OCD and Depression

Question 1

Define OCD

Answer 1

characterized by intrusive and unwanted thoughts (obsessions), and repetitive behaviours that the person with OCD feels compelled to perform (compulsions)
• Classified as an anxiety disorder in the DSM
• Now has its own category
One of the most common disorders (2% of pop

Question 2

Name the 3 main regions of the brain involved in the CSTC model of OCD

Answer 2

Prefrontal cortex
Thalamus
Basal ganglia

Question 3

What are the regions of the PFC involved in the CSTC model of OCD?

Answer 3

anterior cingulate cortex
medial prefrontal cortex
dorsolateral prefrontal cortex
orbitofrontal cortex

Question 4

What are the regions of the basal ganglia involved in the CSTC model of OCD?

Answer 4

caudate
nucleus accumbens
putamen

Question 5

Name the 2 pathways of info in the CSTC model, and say if they are excitatory of inhibitory

Answer 5

Direct-excitatory

Indirect-inhibitory

Question 6

Explain the direct CSTC pathway’s steps

Answer 6

cortical regions (orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC)) excite the striatum, striatum inhibits the globus pallidus internal (GPi) and the substantia nigra - result is that the thalamus is no longer inhibited by those 2 structures, enabling it to excite cortical regions (loop)

Question 7

Explain the indirect CSTC pathway’s steps

Answer 7

OFC and ACC excite the striatum, but the striatum inhibits the globus pallidus external (GPe), which usually inhibits the subthalamic nucleus (STN). The STN will excite the GPi which will inhibit the thalamus
○ It counteracts the direct loop

Question 8

What is the difference in the CSTC model for normal people vs OCD people?

Answer 8

In people with OCD, the direct pathway is over activated, and the indirect pathway is not; resulting in an hyper excitation of the thalamus (the inhibitory processes of the indirect pathway are not sufficient to balance the thalamus)
Ø Exaggerated error messages in the ACC give rise to the feeling that something is wrong - pushes compulsions and obsessions

Question 9

What are the 2 main neurotransmitters involved in OCD? What do they have different than a normal patient?

Answer 9

OCD patients: less serotonin receptors on postsynaptic neurons in frontal lobes, cingulate cortex and parietal/temporal cortices
Ø Increase of dopamine in basal ganglia - overactive basal ganglia

Question 10

Define MDD

Answer 10

Major Depressive Disorder: A psychological disorder characterized by episodes of extremely sad moods accompanied by a loss of pleasure in usual activities. MDD may also include sleep disruptions, changes in appetite, agitation or psychomotor retardation, somatic symptoms, feelings of worthlessness, difficulty concentrating, and recurrent thoughts of suicide.
• 16.6% of pop has it at some point in their lives
• Episodic: recurring episodes of 5 months or +
• Have multiple causes (biological, psychological, environmental)
• NOT the same as depressive periods such as grief

Question 11

Define psychomotor retardation

Answer 11

Psychomotor retardation: slowing down of thoughts and movements

Question 12

Define the role of the orbitofrontal cortex in MDD

Answer 12

More activated in subjects of MDD
• Maintenance of negative thoughts and emotions
Disrupting its activity by electrical stimulation improves mood

Question 13

Define the role of the VMPFC and DLPFC (Ventromedial/dorsolateral PFC) in MDD

Answer 13

Hyperactivity in the VMPFC
• Increased rumination
Hypoactivity in the DLPFC
• Psychomotor retardation and apathy

Question 14

Define what happens to the hippocampus in MDD

Answer 14

Reduced in volume - due to loss of grey matter

• After antidepressant treatment grey matter builds back up

Question 15

Explain the relationship between the hippocampus and glucocorticoids in MDD

Answer 15

Hippocampus regulates levels of glucocorticoids (which are higher in people with MDD)
Effect of glucocorticoids on the hippocampus:
1. High levels of glucocorticoids, due to overactivity of the HPA axis, are toxic to the hippocampus, resulting in decreases of gray matter and smaller hippocampal volumes.
2. Smaller hippocampal volumes in people with MDD disrupt the hippocampus’s ability to regulate levels of glucocorticoids.
3. Activation of the HPA axis results in the release of corticotropin-releasing hormone (CRH) from the hypothalamus. Activation of the HPA axis is triggered by activity in the amygdala.
4. The release of CRH from the hypothalamus causes the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, which promotes the release of glucocorticoids from the adrenal glands.
5. Activation of the HPA axis also promotes the release of what are known as cytokines from macrophages. Cytokines are molecules that are part of the immune system. Microphages are white blood cells that engulf and digest cellular debris and potentially toxic substances. - inhibits the normal functioning of the brain, which on the long term can lead to reduction of grey matter

Question 16

Explain what BDNF is

Answer 16

Brain Derived Neurotrophic Factor: helps the brain with its normal processes (inhibited by cytokines)
The more this process goes over, the less the hippocampus can regulate glucocorticoids levels

Question 17

Define the role of the amygdala in MDD

Answer 17

Heightened activity (same as with anxiety disorders) - related to the levels of glucocorticoids (mentioned earlier)

Question 18

Define the role of the anterior cingulate cortex (ACC) in MDD

Answer 18

Links emotions with attention (emotional self-regulation)
Also processes emotions
Dorsal part involved in cognitive processes
People with MDD have troubles to take corrective action in response to errors they committed

Question 19

Define neuroinflammation; how do we track it? How does it affect MDD patients?

Answer 19

Inflammation of nervous tissue
Medical conditions causing it are associated with MDD
By tracking levels of TSPO (translocator protein) which is a marker for inflammation, using PET scans, scientists discovered that patients with MDD have more inflammation in the PFC, ACC, insula, dorsal putamen, thalamus, ventral striatum, and hippocampus

Question 20

Define the monoamine hypothesis

Answer 20

Monoamine hypothesis: patients with MDD have depleted levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine)

Question 21

What are monoamine oxidase inhibitors?

Answer 21

Monoamine oxidase inhibitors: antidepressants inhibiting monoamine oxidase, enzyme that breaks down monoamines

Question 22

What are tricyclic antidepressants?

Answer 22

Tricyclic antidepressants: drugs that inhibit the reuptake of serotonin and norepinephrine

Question 23

What are selective serotonin reuptake inhibitors?

Answer 23

Selective Serotonin Reuptake Inhibitors (SSRIs): inhibit the reuptake of serotonin

Question 24

What are atypical antidepressants?

Answer 24

Atypical antidepressants: inhibit the reuptake of dopamine and norepinephrine (can also inhibit reuptake of dopamine and norepinephrine)

Question 25

What is vortioxetine?

Answer 25

• Most recent: vortioxetine (inhibits reuptake of serotonin, norepinephrine and dopamine)

Question 26

Besides neurotransmitters, what other substance may play a role in MDD? What drugs can help with this?

Answer 26

MDD may also be due to glutaminergic neurotransmission (higher levels of glutamate)
• Monoamine antidepressants also reduce levels of glutamate, possibly also accounting for the antidepressant effects
• The antidepressant effects of drugs that reduce the neurotransmission of glutamate are being assessed. One of them is ketamine, a NMDA receptor antagonist.