Module 3 Flashcards
1
Q
What is stress commonly defined as?
A
The experiences that cause the feelings of anxiety and frustration
2
Q
Describe the pathway of the HPA axis in the context of stress
A
- Stress causes the hypothalamus to signal to the pituitary gland (via adrenocotroicotophic hormonereleasing factor (CRF) and vasopressin (AVP))
- The pituitary gland signals to the adrenal gland (via adrenocorticotrophic hormone (ACTH))
- ACTH also provides negative feedback to the hypothalamus.
- The adrenal gland releases glucocorticoids and noradrenalin/norepinephrine which will then provide negative feedback to the pituitary gland and hypothalamus.
3
Q
Describe the chronic stress response using general adaptation syndrome (Selye, 1950)
A
- Alarm reaction: blood sugar level drops then quckly compensated
- Stage of resistance: continuous use of resources increases vulnerability to subsequent stress
- Stage of exhausation: prolonged resistance leads to “wear-down”
4
Q
Where are glucocorticoid receptors expressed?
A
Ubiquitously throughout the body
5
Q
How does HPA axis activation lead to energy mobilization? (2)
A
- Facilitates metabolism and physiological functions
- Suppresses pain, hunger etc.
6
Q
How does the HPA axis interact with the limbic system (PFC, hippocampus, amygdala)? (5)
A
- The hippocampus is the second site for negative feedback regulation of the HPA axis
- Normal functions include emotional responses and memory formation
- SSRIs regulate HPA activity in a neurogenesis-dependent manner
- Chronic stress/high CORT level alters nueron morphologies and inhibits neurogenesis
- Stress-affected individuals experience difficulties/deficits in them
7
Q
How does the HPA axis interact with the brainstem (reticular formation)?
A
The reticular formation releases various neuromodulators to regulate HPA activity
8
Q
How does the HPA axis interact with the reward system (VTA, NAcc, striatum, PFC)?
A
Stress affects dopamine signaling and then biases decision making
9
Q
How does the HPA axis interact with the immune system? (2)
A
- Decreased size of thymus and lymph nodes
- Gastrointestinal ulcers (caused by H. pylori bacteria)
10
Q
Explain how acute stress affects effort-based decision making as described in the study by Shafiei et al. 2012
A
Rats exposed to stress induced by restraint for 1 hour show decreased preference for the costly reward in a progressive ratio task, and longer choice latencies.
11
Q
What is the frustration effect?
A
An effect observed by not receiving reward when expecting a reward which creates a source of drive
12
Q
How can stress arise?
A
Through interaction of subject and environment, when the demands of the environment are too much for the individual to cope with.
- Individual differences in what leads to the perception of stress
- Subjective perception of control and capacity to respond effectively plays a role in individual perception of stress
13
Q
What is the Holmes-Rahe (1967) scale?
A
Devised arbitrary measurement of how stressful life events are perceived based on self-report from 394 individuals.
- If total number of points accumulated over events happening w/in last 2 years exceeds 300, illness is significantly more likely
- Controversal over rating being reliable, but major life events undoubtedly contribute to stress levels
14
Q
What does Lazarus (1981) describe hassles as? (4)
A
- “the daily grind”
- Faced more often than significant life events
- Long-term accumulation may set backdrop for response to larger, more tangible stressors
- Lives of “quiet desperation” - may not be obvious to observers
15
Q
What did Weiss (1972 & 1977) find about the physiological effects of lacking control, in the context of ulcer development?
A
Examined the physiological effects of lack of control (focusing on development of ulcers):
- rats hooked up to device which delivers electric shocks to tail
- one rat can predict shocks with cues (sense of control)
- other rat is “yoked” to the “master” rat (hear the same cues, but no predictive relationship)
- yoked rats developed stomach ulcers
- suggesting that perceived control lowers the “damage” by stress
16
Q
Explain anxiety disorders in the context of stress
A
Symptoms: uncontrollable physiological and psychological arousal
- some forms of anxiety disorders are fear-related
17
Q
Explain phobias in the context of stress
A
Excessive fear towards specific stimuli or a specific type of stimuli (generalization)
18
Q
Explain PTSD in the context of stress
A
Symptoms: intrusion, avoidance, arousal
- often triggered by specific stimuli, suggesting a pathological learning component
19
Q
Explain OCD in the context of stress
A
Intrusive thoughts (obsessive) and ritualistic behavoiur (compulsive)
20
Q
Describe 3 types of stressors used in the lab to study the effects of stress
A
- Biological stressors
- Psychological stressors
- Early childhood stressors
21
Q
Give 3 examples of biological stressors
A
- Pain/injury
- Illness
- Extreme physiological/environmental conditions
22
Q
Give 3 examples of psychological stressors
A
- Fear
- Lack of control
- Social stress
23
Q
Describe what early childhood stress is and give an example of an instance in the lab
A
- Essentially a mix of biological + psychological stressors
- Presented in critcial stages during development and may have lifetime effects
- Example: Harlow’s example with baby monkeys
24
Q
What is avoidance learning?
A
When a cue (CS) is associated with arrival of a stressful stimulus or the anticipation of one (US)
- Presenting the cue to the subject not only leads to stress response to the stimulus, but also learning to make an avoidance response in an attempt to prevent the occurrence of the stressful event
- e.g., a person w/ agoraphobia reroutes to avoid the NEST
25
What is escape learning?
Subjects learn to engage in certain behaviour (response) to terminate the aversive stimulus
- e.g., a person with agoraphobia runs out of the NEST building
- based on the principle of negative reinforcement
26
Describe how avoidance learning is used in a lab setting with rats
Rat is given opportunity to avoid shock
- First learn to associate shock and CS (sound) in the shock compartment
- Learn to run through to the "safe" compartment when shock starts
- Eventually runs to safety whenever CS comes on
27
Explain the 2 stage process of avoidance learning
- Classical fear conditioning: fear is conditioned to the CS and the rat learns to be afraid when the CS is presented
- Instrumental conditioning: reaching safety reduces fear. A reduction in fear reinforces the AR and the rat learns that fear is reduced when the AR is made
28
What is the "neurotic paradox"?
Symptoms/behaviours that persist despite their distressing qualities and the desire of the afflicated person to be rid of them
29
What is the relationship between AR and extinction?
AR should extinguish if they do not receive shock, and the fear associated with the CS should thus reduce.
However, avoidance learning is VERY resistant to extinction!
30
What is the habit driven hypothesis of avoidance learning?
Avoidance response becomes habitual; conditioned stimuli no longer produces fear as they learn to make the avoidance response
31
What are 3 pieces of evidence of habit driven avoidance learning?
- rats that successfully avoid the shock do not appear to be afraid anymore: AR latency declines
- the degree to which presentation of the CS disrupts ongoing behaviour declines as animals become proficient at avoiding the shock: indicates the CS is becoming less aversive
- cutting the sympathetic NS does not affect pperformance of the AR: animals need to be able ot experience fear to learn AR, but not to perform it once learnt
32
How would the AR become extinct if it is habit driven?
Extinction of the AR can be "forced" by preventing rats from making the AR and not delivering any shocks; rats are confined to area where shock was delivered while CS is presented (no US)
33
What is the fear-driven hypothesis of avoidance learning?
Fear drives the animal to continously perform the avoidance response
34
What are 5 pieces of evidence that support fear-driven avoidance learning?
- Anxiolytics can decrease well-learned AR
- Even though rats stop making the AR, CS still induces some conditioned suppresion
- Even after successful extinction, rats will not voluntarily return to the shock box
- Animals may stop making the AR after extinction training, because they simply freeze as a species-specific defense reaction
- Very hard to show that shock is truly unsignalled in avoidance learning paradigms. Internal detection of the feedback trace decay can act as a CS and trigger fear
35
What are 4 types of secondary control?
1. Predictive control: even failure can become predictable
2. Illusory control: attributing random events to personal skill e.g., throwing dice
3. Vicarious control: belief that there is a higher power in control, either divine or not
4. Interpretive control: finding meaning in uncontrollable events
36
How does secondary control contribute to the experience of events?
Degree of secondary control reduces aversiveness of an event
- Previous example of rats developing ulcers or not depending on perceived control
- May explain the individual differences in resilience to stress-related disorders, such as PTSD
37
How does learned helplessness arise?
Induced by the perceived lack of control over stressful events
38
What is a key locus of serotonergic cells innervating the forebrain?
Dorsal raphe nucleus
39
What is the PFC-DRN pathway in learned helplessness?
- DRN receives a lot of **inhibitory** cortical input from regions of ventral PFC
- Uncontrollable stress activates DRN and increases 5-HT release to projection areas, including the amygdala
40
How can you inhibit the vPFC and what are the consequences for doing so in the context of learned helplessness?
- Can inactivate the vPFC via injection of a GABA agonist (muscimol)
- Abolishes difference in 5-HT levels between inescapable and escapable shock by increasing DRN activation in escapable shock group (Amat et al., 2005)
- Also abolishes difference in escape learning and freezing behaviour between animals exposed to escapable and inescapable shock: destroys advantage of behavioural control
41
What are the 3 categories of stress management outlined by Monat & Lazarus (1985)?
1. Change environment and lifestyle
2. Change personality and perceptions
3. Modifying biological responses
42
What are 2 categories of behaviours related to environment and lifestyle in the context of stress management?
- "immunogenic behaviours": immunize individuals from the effects of stress
- "pathogenic behaviours": have adverse consequences e.g., drug-use
43
What did Lazarus (1968) find in regards to observers' galvanic skin response while watching a male puberty rite? (3)
- Narration reduced GSR -- minimized the painful nature of the procedure (denial) or "intellectualized" the observations
- Denial defense mechanisms worked better for businessmen, whereas intellectualization worked better for students
- Utility of different defense mechanisms depends on personality and cognitive style
44
How does meditation modify biological responses as a method of stress management? (3)
- Transcendental meditation is a simplification of Zen Buddhism. Initiate is given a mantra e.g., "om" to focus on at the exclusion of all other stimuli or thoughts
- Novel therapeutic approaches incorporate meditation techniques with cognitive-behavioural therapy
- Unclear whether transcendental meditation actually reduces stress response in lab tests (equally strong somatic responses to stressful stimuli were recorded)
45
What is a commonly used therapy for phobia and PTSD?
Systematic desensitization
46
What are the 3 different factors affecting attribution style in the context of depression?
1. Internal vs External locus of control: whether events are attributed to self or to others
2. Stable vs unstable cuases: enduring, permanent cause such as level of intelligence, compared to temporary, transient factors e.g., current level of motivation
3. Global vs specific: whether certain causes are held to happen in all events or just specific to individual events
47
What is the attributional theory of depression proposed by Abramson, Seligman and Teasdale (1978)?
Depression vulnerability depends not on whether a situation is helpless, but whether the person perceives that the situation is helpless
48
What is the most helpless and depressing attribution style?
Internal, stable and global
- low self-esteem arises when person attributes failure to self rather than to the situation
- attributing lack of control to stable factors leads to development of generalized expectancy of no control, extending depressive symptoms to multiple incidents
- global attribution extends depression to multiple situations
49
What is the relationship between attribution style and level of depression?
Correlation between the two is found, but is unclear whether this cognitive bias is involved in the cause or maintenance of depression
50
What is a major depressive episode?
A period of depression which lasts at least 2 weeks
51
What is major depressive disorder?
repeated episodes of depression with at least 2 months of remission between each.
- lifetime prevalence ~16-20%
52
What are 3 instances of depression?
1. Unipolar (depression in absence of mania)
2. Bipolar (presence of mania/hypomania)
3. Post-partum depression
53
What are the symptoms of depression? (7)
- anhedonia
- low energy levels (anergia) or fatigue
- low self-esteem
- cognitive difficulties (problems concentrating or making decisions)
- psychomotor agitation or retardation
- suicidal ideation
- biological symptoms (change in weight, sleep disturbance, low libido, etc.)
54
What is the current view of risk factors for depression?
Biopsychosocial model
- factors in each domain can also interact with other domains
55
Describe the monoamine hypothesis of depression
Proposes that the underlying biological or neuroanatomical basis for depression is a deficiency/underactivity of central noradrengergic and/or serotonergic systems
56
What are 4 commonly prescribed drugs that modulate monoamine systems?
1. Monoamine oxidase inhibitors
2. Tricyclics
3. Selective serotonin reuptake inhibitors
4. Serotonin noradrenaline reuptake inhibitors
57
What are monoamine oxidase inhibitors (MAOIs)?
MAO is an enzyme that degrades excess monoamines in the nerve terminal
- MAOIs inhibit the enzymatic activity to **prolong the effects of monoamines**
- Dietary restrictions essential to prevent attacks of high blood pressure which can lead to stroke (avoid tyramine-containing foods: cheeses, pickled foods, chocolates, certain meats, alcohol)
58
What are tricyclics?
Drugs that inhibit the reuptake of 5-HT and NE, and to some extent DA, leaving them in the synapse for longer
59
What are selective serotonin reuptake inhibitors (SSRIs)?
Selectively inhibit 5-HT reuptake
60
What are serotonin noradrenaline reuptake inhibitors (SNRIs)?
inhibit reuptake of 5-HT and NE
61
What are the problems with the monoamine hypothesis of depression? (4)
- Only ~50% of patients respond to prescription -- figuring out which drug to take is still mainly done through trial + error or tolerance of side effects
- Some claim that MA treatment work best for mild-moderate MDD, not severe, some dispute this notion. Still unclear to whether different forms of MDD have different underlying causes
- Still unclear whether deficits in 5-HT or NE signalling is causing depressive symptoms
- Can take 4-6 weeks for full therapeutic effect to occur, yet neurotransmitter levels should be modulated within hours of administration
62
What is the relationship between the NAcc and anhedonia? (2)
The NAcc is a key area involved in reward processing:
- NAcc is underactive in non-clinical populations with high anhedonia ratings, and non-medicated MDD patients show reduced NAcc activation in response to winning money
- Low NAcc activity could be a source of diminished sensitivity to rewards in anhedonia
63
How is anhedonia an endophenotype?
Endophenotype is a stable, not directly observable phenotype that needs probing to be viewed.
- Anhedonia is present to varying degrees within the normal population, may be a putative "endophenotype" for depression which could reflect underlying vulnerability
64
What did Floresco & Ghods-Sharifi (2007) find in their experiment looking at anhedonia and motivation in a two-armed choice paradigm?
- Inactivating the basolateral amygdala or disconnection of the BLA-NAcc pathway reduced the preference for exerting a greater effort to obtain a larger reward
- Suggests that expected outcomes (value) influence how much effort the subjects are willing to exert for the reward
65
What was found in the study done by Treadway et al. (2009) that looked at the correlation between self-reported anhedonia scores and people's decision-making?
Subjects choose to perform a more/less effortful action to receive a larger/smaller reward. The probability of winning reward on both the hard/easy action was signalled as either low (12%), medium (50%, or high (88%)
Increased self-reported anhedonia score significantly predicted decreased choice of the harder option when the reward level was high, but the probability of winning was most uncertain (50%)
- Potentially pointing to the importance of DA signalling in NAcc
66
What is found about DA depletion in the NAcc of rats, in regards to a progressive ratio task?
Nacc DA depletions make rats more sensitive to high ratio requirements, but do not impair primary food reinforcement
- Rats trained to lever press for food reward on progressively larger fixed ratio schedules (more effort required with each increase in schedule size)
- Control rats learned to adapt to new FR schedules, DA-depleted rats gave up
67
What is evidence for the NAcc/ventral striatum being associated with depression? (2)
- Depression precedes the onset of, and is often comorbid with, Parkinson's disease, where striatal DA neuron death occurs
- Lesions to the ventral striatal DA system in rats induces depressive-like behaviour (more likely to drown in forced swim test)
68
What is evidence for the dorsal anterior cingulate cortex (dACC) involvement in depression?
MDD and healthy controls were split into high and low groups of dACC activation.
During the Stroop task, unmedicated MDD patients would have slower reaction times compared to healthy controls.
- MDD patients who were able to recruit the dACC during high conflict trials performed like controls
Shows heterogenity within MDD, level of cognitive impairment potentially influenced by hypofrontality level
69
What is hypofrontality?
State of decreased cerebral blood flow in the prefrontal cortex of the brain
70
What 2 kinds of receptors for stress hormones are abundant in the hippocampus?
- Type I (mineralocorticoid receptors): high affinity
- Type II (glucocorticoid receptors): low affinity
71
What has MRI data found in regards to hippocampal volume in MDD patients?
Smaller in MDD patients
72
How do type I and II receptors affect hippocampal function?
- Type I may be beneficial for hippocampal function
- Type II may be detrimental, corresponding to U curve
- Long-term exposure to stress + glucocorticoids leads to neuronal death
73
What is the BDNF hypothesis of depression?
Increased 5-HT/NE/DA may lead to increased BDNF, which promotes neuronal growth and development that can increase neurogenesis in the hippocampus.
This would match with the delayed effects of antidepressents.
74
What does Surget et al. (2008) propose about the action of antidepressants and the hippocampus?
- Neurogenesis can be blocked by irradiation of the hippocampus
- Irradiation itself doesn't lead to depressive-like phenotype in mice
- Irradiation of the hippocampus prevents some antidepresseant actions
Changes in hippocampus may contribute to restoring normal function, rather than driving the development of depression
75
Explain how monoamines induce BDNF production
GPCRs -> secondary messengers -> gene expression regulation -> BDNF production
76
What is the relationship between depression and the immune response?
- Cytokines are increased by stress, and could enhance vulnerability to psychiatric disorders
- Similarity between "sickness behaviour" caused by peripheral cytokine administration and depression (anhedonia, loss of appetite, loss of motivation, increased sleep etc.) indicate that inflammation may contribute to depressive symptoms
- Increased circulating cytokine levels observed in MDD patients
77
What is the gliopathy hypothesis of depression?
Glia regulate metabolism, synaptic neurotransmission and communication with neurons
- also release glia-derived neurotrophic fact (GDNF)
- in depression, it is proposed that here is decreased astrocyte activity and increased pro-inflammatory microglia activity
78
What is cyclothymic disorder (cyclothymia)?
a cyclic disorder that cuases brief episodes of hypomania and depression
- another type of bipolar disorder
79
What are the manic symptoms of bipolar disorder? (8)
- Feeling very up, high, elated, or extremely irritable or touchy
- Feeling jumpy or wired, more active than usual
- Having a decreased need for sleep
- Talking fast about a lot of different things ("flight of ideas")
- Racing thoughts
- Feeling able to do many things at once without getting tired
- Having excessive appetite for food, drinking, sex, or oher pleasurable activities
- Feeling unusually important, talented or powerful
80
What are the symptoms of depression in bipolar disorder? (8)
- Feeling very down or sad, or anxious
- Feeling slowed down or restless
- Having trouble falling asleep, waking up too early, or sleeping too much
- Talking very slowly, feeling unable to find anything to say, or forgetting a lot
- Having trouble concentrating or making decisions
- Feeling unable to do even simple things
- Having a lack of interest in almost all activities
- Feeling hopeless or worthless, or thinking about death or suicide
81
What are 4 risk factors of BD?
- Comorbidity with disorders such as anxiety disorders, ADHD, and eating disorders
- Structural and functional differences in mesocorticolimbic system and insula cortex
- Genetics: BD has estimated heritability of 60-80%, voltage-gated Ca channels have been implicated
- Stress: extreme stress and traumatic evets can trigger onset of BD
82
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What are 3 domains of research trying to understand BD at a cellular level?
- Association between glia/stress and neuron death and BD
- Neurotransmitter dysregulation (5-HT, DA, NE, Glutamate, GABA)
- Oxidative stress and mitochondrial pathology
83
What is the current view on the causation of bipolar disorder?
Genetic predisposition-environmental factor interactions are thought to cause BD
84
Where does the term schizophrenia come from?
Eugen Bleuler, who characterized the splitting of affect from cognition
85
What are the 4 clusters of symptoms that characterize schizophrenia?
1. Positive symptoms
2. Negative symptoms
3. Affective symptoms
4. Cognitive symptoms
86
What are the positive symptoms of schizophrenia? (3)
- Hallucination: sensory experiences in the absence of external stimuli. Most common form of hallucinations are auditory, bu can be from other sensory modalities
- Delusion: fixed, false beliefs that remain intct even in the face of contradictory external evidence. Delusions can range from the mundane to bizzare
- Disorganized thinking: loosening logical associations, disorganized speech, or even quite bizarre behaviour
87
What is the "prodrome" phase in Schizophrenia?
Schizophrenia patient has other symptoms prior to positive symptoms
88
What are the cognitive symptoms of schizophrenia? (4)
Impairments in multiple domains, such as:
- Selective attention
- Woring memory
- Learning
- Executive function
89
What are the negative symptoms of schizophrenia? (5)
- Decreased emotional reactivity
- Paucity of speech
- Amotivation
- Anhedonia
- Attentional impairment
90
What are affective dysregulation symptoms of schizophrenia? (6)
- Affective flattening
- Depression
- Mania
- Anxiety
- Impulsivity
- Demoralization
91
What is affective dysregulation?
Often observed as a disconnect between the affective state and the context of the situation
92
What is the relationship between SCZ and demoralization?
demoralization may account for the 10% lifetime risk of completed suicide in SCZ patients
93
What are the risk factors in the development of SCZ? (3)
- Genetic
- Stress: onsets of SCZ are often in adolescence and early adulthood (age 14-25), when many types of biopsychosocial stress factors are introduced. ELS can contribute too
- Drug use in adolescence: some drugs (e.g., cannabis, LSD) produce signs/symptoms similar to psychosis. The developing brain may be more sensitive to drugs' effects on mental states
94
What are the genetic risks of SCZ?
So far, genetic risk factors are the best understood risk factors
- Estimated inheritability is 65-85%
- Concordance in identical twins is 70%, suggesting a strong role for the environment
- No single gene has been identified as causal genes
- Many risk genes likely interact with each other
95
What is the difference in cognitive impairment between BD and SCZ?
SCZ patients significantly underperform BD patients in social cognitive tasks, such as emotion recognition and theory of mind
- Differences between the two disorders seem to be predominantly quantitative rather than qualitative
96
How do BD and SCZ patients respond to different medications?
- Li as a mood stabilizer in BD: individual differences in Li response suggests heterogeneity of BD
- Positive symptoms of SCZ respond best to antipsychotics, whereas negative symptoms and cognitive impairment do not respond well, if at all to conventional drug treatment (consequently, cognitive impairments + negative symptoms, are the best predictors of functional outcomes)
97
How effective is Li treatment in BD patients?
20-30% excellent responders
40% non-responders
98
What are the genetic factors of both BD and SCZ?
- Many genes involved in neurotransmission and neuromodulation are implicated in both
- Copy number variants show stronger influence on SCZ than on BD
99
What is the prevalence of BD and SCZ?
- BD: ~4%
- SCZ: ~1%
100
What symptoms does schizoaffective disorder have?
Symptoms from both BD and SCZ
101
What is the reward hypersensitivity model of BD? (3)
- Reward hypersensitivity is proposed to be the underlying cause of behavioural changes in during manic episodes of BD
- Argues that abnormalities in reward processing and approach-related affect play an important role in the pathophysiology of BD, particularly hypomanic/manic symptoms
- Model predicts that positive and negative reward-related cues lead to manic and depressive symptoms, respectively (research findings only confirmed the role for reward hypersensitivity in mania)
102
How is reward/punishment (probabilistic) learning impaired in BD? (2)
- Altered response patterns toward rewards observed in BD patients
- Reward learning (+ve reinforcement) is impaired in psychotic BD; punishment (-ve reinforcement) learning is impaired in non-psychotic BD
103
How is reversal learning affected in BD patients? (3)
- Impairment observed in BD patients (and unaffected relatives)
- BD patients have more difficulties processing the reversal of contingencies
- Childhood-onset BD patients display reversal learning phenotype early on, and the impairment appeared to transition into young adulthood
104
Which area of the brain shows altered patterns of activity in response to reward in BD patients and relatives (that don't have BD)? (3)
Medial orbitofrontal cortex:
- Increased activation in response to reward delivery
- Decreased deactivation in response to contingency reversal (prediction error)
- Unaffected first-degree relatives of BD 1 patients show similar activity patterns
105
What does the translational study by Enkhuizen et al. (2014) find regarding reward-based decision making in BD? (3)
- IGT performance of BD patients show abnormal preference for high-risk high-reward, disadvantageous choices compared to healthy controls
- Mice with DAT genetic knockdown or treated with acute DAT inhibitors (GBR) showed similar behavioural alteration in IGT performance
- Collectively, hyperactive DA signalling is implicated in reward hypersensitivity in BD
106
What kind of activity is found in the NAcc of BD patients?
Blunted NAcc activity during gain anticipation
- Related to individual differences in the tendency to respond impulsively to positive emotional states
- NO NEUROSIGNATURE OF BD (complicated neural underpinnings)
107
What are 4 pieces of experimental evidence that support the reward hyposensitivity theory?
- Studies found a reduced reward sensitivity during bipolar depression
- No alteration or a reduction of reward sensitivity in bipolar mania have also been reported
- Currently euthymic bipolar patients who last experienced a manic episode showed a bias towards +ve consequences, whereas bipolar patients who last experienced a depressive episode showed a bias towards -ve consequences
- Different BD subtypes show dissociated learning deficits: BD I patients tend to perform better than BD II patients in avoidance learning task
108
What does research evidence for reward sensitivity in BD show overall? (4)
- complex nature of BD suggests neterogenous causes of the disorders that likely involve perturbation of multiple neural components (particularly frontal-striatal reward circuit)
- Reward sensitivity may be better conceptualized as a spectrum in BD
- Instability of mood may reflect the imbalance between brain functions and/or the vulnerability to inducible bidirectional changes
- Better understanding of these differences can lead to better personalized treatment
109
What are the cognitive impairments of BD? (3)
- Psychosis presents in ~40-60% of BD patients, and hallucinations and delusions are commonly observed during manic episode
- Prospective memory deficits: difficulties remembering future time and events
- Verbal memroy deficits: verbal learning impaired due to poor choice of learning strategy
110
What is the aberrant salience hypothesis of schizophrenia?
Proposes that irregular activity in the dopamine circuitry underlies the positive and negative symptoms
- Aberrant salience to irrelevant stimuli results in positive symptoms
- Failing to appropriately respond to meaningful reward cues results in negative symptoms
111
What are 5 pieces of evidence for the aberrant salience hypothesis of schizophrenia?
- upregulated DA binding in psychosis
- fMRI studies found associations between aberrant striatal responses in learning assays and psychotic symptoms
- enhanced prediction error learning for irrelevant stimuli (+ve symptoms)
- SCZ patients frequently self-report neutral affective ratings in response to positively valenced stimuli (-ve symptoms, flattening)
- Discordance between self-reported pleasure and momentary pleasure suggests that -ve symptoms may not reflect a primary deficit in the capacity for hedonic experience, but rather a difficulty in representing rewarding experiences accurately
112
What does evidence for the aberrant salience hypothesis of schizophrenia suggest?
Behavioural processes that are highly sensitive to striatal dopamine levels should show aberrations, reward processing and effort-based decision-making
113
What is adaptive coding?
Neurons adjusting their range of activity based on the reward and cue
114
Where are there adaptive coding deficits in the brains of SCZ and BD patients? (3)
- Anterior right caudate: SCZ
- Posterior right caudate: BD+SCZ
- Right precentral gyrus/insula: SCZ
115
How is effort-based decision making altered in SCZ?
SCZ patients show reduced choice of hard task with matched reward size and winning certainty
116
Compare MDD and BD during a MID task in the fMRI (Wakatsuki et al., 2023)
- BD patients showed decreased activation during reward anticipation in the anterior cingulate cortex, anterior insula and putamen
- MDD patients showed decreased activation in the anterior insula and brainstem
117
Compare the differences in effort-based decision-making between MDD, BD and SCZ (3)
- BD and SCZ reduce the choice of hard task
- Current and past MDD do not significantly reduce the choice of hard task
118
What are 3 types of diabetes
- Type 1: insulin deficiency by loss of insulin-producing cells (reduced ligand)
- Type 2: insulin resistance by receptor defects. Most common type of diabetes (~95%)
- Gestational diabetes: occurs during pregnancy, can recover after delivery
119
What is diabetes?
Group of endocrine diseases, characterized by sustained high blood glucose level
120
What are 4 health complications of diabetes (not directly affecting the NS)
- Heart disease
- Vision loss
- Kidney disease
- Skin conditions
121
What is evidence for insulin affecting neurogenesis? (4)
- Promotes adult neurogenesis in zebrafish
- Rat model of diabetes showed spatial learning deficits and impaired hippocampal neurogensis via reduced BDNF after transient ischemia
- Abnormal blood glucose level due to insufficient insulin signalling could impair neurogenesis and cognitive deficits
- Exercise has benefits on hippocampus neurogensis, diabetes , and AD: exercise increases insulin sensitivity even in insulin resistant populations
122
Describe the conditioned taste aversion (CTA) experiment in food deprived snails (Mita et al., 2014)
- Insulin-injected snails had a significantly lower hemolymph glucose level compared to vehicle-injected snails
- Insulin injection led to better learning and formation of 1-wk memory of CTA
- Insulin receptor antibody injection abolished the effect of insulin of learning and memory of CTA
- Sucrose injection before training led to insulin-spikes, and learning and memory of CTA is observed
123
How can insulin work as a treatment for AD? (3)
- Insulin and insulin-like peptides have been implicated in learning and memory from worms to flies to rodents and to humans
- Internal state of insulin concentration is suggested to be critical for LTM for CTA
- Insulin can pass across the blood-brain barrier through facilitation transport
124
What is IBS?
Chronic irritations of the gastrointestinal tract.
Symptoms: bloating, abdominal pain, and changes in the consistency of bowel movements
125
What are some causes of IBS? (5)
- Food sensitivity
- Stress
- Vitamin D deficiency
- Infection/bacterial overgrowth
- Genetic factors
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What is the prevalence of IBS, and how many IBS patients have comorbid neurological/psychiatric conditions?
- prevalence of IBS: ~10%
- ~60% of IBS patients have comorbidities with neurological/psychiatric conditions such as headache, fibromyalgia, and depression
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What is the microbiota-gut-brain axis? (3)
- Microbiota regulates the bidirectional gut-brain communication directly and indirectly
- Some microbiome can syntehsize GABA, 5-HT, DA, NE that act on enteric nervous system
- Some microbiome can generate neuroactive and antimicrobial metabolites that circulate to other part of the body to regulate behaviour and immune functions
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What is some evidence for IBS as a distrubance of the microbiota-gut-brain axis? (3)
- GWAS revelaed shared genetic pathways between IBS and mood and anxiety disorders
- Association between depressive phenotype and gut microbiome genetic compositions detected
- Depression and healthy cases could be differentiated based on genetic data of microbiome
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What are 4 common types of medications used to treat psychiatric disorders?
- Anxiolytics
- Antidepressants
- Lithium
- Antipsychotics
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What are 6 non-pharmacological therapies for psychiatric disorders?
- Behavioural therapy
- Electroconvulsive therapy
- Deep brain stimulation
- Transcranial magnetic stimulation
- Cannabis therapy
- Psychedelic therapy
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What is behavioural therapy and how effective is it?
Modifying symptoms that stem from maladptive learning through new learning
- 67% patients experience some type of improvement
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What is the procedure of systematic desentization? (3)
- **Relaxation training**: train the body to relax effectively
- **Construction of fear hierarchy**: identify fear/anxiety-inducing stimuli and rank order them
- **Pairing relaxation and stimuli along the hierarchy**: gradually establish incompatible responses to fear/anxiety-inducing stimuli, and eventually replace the unwanted responses with relaxation through counter-conditioning
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What is ECT? (3)
- Therapy that uses 70-120V to electrically induce generalized seizure to treat MDD and mania.
- Performed under anesthesia and w/ muscle relaxant
- Induces transient disruption of neural circuits, followed by enhanced neuroplasticity and rewiring to regain balanced brain states
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What are some side effects of ECT?
- Memory loss
- Confusion
But among treatments for depression in pregnant women, ECT is the least harmful to the fetus
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What is deep brain stimulation therapy? (3)
- Neurosurgiccal procedure that implant electrodes in certain brain areas.
- Electrodes are connected to subcutaneous pacemaker-like device that electrically stimulate these brain areas
- Commonly used in treatment for PD and epilepsy
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What are some potential side effects of deep brain stimulation? (8)
- Neurosurgery is high risk (infection)
- apathy
- hallucinations
- hypersexuality
- cognitive dysfunction
- depression
- euphoria
- personality change
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What is treatment-resistant depression, as defined by Dandekar et al. (2018) in their clinical trias of deep brain stimulation on depression?
Must have failed to respond to at least one approved pharmaceutical therapy
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What are 2 particular brain areas of interest for studying deep brain stimulation in depression patients?
- Subcallosal cingulate gyrus (SCG)
- NAcc/ventral striatum
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How does the subcallosal cingulate gyrus respond to deep brain stimulation in depression patients? (3)
- Seems very effective in open label trials with small sample size, but multi-centre randomized controlled trial was cancelled due to lack of response (placebo effect?)
- Tractography-based targeting appears to improve response (up to 72-81% but small sample size (n=11))
- Mechanism unclear: may alter network activity in the region; may also impact monoamine levels
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How is the NAcc/ventral striatum affected by deep brain stimulation in depression patients? (2)
- Small open label trials suggest long-term benefits in some patients (~50%)
- Mechanism inconclusive: may normalize activity in SCG and other regions, increase monoamine levels
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What is transcranial magnetic stimulation?
TMS is a non-invasive technique to stimulate specific brain regions. Changing magnetic field induces electric current, and by properly placing the magnetic coil and adjusting the generator output, a specific brain region is stimulated.
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What are 2 common side effects of transcranial magnetic stimulation?
- Scalp discomfort/pain
- Fainting/lightheadedness
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What are 3 uncommon side effects of transcranial magnetic stimulation?
- Seizure
- Hypomania
- Hearing loss
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What 2 conditions has transcranial magnetic stimulation shown to treat?
- OCD, when targeting the oFC and supplementary motor area
- treatment resistant MDD, when targeting the dorsolateral PFC
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What 2 psychoactive ingredients are in cannabis?
- Cannabidiol (CBD): weak CB1 agonist; anxiolytic and antiepileptic effects through 5-HT1a receptors
- Tetrahydrocannabinol (THC): CB1 antagonist
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What does the endocannabinoid system consist of?
2-AG and anandamide
- endogenous ligands that activate CB1 and CB2 receptors
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What functions has the endocannabinoid system been implicated in? (5)
1. Memory
2. Appetite
3. Stress response
4. Sensation
5. Sleep
Interestingly, many neuropsychiatric disorders appear to have endocannabinoid biomarkers
148
What are 4 health conditions that show well-supported evidence for cannabis as therapy?
- Chemotherapy-induced nausea
- Chronic pain
- Multiple sclerosis
- Sleep disorders
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What 6 health conditions show limited support for cannabis as therapy?
- weight loss
- dementia
- TBI
- anxiety
- depression
- PTSD
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What 7 health conditions show insufficient evidence for cannabis as therapy?
- cancer (glioma)
- eating disorders
- IBS
- epilepsy
- PD
- BD
- SCZ
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What health condition shows no support for cannabis as therapy?
Addiction
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What are 3 common psychedelics?
1. Psilocybin
2. LSD
3. Mescaline
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How can psilocybin work as an antidepressant?
- 1-2 doses of psilocybin can have long-lasting antidepressant effects
- Psilocybin is a 5-HT2A receptor agonist. Can more selectively activate serotonergic signalling components since they target specific receptor subtypes
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How does psilocybin treatment for MDD compare with escitalopram, an SSRI?
Psilocybin showed better improvement of depression index over the course of 6 weeks compared to escitalopram
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How does psilocybin potentially work mechanistically different than escitalopram?
- Default mode network becomes more engaged in MDD
- Decreased brain modulatrity correlates with treatment response in psilocybin but not escitalopram
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What does a more recent clinical trial show in regards to psilocybin as an effective treatment for MDD?
Shows that 77% of participants experienced adverse events and included headache, nausea, dizziness and fatigue, suicidal ideation and self-injury, which was higher in high dose group.
