Week 5 Flashcards
Depression
** – “mild” depression?
* The main symptom of this disorder is
on most days for at least x years (any two of the criteria shown later)
* People with this illness are ** . They
function ** on a daily basis but** suffer
over time because **
* In children and adolescents, ** instead
of ** and may last for **
Dysthymia- mild depression
* The main symptom of this disorder is a low, dark, or sad mood on most days for at least 2 years (any two of the criteria shown
later)
* People with this illness are mildly depressed for years. They function fairly well on a daily basis but their relationships suffer
over time because of these lasting changes
* In children and adolescents, the mood can be irritable instead of depressed and may last for at least 1 year (note difference
Bipolar Disorder (**)
People with this type of illness change back and forth between
**
* Symptoms of mania may include:
* **
* **
* **
* **
* **
* ** are typically gradual, but can also be **
Bipolar Disorder (Mania)
* People with this type of illness change back and forth between periods of depression and periods of mania (an extreme high).
* Symptoms of mania may include:
* Less need for sleep
* Overconfidence
* Racing thoughts
* Reckless behavior
* Increased energy
* Mood changes are typically gradual, but can also be sudden
Major Depressive Disorder
* ** onset, possibly triggered by **
* Interfere with **
* Continue for ** or ** (typically ** to ** months)
* It is possible for a person to have **
* It is more common for episodes to be **or to occur **
Major Depressive Disorder
* Sudden onset, possibly triggered by a loss, crisis or change (all bad?)
* Interfere with normal functioning
* Continue for months or years (typically 7 to 14 months)
* It is possible for a person to have only one episode of major depression however…
* It is more common for episodes to be long lasting or to occur several times during a person’s life (recurrence)
Interesting epidemiology
* Median age of onset is **
* Major cause of disability ages ** (recall earlier figure – plus
this is a very important age range!)
* Affects more ** than ** (consistently show **
ratio) – in other words **!
Interesting epidemiology
* Median age of onset is 30 years
* Major cause of disability ages 15-44 (recall earlier figure – plus
this is a very important age range!)
* Affects more females than males (consistently show ~3:1
ratio) – in other words the incidence is high!
Changes in feelings which may include:
* **
* **
* **
* **
* **
* **
* **
* **
* **
* **
* **
Changes in feelings which may include:
* Inability to enjoy anything (Anhedonia)
* Loss of sexual desire
* Loss of warm feelings for family or friends
* Hopelessness and self blame or guilt
* Self-injury (i.e. suicide)
* Inability to do anything (Psychomotor effects)
* Vegetative symptoms
* Disruptions in sleep cycles
* Appetite changes
* Stress responses
* Rhythmic patterns?
Can we use the same approaches that we did for other disorders and diseases?
Difficult since it appears that most depression is idiopathic – so we don’t know many of the risk factors other than stress,
hormone disorders, some cancers (such as pancreatic adenocarcinoma and some breast tumours) as well as drugs (isotretinoin and interferon-a)
Depression as a model system
Changes in activity:
* **
(area Cg25)
* Area shows **when
you are sad
* Chronically activated in **
* Target for **
* Helen Mayberg and other experts on this
area suggest **
Changes in activity:
* Subgenual cingulate cortex within PFC
(area Cg25)
* Area shows increased activation when
you are sad
* Chronically activated in some treatment
resistant depressives
* Target for DBS (deep brain stimulation)
* Helen Mayberg and other experts on this
area suggest this area is responsible for
certain types of depression
Using resting-state fMRI
* Neuroimaging biomarkers of ** have proven utility in the assessment of ** and have also shown promise for **, for both the **and **
* Resting-state fMRI (rsfMRI) is an especially useful measure because **
* Depression is associated with **, mirrored by ** models in rodents
* This raises the possibility that fMRImeasures of connectivity could be used to **
4 biotypes identified
* Resting state fMRI analyses showed four biotypes that were defined
by **
* Importantly, these biotypes were also useful in predicting **
* Some evidence that resting state DMN **
* Think of this as an cardiovascular analogy.
- Neuroimaging biomarkers of abnormal brain function have proven utility in the assessment of pain and have also shown promise for depression, for both the prediction of treatment response and treatment selection
- Resting-state fMRI (rsfMRI) is an especially useful measure because it can be used easily in diverse patient populations to quantify functional network connectivity in terms of correlated, spontaneous MR signal
changes - Depression is associated with dysfunction and abnormal functional connectivity in frontostriatal and limbic brain networks, mirrored by morphological and synaptic changes in chronic stress models in rodents
- This raises the possibility that fMRI measures of connectivity could be
used to identify novel subtypes of depression with stronger neurobiological correlates that predict treatment responsiveness
- Small ** consistently found in ** levels in depressed individuals
- Some animal models by injection of high levels of ** (**)
a) **, ** - Different times of ** (depression associated)
- Menarche to Menopause greatest risk?
- Small increases consistently found in glucocorticoid levels in depressed individuals
- Some animal models by injection of high levels of glucocorticoids (corticosteroids)
a) immobility, decreased responding in an operant conditioning task of motivation - Birth and post-partum depression
- Different times of period (depression associated)
- Menarche to Menopause greatest risk?
Cushing’s syndrome
* Glucocorticoids also decrease **
* CS results in **
Cushing’s syndrome
* Glucocorticoids also decrease dopamine
* CS results in Falling into depression as well
1950s set us up for our models.
* two things identified in the 1950s
* Reserpine originally used as s and produced
* Classic drugs ** and ** were originally developed for non psychiatric conditions (i.e. ** etc.)
* These drugs were shown to have good effects as **
* Later in the 1960s shown to enhance ** or ** transmission in the ** (effects on **enzymes)
1950s set us up for our models.
* Experimental evidence from rats identified in the 1950s
* Classical neurosurgery pathways also 1950s
* Reserpine originally used as anti hypertensive depleted monoamines and produced depression in some patients
* Classic drugs iproniazid and imipramine were originally developed for non psychiatric conditions (i.e. tuberculosis etc.)
* These drugs were shown to have good effects as antidepressants
* Later in the 1960s shown to enhance serotonin or noradrenaline transmission in the brain (effects on MAO (monoamine oxidase) enzymes)
Catecholamines (Noradrenaline etc)
** major neuronal tracts within CNS
** and **
** and **
Involved in many different behaviours
Involved in **
Involved in **
Involved in **
? Interesting phenomena
Catecholamines (Noradrenaline etc)
2 major neuronal tracts within CNS
Locus ceruleus and lateral tegmental neurons
Dorsal bundle and medial forebrain bundle
Involved in many different behaviours
Involved in vigilance/altertness
Involved in sleep/wake cycles
Involved in reward and reinforcement
Anterior strokes? Interesting phenomena
- Neurotransmitter hypothesis
* Most commonly used theory to explain
**
* Most ** (aka **) play pivotal roles in behaviour
* Initial experiments with animal models
show that **
* ** often show signs
of depression
* PET studies show ** - Drugs and neurotransmission
* Simple – **
* Increase their levels at the ** – block ** or **
* **, **
* **, ** (Zoloft)
* ** (Eli- Lilly 1987) SSRIs
* ** (latest class of dual SRIs or SNRIs)
- Neurotransmitter hypothesis
* Most commonly used theory to explain
changes in mood
* Most monoamines (aka biogenic
amines) play pivotal roles in behaviour
* Initial experiments with animal models
show that they might play a role
* Substance abusers often show signs
of depression
* PET studies show differences in areas
of the brain associated with specific
NTs - Drugs and neurotransmission
* Simple – not enough of the neurotransmitters are around
* Increase their levels at the synapse – block degradation or reuptake
* TCAs, MAO-Is
* SSRIs, Sertraline (Zoloft)
* Fluoxetine (Eli- Lilly 1987) SSRIs
* Duloxetine (latest class of dual SRIs or SNRIs)
Changes to the brain - considerations
* Less , reduced size of **r and less ** consistently found in hippocampus and ** (worthlessness and guilt?)
* Anterior cingulate cortex
a) resting level of activity ** in depressives
* Amygdala
a) ** in depressives (and also **) - anxiety
* Left PFC () -> d**
* HPA axis -> ** in some depressives but **
(remember first theory)
* There is a decrease in ** but….after taking ** – why such a long delay?
Changes to the brain - considerations
* Less gray matter, reduced size of white matter and less glia consistently found in hippocampus and prefrontal cortex (worthlessness and guilt?)
* Anterior cingulate cortex
a) resting level of activity higher in depressives
* Amygdala
a) hyperactive in depressives (and also larger) - anxiety
* Left PFC (positive mood) -> decreased activity and size
* HPA axis -> overactive in some depressives but not universal in all cases
(remember first theory)
* There is a decrease in neurotransmitter levels but….almost immediate recovery after taking ADMs – why such a long delay?
Personalized medicine era
One of the biggest questions/controversies surrounding this field of study
* More depression as you look s (i.e. even within **
* So, some degree of **
* Identical twin studies – ** risk of depression in the other twin
* Genetic component may not be about ** or ** but ** – i.e. polygenetic most likely but also similar to
neurodegeneration?
Personalized medicine era
One of the biggest questions/controversies surrounding this field of study
* More depression as you look within closer relatives (i.e. even within other mental disorders)
* So, some degree of heritability
* Identical twin studies – 35-50% risk of depression in the other twin
* Genetic component may not be about likelihood or inevitability but vulnerability – i.e. polygenetic most likely but also similar to
neurodegeneration?
