Anxiety Disorders: Neurobiology, Neurochemistry and Treatment Flashcards
1
Q
What structure controls fear?
A
Integration of fear components controlled by the amygdala
2
Q
T…-weighted imaging is used to differentiate anatomical structures mainly on the basis of T… values; i.e. the scanning parameters are set (short TR/short TE) to minimize T… relaxation effects. Tissues with high fat content (e.g. white matter) appear bright and compartments filled with water (e.g. CSF) appears dark. This is good for demonstrating anatomy.
A
T1-weighted imaging is used to differentiate anatomical structures mainly on the basis of T1 values; i.e. the scanning parameters are set (short TR/short TE) to minimize T2 relaxation effects. Tissues with high fat content (e.g. white matter) appear bright and compartments filled with water (e.g. CSF) appears dark. This is good for demonstrating anatomy.
3
Q
T…-weighted imaging is used to differentiate anatomical structures mainly on the basis of T… values; i.e. the scanning parameters are set (long TR/long TE) to minimize T… relaxation effects. Compartments filled with water (e.g. CSF compartments) appear bright and tissues with high fat content (e.g. white matter) appear dark. This is good for demonstrating pathology since most (not all) lesions are associated with an increase in water content.
A
T2-weighted imaging is used to differentiate anatomical structures mainly on the basis of T2 values; i.e. the scanning parameters are set (long TR/long TE) to minimize T1 relaxation effects. Compartments filled with water (e.g. CSF compartments) appear bright and tissues with high fat content (e.g. white matter) appear dark. This is good for demonstrating pathology since most (not all) lesions are associated with an increase in water content.
4
Q
Characteristics of the stress response:
- … behaviour
- Increased … and a…
- Activation of the … division of the ANS
- Release of … from the adrenal glands
A
- Avoidance behaviour
- Increased vigilance and arousal
- Activation of the sympathetic division of the ANS
- Release of cortisol from the adrenal glands
5
Q
Characteristics of the stress response:
- … behaviour
- Increased vigilance and arousal
- Activation of the … division of the ANS
- Release of cortisol from the … …
A
- Avoidance behaviour
- Increased vigilance and arousal
- Activation of the sympathetic division of the ANS
- Release of cortisol from the adrenal glands
6
Q
Fearful stimuli elicit stress responses
- Sensory information channeled to …
- … excites locus coeruleus + hypothalamus
- Acute Stress Response
- HPA axis:
- … releases CRH
- … releases ACTH
- … … releases cortisol (stress hormone)
- Locus Coeruleus (LC) releases … which triggers “fight or flight” responses
A
- Sensory information channeled to amygdala
- Amygdala excites locus coeruleus + hypothalamus
- Acute Stress Response
- HPA axis:
- Hypothalamus releases CRH
- Pituitary releases ACTH
-
Adrenal cortex releases cortisol (stress hormone)
- (CRH: corticotropin releasing hormone
- (ACTH: adrenocorticotropic hormone)
- Locus Coeruleus (LC) releases norepinephrine which triggers “fight or flight” responses
7
Q
Fearful stimuli elicit stress responses
- Sensory information channeled to amygdala
- Amygdala excites locus coeruleus + hypothalamus
- Acute Stress Response
- HPA axis:
- Hypothalamus releases …
- Pituitary releases …
- Adrenal cortex releases … (stress hormone)
- Locus Coeruleus (LC) releases norepinephrine which triggers “… or …” responses
A
- Sensory information channeled to amygdala
- Amygdala excites locus coeruleus + hypothalamus
- Acute Stress Response
- HPA axis:
- Hypothalamus releases CRH
- Pituitary releases ACTH
- Adrenal cortex releases cortisol (stress hormone)
- (CRH: corticotropin releasing hormone
- (ACTH: adrenocorticotropic hormone)
- Locus Coeruleus (LC) releases norepinephrine which triggers “fight or flight” responses
8
Q
Push-pull regulation of the HPA axis
A
9
Q
In situations of chronic stress:
- Chronic activation of … receptors in hippocampus
- increased Ca2+ entry into neurons
- too much Ca2+ - excitotoxic - cells die
- Hippocampus can’t feedback to limit … production
- Thus some anxiety disorders may result from:
- diminished activity of hippocampus
- loss of feedback to the …
- inappropriate … responding
- (evidence - hippocampal volume in PTSD patients reduced)
A
- Chronic activation of glucocorticoid receptors in hippocampus
- increased Ca2+ entry into neurons
- too much Ca2+ - excitotoxic - cells die
- Hippocampus can’t feedback to limit cortisol production
- Thus some anxiety disorders may result from:
- diminished activity of hippocampus
- loss of feedback to the amygdala
- inappropriate fear responding
- (evidence - hippocampal volume in PTSD patients reduced)
10
Q
In situations of chronic stress:
- Chronic activation of glucocorticoid receptors in hippocampus
- … Ca2+ entry into neurons
- too … Ca2+ - excitotoxic - cells die
- Hippocampus can’t feedback to limit cortisol production
- Thus some anxiety disorders may result from:
- diminished activity of …
- loss of … to the amygdala
- inappropriate fear responding
- (evidence - hippocampal volume in PTSD patients reduced)
A
- Chronic activation of glucocorticoid receptors in hippocampus
- increased Ca2+ entry into neurons
- too much Ca2+ - excitotoxic - cells die
- Hippocampus can’t feedback to limit cortisol production
- Thus some anxiety disorders may result from:
- diminished activity of hippocampus
- loss of feedback to the amygdala
- inappropriate fear responding
- (evidence - hippocampal volume in PTSD patients reduced)
11
Q
Brain damage caused by stress
A
Photomicrographs showing a. section through the hippocampus of a normal monkey,
and b. of a monkey of low social status subjected to stress. The regions between the arrowheads are normally filled with large pyramidal cells.
12
Q
Both amygdala and hippocampus respond to highly processed information from other brain areas (e.g. diffuse modulatory systems)
- … system - arousal and attention (fight / flight etc)
- … system - mood and emotion
- These systems both project diffusely throughout the … to both cortical and limbic areas, as well as connections to each other.
- They are often thought to … one another e.g. serotonin inhibits LC firing
- dysregulation of limbic systems or connections to them may result in inappropriate … and … responses
- Pathways involved can be determined by which drugs have anxiolytic effects
A
- Noradrenergic system - arousal and attention (fight / flight etc)
-
Serotonergic system - mood and emotion
- These systems both project diffusely throughout the forebrain to both cortical and limbic areas, as well as connections to each other.
- They are often thought to balance one another e.g. serotonin inhibits LC firing
- dysregulation of limbic systems or connections to them may result in inappropriate fear and anxiety responses
- Pathways involved can be determined by which drugs have anxiolytic effects
13
Q
Anxiety Disorders (5)
A
- 1.Post Traumatic Stress Disorder (PTSD): persistent psychological stress following exposure to extreme stress, e.g. war, physical assault
- 2.Panic Disorder (PD): rapid-onset attack of extreme fear and severe stress
- 3.Generalized Anxiety Disorder (GAD): stress and anxiety in the absence of obvious precipitating stimulus
- 4.Phobias: similar to GAD, but triggered by particular objects (e.g. spiders, birds) or situations (e.g. crowds, darkness)
- 5.Obsessive Compulsive Disorder (OCD): frequently recurring, uncontrollable, anxiety-producing thoughts (obsessions) and impulses (compulsions). Responding to them, e.g. repeated, compulsive hand washing, dissipates associated anxiety.
14
Q
Panic Disorder
- Characterized by …, unfounded fear and anxiety; … and unremitting terror for variable … of time (sec to hours).
A
Characterized by unrealistic, unfounded fear and anxiety; acute and unremitting terror for variable lengths of time (sec to hours).
15
Q
Panic Disorder
- Anxiety is normally …
- Universal basic symptoms, e.g. shortness of breath, “impending death”, irregular heartbeat, clammy sweat, dizziness, faintness
- Onset in … …
- More likely to appear in ….
- Treatable
- … anxiety (fear that another panic attack will strike) often leads to development of …
- Often accompanied by other serious problems: depression, alcoholism or drug abuse
A
- Anxiety is normally useful/adaptive
- Universal basic symptoms, e.g. shortness of breath, “impending death”, irregular heartbeat, clammy sweat, dizziness, faintness
- Onset in young adulthood
- More likely to appear in women
- Treatable
- Anticipatory anxiety (fear that another panic attack will strike) often leads to development of agoraphobia
- Often accompanied by other serious problems: depression, alcoholism or drug abuse
16
Q
Panic Disorder
- Anxiety is normally useful/adaptive
- Universal basic symptoms, e.g. … of …, “impending …”, irregular …, clammy sweat, d…, f…
- Onset in young adulthood
- More likely to appear in women
- Treatable
- Anticipatory anxiety (fear that another panic attack will strike) often leads to development of agoraphobia
- Often accompanied by other serious problems: …
A
- Anxiety is normally useful/adaptive
- Universal basic symptoms, e.g. shortness of breath, “impending death”, irregular heartbeat, clammy sweat, dizziness, faintness
- Onset in young adulthood
- More likely to appear in women
- Treatable
- Anticipatory anxiety (fear that another panic attack will strike) often leads to development of agoraphobia
- Often accompanied by other serious problems: depression, alcoholism or drug abuse
17
Q
Treatment for Panic Disorder
- …, partial agonists of the GABA(A) receptor, anxiolytic [sedation & sleep induction, reduced muscle tone & coordination, anticonvulsant effects, anterograde amnesia]
- (… …, e.g. flumazenil, produce panic attack in patients with PD, but not controls. So, anxiety disorders perhaps result from fewer Benzo receptors, or by a neuromudulator that blocks the benzo binding site on the GABA(A) receptor.)
- S…
- … (CBT)
A
-
Benzodiazepines, partial agonists of the GABA(A) receptor, anxiolytic [sedation & sleep induction, reduced muscle tone & coordination, anticonvulsant effects, anterograde amnesia]
- Benzo antagonists, e.g. flumazenil, produce panic attack in patients with PD, but not controls. So, anxiety disorders perhaps result from fewer Benzo receptors, or by a neuromudulator that blocks the benzo binding site on the GABA(A) receptor.
- Serotonin, SSRIs (serotonin selective reuptake inhibitors)
- Cognitive Behavioural Therapy (CBT)
18
Q
Treatment for Panic Disorder
- Benzodiazepines, partial agonists of the … receptor, anxiolytic [sedation & sleep induction, reduced muscle tone & coordination, anticonvulsant effects, anterograde amnesia]
- (Benzo antagonists, e.g. flumazenil, produce panic attack in patients with PD, but not controls. So, anxiety disorders perhaps result from fewer Benzo receptors, or by a neuromudulator that blocks the benzo binding site on the GABA(A) receptor.)
- Serotonin, SSRIs (serotonin selective reuptake inhibitors)
- Cognitive Behavioural Therapy (CBT)
A
- Benzodiazepines, partial agonists of the GABA(A) receptor, anxiolytic [sedation & sleep induction, reduced muscle tone & coordination, anticonvulsant effects, anterograde amnesia]
- (Benzo antagonists, e.g. flumazenil, produce panic attack in patients with PD, but not controls. So, anxiety disorders perhaps result from fewer Benzo receptors, or by a neuromudulator that blocks the benzo binding site on the GABA(A) receptor.)
- Serotonin, SSRIs (serotonin selective reuptake inhibitors)
- Cognitive Behavioural Therapy (CBT)
27
Q
Evidence of GABAergic dysfunction in anxiety disorders
- PET study with radiolabelled Flumazenil (indicating BZD binding sites)
- Patients with Panic Disorder have … benzodiazepine binding sites
- PD patients lack sufficient inhibitory control in … and … regions to suppress inappropriate fear responses and subsequent panic attack?
- the frontal cortex normally shows … activity during periods of anxiety
A
- PET study with radiolabelled Flumazenil (indicating BZD binding sites)
- Patients with Panic Disorder have fewer benzodiazepine binding sites
- PD patients lack sufficient inhibitory control in cortical and limbic regions to suppress inappropriate fear responses and subsequent panic attack?
- the frontal cortex normally shows increased activity during periods of anxiety
28
Q
Evidence of GABAergic dysfunction in anxiety disorders
- PET study with radiolabelled F… (indicating BZD binding sites)
- Patients with Panic Disorder have fewer … binding sites
- PD patients lack sufficient inhibitory control in cortical and limbic regions to suppress inappropriate fear responses and subsequent panic attack?
- the … cortex normally shows increased activity during periods of anxiety
A
- PET study with radiolabelled Flumazenil (indicating BZD binding sites)
- Patients with Panic Disorder have fewer benzodiazepine binding sites
- PD patients lack sufficient inhibitory control in cortical and limbic regions to suppress inappropriate fear responses and subsequent panic attack?
- the frontal cortex normally shows increased activity during periods of anxiety
29
Q
The serotonergic system and anxiety
- SSRIs (e.g. …/…) - Selective serotonin reuptake inhibitors
- SSRIs prolong action of 5-HT in the synapse
- … - 5HT1A partial agonist
- Somatodendritic receptors - autoreceptors
- No symptomatic change until … into treatment
A
- SSRIs (e.g. Fluoxetine/Prozac) - Selective serotonin reuptake inhibitors
- SSRIs prolong action of 5-HT in the synapse
-
Buspirone - 5HT1A partial agonist
- Somatodendritic receptors - autoreceptors
- No symptomatic change until weeks into treatment (SSRIs anxiogenic over first few days)
38
Q
Indirect & Direct Pathways
- Two types of dopamine receptors (D1 and D2) are located on different sets of output neurons in the striatum that give rise to the direct and indirect pathways.
- Inhibitory pathways are shown as … arrows; excitatory pathways, as … arrows.
- GPe = external segment of the globus pallidus;
- GPi = internal segment of the globus pallidus;
- SNc = substantia nigra pars compacta;
- STN = subthalamic nucleus.
A
- Two types of dopamine receptors (D1 and D2) are located on different sets of output neurons in the striatum that give rise to the direct and indirect pathways.
- Inhibitory pathways are shown as BLACK arrows; excitatory pathways, as pink arrows.
- GPe = external segment of the globus pallidus;
- GPi = internal segment of the globus pallidus;
- SNc = substantia nigra pars compacta;
- STN = subthalamic nucleus.
42
Q
OCD and OFC dysfunction
- … of OFC in a reversal learning task in patients with OCD and their unaffected relatives,
- New endophenotype for OCD. (vulnerability marker)
A
- Underactivation of OFC in a reversal learning task in patients with OCD and their unaffected relatives,
- New endophenotype for OCD. (vulnerability marker)
45
Q
Treatment strategies - Anxiety Disorders
- …: good immediate effects, but patients can develop tolerance and there is potential for abuse, and anxiety during withdrawal
- … are effective, but have a delayed onset. Initially can be anxiogenic.
- Combining … and … initially and then tapering off the … as the … take effect is an alternative treatment strategy.
A
- Benzodiazepines: good immediate effects, but patients can develop tolerance and there is potential for abuse, and anxiety during withdrawal
- SSRIs are effective, but have a delayed onset. Initially can be anxiogenic.
- Combining benzodiazepines and SSRIs initially and then tapering off the BDZs as the SSRIs take effect is an alternative treatment strategy.
46
Q
Treatment strategies - Anxiety Disorders
- Benzodiazepines: good immediate effects, but patients can develop … and there is potential for abuse, and anxiety during …
- SSRIs are effective, but have a … onset. Initially can be …
- Combining benzodiazepines and SSRIs initially and then tapering off the … as the … take effect is an alternative treatment strategy.
A
- Benzodiazepines: good immediate effects, but patients can develop tolerance and there is potential for abuse, and anxiety during withdrawal
- SSRIs are effective, but have a delayed onset. Initially can be anxiogenic.
- Combining benzodiazepines and SSRIs initially and then tapering off the BDZs as the SSRIs take effect is an alternative treatment strategy.
