Serotonin and Depression

Question 1

What is the Monoamine deficiency Hypothesis?

Answer 1

The “monoamine deficiency hypothesis” of depression postulates that depressive symptoms arise from insufficient levels of monoamine neurotransmitters serotonin (or 5-hydroxytryptamine , 5-HT), norepinephrine, and/or dopamine.

Question 2

What is the indirect evidence for Serotonin hypofunction in depression?

Answer 2

5-HT depletion by the antihypertensive drug reserpine could cause depression.

Clinically useful antidepressants all increase synaptic monoamine (some selectively 5-HT) concentrations.

Post-mortem evidence of reduced 5-HT levels in brainstem of individuals who committed suicide. (Mann 2013).

Lower levels of 5-HT1A-receptors (Bhagwagar 2004, Sargent 2000) and 5-HT4-receptors (Madsen 2014).

Monoamine oxidase A  in MDD

Question 3

What is the indirect evidence for 5-HT Hypofunction in depression?

Answer 3

Blockade of serotonin synthesis by the tryptophan hydroxylase inhibitor p-chlorophenylalanine prevents the antidepressant effects of both MAOIs and TCAs (Shopsin 1975 & 1976)

Tryptophan depletion ( brain serotonin decreases) triggers relapse in MDD successfully treated with SSRIs (Delgado 1999) or cognitive behavioural therapy (CBT) (Smith 1997).

Monoamine depletion correlates with low mood both in at risk and MDD in remission (Ruhe 2007) .

Depression-related traits; “pessimism” (Meyer 2003)and “dysfunctional attitudes” (Bhagwagar 2006) in MDD, and traits “negativism” (Soloff 2010) and “neuroticism” (Frokjaer 2008 & 2010) in healthy, related to 5-HT2A-receptor increased(? Serotonin decreased).

Question 4

What is the best way to measure receptors and transmitters in the living human brain?

Answer 4

PET imaging

Question 5

Why is PET used compared to fMRI?

Answer 5

Selective, but invasive, radioactive, and expensive, and with less optimal temporal and spatial resolution

Question 6

How does pet imaging take place?

Answer 6

Injection of a radioactive pharmaceutical (= tracer = ligand)

The tracer binds to a specific target (e.g. a receptor)
Decays, accumulating on that target when it decays it send out positrons, you can then back translate that to see where the tracer has bound.

Question 7

How could we quantify dopamine receptors in the brain?

Answer 7

2 X PET with a pharmacological challenge.
Following a PET scan give an amphetamine challenge which will release dopamine, which would show competition with the radiotracer, you can subtract the two scans with the difference representing the measure of how much dopamine was released from the challenge given. Could try to develop similar method in serotonin system

Question 8

What is a possible reason for lack of success in the 2 X PET with a pharmacological challenge in serotonin?

Answer 8

THESE ANTAGONIST PET TRACERS HAVE NOT BEEN SUFFICIENTLY SENSITIVE TO PHARMACOLOGICAL
CHALLENGES !!
Agonists used very recently have been much more successful

Question 9

Define Personality disorders

Answer 9

Maladaptivepatterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual’s culture. These patterns develop early, are inflexible, and are associated with significant distress or disability.

Question 10

Describe Antisocial

Answer 10

pervasive pattern of disregard for and violation of the rights of others, lack of empathy, bloated self-image, manipulative and impulsive behaviour.

Question 11

Describe Borderline

Answer 11

pervasive pattern of abrupt mood swings, instability in relationships, self-image, identity, behavior andaffect, often leading to self-harm and impulsivi

Question 12

Describe Narcissistic

Answer 12

pervasive pattern ofgrandiosity, need for admiration, and a perceived or real lack of empathy

Question 13

What are the differentials between Bipolar Affective disorder & Borderline personality disorder?

Answer 13

BPAD - runs in family, grandiosity, Mood states typically less affected by environment

BPD - Poor self image, fear of abandonment, Feelings of emptiness.

Same in both - Rapid mood swings, unstable interpersonal relationships, Impulsive sexual behaviour, suicidality

Question 14

What are the differentials between BPAD & Schizophrenia?

Answer 14

BPAD - Episodic dellusions/hallucinations

Schizophrenia - Chronic Hallucinations/ delusions

Same in both - depression, negative symptoms, apathy, low energy, Hallucinations

Question 15

What are the differentials for BPAD & Attention deficit disorder?

Answer 15

BPAD - family history, recurrent depressive episodes, amphetamines worsen mania.

ADD -

Same for both - Impaired concentration, impaired executive function, abnormal working & short term memory

Question 16

What are other possible organic causes of depression?

Answer 16

Endocrine: (Hyper- and) hypothyroidism, hyper- and hypoparathyroidism, hyper- and hypoadreno-corticism, hypoglycaemia, Cushing’s syndrome, Addison’s disease.
Other systemic conditions incl. infections; Viral infections, systemic lupus erythematosus, HIV infection, pancreatic (and other) cancer. [Cytokines manifested in systemic diseases are considered to be a cause of depression].
Deficiencies incl. of; vit B12 or folic acid.
Neurological conditions, incl. Multiple Sclerosis, Alzheimer’s, Parkinson’s
Medications; incl Beta-blockers, steroids, anti-Parkinson’s, anti-cholinergics (e.g. for irritable bowel syndrome (IBS) with such as dicyclomine), some antibiotics (incl. ciprofloxacin), statins, oestrogen, opiate pain killers, acne medications.

Question 17

What are other causes/differentials for depression?

Answer 17

Vascular Depressionor early sub-cortical dementia is common in late life depression. Vascular depression is associated withWhite Matter Hyperintensities. These can impact on cognitive function making the individual more vulnerable to stressors. It is important to treat vascular risk factors such as Diabetes, Hypertension and address smoking and alcohol use.
Poststroke depression sometimes becomes persistent. Retardation in thinking and behavior is prominent. It has been reported that lesions in the left frontal lobe or basal ganglia are apt to cause depression, with the tendency that the more frontal the lesion, the severer the symptoms