Biochemistry Of Depression Flashcards
–GABA – major inhibitory neurotransmitter.
•Suppress seizure, anxiety and mania.
GABA
major excitatory neurotransmitter and precursor to gamma amino-butyric acid. Important in memory and learning.
Glutamate
inhibitory neurotransmitter
•it participates in the processing of motor and sensory information that permits movement, vision, and audition
Glycine
- is a neurotransmitter that helps control the brain’s reward and pleasure centers. Dopamine also helps regulate movement and emotional responses, and it enables us not only to see rewards, but to take action to move toward them.
- Excitatory and inhibitory neurotransmitter
Dopamine
- mental arousal, elevated mood, and pleasure
- excitatory neurotransmitter
- fight or flight response.
Norepi
Epi
–Inhibitory neurotransmitter
–Mood, activity, aggression irritability, and cognitive.
Serotonin
produced on ribosomes and stored in the endocrine cell in membrane bound secretory granules. They typically do not cross cell membrane readily and act through membrane bound receptors.
Protein or peptides
synthesized in the cytosol and secretory granules. They typically do not cross cell membrane readily and act through membrane bound receptors.
Cathecolamines
are not stored in the tissues and generally cross the cell membranes. They act through the intracellular receptors
Steroids
feel-good’ chemical. It has a profound effect on mood and anxiety.
Serotonin
modulate pain, reduce stress and promote sensation of floaty, and oceanic calm.
Enkepalins
-leads one to feel positive emotions towards the opposite sex like love or infatuation.
Oxytocin
States that depression is a consequence of diminished neurotransmission involving monoamines(NA, DA, 5-HT) due to a decrease in their concentrations
Biogenic amine hypothesis
antihypertensive drug, causes depletion of presynaptic stores of NE, 5-HT and DA, induced a syndrome resembling depression
Reserpine
used for treatment of tuberculosis; increased NE and 5-HT concentrations by inhibiting MAO, causes euphoria and hyperactive behavior
Iproniazid
•is the enzyme ultimately responsible for the catabolism of the neurotransmitter into its respective metabolites
Monoamine oxidase
- Other enzyme involved in the catabolism of monoamine transmitters
- Provides alternate pathway forming different metabolites than if compound went straight through MAO
Catechol-O-methyl trasferase (COMT)
- Chronic administration of TCAs or MAOIs is thought to alter the responsiveness and/or the number of postsynaptic receptor sites.
- Antidepressant drugs achieve their clinical effect by reducing receptor supersensitivity. This theory is an important step toward understanding the long delay between administration of TCAs and MAOIs and clinical response.
Receptor sensitivity hothesis
-Supersensitivity: compensatory response
of the postsynaptic neuron when it receives too little stimulation.
-The neuron tries to make up for a lack of stimulation by increasing receptor responsiveness.
-Over time, the postsynaptic neuron may also compensate for lack of stimulation by synthesizing additional receptor sites.
Up regulation
-By increasing the amount of
neurotransmitter in the cleft, you can normalize responsiveness.
-Increased neurotransmitter increases stimulation of receptor sites, which prompts the postsynaptic neuron to compensate by decreasing receptor sensitivity
Desensitization
-The postsynaptic neuron is also thought to compensate for increasing stimulation by decreasing the number of receptor sites.
Down regulation
- Emphasizes the role of serotonin in depression and downplays noradrenaline.
- Development of Serotonin-Selective Reuptake Inhibitors (SSRIs)
The serotonin only hypothesis
•Emphasizes importance of balance between
Norepinephrine and Serotonin in regulating
mood.
The permissive hypothesis
- Pathological mood states are explained or contributed to by altered endocrine function.
- Altered mood states were associated with thyroid or Cushing’s disease
- More often signs and symptoms of Hypothyroidism (fatigue, weight gain) and Hyperthyroidism (sleep disturbances and weight loss) are associated with depression.
The neuro endocrine hypothesis
is a 41-amino-acid neuropeptide involved in mediating neuroendocrine, autonomic and behavioural responses to stress, and clinical studies provide evidence for the role of CRF in the development of depression and anxiety disorders
Corticotropin releasing factor
- Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
- In the brain, Gr has been proposed to modulate emotional behaviour, cognitive functions and addictive states
Glucocorticoid receptor GENE
- This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons.
- A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in depression-susceptibility in people experiencing emotional trauma.
Serotonin transporter GENE
- The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase.
- In the brain, catechol-O-methyltransferase helps break down neurotransmitters.
- 22q11.2 deletion syndrome - associated with the COMT gene
CATECHOL-O-METHYLTRANSFERASE GENE
Treatment
increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin.
SSRI
Treatment
Mechanism of action: Increase monoamines by blocking the process of reuptake into the presynaptic neuron.
These are less used because of the need to titrate the dose to a therapeutic level and because of their considerable toxicity in overdose. Relatively Cheap and used for other psychiatric disorders
TCA
Treatment
Inhibits the activity of monoamine oxidase thereby blocking the metabolism of biogenic amines (norepinephrine, serotonin, dopamine) thereby increasing the synaptic concentration of these neurotransmitters.
Maois
MAOIs should not be used concomitantly with
SSRI and TCA
is an herbal remedy. It is considered a first-line antidepressant in many European countries.
Hypericum perforatum
Therapy
first-line treatment for depression. It is directed and time limited, usually involving between 10 and 20 treatment
Cognitive behavioral therapy
It is based on two principles, first is that many illnesses are made worse by a dysfunctional family and second, close family relationships are often the most important supports a person has, and therefore are extremely important in any long term treatments.
Family therapy
This focuses on problem areas of grief, interpersonal roles, disputes, role transitions, and interpersonal difficulties
Interpersonal psychotherapy
