Test 2C Flashcards
Know which disorders go with the latent factors externalizing and internalizing respectively.
External: antisocial behavior and substance use disorders
Internal: Disorders characterized by negative mood states and inhibition (e.g., depression, anxiety)
Understand the benefit of clustering disorders into externalizing and internalizing broadly, as opposed to talking about the individual disorders each on their own.
- Both externalizing and internalizing run in families
- Evidence suggests that rather than risk for specific disorders, what is transmitted from parents to offspring is a broad liability that increases risk for that spectrum
Know whether alcoholism rates are similar across countries or whether they vary. If they do vary, where are rates highest/lowest.
Vary
highest: Europe to Russia
lowest: Northern Africa to India to Indonesia
How heritable is alcoholism?
0.51
How do the effects of the unique (e) and common (c) environment change over time in regards to this phenotype
.
Understand the alcohol metabolism model.
Alcohol - ADH breaks down - acetaldehyde - ALDH - acetate
both are protective again alcohol
What symptoms arise when a buildup of acetaldehyde occurs?
Dysphoric effects that can occur w/in 15 minutes of drinking: Heart palpitation (tachycardia) Facial reddening Nausea, dizziness Sweating
How does the inactive form of ALDH is protective against alcoholism, and
how this has changed over time.
Inactive ALDH2 is thought to cause high blood acetaldehyde concentrations and a painful flushing response, which suppresses alcohol consumption.
The importance of the environment related to alcoholism
.
What are the core defining symptoms of individuals with autism spectrum disorder (ASD)?
Difficulties with socializing and communication and narrow interests and repetitive behavior
Autism Spectrum Disorder: Which symptoms might be found in some patients but not others?
Language delay
What has been happening to the prevalence of ASD over time?
What is the current prevalence?
Prevalence of autism was ~0.04%.
- The prevalence of ASD will necessarily be higher because it is a broader label, and it is now approaching 1%.
- Accepting the uncertainty over the causes of the increasing prevalence, we can still point to exemplary cases to show that there is a “core” of true disability.
What is savant syndrome?
Condition in which someone with significant mental disabilities demonstrates certain abilities far in excess of average.
- The skills at which savants excel are generally related to memory.
- exceptional ability in some narrow domain such as music, drawing, or arithmetic—even while showing impairment in most other domains.
At what rate do we see savant syndrome in those with autism?
10%
Understand the liability model.
Assume that the disease state manifests itself when a continuous variable called liability crosses a certain threshold.
- Liability can be interpreted as an aggregate of genetic and environmental causes. If you are unlucky enough to inherit many + genes with respect to the disease and to suffer many adverse environmental events, your liability will be high.
- Liability is just like any other continuous phenotype (e.g., height, IQ). It has a heritability that does not depend on the threshold.
How do the threshold differ for males and females?
Females will carry more mutation than males
- Female threshold is further than male
- Female is protected, males at risk
What does this mean in terms of number of + genetic variants (e.g.,mutations) carried by males and females who have ASD?
Males: risk factors decrease liability threshold
Females: protective factors increase liability threshold
What are the genetic correlations with autism?
High to low:
- PGC-IQ
- iPsych-IQ
- EduYears
- Schizophrenia
- Bipolar Disorder
Does evidence suggest these correlations are genuine or simply the result of a biased sample?
Genuine
- A recent within-family study strongly suggests a genuine genetic correlation between IQ and ASD rather than biased samples of cases in the GWAS (Weiner et al., 2017).
- In parent-offspring trios where the offspring has been diagnosed with ASD, the offspring is more likely to have inherited EduYears + alleles from the parents
What is the biology suggested by the protein-coding regions in those diagnosed with ASD?
Synaptic transmission
- Early brain development
Neurons
- Many of the protein-coding regions containing new mutations in ASD cases encode molecular parts used in synaptic transmission.
- ASD thus seems to reflect disordered communication between neuron
What symptoms do schizophrenia and bipolar disorder share in common?
Individuals with schizophrenia experience symptoms of psychosis, such as hallucinations or delusions.
- Some people with bipolar disorder also experience psychotic symptoms.
In what ways are schizophrenia and bipolar disorder different?
In individuals with SCZ there tends to be:
- reduced gray matter and hippocampal volume
- Slightly larger ventricles
- Neurological insults (e.g., those assoc. obstetrical complications), later life stressors, nonhereditary genetic risk factors (e.g., older fathers – possible mutations)
What percent of the US population has schizophrenia?
1%
Does this rate of occurrence differ in other nations?
Three “hits” were found that had not been previously reported by Ripke et al. (2014).
- Of the 117 SNPs that were hits in Europeans, 109 showed a consistent direction of effect in Chinese.
- These researchers found that the genetic correlation between SCZ and major depression in Chinese (0.43) is very similar to what has been reported in Europeans.
- Overall, this study strongly supports the notion that the genetics of SCZ is more or less the same in these two populations.
Given the available data so far, what can we say about whether the genetics of schizophrenia is similar in different continental populations?
Study found that h2 of SCZ appears to be very similar in Europeans and Chinese.
Why do individuals suffering from schizophrenia and bipolar disorder show a reduction in life expectancy? What causes this reduced life expectancy?
Schizophrenics have a life expectancy that is 10-20 years shorter
- Most likely as a result of poor diet, lack of physical activity, obesity, substance abuse, and lack of connections to the community.
- Roughly 5 percent of schizophrenics commit suicide—many times the baseline rate.
What predictions following from the hypothesis that schizophrenia and bipolar disorder share some biological causes have been confirmed?
- The fact that SCZ is linked to readily observed brain abnormalities and low intelligence suggests that it reflects greater biological damage.
- They also show that the biological bases of certain mental diseases are relatively distinct.
If twin one has schizophrenia, what is the risk of the other twin having schizophrenia if they are monozygotic twins? how about dizygotic twins? What does this suggest?
Monozygotic: 48%
Dizygotic: 17%
- These studies find that effects of shared family environment are very small (< 5% of the liability variance).
- These studies also find that SCZ and BP co-occur in biological families.
Results from GWAS of schizophrenia been confirmed in within-family studies?
108 hits
Schizophrenia is polygenic. What does this mean? Roughly how many SNPs are estimated to affect schizophrenia liability?
It has been estimated from GWAS data that there are more than 20,000 causal sites responsible for the h2 of SCZ
What is the underlying biology suggested by initial “hits” discovered in GWAS of schizophrenia broadly
Brain - Cortex
What part of this biological theme is shared with bipolar disorder?
Brain tissue
- Synaptic transmission: neurons communicating with one another
- glutamate receptor
Know the genetic correlation between schizophrenia and bipolar, and which personality trait the two correlate with most strongly.
Openness to experience
Polygenic
Refers to DNA traits such as skin color, hair color, eye color, and stature that are influenced by multiple genes rather than other traits that exist as a yes or no (such as gender or blood type).
