety?
SSRI
What areas of the brain produce response to anxiety provoking stimuli?
- Thalamus
- Amygdala
- Cortex
- Hypothalamus
Brain areas provuce ax provoking sx -> Activates HPA axis, stress hormones, and autonomic NS (fight or flight)
What is the function of the amygdala?
Control of emotion: essential for the acquisition and expresison of fear
How is the amygdala affected by those with phobias?
The amygdala is activated more rapidly and to a greater extent -> fight or flight
What are examples of somatic sx?
Rx that are inappropriate to the situation:
1. Lock of concentration
2. Self-focused preoccupation
3. AUtonomic arousal
4. Easily startled, avoidance behaviors, restlessness
How many of anxiety patient will eventually suffer from MDE?
1/3
Common behavioral sx of ax?
Anything where the reaction is inappropriate to the situation.
What is GAD?
- Involves chronic, excessive, uncontrollable worry about everyday things
- This constant worry affects daily functioning and can cause physical symptoms -> autonomic hyperactivity
- Can occur with other axiety disorders
What is the most common comorbid Axis I disorder?
DEPRESSION
What are types of Axis 1 disorders?
- Dissociative disorders
- Eating disorders
- Mood disorders
- Psychotic disorders
- Substance use disorders
What is the Benzodiazepine / GABA Receptor Model?
Benzodiazepines enhance GABA’s inhibitory effects by acting at the BZD binding site on the GABA-A receptor:
* Increased GABA = decreased anxiety
What is the noradrenergic model?
Hypersensitive autonomic nervous system due to defects of the locus coeruleus and fight or flight response
What is the serotonin model?
Buspirone, a selective serotonin anxiolytic, and the general effectiveness of SSRIs provides evidence for serotoninergic involvement
What are the types of neurochemical theories for GAD?
- Benzodiazepine / GABA Receptor Model
- Noradrenergic model
- Serotonin model
What is PTSD?
Reaction to intense fear, helplessness, or horror
What are the sx classes of PTSD?
- Re-experiencing the traumatic event: nightmares, intrusive thoughts, flashbacks
- Avoidance of stimuli
- Increased arousal
What are the causes of PTSD?
- Conditioned fear response
- Genetics
- Stress-induced neurotransmitter release of NE, CRF, cortisol
- The level of autonomic arousal immediately after the traumatic event predicts PTSD
What is a panic disorder?
Unexpected, recurrent panic attacks
What are panic attacks?
Sudden onset, peaks within 10 minutes:
* Abrupt Autonomic Surge
* Physical: SOB, DZ, Chills/heat
* Emotional: terror
* Cognitions: feelings of being out of control
What are the sx of panic disorrders?
Feeling of imminent danger or doom
Differentiate the types of panic attacks?
Unexpected: The attack “comes out of the blue” without warning and for no discernable reason.
Situational: Situations in which an individual will almost always have an attack. For example, entering a tunnel.
Situationally Predisposed: Situations in which an individual is likely to have a panic attack, but does not always have one.
How do panic attacks cause issues with respiratory control?
Patients with panic disorder may have a hypersensitive respiratory control system, which operates at the level of brainstem chemoreceptors
Describe the neurobiological aspects of panic attacks?
- Fear circuit overactivity (amygdala)
- Seratonin, GABA, NE
What are the genetic aspects of panic attacks?
Heritability (50%)
*
What is the NT hypothesis of panic disorders?
Dysregulation of norepinephrine, primarily with regard to function of the locus ceruleus
What is agoraphobia?
fears or avoids situations because escape might be difficult or help might not be available
What is a phobia?
where the anxiety is out of proportion to the actual threat posed by the situation
What are specific phobias?
Unwarranted, excessive fear or anxiety evoked from specific objects or situations
What are social phobia?
Marked and persistent fear of social situations which may involve “negative evaluation” by others (i.e. public speaking)
What is OCD?
Uncontrollable obsessions and compulsions which the sufferer usually recognizes as being excessive or unreasonable
How do you define obsessions?
Recurrent and persistent thoughts, impulses or images that are intrusive and unwanted that cause marked anxiety or distress
How do you define compulsion?
Repetitive, purposeful behaviors that the person feels driven to perform in response to an obsession
