Lecture 1: Translational Neuroscience Flashcards
List the 3 factors that can be considered abnormal
- Infrequency
- Norm violation
- Personal suffering
What is infrequency?
Statistical infrequency considers behavior that is atypical or rare to be abnormal
Some behavior that is rare, such as high IQ, but is not dysfunctional; therefore, statistical infrequency alone is not an adquate criterion
What is norm violation?
People who behave in ways that are bizarre unusual or disturbing enough to violate social norms or cultural rules are termed abnormal.
What is personal suffering?
Psychological problems causing distress require treatment
Why can’t personal suffering be the only criterion for abnormality?
Some people with disorders may not experience distress
What is used to currently diagnose mental disorders?
DSM-5 (Diagnostic and Statistical Manual of Mental Disorders)
What are the goals of the DSM-5/diagnosis (2)?
- Help identify the appropriate treatment for clients
- To accurately and consistently group patients with similar disorders, so that research efforts can more easily identify underlying causes of mental illness
What are the limitations of the DSM-5/diagnosis (3)?
- Validity
- Interrate reliability
- Confounders
List the different Confounders that can impact diagnosis
Low yield
- Similar symptoms cann can result from
- head injuries
- brain tumors
- hormone shifts
- substance use
- other illnesses
- Co-morbidity of disorders or other diseases
- Other psychological disorders
- cancer
- neurodengerative diseases
- Substance use is common in mood disorders
______ use is common in mood disorders
Substance
How many adults in the United States in 2020 lived with a mental illness?
Nearly 1 in 5
- 52.9 million
- Slide 11
Did males or females have a higher prevalence of any mental illness in 2020? What percentage?
Females = 25.8%
Slide 11
What age group in 2020 had a high prevalence of any mental illness?
18 - 25 = 30.6%
Slide 11
What model attempts to explain psyhological disorders?
Diathesis-Stress Model
aka Vulnerability-Stress Model
What are the two components that make up the Diathesis-Stress Model? What are the factors for each?
- Diathesis (vulnerability): Genetic factors, Biological characteristics
- Stressors: Traumatic life events, Negative family life, Economic disadvantages, Environment
What is major depressive disorder (MDD) commonly called?
depression
What characterizes MDD (1)?
Characterized by at least one major depressive episode
What is recurrent MDD?
- individuals experience multiple episodes
- absence of manic or hypomanic states = bipolar disorder
Absence of ______ is a more reliable symptom than increased ______.
- happiness
- sadness
What system does MDD affect?
MDD=Major Depressive DIsorder
Corticolimbic system (amygdala and PFC)
PFC=Pre-frontal cortex
How is MDD diagnosed by the DSM-5?
MDD=Mood Depressive Disorder
DSM-5=Diagnostic and Statisical Manual of Mental DIsorders
> 5 of the following symptoms need to be present for ≥ 2 weeks
1. Depressed mood every day
2. Diminished pleasure/interest in daily activities every day
3. Significant change in weight
4. Insomnia or hypersomnia every day
5. Psychomotor agitation and recessive guilt
6. Fatigue every day
7. Feelings of worthlessness and excessive guilt
8. Decreased ability to concentrate
9. Recurrent thoughts of death
Did males or females have a higher prevalence of MDD episode among U.S. adolescents in 2020?
Female = 25.2%
Slide 17
What are the risk factors of depression (4)?
- Biological differences: Physical changes in the brain (corticolimbic circuit)
- Brain chemistry: Regulation of neurotransmitters and their effect on mood stability
- Hormones: Changes in the body’s balance of hormones may be involved in causing triggering depression
- Inherited traits: Depression is more common in people whose blood relatives also have this condition
What structure is hyperactive in MDD? What does it predict?
- Amygdala
- Predicts symptom severity
Connectivity between the _____ and the _____ is decreased in MDD and predicts symptom severity.
- amygdala
- mPFC (medial prefrontal cortex)
What is the monoamine hypothesis?
Depression
Drugs used for other purposes, like Reserpine for HTN can cause depression-like symptoms = deplete serotonin, dopamine, and norepinephrine
What do monoamine oxidase inhibitors (MAOIs) inhibit?
1st Generation
- Inhibit monoamine oxidases = prevents breakdown of neurotransmitters
- Rarely used due to toxicity and potentially lethal food and drug interactions
What do tricyclic antidepressants (TCAs) inhibit?
1st Generation
- Inhibit reuptake of neurotransmitters (epinephrine and serotonin)
- Seldom used due to side effects and potentially fatal overdose
What do SSRIs inhibit?
2nd Generation
- Inhibit reuptake of serotonin
- High toxic dose and mild side effects
SSRIs: Selective Serontonin Reuptake Inhibitors
Most widely prescribed antidepressant in many countries
What do SNRIs inhibit?
2nd Generation
- Inhibit both serotonin and norepinephrine reuptake
- Studies show modest increase in efficacy compared to SSRIs
SNRIs: Serotonin-Norepinephrine Reuptake Inhibitors
What is the Serotonin Hypothesis?
Antidepressant drug (SSRIs, SNRIs) block reuptake of serotonin which increases serotonin levels outside of the cells = leads to decreasing depressive symptoms
Which gene has an association with an increased likelihood of depression after stressful events?
A) s/l
B) l/l
C) s/s
D) l/s
C) s/s
What is SERT? What does it control (2)?
- A gene identified through candidate studies to have variants that increase susceptibility to depression
- Controls the serotonin transporter protein
- Controls the ability of the axon to reabsorb the neurotransmitter after its release
What genetic trait increases the likelihood of depression after stressful events?
Two “short forms” of the SERT gene
Which class of antidepressant drugs has a low efficacy?
SSRIs
How can SSRIs restore balance to the corticolimbic circuit function?
2nd Generation
Decrease amygdala hyperactivity and increase functional connectivity between the amygdala and mPFC
SSRIs=Selective Serotonin Reuptake Inhibitors
Which 2 genes may have a moderate connection with increasing susceptibility to MDD following negative life events?
- FKBP5 (FK506-binding protein)
- CHR1 (corticotrophin-releasing hormone)
Which 2 genes regulate the stress response through the hypothalamic-pituitary-adrenal (HPA) axis?
- FKBP5 (FK506-binding protein)
- CHR1 (corticotrophin-releasing hormone)
What does schizophrenia cause?
Loss of executive control of emotional responses and information processing
What system does schizophrenia affect?
Corticolimbic system (dlPFC)
dlPFC = dorsal lateral prefrontal cortex
What do positive symptoms of schizophrenia refer to? What symptoms does it include (3)?
- Refers to overt symptoms that should not be present
- Hallucinations, Delusions, Disorganized thoughts
What do negative symptoms of schizophrenia refer to? What symptoms does it include (5)?
- Does not refer to a person’s attitude, but instead to a lack of characteristics that should be present
- Symptoms include:
1. Reduced speech, even when encouraged to interact (alogia)
2. Lack of emotional and facial expression (affective flattening)
3. Diminished ability to begin and sustain activities (avolition)
4. Decreased ability to find pleasure in every day (anhedonia)
5. Social withdrawal (asociality)
What do cognitive deficits of schizophrenia refer to? What symptoms does it include (4)?
Difficulties with the following aspects of cognition can make it hard to live a normal life or earn a living:
- Memory
- Attention
- Planning
- Decision making
What are the risk factors for schizophrenia (2)?
- Genes and environment
- Different brain chemistry and structure
What are the risk factors of genes and environment for schizophrenia (5)?
- Genetics
- Environment:
- Exposure to viruses
- Malnutrition or exposure to toxins/infections before birth
- Problems during birth can increase the risk
What are the risk factors of different brain chemistry and structure (2)?
Schizophrenia
- Imbalance in neurotransmitters: Dopamine, Glutamate/GABA
- Brain development (thought to be most affected before birth or during puberty)
What is the DISC1 gene?
- Disruputed in schizophernia 1
- Controls the rate of generation of new neruons in the hippocampus
How does schizophrenia cause structural abnormalities in the diPFC of the Corticolimbic system (4)?
- Reduced connections (spine density) between glutamatergic and GABAergic neurons
- There is no overt death of neurons
- Defects in dopaminergic signaling
- Abnormal development of the dIPFC - exaggerated loss of gray matter
How does schizophrenia lower working memory capacity in the Corticolimbic system (2)?
- Increases dIPFC activity at low levels of working memory
- Decreases dIPFC activity at high levels of working memory
What is the neurodevelopmental hypothesis?
Schizophrenia
Abnormalities in the prenatal or neonatal development of the nervous system can lead to subtle abnormalities of brain anatomy and major abnormalities in behavior
What are the 3 factors of the neurodevelopment hypothesis?
Schizophrenia
- Abnormalities from genetics, trouble during prenatal development, birth, or early postnatal development.
- Several kinds of prenatal or neonatal difficulties are linked to later early in life.
- People with schizophrenia have minor brain abnormalities that originate early in life.
What are the limitations of the neurodevelopmental hypothesis? (2)
Schizophrenia
- Evidence suggests more than one “hit” is required
- Does not account for genetic and environmental effects that clearly influence the disorder
What are the 3 parts of the Glutamate hypothesis?
Schizophrenia
- Genetic link – genetic variants of multiple genes associated with glutamatergic neurotransmission were identified by GWAS = mGlu3 (GRM3), the GluN2A (GRIN2A), SR (SRR), and AMPA receptor 1 (GRIA1)
- Postmortem studies show abnormalities in the connections between glutamatergic and GABAergic neurons in the dlPFC and between the dlPFC and other cortical regions
- Schizophrenia is associated with lower-than-normal release of glutamate and fewer receptors in the prefrontal cortex and hippocampus. (Further support comes from the effects of phencyclidine (PCP/angel dust).
What are the 3 factors of the Dopamine hypothesis?
Schizophernia
- Genetic link – genetic variant of DRD2 (dopamine receptor) identified in GWAS
- Substance-induced psychotic disorder is characterized by hallucinations and delusions resulting from repeated large doses of amphetamines, methamphetamines, or cocaine—each prolongs activity of dopamine
- Antipsychotics block dopamine D2 receptor
What are the limitations of the Dopamine Hypothesis (3)?
Schizophrenia
- Does not explain cognitive defects or psychomimetic effects of activation of other neurotransmitter pathways
- Levels of dopamine and its metabolites are relatively normal
- Antipsychotic drugs block dopamine within minutes but effects on behavior gradually build over 2 to 3 weeks. Not all patients respond.
What are the 4 types of schizophrenia treatments?
- Antipsychotic/neuroleptic drugs
- Psychosocial/psychotherapeutic treatment= increase adherence and reduce relapses
- Electro-convulsive therapy
- Can ease delusions, hallucinations, and disorganized thinking
- More effective when mood symptoms are also present
- Anxiolytics
- Reduce anxiety and shorten psychotic episodes
What type of receptors are 1st-generation (typical) antipsychotics?
Schizopernia
- Mostly dopamine receptor (D2) antagonists
- Relief is usually experienced 2-3 weeks after taking the drug
- Must be taken indefinitely
What type of symptoms (positive, negative, cognitive deficit) do 1st-generation antipsychotics treat?
Treat positive symptoms
What symptoms can 1st-generation antipsychotics cause?
- Can cause extrapyramidal symptoms (EPS) = Spasms/motor issues
What receptors do 2nd-generation antipsychotics affect?
Have less effect on dopamine DA receptors and more strongly antagonize serotonin type 5-HT receptors.
What type of symptoms (positive, negative, cognitive deficit) do 2nd-generation antipsychotics treat?
Treat positive symptoms and have some benefit for negative symptoms
What type of receptors are 3rd-generation (typical) antipsychotics?
Dopamine partial agonists
Dopamine system stabilizers
What type of symptoms (positive, negative, cognitive deficit) do 3rd-generation antipsychotics treat for Schizophrenia?
Treat positive symptoms and have some benefit for negative symptoms
Which of the following demographics has the largest prevalence of mental illness in the U.S.?
A. Females age 18-25
B. Males age 18-25
C. Females age 26-49
D. Males age 26-49
A. Females age 18-25
All of the following accurately describe major depressive disorder (MDD) EXCEPT:
A. Characterized by at least one major depressive episode
B. Presence of manic or hypomanic states
C. Hyperactivity of the amygdala
D. Absence of overall happiness
B. Presence of manic or hypomanic states
A 26-year-old woman is diagnosed with a severe form of major depressive disorder (MDD) likely associated with a genetic mutation. Which of the following genes is least likely to cause the woman’s condition?
A. SERT
B. FKBP5
C. DISC1
D. CHR1
C. DISC1
Which of the following is considered a negative symptom associated with schizophrenia?
A. Hallucinations
B. Avolition
C. Disorganized thoughts
D. Delusions
B. Avolition (diminished ability to begin and sustain activities)
A 22-year-old man is diagnosed with Schizophrenia after experiencing severe paranoia and social isolation for over 6 months. Psychiatrists would like to begin treatment with an antipsychotic medication but are concerned about significant side effects. Which of the following antipsychotics is most likely to cause extrapyramidal symptoms?
A. First generation
B. Second generation
C. Third generation
D. Fourth generation
A. First generation
