Neurobiology of Disease 2 Flashcards
Is ADHD a neurodevelopmental or a neurodegenerative condition? (1)
Neurodevelopmental
In what year was ADHD defined as a condition? (1)
a) 2007
b) 1968
c) 1824
d) 1921
b) 1968
Give two possible reasons why 20% of prison inmates are thought to suffer with ADHD. (2)
- Impulsiveness
- Inability to see future consequences of an event or decision
Name the criteria used to diagnose ADHD. (1)
DSM-V
Complete the sentence relating to ADHD. (2)
According to the DSM-V, the prevalence of ADHD is thought to be …………………….., with the …………….. gender being twice as likely to have the condition.
3-5%
males
What is hyperkinetic disorder, and how does it relate to ADHD? (2)
WHO previously defined a hyperkinetic disorder as a similar condition to ADHD
however it had more stringent criteria and a lower prevalence than ADHD.
Name two symptom categories which are applicable to ADHD. (2)
- Inattentive symptoms
- Hyperactivity/Impulsivity symptoms
Give nine possible inattentive symptoms of ADHD. (9)
- Lack of attention to detail
- Difficulty to sustain attention
- Avoid sustained attention
- Not listening
- Cannot follow through instructions
- Difficulty organising tasks
- Lose or misplace objects
- Easily distracted
- Forgetful
Give 8 possible hyperactivity/impulsivity symptoms of ADHD. (8)
- Fidgeting
- Restless during activities
- Running about
- Excessively loud
- Always ‘on the go’
- Talks excessively
- Blurts out answers
- Interrupts or intrudes on others
Give three criteria, regarding the symptoms of ADHD in children, which must be fulfilled before a diagnosis can be made. (3)
- 6 or more symptoms, for at least 6 months, before age 12
- Symptoms present in at least 2 life areas (school, home, social setting)
- Behaviours must be developmentally inappropriate for the age of the child
How many symptoms of ADHD must adults show to get a diagnosis? (1)
5
Name the term that is applied to ADHD in adults, when they currently no longer have enough symptoms to meet the criteria but have had in the past. (1)
Partial remission
When ADHD is diagnosed, it can be put into one of three categories. Name the three categories. (3)
- Combined
- Predominantly inattentive
- Predominantly hyperactive/impulsive
What is the heritability of ADHD between identical twins? (1)
70-90%
Complete the sentence relating to ADHD. (1)
Having a first degree relative with ADHD increases risk by ……………..
5%
True or false? Explain your answer if applicable.
ADHD is among the most heritable of psychological disorders.
True
What is meant by ‘heritability’? (1)
A measure of how well differences in people’s genes account for differences in traits.
Name six possible genes which are thought to be associated with ADHD. (6)
For an extra six marks, state (in brackets) what type of protein each gene encodes. (6)
SLC6A3 (DAT)
DRD4 (D4 receptor)
DRD5 (D5 receptor)
SLC6A4 (5HT reuptake transporter)
HTR1B (5HT1B receptor)
SNAP25 (SNAP25 vesicle protein)
Which of the following statements best applies to gene polymorphisms associated with ADHD? (1)
a) A polymorphism in a single gene, inherited from a parent, is enough to cause ADHD in the offspring
b) There are multiple gene polymorphisms possible, each conferring a small risk - no single gene is sufficient or causal on its own
b) There are multiple gene polymorphisms possible, each conferring a small risk - no single gene is sufficient or causal on its own
An odds ratio of what number means that there is no association between an exposure and an outcome? (1)
1
Regarding the genes thought to be associated with ADHD, which of the following ranges would you expect the odds ratios to be? (1)
a) 0-1
b) 1-2
c) 2-3
d) 3-4
b) 1-2
In ADHD, give two phenotypic traits which may be associated with D4 receptor polymorphisms. (2)
- Novelty seeking behaviour
- Inattention
In relation to ADHD, give the precise location of the DRD4 receptor gene on the chromosome. (1)
Use the structure of 00A00.0
11p15.3
In what brain network is the DRD4 receptor gene particularly prevalent? (1)
Frontal-cortical network
Describe the specific polymorphism of the DRD4 receptor gene which confers high risk (OR1.9) for ADHD. (1)
48 base pair repeat
7 repeat allele confers high risk
Describe the molecular/cellular result of a mutation in the DRD4 receptor gene in ADHD. (2)
- Attenuated/reduced AC coupling of the dopamine receptor
- Reduced cAMP response
In relation to ADHD, give the precise location of the DAT1 gene on the chromosome. (1)
Use the structure of 00A00.0
5p15.3
In ADHD, if there is a mutation in the DAT1 gene, in which brain region is DAT expression likely to be affected? (1)
Striatum
Describe the specific polymorphism of the DAT1 gene which confers high risk (OR1.16) for ADHD. (1)
480 base pair repeat
10x repeats
Describe the molecular/cellular result of a mutation in the DAT1 gene in ADHD. (2)
Elevated DAT expression
Less synaptic dopamine
Give eight environmental risk factors for ADHD. (8)
Also give one which has been suggested, but for which there is currently not enough evidence. (1)
- Extreme prematurity and low birth weight
- Maternal smoking/toxins/alcohol
- Neonatal hypoxia
- Low social class / social depravation
- Learning disability
- Institutional rearing
- Lead exposure
- Other neurological disorders such as epilepsy, encephalitis, brain trauma
Food allergies have been suggested but not enough evidence
Do individual environmental risk factors or genetic risk factors have larger odds ratiosin ADHD? (1)
Which category has the larger impact when combined? (1)
Environmental
Genetics have larger impact when combined
Complete the passage related to ADHD. (4)
Environmental and genetic risk factors interact to result in fronto-striatal ………………………….. dysfunction.
This results in developmentally inappropriate …………………, …………………., and ……………….. behaviour.
monoamine
hyperactive
impulsive
inattentive
Briefly describe three volumetric changes in the brain seen in ADHD. (3)
- Smaller brain (particularly right frontal lobe)
- Smaller basal ganglia
- Smaller cerebellum
Match the percentage reduction in brain size, to the brain region, as seen in ADHD. (4)
4%
12%
6%
8%
Right frontal lobe
Basal ganglia
Whole brain
Cerebellum
4% - whole brain
12% - cerebellum
6% - basal ganglia
8% - right frontal lobe
In ADHD, a reduction in the size of the right frontal lobe is seen.
Give nine functions of the right frontal lobe. (9)
- Motor function
- Problem solving
- Spontaneity
- Memory
- Language
- Initiation
- Judgement
- Impulse control
- Social behaviour
Describe how you would expect the volumetric change in the basal ganglia to develop throughout the childhood/adolesence of someone with ADHD. (1)
Transient change which usually normalises by about 18yrs of age
Describe how you would expect the volumetric change in the cerebellum to develop throughout the childhood/adolesence of someone with ADHD. (1)
Still pronounced at 18yrs, does not usually normalise
At what age do the volumetric changes in the brain seen in ADHD manifest? (1)
About 6yrs
True or false? Explain your answer if appropriate. (1)
In ADHD, the volumetric changes seen in the brain correlate with severity.
True
True or false? Explain your answer if appropriate. (1)
In ADHD, the volumetric changes in the brain are seen irrespective of medication status and co-morbidities.
True
Name six areas of the brain where functional changes are seen in ADHD. (6)
All of these brain areas are related to what two functions? (2)
- Dorsolateral prefrontal cortex
- Ventrolateral prefrontal cortex
- Parietal cortex
- Dorsal anterior midcingulate cortex
- Striatum
- Cerebellum
All these areas are related to cognitive and attentive functions.
Functional abnormalities are particularly seen in the dorsolateral prefrontal cortex in ADHD.
Give three cognitive processes that this area of the brain is associated with. (3)
Decision making
Mood regulation
Conflict management
Functional abnormalities are particularly seen in the striatum in ADHD.
Give two cognitive processes that this area of the brain is associated with (related to ADHD). (2)
- Cognition
- Social behaviour
In three words, describe the main neurotransmitter pathology in ADHD. (1)
Fronto-striatal dopaminergic hypofunction
Give two findings that you would expect to see on an fMRI in ADHD, regarding the fronto-striatal complex. (2)
- Smaller
- Less active
Give a PET finding in ADHD related to the striatum. (1)
Reduced metabolism
Describe the striatal density of DAT that you would expect to see in ADHD. (1)
Higher density
How might the sensory cortex be changed in ADHD, and what effect/symptom might this have? (2)
Hyperactive sensory cortex
which results in enhanced perception.
Briefly describe the double hit mechanism of hypodopaminergic dysfunction seen in ADHD, in terms of the molecular changes in the brain. (2)
Why do these molecular changes happen? (1)
- Increased DAT uptake
- Reduced D4 activation
The molecular changes happen due to genetic polymorphisms.
Name a developmental impact of ADHD which may happen at pre-school age. (1)
Behavioural disturbance
Name 4 developmental impacts of ADHD which may happen at school age. (4)
- Behavioural disturbance
- Academic impairment
- Poor social interaction
- Peer acceptance
Name 5 developmental impacts of ADHD which may happen in adolescence. (5)
- Academic impairment
- Poor social interaction
- Lower self-esteem
- Smoking/drugs
- Criminality
Name 5 developmental impacts of ADHD which may happen at college age. (5)
- Academic failure
- Occupational difficulties
- Low self-esteem
- Alcohol and substance abuse
- Injury/accidents
Name 6 developmental impacts of ADHD which may happen in adulthood. (6)
- Unemployment
- Low self-esteem
- Relationship problems
- Motor accidents
- Marital discord
- Alcohol and substance abuse
Name five disorders that often co-occur with ADHD. (5)
- Conduct disorder
- Tics
- Mood disorders
- Anxiety disorder
- Oppositional defiant disorder
Complete the sentence relating to ADHD. (1)
Only …………….. percent of all people diagnosed with ADHD are diagnosed with ADHD alone.
31
Match the conditions up with the percentage of people diagnosed with ADHD who also have that condition. (5)
Conduct disorder
Oppositional defiant disorder
Tics
Anxiety disorder
Mood disorders
14%
11%
4%
34%
40%
Conduct disorder - 14%
Oppositional defiant disorder - 40%
Tics - 11%
Anxiety disorder - 34%
Mood disorders - 4%
Apart from dopamine, name another neurotransmitter which is thought to be involved in the pathophysiology of ADHD. (1)
Glutamate
In regards to ADHD, name two areas of the brain where dopaminergic and glutamatergic neurotransmission are able to interact with each other. (2)
Striatum
Prefrontal cortex
Several polymorphisms in the genes encoding which glutamate receptors (inotropic or metabotropic) are thought to be associated with ADHD? (1)
Both
Complete the sentence relating to ADHD. (1)
Alterations to glutamatergic signalling caused by inotropic receptor changes may result in …………………. symptoms.
Attention deficit
Complete the sentence relating to ADHD. (1)
Alterations to glutamatergic signalling caused by metabotropic receptor changes may result in …………………. symptoms.
hyperactivity/impulsivity
Very briefly describe the effect that hypodopaminergic neurotransmission in ADHD may have on glutamatergic neurotransmission. (2)
- Decreased dopamine causes more active NMDARs/AMPARs
- Increase in glutamate activity
What would be the usual effect of D2 stimulation on glutamatergic neurotransmission? (1)
NMDAR inhibition
What would be the usual effects of D4 stimulation on glutamatergic neurotransmission? (2)
Depression of AMPAR-mediated excitation of PFC neurones
Decreased AMPAR expression at synapse
In ADHD, what is the effect of striatal glutamate release on dopaminergic neurotransmission? (1)
Facilitates DA release by acting on NMDARs
In ADHD, AMPA KO mice display what change to their striatal DA concentration? (1)
Elevated
Name three possible psychostimulants which can be used to treat ADHD. (3)
- Methylphenidate
- Dexamphetamine
- Lis-dexamphetamine
Complete the sentence relating to psychostimulants in ADHD. (2)
Psychostimulants bind to ………………….., and may also inhibit ……………
DAT
NET
What is the difference between dexamphetamine and lis-dexamphetamine to treat ADHD? (1)
Lis-dexamphetamine is a prodrug and has to be converted in the body.
Name a common form of methylphenidate used to treat ADHD. (1)
Ritalin
Name a common form of dexamphetamine used to treat ADHD. (1)
Adderall
Stimulants (such as methylphenidate and amphetamine) tend to have mixed effects on dopamine and norepinephrine neurotransmission in ADHD.
Name a medication that acts solely on dopaminergic neurotransmission. (1)
Bupropion
Stimulants (such as methylphenidate and amphetamine) tend to have mixed effects on dopamine and norepinephrine neurotransmission in ADHD.
Name two medications that act solely on noradrenergic neurotransmission. (2)
Guanfacine
Atomoxetine
What type of medication is atomoxetine, as used in ADHD? (1)
Noradrenaline reuptake inhibitor
Give an advantage of using non-stimulant medications to treat ADHD. (1)
Potentially less addiction
What type of medication is guanfacine, as used in ADHD? (1)
Alpha2 adrenoreceptor agonist
Give two more recently licenced treatments (and their general effects on NTs) for ADHD. (2)
- Alpha2 adrenoreceptor agonists (increase NA)
- Tricyclic antidepressants (inhibit NET)
How might the levels of noradrenaline be different in people with ADHD? (1)
Too low
Name two types of medications used in ADHD which affect glutamatergic neurotransmission. (2)
Give an example of each of these. (2)
NMDA antagonist (memantine)
mGluR agonist (fasoracetam)
Give five beneficial effects of increasing dopamine and NE in ADHD. (5)
- Increased cognitive function
- Increased attentiveness
- Decreased distractibility
- Decreased hyperactivity
- Decreased behavioural disruption
Give eight potential effects of medications used to treat ADHD. (8)
- Insomnia
- Increased HR/BP
- Nausea/vomiting
- Abdominal pain
- Tics
- Decreased appetite
- Decreased bodyweight
- Decreased growth rate
What would you expect to see in a DAT radiolabelled binding study in ADHD? (1)
How would this be different after four weeks of methylphenidate treatment? (1)
How would this be different after 12 months of methylphenidate treatment? (1)
Increased DAT binding (so increased DAT levels)
After 4 weeks methylphenidate this binding would be reduced
After 12 months methylphenidate this binding would be increased
What are the effects on DAT expression of long-term methylphenidate use? (1)
What effect might this have on the efficacy of the treatment? (1)
Compensatory increase in DAT
Treatment efficacy reduced
Describe the mechanism of how methylphenidate is able to enhance dopaminergic neurotransmission in ADHD. (3)
- Block DAT transporter
- Less DA taken up into presynaptic terminal
- More DA in synaptic cleft to bind to postsynaptic receptors
Describe the mechanism of how amphetamine is able to enhance dopaminergic neurotransmission in ADHD. (6)
- Inhibits DAT by binding to alternative site
- Amphetamine also taken up by DAT into presynaptic neurone
- Blocks VMAT2 on vesicles
- Less DA loaded into vesicles
- More DA in cytoplasm
- DA released from neurone via reverse DAT transport
With regards to stimulant pharmacology in ADHD, is methylphenidate firing rate dependent or independent? (1)
Firing rate dependent
With regards to stimulant pharmacology in ADHD, is amphetamine firing rate dependent or independent? (1)
Firing rate independent
11C-Raclopride is used in PET scans and binds to D2 receptors in the striatum. This technique is commonly used in ADHD research.
What would you expect to see in terms of the PET signal given off if methylphenidate is added? Explain your answer. (2)
Reduced signal
Because methylphenidate increases DA, which competes with raclopride and displaces it from the receptor.
True or false? Explain your answer if appropriate. (1)
In addition to medications, it has been found that rewards (either physical or psychological) also have a positive effect in ADHD.
True
Complete the sentence relating to rewards as a way of improving ADHD symptoms. (3)
Rewards (either physical or psychological) have been shown to increase dopaminergic function in the ………………….. and …………………………, as well as increasing both DA and NA in the ……………………..
Striatum
Nucleus accumbens
Frontal cortex
Give six positive effects of reward on behaviour and functioning in ADHD. (6)
- Increased motivation
- Enhanced executive function
- Increased focus
- Increased attention
- Increased effort
- More on-task behaviour
Give five medical conditions which can present with anxiety. (5)
- Generalised anxiety disorder (GAD)
- Panic disorder
- Obsessive compulsive disorder (OCD)
- Post-traumatic stress disorder (PTSD)
- Phobias
Briefly describe the diagnostic criteria for GAD. (6)
- Excessive anxiety or worry
- Which is difficult to control
- About a number of events or situations
- Associated with a number of other psychological or physical symptoms
- Which causes significant distress or impairment of functioning
- And not better explained by substance use or another medical condition
Give seven potential symptoms, along with anxiety, which form part of the diagnostic criteria for GAD. (6)
- Restlessness (or feeling on edge)
- Fatigue
- Difficulty concentrating
- Irritability
- Muscle tension
- Sleep disturbance
Name two physical symptoms that can often be experienced in GAD, however do not form part of the diagnostic criteria. (2)
HINT: these symptoms can often be controlled using beta blockers
Dizziness
Heart palpitations
How does panic disorder differ from GAD? (1)
Panic disorder features regular panic attacks
Describe the onset and duration of a panic attack. (2)
Come on quickly
Lasts for about 5-20 minutes
Describe two general aspects of the diagnostic criteria for panic disorder. (2)
- Recurrent, unexpected panic attacks
- Followed by persistent worry about having another, or a maladaptive behaviour to avoid having attacks
Define a panic attack. (1)
Abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and features a range (4 or more) of symptoms.
Give 13 potential symptoms of a panic attack. (13)
- Palpitations, pounding heart, or accelerated heart rate
- Sweating
- Trembling or shaking
- Sensations of shortness of breath or smothering
- Feelings of choking
- Chest pain or discomfort
- Nausea or abdominal distress
- Dizziness, unsteady, light-headed, faint
- Chills or heat sensations
- Paresthesias (numbness or tingling)
- Derealisation or depersonalisation
- Fear of losing control or going crazy
- Fear of dying
Define ‘obsessive compulsive disorder’. (3)
A combination of obsessive thoughts and compulsive activity
which are time consuming
and impact on day-to-day functioning.
What is an obsession, in terms of OCD? (1)
Unwanted/unpleasant thoughts that cause anxiety
What is an compulsion, in terms of OCD? (1)
Repetitive behaviour undertaken to supress negative thoughts.
What proportion of people exposed to trauma will be affected by PTSD? (1)
1 in 3
Briefly describe what is meant by PTSD. (3)
An anxiety disorder caused by traumatic events
which are relived through nightmares or flashbacks
with sufferers also showing avoidance of linked memories.
Give eight criteria that must be met for a diagnosis of PTSD. (8)
- Exposure to traumatic stressor
- Reexperiencing symptoms
- Avoidance behaviours
- Cognitive distortions
- Increased arousal
- Symptoms for more than 1 month
- Symptoms create distress or functional impairment
- Symptoms not caused by medication, substance use, or illness
Define ‘phobia’. (1)
Overwhelming and debilitating fear of something that is often of little or no actual danger.
Give four examples of specific phobias. (4)
And two examples of complex phobias. (2)
- Spiders
- Heights
- Flying
- Injections
- Agoraphobia
- Social phobia
Give four possible techniques or ways of gaining evidence that can be used to determine the neurobiology of GAD. (4)
- Neuroimaging
- Genetic studies
- Neurotransmitters and responses to treatment
- Neuroendocrine studies
What is the normal, physiological role of the prefrontal cortex in anxiety? (1)
Controls rational, logical thought to reduce anxiety.
What is the normal, physiological role of the anterior cingulate cortex in anxiety? (1)
Amplifies negative information (from the amygdala) which increases anxiety.
What is the normal, physiological role of the amygdala in anxiety? (1)
Inhibits the prefrontal cortex and initiates fight-or-flight response
Describe a hypothesis of anxiety disorders relating to the prefrontal cortex, ACC, and amygdala. (3)
- Amygdala function disrupted (and amygdala increased in size)
- PFC-amygdala connectivity disrupted
- Imbalance between ACC amplifying anxiety and PFC dampening anxiety (ACC may hyperactivate amygdala)
What is a possible technique that could be used to investigate connectivity between the prefrontal cortex and amygdala in GAD? (1)
resting state fMRI
Patients with GAD and healthy controls underwent resting state fMRI scans.
What would you expect to see in these two groups, in relation to the functional connectivity between the PFC and amygdala? (1)
Patients with GAD showing weaker functional connectivity.
Family studies show how much heritability in GAD? (1)
About 30%
In general, give two brain processes that are controlled by the risk genes for GAD. (2)
- Monoamine neurotransmission
- Neurotrophic signalling
Name four risk genes for GAD. (4)
- 5HT reuptake transporter (SERT)
- 5HT-1A receptor
- Monoamine oxidase A
- BDNF gene
Describe the change in the SERT gene which may confer greater risk of GAD. (1)
Short allele
Describe the change in the 5HT1A gene which may confer greater risk of GAD. (1)
What is the functional consequence of this gene mutation? (1)
C1019G polymorphism
Results in increased negative feedback and decreased serotonergic signalling
Describe two changes in the monoamine oxidase A gene which may confer greater risk of GAD. (2)
What is the functional consequence of these gene mutations? (1)
T941G polymorphism
Long allele
Result in increased monoamine metabolism and decreased monoamine signalling.
Describe the change in the BDNF gene which may confer greater risk of GAD. (1)
What is the functional consequence of this gene mutation? (1)
Val66Met polymorphism
Decreased BDNF activity
Give three environmental risk factors for GAD. (3)
- Childhood trauma
- Stressful family circumstances
- Natural disasters
Gene-environment interactions are thought to play a role in the development of GAD.
Which gene changes are thought to interact with childhood trauma to increased risk of GAD? (3)
5HT Transporter (SERT)
COMT
MAOA
Gene-environment interactions are thought to play a role in the development of GAD.
Which gene changes are thought to interact with hurricane victims to increased risk of GAD? (1)
Neuropeptide Y variants
Gene-environment interactions are thought to play a role in the development of GAD.
Which gene changes are thought to interact with daily life stress to increase risk of GAD? (1)
5HT transporter variants
Gene-environment interactions are thought to play a role in the development of GAD.
Which gene changes are thought to interact with family relationship stress to increase risk of GAD? (1)
Neuropeptide S receptor 1 variants
Give three neurotransmitters which may be implicated in GAD. (3)
- GABA
- 5HT
- Neuropeptides
Give two ways in which GABA may be implicated in GAD. (2)
Give a piece of evidence that supports this. (1)
- Dysregulated inhibitory neurotransmission
- GABAa receptor downregulated
Symptoms may be treated with GABAa agonists, which supports the theory of GABA being involved.
Briefly describe how 5HT may be associated with GAD, and give a piece of evidence that supports this. (2)
Decreased 5HT may be associated with GAD
given that symptoms can be treated with SSRIs (which increase 5HT).
Briefly describe a piece of evidence suggesting why neuropeptides are thought to play a role in GAD. (1)
What are current clinical trials showing surrounding this relationship? (1)
Patients are hypersensitive to cholecystokinin agonists
However trials investigating CCK antagonists have been unsuccessful.
Name a neuroendocrine pathway which may be altered in GAD. (1)
HPA axis
How is the HPA axis thought to be altered in GAD? (1)
Negative feedback may be lost leading to increased cortisol.
Give five considerations during the assessment and treatment of GAD. (5)
- Mental health history
- Environmental stressors
- Medical and drug history
- Degree of distress and functional impairment
- Risk of suicide
Give three general aims of GAD treatment. (3)
- Relieve symptoms
- Improve quality of life
- Prevent relapse
Name two possible treatment routes that can be taken for GAD. (2)
- Pharmacological management
- Non-pharmacological management
Suggest five possible non-pharmacological treatment options for GAD. (5)
- Self help
- Meditation/relaxation/mindfulness
- Exercise
- Lifestyle changes
- Psychotherapy
Suggest a pharmacological way of treating autonomic symptoms in GAD. (1)
Give an example. (1)
Beta-adrenoreceptor antagonists
Propranolol
Suggest four possible pharmacological ways of treating anxiety symptoms in GAD. (4)
SSRIs
SNRIs
Atypical antidepressants
Benzodiazepines
What target are atypical antidepressants thought to work on in the brain? (1)
5HT receptors
In what situation would benzodiazepines be useful to treat GAD? (1)
In a crisis (short-term use)
Apart from GAD, give three uses for benzodiazepines. (3)
- Insomnia
- Epilepsy
- Pre-surgical medication
(Using four words), give a very brief description of how benzodiazepines work. (1)
Enhance effects of GABA
Describe the structure of a GABAa receptor. (1)
5 SUBUNITS:
2x alpha
2x beta
1x gamma
Going in a circle,
y, a, b, a, b, y, a, b, a, b, y
Where on a GABAa receptor does GABA usually bind? (1)
Between a and b subunits
Where on a GABAa receptor does a benzodiazepine usually bind? (1)
Between a and y subunits
What is the effect of a benzodiazepine molecule binding to a GABAa receptor? (5)
- Confirmational change
- Enhanced GABA binding
- More channel opening
- More Cl- influx (hyperpolarisation)
- Reduced neuronal activity
Benzodiazepines do not directly activate GABAa receptors, but enhance GABA binding.
What is the name given to benzodiazepines (and other molecules) that act in this way? (1)
Positive allosteric modulators (PAMs)
Give three general issues that are faced with current treatments for GAD. (3)
- Non-responsive patients
- Relapse
- Side effects
Give three particularly troubling side effects that patients experience with GAD treatments. (3)
- Sexual dysfunction
- Drowsiness
- Weight gain
Ketamine, riluzole, and xenon may be next generation, novel treatments for GAD.
Briefly describe how these drugs are thought to work. (1)
Tend to decrease glutamatergic signalling
Apart from glutamatergic drugs, give four other potential next generation, novel treatments for GAD. (4)
- Neurosteroids
- Cannabinoids
- MDMA
- L-DOPA
