Mental disorders & Drug abuse Flashcards
(145 cards)
1
Q
Are most gene variants specifically labelled as schizophrenia genes or autism genes or bipolar genes?
A
- No, most of gene variants can’t be labelled as a specific illness related gene
- There just seems to be hundreds of common gene variants that increase one’s risk of developing some mental illness (in general)
2
Q
What has a high rate of comorbidity?
A
Psychiatric disorders have a high rate of comorbidity (more than one diagnosis at the same time)
3
Q
What are the reasons why mental disorders aren’t discrete, unitary diseases?
A
There is too much:
- Heterogeneity within diagnostic categories
- Comorbidity across categories
- Continuity with normality
4
Q
What makes people more likely to self-diagnose?
A
- Prototypes of illnesses
- But mental illnesses often more complicated and symptoms could be explained by other things
- Sometimes symptomology looks different across different groups of people
5
Q
What’s the purpose of diagnostic categories?
A
- Diagnostic categories partly reflect historical convention, diagnostic convenience, and innate categorization biases in our perception of behaviour
- Diagnostic categories are useful for describing clusters of symptoms that tend to appear together, but we now know that similar symptoms can arise form completely different neural circuit disruptions
6
Q
How do gene variants associated with mental illnesses cause mental illnesses?
A
- Many of the gene variants associated with increased risk of mental illness regulate brain development and neural plasticity
- Their expression in the brain gives rise to altered patterns of neural activity throughout the brain
- The problematic protein variants slightly alter the dynamic interactions of the thousands of proteins expressed in the brain across different cell types during development and maturation
7
Q
What’s the mutation-selection balance theory as to why gene variants that increase the risk of developing a psychiatric illness persist in the population and why they haven’t been selected out?
A
- Mental disorder susceptibility genes are continually being selected out through evolution, but new mutations keep arising
- There are about 20,000 protein-encoding genes in the human genome and about half of them are expressed in the brain at some point
- All of us have gene mutations associated with a slight reduction in “fitness” that arose within the last 100 generations or so of our family tree
- Most bad genes are a family legacy, old mutations that have yet to go extinct, rather than new mutations specific to the individual
- These mutations will get eliminated over time, but new ones keep coming
- With each generation, some mutations are selected out and some remain
8
Q
What are the different “insults” that the human genome has evolved to buffer?
A
- Environmental variation
- Genetic variation
- Molecular noise
- This robustness allows genetic variation to accumulate in the population if the individual mutations are not too severe
9
Q
What could reduce the overall robustness of brain development and function?
A
Slightly bad gene mutations that do not directly cause a disease can collectively compromise the evolved interactions of everything in the brain
10
Q
What does human brain development often depend on?
A
- Despite the large number of redundancies, error checking mechanisms, and quality control efforts that are put in place to guide proper brain development, much depends on chance
- There’s so much unavoidable randomness at the molecular level impacting brain development that even identical twins can have very different brains (e.g., one may develop schizophrenia)
- Brain development can be compared to a game of pick-up sticks
- It’s impossible to write in the genetic code exactly how the brain will act/react…there’s gonna be some inherent randomness to the brain
11
Q
How could the body’s symmetry be indicative of the robustness of the underlying genetic instructions?
A
- Body symmetry is partially heritable and slightly correlates with intelligence, physical attractiveness, and physical health
- The 2 sides of the body develop independently from the same set of genomic instructions
- If the instructions are clear then the body should be symmetrical.If the instructions are a bit confusing or open to interpretation, however, then the person may be more asymmetric.
- Genetic studies have identified hundreds of gene variants that correlate with a very small statistical increase in intelligence
- Some of the gene variants associated with intelligence overlap with the gene variants associated with physical attractiveness, physical health, and longevity
- These gene variants are thought to be indicative of neurodevelopmental robustness (due to clear genetic instructions)
12
Q
What are ways someone can prevent getting a psychiatric disorder?
A
- For most psychiatric disorders, there are few preventive measures that can be taken beyond avoiding trauma and generally looking after oneself
- The best advice for maintaining a healthy brain neural pathways and healthy body, based on the available data, is to:
- Stay active - physically and mentally (exercise, socialize, set goals)
- Eat well (more vegetables, less sugar)
- Reduce stress, lower blood pressure
- Maintain good sleep habits
- Limit alcohol intake and avoid tobacco and hard drugs
13
Q
What are future directions for psychiatric disorder treatment?
A
- By identifying the gene variants and neural circuit disruptions associated with mental illness, researchers hope to develop new treatment and prevention strategies
- One idea is to develop gene editing techniques that could be used in living people, or as a part of in vitro fertilization
- There is also still hope for better disease management through new pharmacological treatments, perhaps ones that directly target intracellular signaling cascades rather than neurotransmitter signaling
14
Q
Describe schizophrenia and the statistics surrounding the disorder
A
- Schizophrenia is characterized by social withdrawal, disorganized thinking, abnormal speech, and an inability to understandreality
- Schizophrenia is very heterogenous (shows an array of symptoms)
- It affects approximately 1% of world’s population
- Symptoms typically come on gradually, begin in young adulthood, and in many cases never resolve (although 20% of people eventually do quite well)
- About 30-50% of people with schizophrenia don’t believe they have an illness or comply with their recommended treatment (this leads to poor outcomes)
- Illness is associated with subtle differences in brain structure
15
Q
What are reasons we explain for as to why schizophrenia develops in early teenage and young adulthood years?
A
- There’s some connection to sex hormone signaling during puberty and menopause that’s affecting the brain development and brain function
- In the end of brain development (during late teenage years) is where there’s an end of myelination in the prefrontal cortex
- When the brain fully matures and myelination ends, there’s synaptic pruning, a lot of synapses get compromised/eliminated (these are eliminated to optimize the neural network)
- People believe that people are born with the schizophrenia gene and when the brain matures and myelination of the frontal lobe occurs and synaptic pruning occurs, that’s when the brain revels itself for having problematic wiring and neural networking issues
- The schizophrenia disease is in a latent state till pruning occurs
16
Q
What are the negative symptoms of schizophrenia?
A
- Negative = absence of behaviours that other healthy people have
- Social withdrawal
- Reduced emotional expression
- Poverty of speech
- Reduced motivation
17
Q
What are the cognitive symptoms of schizophrenia?
A
- Disorganized and irrational thinking
- Deficits in learning and memory
- Poor abstract thinking
- Poor problem solving
18
Q
What are the positive symptoms of schizophrenia?
A
- Positive = presence of symptoms other people don’t have
- Delusions (typically delusions of persecution, grandeur, or control - beliefs that contradict/are not accurate of reality)
- Hallucinations (perception of stimuli that are not actually present - most common = voices)
19
Q
What are delusions of persecusion?
A
Belief that everyone around you is out to get you and persecute you
20
Q
What are delusions of grandeur?
A
Belief that they are the person needed to save society at this time, that they have special information and abilities and that they have a special role in doing something great
21
Q
What are delusions of control?
A
You think other people can control things that you can’t or you can control things
Ex: control over the weather or control over the stock market
22
Q
What are the 3 categories of symptoms for schizophrenia?
A
- Negtaive symptoms
- Cognitive symptoms
- Positive symptoms
- Many patients with schizophrenia also exhibit neurological symptoms
23
Q
What are neurological symptoms of schizophrenia?
A
- Poor control of eye movements
- Unusual facial expressions
24
Q
What’s the difference between normal behaviour and schizophrenic behaviour?
A
- All of the symptoms of schizophrenia are a continuity of normal behaviour (believing in delusions like superstitions or hallucinating like talking to a loved one that has died)
- It’s important to know where to draw the line between normal weird behaviour and symptomatic of schizophrenia
25
What's the general timeline of the appearance of the different types of symptoms in schizophrenia?
Negative symptoms typically emerge first, followed by cognitive symptoms and, years later, by positive symptoms
26
What are the causes of schizophrenia and what are the statistics behind its heritability?
- Environmental and genetic factors
- Estimates of the heritability of schizophrenia is around 80%
27
What's heritability?
- Measures the fraction of phenotype variability that can be attributed to genetic variation
- It’s hard to measure the environmental influence when there’s high genetic influence
28
What are the statistics behind the risk of developing schizophrenia?
Risk of developing schizophrenia if:
- both of you parents have it (or an identical twin has it) is ~50%
- one of your parents has it is ~13%
- your sibling has it is ~8%
- once you get away from immediate family of having it, then it drops down to the general population likelihood
- around 5% of cases are attributed to rare gene copy number variations (duplicated or missing genes - chromosomal variations), which are frequently comorbid with autism and intellectual disabilities
29
What are the environmental factors that could cause schizophrenia?
- mother’s nutrition during pregnancy
- mother’s stress during pregnancy
- certain infections (particularly during pregnancy)
- birth month
- being raised in a city
- childhood trauma
- social isolation
- perinatal hypoxia / brain damage -> when the umbilical cord wraps around the baby’s neck and leads to lack of oxygen to the brain that leads to cells dying off
30
Schizophrenia is related to what environmental factors that could affect development in utero?
- season of birth
- viral epidemics
- population density
- parental smoking
31
What's the seasonal effect on developing schizophrenia?
- A disproportionately large number of schizophrenic patients are born in February, March, April, and May
- If it’s cold outside, people go inside more and are more prone to getting a viral infection -> this leads to certain birth months making it more likely for babies to be born with schizophrenia
- The number of schizophrenic births in late winter and early spring is especially high if the temperature was lower than normal during previous autumn
32
What's the population density effect on developing schizophrenia?
- Schizophrenia is about 3x more prevalent in people who live in the middle of large cities as compared to those who live in rural areas
- This result suggests transmission of infectious illnesses is facilitated by increased population density
33
What kind of twins are more likely to both be born with schizophrenia?
- Some evidence suggests that the concordance rate for schizophrenia is much higher for monochorionic twins than in dichorionic twins, which suggests the prenatal environment is an important factor
- Prenatal environments of monochorionic twins (i.e., they share one placenta) are more similar than those of dichorionic twins
34
What's some biological evidence of schizophrenia in children that indicates that abnormal prenatal development is associated with schizophrenia?
- Children who go on to develop schizophrenia display less sociability and deficient psychomotor functioning as kids
- This is observed by having 2 groups of kids play with each other, one group whose parents have schizophrenia and one who doesn’t and observe how they play with each other
35
What's some anatomical evidence of schizophrenia in children that indicates that abnormal prenatal development is associated with schizophrenia?
Minor physical abnormalities are often seen in children who go on to develop schizophrenia, such as partial webbing of the two middle toes and a high-steepled palate
36
What's the treatment for schizophrenia?
- There's no cure for schizophrenia
- Main treatment is medication, often in combination with psychological and social supports
- Many drugs have been developed that relieve the positive symptoms of schizophrenia. They typically block dopamine D2 receptors and are called antipsychotics or neuroleptics (only kind of drugs used up until 1990s)
- The atypical antipsychotic clozapine has been found (in monkeys) to simultaneously decrease dopamine levels in the striatum and increase dopamine levels in the prefrontal cortex (more recent experimental/dirty drug used for treating schizophrenia)
37
What drug tends to temporarily elicit certain aspects of the positive symptoms of schizophrenia in people who don't have the disorder?
Dopamine receptor agonists, like crystal meth and cocaine
38
What's the dopamine hypothesis for schizophrenia?
- Excessive dopamine D2 receptor activity, particularly in the nucleus accumbens (striatum), underlies the positive symptoms of schizophrenia
- Dopamine D2 receptor antagonists typically reduce the positive symptoms of schizophrenia but not the negative symptoms
- Dopamine system is trying to make habits of movement and of thought
- Unhealthy patterns of thought
39
How is the prefrontal cortex associated with the negative symptoms of schizophrenia?
- Some evidence suggests that the negative symptoms of schizophrenia result from abnormal activity (reduced dopamine signaling) in the prefrontal cortex
- For example, the negative symptoms of schizophrenia are similar to those produced by damage to the prefrontal cortex, and schizophrenic patients do poorly on neuropsychological tests that are sensitive to prefrontal damage
- In general, the negative symptoms of schizophrenia may be caused by hypofrontality, which is decreased activity of the frontal lobes, particularly the dorsolateral prefrontal cortex, which may relate to hypoactivity (insufficient activity) of local dopamine D1 receptors
40
What are atypical antipsychotic medications?
- Recently developed medications which aim to reduce both the positive symptoms and negative symptoms of schizophrenia
- They typically influence the activity of several neurotransmitter receptors (beyond blocking the dopamine D2 receptor)
41
What's Clozapine?
- First of the atypical antipsychotic medications
- It blocks both dopamine D2 and serotonin 2A receptors
42
What's Aripiprazole?
- Atypical antipsychotic
- It acts as a partial agonist at the dopamine D2 and D3 receptors
- It's thought to reduce dopamine receptor activity in the striatum (nucleus accumbens) but boost it in the prefrontal cortex
43
What's a partial agonist?
- A drug with very high affinity for a receptor but it activates it less than the normal ligand does
- Can act as an agonist in regions of low concentration of normal ligand and as antagonist in regions of high concentrations
- The partial agonist will outcompete the neurotransmitter
- Partial agonists decrease the mean opening of ion channels when the extracellular concentration of the neurotransmitter is high and increase it when the extracellular concentration of the neurotransmitter is low
44
What are dirty drugs?
Drugs that bind to multiple receptors and change activity in multiple different ways
45
Describe autistic spectrum disorder
- Describes a wide range of developmental disorders that are characterized by troubles with social interaction and communication (reciprocal communication), and by restricted and repetitive behavior
- Incidence of autism is around 1% of population
- In many cases there are clear cognitive impairments, intellectual disability, or reduced imaginative ability, but this is not always the case
- Some infants with autistic disorder do not seem to care whether they are held. Some arch their backs when picked up, as if they do not want to be held
- Symptoms exist on a continuum among the population
46
How early on can parents detect whether their child has autism?
- Parents usually notice signs during the first two or three years of their child's life
- Social impairments are often the first symptoms to emerge
- When calling the child’s name they don’t turn to look at you, avoid eye contact and push back when getting hugged (initial symptoms)
47
What are the causes of autism and what are the statistics behind its heritability?
- Associated with a combination of genetic and environmental factors that affect early brain development
- Many cases have been linked to spontaneous rare gene mutations that have severe effects. These include chromosomal abnormalities involving deletions, duplications or inversions of genetic material
- Other cases are associated with multigene interactions across common gene variants
- Some cases have been linked to maternal viral infections during pregnancy
- Estimates of the heritability of autism are around 70%, but as high as 90% for autism spectrum disorder
- Autism tends to run in family
48
What are symptoms of autism?
- Many people with autism have abnormal or even nonexistent language
- About a third to a half of individuals with autism do not develop enough natural speech to meet their daily communication needs
- They may echo what is said to them or they may refer to themselves as others do—in second or third person
- People with autism generally have atypical interests and behaviors
- They may show stereotyped movements, such as flapping their hand back and forth or rocking back and forth
- They may exhibit compulsive or ritualistic behaviour
- They show sensory integration issues
- 1/3 of people with autism have very clear intellectual disability
- 1/3 of people with autism have a seizure disorder
- More than ½ of people with autism have sensory processing issues
- All of these aren’t considered key components of the disorder -> these are considered comorbid with the disorder
49
How might someone with autism cope with sensory integration issues?
- Too loud sensory information or too quiet sensory feedback -> either rock back and forth to calm down anxiety from high stimulus or stomping feet cuz too low stimulus (too quiet)
- They will attempt to make the sensory stimuli more predictable and calm their brains down
50
What's Asperger's syndrome?
- Mild forms of autism
- Mostly just involve deficient or absent social interactions and repetitive and stereotyped behaviors along with obsessional interest in narrow subjects
- They have a hard time comprehending social dynamics
- Social dynamics and cues are very subtle and non-verbal which makes it difficult for people with autism to comprehend
- Mild forms of autistic spectrum disorder often do not include a delay in language development or the presence of important cognitive deficits
- Know their interests but can’t verbalize them like everyone else
51
What are the statistics and gender differences behind having autistic disorder?
- Incidence of autistic disorder is around 1% of population
- Disorder is 4x more common in males than in females
- If only cases of autism with intellectual disability are considered, the ratio falls to 2:1 (males:females)
- If only cases of high-functioning autism are considered (those with average or above-average intelligence and reasonably good communicative ability), the ratio rises to approximately 7:1 (males:females)
- There are disorders that affect females more than males (ocd, anxiety disorder, depression)
- This is explained by the difference of sex hormone signaling
52
How do sex chromosomes and genes correlate with autism?
- The X chromosome has 1000 genes on it and the Y chromosome has less
- When you have 2 copies of a gene (XX for females) you have more chances of having a successful protein being made
- More variability and morphology of the body and of the brain among the heterogametic sex of the species (XY or ZW)
- With chromosomes, you either have 2 copies of the instructions or 1
- When you have 2 copies of a gene, you have the option to take one or the other
53
Describe the abnormalities in the development of the brains of autistic children
- Kids who develop autism tend to have a slightly smaller brain at birth, but it grows abnormally fast and by 2–3 years of age is often about 10% larger than a normal brain
- Following this early spurt, growth of the autistic brain slows down, and by adolescence it is only about 1–2% larger than normal
54
What are hypotheses for the cellular and molecular bases of early brain overgrowth among children with autism?
- Altered neuronal migration during early gestation
- Abnormal formation of synapses and dendritic spines
- Overconnectivity in key brain regions
- Unbalanced excitatory–inhibitory neural networks
55
What have fMRI studies on people with autism revealed?
- Marked abnormalities in brain activity
- There is little or no activity in fusiform face area of autistic adults looking at pictures of human faces
- This could be explained by the fact that when development happens, the average kid craves social interaction and staring at faces and through this act some brain regions specialize more
- Since kids with autism have different interests, their brain will evolve differently
56
What are treatments for autism?
- Main goals are to lessen the impact of the associated deficits and family distress, and to increase quality of life and functional independence
- Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, communication, and life skills, and often improve functioning and decrease symptom severity and maladaptive behaviors
- Medications generally do not address the core symptoms, but often help reduce the irritability, inattention, and repetitive behaviors
- Medications often relate to what the comorbidity is
- Healthy home environments
57
What are medications that can be used to treat autism?
- Anticonvulsants (↑ GABA receptor activity) -> for those that also have seizure disorder and to relieve the anxiety and stabilize mood
- Antidepressants (↑ serotonin receptor activity) -> stabilize mood and relieve depression
- Antipsychotics (↓ dopamine receptor activity) -> calm people down and make it easier to care for them, and stabilize mood
- Stimulants (↑ dopamine receptor activity) (ex: Adderall and Ritalin) -> ADHD symptoms
58
Symptoms of what other disorder are often common among people with autism?
ADHD
59
What's affect?
- Refers to feelings or emotions
- As the primary symptom of schizophrenia is disordered thoughts, affective disorders (mood disorders) are characterized by disordered feelings
60
What's a mood (affective) disorder?
- Serious mood disorder
- People with mood disorders -> their emotions don’t match the environment…there’s a disregulation in feelings
- Affective disorders are prevalent and dangerous
- People with mood disorders have a risk of self-harm and suicide
- Environmental factors for mood disorders include traumatic/abusive childhood experiences.
61
What are the 2 principal types of mood disorders?
- Bipolar disorder
- Major depressive disorder
62
What are the statistics behind the gender differences in mood disorders?
- A diagnosis of depression has a prevalence of approximately 7% in women and 3% in men
- Depression is 2x as common in women than in men
63
Describe bipolar disorder, the statistics behind it and its causes?
- Serious mood disorder characterized by cyclical periods of mania and depression
- Affects ~1% of the population
~80% of the risk is attributed to genetics
64
Describe major depressive disorder (MDD), the statistics behind it and its causes?
- Serious mood disorder that consists of unremitting depression or periods of depression (that don't alternate with periods of mania)
- ~40% of the risk is attributed to genetics
- Severely depressed people usually feel unworthy, hopeless, and have strong feelings of guilt
- Depression exists on a continuum –> some people have severe symptoms and some less
65
What's 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
- People with mania just seem happy or excited
- Tend not to eat well, tend not to sleep much
- They’ll engage in activities that don’t rlly do much
- Similar to schizophrenia in that they’ll have delusions
- They’ll sometimes have periods of psychosis
66
What's Lithium and how could it be used to treat bipolar disorder?
- Chemical element and an atom on the period table (it’s a metal)
- A mood stabilizer
- It doesn’t work in low doses…similar to alcohol
- Lithium on a high concentration will be toxic -> issues with prescribing it
- 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 or minimized, depression usually does not follow
- Therapeutic effect of lithium is very rapid
- The mechanism of action is unknown
- There’s a big range in side effects -> side effects vary among one person and among different people
67
What are the 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) -> at low doses it has similar effects of alcohol & it lifts the mood up leads to happier mood
- Electroconvulsive therapy (ECT)
- Deep brain stimulation
- Transcranial magnetic stimulation
- Vagus nerve stimulation
- Bright-light therapy (phototherapy)
- Sleep deprivation
68
What are tricyclic antidepressants?
- Inhibit reuptake of serotonin and norepinephrine but also affect other neurotransmitters
- Named for the molecular structure
69
What are serotonin specific reuptake inhibitors (SSRI)?
- A class of drugs that specifically inhibit the reuptake of serotonin without affecting the reuptake of other neurotransmitters
- It’s hard to make a serotonin reuptake without affecting the reuptake of other neurotransmitters
- Most common one is Prozac (fluoxetine)
- Similar drugs are Celexa, Paxil, Zoloft, etc...
70
What are serotonin and norepinephrine reuptake inhibitors (SNRI)?
Antidepressant drug that specifically inhibits reuptake of norepinephrine and serotonin without affecting reuptake of other neurotransmitters
71
What's the monoamine hypothesis of major depressive disorder (MDD)?
- Based largely on the success tricyclic and SSRI treatments, the monoamine hypothesis of depression was developed
- Idea: 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
72
What method was created to test the monoamine hypothesis of major depressive disorder (MDD)?
- A diet that lowers serotonin signaling
- 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
73
Why are SSRIs and SNRIs often not as effective to treating major depressive disorder (MDD)?
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
74
What was found for treatments of major depressive disorder through Functional imaging scans?
That one area of the anterior cingulate cortex (the subgenual region known as area 25) becomes less active after successful treatments
75
What form of treatment for major depressive disorder shows most decreased activation in the brain?
Deep brain stimulation
76
What area of the brain was most commonly said to have less activation among patients whose depression was lifted through experimental means?
In the Subgenual anterior cingulate cortex
77
Describe the deep brain stimulation approach to treating depression
- Deep brain stimulation has been tried in the subgenual anterior cingulate cortex as well as in the nucleus accumbens
- Hard to know where to stimulate, when to stimulate and at how much frequency should we stimulate
78
Other than deep brain stimulation, what are other promising approaches to treating major depressive disorder?
- Transcranial magnetic stimulation (TMS) directed to areas of the PFC -> you can get electrical signals to stimulate parts of the brain and change neural activity (can change the excitability in the prefrontal cortex)
- Vagal nerve stimulation (VNS) -> 80% of sensory nerves in this nerve are affect
- Some people notice a rapid change in their mood when stimulating their vagal nerve
79
What's electroconvulsive therapy (ECT)?
- Used therapeutically to alleviate severe depression and bipolar disorder
- Seizures are electrically induced by applying brief electrical shocks to the head
- The seizures induced by ECT often reduce symptoms within days
- Most effective treatment we have…it works very well and fast for vast majority of people
- Put people under muscle relaxants to reduce risk of convulsions and put them under general anesthesia
- Used very highly for people with catatonic therapy
- We tend to localize the current injections and give the minimal amount needed to restore
- People generally hate this treatment because some have bad side effects, local memory seems to be affected
80
What forms of treatment for depression offer the quickest results?
- ECT
- lithium
- DBS
- VNS
- sleep deprivation
- In contrast to the delayed therapeutic effects seen with monoamine related treatments
81
What's the relationship between sleep and depression?
- 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 the morning
- In general, they spend more time in stage 1 sleep (light 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 and it gets and this gets shorter and shorter throughout the night
- Reduced sleep latency, reduce REM latency, reduction in slow-wave sleep (stages 3 & 4) and general fragmentation of sleep
82
Describe the total sleep deprivation treatment for depression
- 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
- When staying up late, people tend to feel very happy and giggly -> this can relieve symptoms of depression
- 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)
- A lot of antidepressant medications reduce our REM sleep (almost seems like people don’t even enter REM sleep)
83
What are anxiety disorders?
- A variety of psychological disorders characterized by unrealistic and unfounded fear and anxiety
- Includes muscle tension, overactivity of the autonomic nervous system, expectation of an impending disaster, and continuous vigilance for danger
- Extremely common
- Anxiety can appear randomly at around 19 or 20 years old (a sudden realization that we’re freaking out out of nowhere)
- People often have more than one type of anxiety disorder
- Characterized by fear learning -> unconscious fear learning
- Anxiety disorders often occur with other mental disorders, particularly major depressive disorder, personality disorder, and substance use disorder
84
What's generalized anxiety disorder?
Disorder characterized by excessive anxiety and worry serious enough to cause disruption of their lives
85
What's 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
- Social situations often bring anxiety out in adolescence
- The brain is learning at a subconscious level what’s a good or bad environment
- The unconscious part of the brain is saying -> no I learned that this is a bad environment
- The body says “I am so afraid of this situation”
- The people consciously try to get over a situation but the body doesn’t allow it
86
What's 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
87
What's anticipatory anxiety?
Fear of having a panic attack promotes anticipatory anxiety that sometimes leads to the development of agoraphobia
88
What's agoraphobia?
Fear of being away from home or other protected places
89
What are the different types of anxiety?
- Generalized anxiety
- Social anxiety
- Panic disorder
- Anticipatory anxiety
- Agoraphobia
90
What are the statistics and gender differences behind anxiety disorder?
- In a given year, about 12% of people are affected by an anxiety disorder
- It appears twice as often in females than males (ages 15-25) and almost 3x as often in females than males (ages 35-44)
- 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
- There's a clear relationship with fluctuations of sex hormone signalling and changes in anxiety
- Can be exacerbated during pregnancy or menopause
91
What are the causes of anxiety disorder?
- A combination of genetic and environmental factors
- Environmental risk factors include a history of child abuse and poverty
- Older people who have dementia often have problems with anxiety
- When people have a neurodegenerative disease, anxiety comes on very strong and intensely
- People wake up with intense anxiety in the middle of the night which can come on from PTSD
92
What parts of the brain are involved with anxiety (as determined by functional brain imaging)?
- Amygdala
- Prefrontal cortex
- Adolescents with generalized anxiety disorder showed increased activation of the amygdala and decreased activation of the ventrolateral prefrontal cortex while looking at angry faces
93
What are treatments for anxiety disorder?
- Lifestyle changes: exercise, regularizing sleep patterns, and reducing caffeine intake and smoking
- Cognitive Behavioral Therapy (CBT) is often effective and is a first line treatment
- Exposure therapy to rework an anxiety
- Medication:
- Benzodiazepines are sometimes used, particularly in emergency settings because of their rapid onset effect
- Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first line treatment for anxiety disorders
94
What's obsessive-compulsive disorder (OCD)?
- Characterized by
repeatedly having certain thoughts ("obsessions") and a need to repeatedly check things or repeatedly perform certain routines ("rituals“ or “compulsions”)
to an extent that it causes distress & impairs general functioning
- Affects less than 2% of population
95
What are the 4 groups of symptoms for OCD?
- Symmetry
- Cleaning
- Hoarding
- Forbidden thoughts (intrusive thoughts)
96
Describe the "forbidden thoughts" cluster of OCD symptoms?
Associated with intrusive and distressing thoughts of a violent, religious, or sexual nature
97
Describe the "cleaning" cluster of OCD symptoms?
Associated with intrusive and distressing thoughts about germs, bodily fluids, and contamination
98
What are the compulsions involved with OCD?
- Compulsive behaviours are driven by intrusive thoughts, and they often involve obsessive hand washing, cleaning, counting, or checking on things (e.g., to see if a door is locked)
- Some people have difficulty throwing things out
- The compulsions are often performed to seek relief from obsession-related anxiety, driven by a fear that something bad will happen if the ritualistic behaviour is not done properly or a belief that life cannot proceed as normal while the imbalance remains
- Most adults with OCD realize that their behaviors don't make sense, they understand that their notions do not correspond with reality; however, they feel that they must act as though their notions are correct, and they are typically unable to control their obsessions or compulsions for more than a short period of time
- Unconscious part of the brain that is pushing compulsions and obsessive intrusive thoughts
99
What are the statistics and gender differences behind OCD?
- Incidence of OCD is less than 2%
- Lifetime prevalence rates are slightly higher in women than men
- Diagnosis typically occurs later in women (after age 18) than men (during adolescence)
- In women, you often see symptom severity fluctuate especially during hormonal changes
- Symptoms usually start before age 25 in both sexes
100
What are the causes of OCD?
- A combination of genetic and environmental factors
- Genetic factors account for ~50% of the variability
- Environmental risk factors include a history of child abuse or other adverse events
- Some cases have been documented following infections
- Loop in basal ganglia that infection in here could lead to ocd
- Sometimes OCD symptoms appear after brain damage
101
What parts of the brain are associated with OCD?
- Sometimes OCD symptoms appear after brain damage, particularly to the basal ganglia, cingulate gyrus, or prefrontal cortex
- Several functional imaging studies have found evidence of increased activity in the frontal lobes and striatum in patients with OCD
102
What are treatments for OCD?
- Treatment for severe cases can include a brain lesion, specifically a cingulotomy, which is the cutting (with a syringe) of a fiber bundle between PFC and anterior cingulate (in frontal lobe)
- This is a severe surgery and there’s no going back from it
- Important to find an area that we can cut without reducing cognitive functions and only reduce symptoms
- Deep brain stimulation within basal ganglia areas is an active area of research
103
What's Attention-Deficit/Hyperactivity Disorder (ADHD)?
- ADHD is a mental disorder characterized by problems paying attention, hyperactivity, or difficulty controlling (inhibiting) behavior in an age-appropriate manner
- ADHD is usually first discovered in the classroom, where children are expected to sit quietly and pay attention to teacher or work steadily on project
- Often comorbid with other illnesses and/or conditions
104
What are the statistics and gender differences behind ADHD?
- More than 5% of children in North America are now being treated for ADHD
- The symptoms generally appear before a person is 12 years old, are present for more than six months, and cause problems in school, home, or elsewhere
- Prevalence rates vary widely across different communities, ranging from 1 to 10% of children
- Boys are diagnosed 3x more often than girls
105
What are the symptoms of ADHD?
- Show reckless and impetuous behavior
- Act without reflecting
- Let interfering activities intrude into ongoing tasks
- Have difficulty withholding a response
- Often associated with aggression, conduct disorder, learning disabilities, depression, anxiety, and low self-esteem
106
Why is diagnosis difficult for ADHD?
- Diagnosis can be difficult because the symptoms are not well defined
- Many children with ADHD have a good attention span for tasks they find interesting, and some hyperactivity, inattention, and impulsivity are within the range of normative behaviors
- How do we draw the line for diagnosis
107
What are the causes of ADHD?
- Environmental and genetic factors
- Estimated heritability of ADHD ranges from 75 to 91%
- Certain cases are related to previous infection of or trauma to the brain
- Drug and alcohol use and infections during pregnancy are associated with increased risk for the child, as is low birth weight (early delivery)
108
What are the treatments for ADHD?
- Management of ADHD typically involves counseling (teaching people to think before they act, to think about the impact of their actions on other people in the class) and medications, often stimulants that raise dopamine levels by blocking or reversing the dopamine reuptake transporter (e.g., Ritalin and Adderall)
- Antidepressants may also be helpful
- By raising dopamine levels (dopamine reuptake transporter), we think that we’re training the brain into believing that the task is very important, however it also makes the focus on the task way too high that extraneous tasks are given little to no attention
109
What's stress and what does it do?
- 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
- Everybody has a stress response
- Stress dramatically affects the body and brain
110
What's the physiology of the stress response?
- Stress activates the sympathetic branch of the autonomic nervous system
- Stress also activates the adrenal glands to release hormones into the blood, including epinephrine, norepinephrine, and glucocorticoids such as cortisol -> to help boost energy
- The autonomic and hormone responses work together to increase heart rate, blood pressure, and blood flow to muscles to make nutrients stored become available
111
What are glucocorticoids?
A group of hormones (corticosteroids) that are important in protein and carbohydrate metabolism, secreted especially in times of stress
112
What's cortisol?
A specific glucocorticoid (steroid hormone) secreted by adrenal cortex in response to stress
113
Secretion of glucocorticoids is controlled by what part of the brain?
The hypothalamus
114
Describe the process of the secretion of glucocorticoids?
1. In response to stress, the hypothalamus starts a chain of events by releasing CRH/CRF (corticotropin-releasing hormone/factor).
2. CRH stimulates the pituitary to secrete ACTH (adrenocorticotropic hormone)
3. ACTH stimulates the adrenal gland to produce glucocorticoids
115
What part of the brain can control the secretion of glucocorticoids?
The adrenal cortex
116
What part of the brain can control the secretion of catecholamines?
The adrenal medulla
117
What are glucocorticoids?
- Help to break down and convert proteins into glucose, make fats available for energy, increase blood flow, suppress secretion of sex and growth hormones and stimulate behavioral responsiveness
- Females will have a hard time menstruating and men will have a hard time getting an erection
- They have other physiological effects, too, some of which are not well understood
- Almost every cell in the body contains glucocorticoid receptors (to know how much fat and glucose they have to take in for energy), which means that few of them are unaffected by these hormones
- These systems regulate metabolism throughout the body and brain
118
What's the difference between the short-term and long-term effects of glucocorticoids?
- Short-term effects of glucocorticoids are essential for survival
- Long-term effects are damaging
119
What are the long-term effects of glucocorticoids?
- Increased blood pressure
- Damage to muscle tissue
- Steroid diabetes
- Infertility -> blocking sex hormones (no erections, no pregnancy)
- Inhibition of growth (neural plasticity is conducted by growth hormones)
- Inhibition of the inflammatory responses
- Suppression of the immune system
- Stress slows the healing of (flesh) wounds and predisposes people to infections
120
What's an example of how stress slows the healing of (flesh) wounds and predisposes people to infections?
- During 3-5 day period just before showing symptoms of upper respiratory infection, people experienced an increased number of undesirable, stressful events
- When stressful/bad events occur, the immune system takes a backseat which can lead to infections and people can get sick after some stressful event
121
What are psychological and physiological effects of stress?
- 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 (tearing of stomach lining), enlarged adrenal glands, and damaged hippocampi
- Episodes of emotional maltreatment during childhood has been associated with a small reduction (7.2%) in volume of dorsomedial prefrontal cortex
122
What's Post-traumatic stress disorder (PTSD)
- Mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, or other threats on a person's life
- The symptoms can interfere with social activities, cause feeling of hopelessness, and increase risk for suicide
- One of the few mental disorders related directly to an environmental trigger
123
What are symptoms of PTSD?
- Disturbing thoughts
- Feelings
- Dreams related to the events
- Mental or physical distress to trauma-related cues and efforts to avoid them
- Increase in the fight-or-flight response
- Severe symptoms of helplessness, guilt, shame
124
What are the causes of 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
125
What are the treatments for PTSD?
- Cognitive Behavioural Therapy
- Group therapy
- Medication: selective serotonin reuptake inhibitors (SSRIs) are the first-line medications and result in benefit in about half of people
126
What brain areas are associated with PTSD?
- 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
127
What are the main drugs found in drug addiction and how does addiction to these happen?
- Alcohol
- Opiates
- Cocaine
- Meth
- Nicotine
- Barbiturates
- Benzos
- These are the drugs that create the psychological dependance on recreational drugs
- The more your brain thinks these drugs are critical for your survival the more dependent you become on it
-Alcohol addiction becomes a problem relatively slowly -> it creeps up on people and when they realize it , they can’t stop consuming it, it’s too late
- Some people’s personalities are addictive and some person’s addictive personality only matches with a particular substance
128
What are problems that arise with alcohol abuse?
- Automobile accidents
- Fetal alcohol syndrome
- Cirrhosis of the liver
- Korsakoff's syndrome
- Increased rate of heart disease
- Increased rate of intracerebral hemorrhage
- Pancreatitis, diabetes, etc.
129
What are the statistics behind the heritability of drug abuse?
- Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism
- Alcohol consumption is not distributed equally across the population; in the US, 10% of the people drink 50% percent of the alcohol
- Many twin studies and adoption studies confirm that the primary reason for this disparity is genetic
130
What's drug reinforcement?
- Drugs that lead to dependency must first reinforce people's behavior
- If, in a particular situation, a behavior is regularly followed by reinforcement that behavior will become more frequent in that situation
- Reinforcement learning is ALWAYS context dependent -> drug abuse gets around these context dependent cues
- Effectiveness of a reinforcing stimulus is greatest if it occurs immediately after a response occurs
- If reinforcing stimulus is delayed, it becomes considerably less effective
- The consequences of the actions teach us whether to repeat that action, and events that follow a response by more than a few minutes were probably not caused by that response (It’s hard to feel cause and effect with drugs that are taken with immediate effects)
131
What explains the relative addictive potential of different drugs?
The speed by which the brain perceives reinforcement
Ex: Heroin crosses the blood brain barrier instantly, it’s extremely addictive
132
How does drug abuse generally get around reinforcement context dependent cues?
- People who are addicted to smoking, as soon as they enter an area where they can’t smoke, their craving levels become very low but as soon as they get out of that area, their cravings shoot up
- You generally won’t experience cravings if you’re in a context where you can’t take the drugs
133
What are the neural mechanisms behind drug addiction?
- All reinforcers, natural or otherwise, elicit dopamine release in the striatum, particularly in the nucleus accumbens
- All addictive drugs rapidly increase dopamine levels in the nucleus accumbens
- Dopamine release in the nucleus accumbens is not as simple as it sounds...
- Aversive stimuli can also trigger release of dopamine, and some areas of the nucleus accumbens seem to promote avoidance behaviors
134
What's tolerance?
- Fact that increasingly large doses of drugs must be taken to achieve a particular effect
- Caused by compensatory mechanisms that oppose the effect of the drug
- Not all addictive drugs produce tolerance and withdrawal
- Anything we take we develop tolerance to
135
What are withdrawl symptoms?
- Appearance of symptoms opposite to those produced by drug when the drug is suddenly no longer taken
- Caused by presence of compensatory mechanisms (that relate to drug tolerance)
- Ex: as soon as you remove opiates (opposite effects = diarrhea, generally feeling bad)
136
What's negative reinforcement?
- Removal or reduction of an aversive stimulus that is contingent on a particular response, with an attendant increase in the frequency of that response
- Making a behaviour more likely to occur by taking away something bad
137
People with a history of drug abuse show structural abnormalities and deficits on tasks involving what region of the brain?
- Show the same deficits on tasks that involved the PFC as do people with damage to this region
- Addicts also show structural abnormalities in the PFC
- When addicts (who are not currently high) perform tasks that normally activate the prefrontal cortex, their medial prefrontal cortex is less activated than that of healthy control subjects, and they perform more poorly on the tasks
- In cocaine addicts, the more cocaine they took, the less brain activity in their PFC
138
Studies have shown a high level of comorbidity between substance abuse and what other 2 disorders?
- Schizophrenia and ADHD
- 70-90% of schizophrenics smoke cigarettes and almost half are addicted to drugs other than nicotine
- In one study from 2004 it was estimated that 7% of the population had some form of mental illness and a third of all cigarettes were smoked by this group
- Abnormalities in the prefrontal cortex and its interactions with the striatum and dopamine system may be common factor in these disorders
- People with mental illness tend to engage more in substance abuse -> self-treatment
139
What's Naltrexone?
- A somewhat long-acting, slow onset opioid receptor antagonist that is prescribed to alcoholics and opiate addicts
- It reduces the high produced by opiates (because the opiates can't bind to the receptor), but it also tends to reduce drug, alcohol, and food cravings in certain people
140
What's Naloxone (Narcan)?
- Extremely rapid (and short lived) opioid receptor antagonist that reverses the effects of an opiate overdose
- Given in instances of overdose
- During an opiate overdose, people can lose consciousness and stop breathing
- A naloxone injection can immediately reverse these effects and even elicit withdrawal symptoms (but naloxone is short-lived and cleared in 20-80 minutes)
141
What's methadone maintenance?
- Potent opiate, similar to morphine or heroin but with a slower onset and offset
- Methadone maintenance programs administer the drug to their patients in liquid form, which they must drink in the presence of supervising personnel
- Reduces the euphoria that you get on the onset
- Similar maintenance treatments are used with nicotine addiction (nicotine patches, gum, vaping, etc.)
142
What's Buprenorphine?
- A high affinity partial opioid receptor agonist
- It strongly binds to opioid receptors but produces only a weak effect while blocking the effect of other opiates
- Relatively new treatment for opiate addiction
- To reduce the potential for abuse, it is commonly mixed with a little naloxone (an opiate receptor antagonist)
143
What's Varenicline?
- Approved to treat nicotine addiction
- It's a partial agonist at nicotinic (acetylcholine) receptors, just as buprenorphine is a partial agonist at opioid receptors
144
What's the cocaine vaccine?
- Compounds have been developed that cause a person's own immune system to create antibodies against a drug, like cocaine
- When antibodies bind to the drug, it can no longer cross the blood brain barrier
- This approach is being explored for cocaine, heroin, meth, and nicotine
145
How can DBS and TMS be used as a treatment for drug abuse?
- DBS: researchers have tried DBS (deep brain stimulation) in many areas of the brain, including the basal ganglia and PFC
- TMS: TMS (transcranial magnetic stimulation) of the PFC is also currently being tested
