Lecture 26 Flashcards
Affect
As a noun, affect refers to feelings or emotions
Just as the primary symptom of schizophrenia is disordered thoughts, affeactive disorders (mood disorders) are charcterized by disordered feelings
Mood (affective)disorder
Serious mood disorder
There are two principal types of mood disorders: bipolar disorder and major depressive disorder
Mood Disorders
Affective disorders are prevalent and dangerous
A diagnosis of depression has a prevalence of approximately 7% in women and 3% in men.
Severely depressed people usually feel unworthy, hopeless, and have strong feelings of guilt
People with mood disorders have a very risk of self-harm and suicide
Bipolar disorder
Serious mood disorder characterized by cyclical periods of mania and depression.
It affects ~1% of the population.
~80% of the risk is attributed to genetics.
Major depressive disorder (MDD)
Serious mood disorder that consists of unremitting depression or periods of depression (that do not alternate with periods of mania).
~40% of the risk is attributed to genetics.
Environmental factors for mood disorders
Environmental factors for mood disorders include traumatic/abusive childhood experiences.
Mania
Episodes of mania are characterized by sense of euphoria that does not seem to be justified by circumstances
People with mania usually exhibit nonstop speech and motor activity
Diagnosis of mania is partly a matter of degree; one would not call exuberance and a zest for life pathological
Lithium
Chemical element
Lithium salts (and anticonvulsants) are commonly prescribed for bipolar disorder
Lithium is most effective for treating the manic phase of bipolar disorder
Once mania is eliminated, depression usually does not follow
Therapeutic effect of lithium is very rapid. The mechanism of action is unknown.
High dose is needed so is not specific to a receptor
Biological treatment for MDD
There are several established and experimental biological treatments for major depressive disorder (MDD)
Drugs that increase serotonin and/or norepinephrine signaling by inhibiting their enzymatic breakdown (e.g., monoamine oxidase inhibitors, MAOi) or by blocking their reuptake (e.g., tricyclics and serotonin specific reuptake inhibitors, SSRIs). Ketamine (NMDA glutamate receptor blocker) Electroconvulsive therapy (ECT) Deep brain stimulation Transcranial magnetic stimulation Vagus nerve stimulation Bright-light therapy (phototherapy) Sleep deprivation
Tricyclic antidepressant
Inhibits reuptake of serotonin and norepinephrine but also affects other neurotransmitters;
Named for the molecular structure
Serotonin specific reuptake inhibitor (SSRI)
A class of drugs that specifically inhibit the reuptake of serotonin without affecting the reuptake of other neurotransmitters.
The most common one is Prozac (fluoxetine).
Similar drugs are Celexa, Paxil, Zoloft, etc…
Serotonin and norepinephrine reuptake inhibitor (SNRI)
Antidepressant drug that specifically inhibits reuptake of norepinephrine and serotonin without affecting reuptake of other neurotransmitters.
Monoamine Hypothesis of Depression
Based largely on the success tricyclic and SSRI treatments, the monoamine hypothesis of depression was developed. The idea is that depression is caused by insufficient monoamine receptor activity (the monoamines are serotonin, norepinephrine, and dopamine).
Because symptoms of depression are generally not relieved by potent dopamine receptor agonists such as amphetamine or cocaine, most investigators have focused their research efforts on the other two monoamines: norepinephrine and serotonin.
Tryptophan is the molecular precursor to serotonin. Giving people a low-tryptophan diet and then a tryptophan-free amino acid “cocktail” lowers brain tryptophan levels and consequently decreases their synthesis of serotonin (5-HT). This tryptophan/serotonin depletion procedure can elicit a depressive episode in people susceptible to depression.
Although SSRIs and SNRIs increase the levels of 5-HT and norepinephrine in the brain very rapidly, the drugs do not relieve symptoms of depression until they have been taken for several weeks
This suggests that something other than a simple increase in monoamine receptor activity is responsible for the normalization of mood
Role of the Frontal Cortex
Functional Imaging Scans
Functional imaging scans have been done on many depressed patients, both before and after a variety of successful treatments.
There are few (if any) correlations. However, the argument has been made that one area of the anterior cingulate cortex (the subgenual region known as area 25) becomes less active after successful treatments.
Deep brain stimulation and transcranial magnetic stimulation
Deep brain stimulation has been tried in the subgenual anterior cingulate cortex as well as in the nucleus accumbens
Other promising approaches involve transcranial magnetic stimulation (TMS) directed to areas of the PFC or vagal nerve stimulation (VNS).
In a small study it worked. In larger ones it usually does not
Electroconvulsive therapy (ECT)
Used therapeutically to alleviate severe depression and bipolar disorder.
Seizures are electrically induced by applying brief electrical shocks to the head
In contrast to the delayed therapeutic effects seen with monoamine related treatments, the effects of other treatments (including ECT, lithium, DBS, VNS, and sleep deprivation) are more rapid. The seizures induced by ECT often reduce symptoms within days.
Dunno why it wors
Role of sleep
One of the most prominent symptoms of depression is disordered sleep.
People with depression often have shallow, fragmented sleep. They tend to awaken frequently, especially toward morning.
In general, they spend more time in stage 1 sleep and less time in deep, slow-wave sleep (stages 3 and 4).
They also enter REM sleep soon after falling asleep, much earlier in the night in comparison to other people
Total Sleep Deprivation
One of most effective antidepressant treatments is total sleep deprivation.
Total sleep deprivation has immediate antidepressant effects in some people
Typically, depression is lifted by staying up overnight, but it returns after a normal night’s sleep
This suggests that a chemical builds up during waking hours that has some antidepressant effect, and it gets cleared away during sleep.
REM sleep deprivation also works, although more slowly, over the course of several weeks (similar to SSRIs).
Anxiety disorder
A variety of psychological disorders characterized by unrealistic and unfounded fear and anxiety. Includes muscle tension, over activity of the autonomic nervous system, expectation of an impending disaster, and continuous vigilance for danger.
People often have more than one type of anxiety disorder.
Generalized anxiety disorder
Disorder characterized by excessive anxiety and worry serious enough to cause disruption of their lives
Social anxiety disorder
Disorder characterized by excessive fear of being exposed to the scrutiny of other people that leads to avoidance of social situations in which person is called on to perform
Panic disorder
Disorder characterized by episodic periods of severe and unremitting terror. Includes symptoms such as shortness of breath, irregularities in heartbeat, and other autonomic symptoms, accompanied by intense fear
Anticipatory anxiety
Fear of having a panic attack promotes anticipatory anxiety that sometimes leads to the development of agoraphobia
Agoraphobia
Fear of being away from home or other protected places
Is a panic disorder
Anxiety disorder prevalence
In a given year, about 12% of people are affected by an anxiety disorder.
It appears twice as often in females as males and generally begins before the age of 25.
12% of people will develop a specific phobia and 10% will develop social anxiety disorder at some point in their life.
Anxiety disorder causes
The cause of anxiety disorders is a combination of genetic and environmental factors.
Environmental risk factors include a history of child abuse and poverty.
Anxiety disorders often occur with other mental disorders, particularly major depressive disorder, personality disorder, and substance use disorder.
Older people who have dementia often have problems with anxiety.
Anxiety disorder brain activity
Functional brain imaging studies suggest that the amygdala and prefrontal cortex are involved in anxiety disorders
Adolescents with generalized anxiety disorder showed increased activation of the amygdala and decreased activation of the ventrolateral prefrontal cortex while looking at angry faces
College students with a high level of anxiety showed increased activation of the amygdala, which positively correlates with students’ anxiety measures
Anxiety Disorder treatments
Treatment options include lifestyle changes, behavioural therapy, and medications.
Lifestyle changes may include exercise, regularizing sleep patterns, and reducing caffeine intake and smoking.
Cognitive behavioral therapy(CBT) is often effective and is a first line treatment.
When medication is called for
Benzodiazepines are sometimes used, particularly in emergency settings because of their rapid onset
Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first line treatment for anxiety disorders
Stress Disorders
Stress refers to the physiological reaction caused by the perception of aversive or threatening situations.
These physiological responses prepare people for fight or flight situations and include autonomic and endocrine responses that help to mobilize the body’s energy resources and support vigorous activity.
Stress-related autonomic and endocrine responses can cause adverse effects on health over time.
Physiology of the Stress Response
Stress activates the sympathetic branch of autonomic nervous system
Stress also activates the adrenal glands to release hormones into the blood, including epinephrine, norepinephrine, and glucocorticoids such as cortisol.
The autonomic and hormone responses work together to increase heart rate, blood pressure, and blood flow to muscles to make nutrients stored become available
Glucocorticoids
A group of hormones (corticosteroids) that are important in protein and carbohydrate metabolism, secreted especially in times of stress
Cortisol
A specific glucocorticoid (steroid hormone) secreted by adrenal cortex in response to stress
Hormonal control of stress hormones
Secretion of glucocorticoids is controlled by the hypothalamus.
In response to stress, the hypothalamus starts a chain of events by releasing CRH/CRF (corticotropin-releasing hormone/factor).
CRH stimulates the pituitary to secrete ACTH (adrenocorticotropic hormone).
ACTH stimulates the adrenal gland to produce glucocorticoids.
Stress
Glucocorticoids
Help to break down and convert proteins into glucose, make fats available for energy, increase blood flow, suppress secretion of sex hormones and stimulate behavioral responsiveness
Glucocorticoids have other physiological effects, too, some of which are not well understood. Almost every cell in the body contains glucocorticoid receptors, which means that few of them are unaffected by these hormones.
Health Effects of Long-Term Stress
Short-term effects of glucocorticoids are essential for survival.
Long-term effects are damaging. These effects include increased blood pressure damage to muscle tissue steroid diabetes infertility inhibition of growth inhibition of the inflammatory responses suppression of the immune system
Stress slows the healing of (flesh) wounds and predisposes people to infections.
During three-to-five-day period just before showing symptoms of upper respiratory infection, people experienced an increased number of undesirable, stressful events.
Effects of Stress on the Brain
Monkeys near bottom of their social hierarchy are almost continuously stressed.
These monkeys seem to die more often than others from stress-related issues.
Examinations post-mortem found them to have signs of chronic stress, such as gastric ulcers, enlarged adrenal glands, and damaged hippocampi.
Episodes of emotional maltreatment during childhood has been associated with an average 7.2 percent reduction in volume of dorsomedial prefrontal cortex
PTSD
Most people who have experienced a traumatic event will not develop PTSD.
The likelihood of developing PTSD increases with the number of traumatic events the person has experienced
Approximately 30% of the variance in PTSD is caused from genetics alone.
The main treatments for people with PTSD are cognitive behavioural therapy, group therapy, and medication. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medications and result in benefit in about half of people.
Some evidence suggests that PTSD is associated with abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates hormonal response to stress.
Several studies found evidence that increased activity in the amygdala is responsible for emotional reactions in people with PTSD
Functional imaging studies have found that when shown pictures of faces with fearful expressions, people with PTSD show greater activation of amygdala and smaller activation of prefrontal cortex than did people without PTSD
