Neuroscience Exam #2 - Anxiety

Anxiety disorders facts:

Age of onset for anxiety disorders is

Which of the following is NOT a medical rule out for anxiety

DSM Anxiety Disorders include [blank_start]anxiety[blank_end] disorders, [blank_start]obsessivecompulsive[blank_end] disorders and [blank_start]trauma or stressor related[blank_end] disorders

Eustress vs. Distress: remember stress isn't always negative [blank_start]Eustress:[blank_end] Motivating, short-term, exciting [blank_start]Distress:[blank_end] Short- or long-term, perceived as beyond coping ability, unpleasant

“Anxiety and fear are cousins but not twins. [blank_start]Fear[blank_end] sees a threat. [blank_start]Anxiety[blank_end] imagines one.” – Max Lucado

Neuroanatomy of anxiety. Which parts of the brain are involved. [blank_start]Prefrontal cortex[blank_end] [blank_start]orbitofrontal cortex[blank_end] [blank_start]ventromedial prefrontal cortex[blank_end] [blank_start]limbic system[blank_end]

In neuroanatomy of anxiety, what is the function of the prefrontal cortex

In the neuroanatomy of anxiety, the [blank_start]orbitofrontal[blank_end] cortex controls impulses, regulates mood, and drives moral judgment

Which is not a feature of the limbic system

[blank_start]Ventromedial prefrontal[blank_end] cortex is in charge of reward processing – think and visceral response to emotions

[blank_start]Hippocampus[blank_end] -Spatial navigation. Memory formation/storage [blank_start]Amygdala[blank_end] – Processes emotional stimuli. Receives information about physical needs. Initiates behavioral response [blank_start]Hypothalamus[blank_end] – Receives unprocessed sensory input. Connects endocrine system to nervous system via pituitary gland [blank_start]Thalamus[blank_end] – sensory processing. Hub of information transfer. Directs sensory input for processing

The [blank_start]hippocampus[blank_end]: Shifts short-term memory to long-term memory Encodes our memory with emotions by interacting with amygdala Interacts with amygdala to encode emotional memories Active in imaging studies during fearful situations

Neuroanatomy of the hippocampus in anxiety

The hippocampus is related to stress sensitivity and resiliency. A [blank_start]large[blank_end] hippocampus is protective agains anxiety disorders. A [blank_start]small[blank_end] hippcampus has increased risk of PTSD in the context of trauma

The amygdala has three groups, a medial group, a basal-lateral group, and a central group. Which group has connections with the hypothalamus and the brain stem, cues the endocrine system response, and influences expression of emotion, and triggers the autonomic nervous system?

Neuroendocrine pathways for the HPA (hypothalamic-pituitary-adrenal) axis. Let's review as this is probably an exam question: Activated by [blank_start]stress[blank_end] Hypothalamus releases [blank_start]corticotropin-releasing factor (CRF)[blank_end] CRF binds to receptors on [blank_start]anterior pituitary gland[blank_end] [blank_start]Adrenocorticotropic hormone (ACTH)[blank_end] is released ACTH binds to receptors on [blank_start]adrenal cortex[blank_end] [blank_start]Cortisol and adrenaline[blank_end] are released!

Function of the HPA axis is SAFETY & PROTECTION

Cortisol

Adrenaline Increases [blank_start]heart[blank_end] rate, [blank_start]blood[blank_end] pressure, respiratory [blank_start]rate,[blank_end] and [blank_start]carbohydrate[blank_end] metabolism

Chronic/prolonged stress = repeated/sustained HPA axis activation

[blank_start]Calming NT[blank_end]: γ-amino-butyric-acid (GABA) [blank_start]Excitatory NT:[blank_end] Glutamate [blank_start]Monoaminergic neurotransmitters[blank_end] Serotonin Norepinephrine Dopamine

Excessive [blank_start]glutamate[blank_end] activity causes anxiety, agitation, and seizures

Benzodiazepines increase [blank_start]GABA[blank_end] activity at amygdala and PFC

[blank_start]GABA[blank_end] Principal inhibitory neurotransmitter [blank_start]Glutamate[blank_end] Principal excitatory neurotransmitter [blank_start]GABA[blank_end] Decreases neurons’ electrical excitability [blank_start]Glutamate[blank_end] Increases neurons’ electrical excitability [blank_start]Glutamate[blank_end] Necessary for attention/coordination [blank_start]GABA[blank_end] Calm, relaxation, sleep

Enhancing 5-HT input to the amygdala can [blank_start]reduce[blank_end] anxiety/fear

Serotonin

Norepinephrine

Dopamine

Catecholamine-O-methyltransferase (COMT) met genetic allele:

Met genotype: [blank_start]Lower[blank_end] COMT activity = [blank_start]higher[blank_end] NT levels = [blank_start]excessive[blank_end] NT release under stress = WORRIER Val genotype: [blank_start]Higher[blank_end] COMT activity = [blank_start]lower[blank_end] NT levels = [blank_start]decreased[blank_end] NT release under stress = WARRIOR

Which gene regulates the HPA axis and monoaminergic signaling

The [blank_start]short (S)[blank_end] allele of 5-HTTLPR: Serotonin transporter puts a patient as risk for anxiety

What environmental factors play a part in increasing anxiety?

Substance-Induced Anxiety Disorders can be caused by the following drugs except

Panic disorder usually starts before the age of 24 and usually has lots of comorbidities as patients try to self-medicate

DSM-5 Criteria for Panic Disorder include recurrent UNEXPECTED panic attacks, followed by 1 month of:

Agoraphobia is fear of situations with

Neuroanatomy of panic disorder includes: [blank_start]Elevated[blank_end] glucose uptake in amygdala, hippocampus, and thalamus [blank_start]Decreased[blank_end] frontal lobe activity

Neurotransmitter pathways in panic disorder: [blank_start]Decreased[blank_end] GABA concentrations, elevated glutamatergic signaling [blank_start]Decreased[blank_end] serotonin receptor binding, increased norepinephrine concentration

Panic disorder is the most heritable of all anxiety disorders with first-degree relatives of patient with panic DO means that patient has 7X increased risk

Neuroendocrine pathways in panic disorder include: (on exam study guide)

Specific phobia (like clowns) is the most common anxiety disorder, women twice as likely to suffer as men, and typical age of onset is childhood to adolescence

Specific phobia is a persistent fear of clearly discernible objects or situations that provoke immediate anxiety and cause social or occupational impairement

Specific Phobia Neuroanatomy: activation of [blank_start]amygdala[blank_end], decreased [blank_start]prefrontal cortex response[blank_end]

Social anxiety disorder is twice as likely in women as men, onset is childhood or adolescence and is often seen with MDD or substance abuse disorders

DSM 5 criteria for social anxiety disorder is a persistent fear of situations in which exposure to unfamiliar people o scrutiny is possible. Fear that actions will expose anxiety or possible humiliation or embarrassment.

Neuroanatomy of Social Anxiety Disorder: [blank_start]Hyperactive[blank_end] prefrontal cortex - misinterpreting social cues [blank_start]Hyperreactive[blank_end] amygdala - receives sensory information before analysis and signals the sympathetic nervous system

Genetics of social anxiety disorder involve Serotonin transporter (5-HTT) which governs reuptake of serotonin into the neuron. The [blank_start]short[blank_end] allele is involved in increased risk of anxiety and depression in context of stressful environment, Increased startle response and a stronger amygdala activation in response to angry faces

Generalized anxiety disorder has the youngest age of onset for an anxiety disorder

Excessive worries/anxiety for at least [blank_start]6 month[blank_end]s. Worry about a number of events, situations, activities. Difficulty controlling the worry. Three or more of the following: Restless/on edge Easily fatigued Difficulty concentrating Irritability Muscle tension Sleep disturbance

Neuroendocrine pathways of generalized anxiety disorder include all the following EXCEPT:

5-HTTLPR [blank_start]short[blank_end]-allele carriers are highly sensitive to environmental threats. Hypervigilance

The following are all forms of obsessive-compulsive disorders:

Tourette's Syndrome is a frequent comorbidity of obsessive compulsive disorder

The following are all true about OCD DSM-5 criteria

OCD is real anatomical issue

In obsessive compulsive disorder there is [blank_start]orbitofrontal[blank_end] cortex overactivity but smaller volume which leads to context-related processing and response inhibition

In obsessive compulsive disorder there is abnormal activity in [blank_start]cortico-striatal-thalamo-cortical (CSTC)[blank_end] feedback loop. These circuits use “direct” (excitatory) or “indirect” (inhibitory) routes from cortex through [blank_start]basal ganglia[blank_end] to [blank_start]thalamus.[blank_end]

CSTC or "worry" loop is involved in obsessive compulsive disorder. It includes the [blank_start]basal ganglia[blank_end] which nuclei grouped together based on interconnected roles in movement and cognition. It includes Includes [blank_start]globus pallidus[blank_end], putamen, caudate nucleus. Specifically the striatum Includes [blank_start]putamen[blank_end] and caudate nucleus.

In obsessive compulsive disorder, the CSTC loop receives input to [blank_start]basal ganglia[blank_end] from [blank_start]cortex[blank_end] and [blank_start]thalamus[blank_end]

In obsessive compulsive disorder, the CSTC or "worry" loop has two pathways. The "direct" basal ganglia and the "indirect' basal ganglia pathway that are antagonistic to each other

“Direct” basal ganglia pathway: Direct projections from [blank_start]striatum[blank_end] to [blank_start]globus pallidus[blank_end] Increases [blank_start]excitatory[blank_end] thalamic input to the cortex Turns [blank_start]up[blank_end] motor activity

The [blank_start]"direct"[blank_end] basal ganglia pathway is involved in the activation of tics, compulsions, and obsessions. It is [blank_start]overactive[blank_end] in OCD.

“Indirect” basal ganglia pathway has [blank_start]Indirect[blank_end] projections from [blank_start]striatum[blank_end] to [blank_start]globus pallidus[blank_end] [blank_start]Inhibitory[blank_end] effect on [blank_start]thalamus[blank_end] and frontal cortex

"Direct" basal ganglia pathway is the "gas" and the "indirect" basal ganglia is the brake when it comes to motor activity

OCD occurs when delicate balance between inhibition and excitation of basal ganglia pathway is disrupted

Neuroanatomy of OCD involves Increased activity in CSTC circuit running from [blank_start]frontal cortex[blank_end] to [blank_start]striatum[blank_end] to [blank_start]globus pallidus[blank_end] to [blank_start]thalamus[blank_end] and back to [blank_start]cortex[blank_end]

In OCD, there is increased Increased activity in prefrontal cortex, basal ganglia, and [blank_start]amygdala[blank_end]

What is the treatment for OCD

Serotonin, dopamine and glutamate are involved in OCD. There are [blank_start]reduced[blank_end] serotonin transporters in midbrain. There is [blank_start]increased[blank_end] dopamine. There is [blank_start]increased[blank_end] glutamate.

Considering what we know about 5HT, DA, and Glu in OCD, which drugs are most effective

A patient with OCD will be in a hyperglutamatergic state in prefrontal regions and have elevated glutamate in cerebrospinal fluid

An [blank_start]earlier[blank_end] onset of OCD is indicative of a higher risk of heritability

Of the following comorbidities with seen OCD, which has the highest incidence of PTSD

DSM 5 criteria for PTSD involve exposure to [blank_start]trauma[blank_end], [blank_start]re-experiencing,[blank_end] [blank_start]avoidance[blank_end], [blank_start]negative alterations in mood/cognition[blank_end], and [blank_start]increased arousal.[blank_end]

The neuroanatomy of the PTSD involves: [blank_start]Reduced[blank_end] volume of hippocampus and frontal cortex Amygdala [blank_start]hyperresponsiveness[blank_end] [blank_start]Decreased[blank_end] activity in PFC

The following NT are involved in PTSD EXCEPT:

Which drug exhibits inhibitory effects on glutamate transmission and thus is good for PTSD

Glutamate

What medication should you not give to PTSD because of the unremitting elevation in NE in the CSF of patients with PTSD?

In PTSD, patients have a [blank_start]decreased[blank_end] cortisol concentrations and a/n [blank_start]flattened[blank_end] cortisol slope

Treatment for anxiety disorders include:

MOA of BZ in anxiety involves BZ [blank_start]increasing[blank_end] the efficiency of GABA to [blank_start]decrease[blank_end] the excitability of neurons. BZ bind to the y sub-unit of the [blank_start]GABA-A[blank_end] receptor. Binding causes a structural modification of the receptor that results in an increasein GABA-A activity. The result is an [blank_start]increase[blank_end] in the frequency of the [blank_start]Cl-[blank_end] channel (making the cell more negative) and [blank_start]inhibiting[blank_end] the action potential.

Chronic/prolonged stress = repeated/sustained HPA axis activation which causes: [blank_start]Musculoskeletal:[blank_end] Chronic muscle tension, tension headaches, migraines [blank_start]Respiratory:[blank_end] Exacerbation of existing conditions (asthma, emphysema, etc.) [blank_start]Cardiovascular:[blank_end] Increased risk of heart attack, hypertension, stroke [blank_start]Endocrine:[blank_end] Increased risk of diabetes in vulnerable populations [blank_start]Gastrointestinal:[blank_end] Acid reflux, ulcers, diarrhea, constipation, nausea/vomiting Reproductive: [blank_start]Male:[blank_end] Impaired testosterone production and sperm maturation, impotence [blank_start]Female:[blank_end] Irregular menstrual cycles, impaired sexual desire