lecture 33 Flashcards
What are mental disorders?
- mental disorders have complex aetilogies that involve interactions among multiple genetic and non-genetic risk factors
- gender is related to risk in many cases:
- males have higher rates of attention deficit hyperactivity disorder, autism, and substance use disroders
- females have higher rates of major depressive disorder, most anxiety disorders, and eating disorders
What are the most significant mental disorders?
- schizophrenia
- bipolar affective disorder
- major depressive disorder
- panic disorder
What are further categories of bipolar affective and major depressive disorder?
- bipolar disorder
- cyclothymia (milder form)
- major (monopolar) depression
- dysthymia (milder form)
What is the definition of a major depressive episode?
A. Five (or more) of the following symptoms have been present during hte same 2-week period and represent a change from previous functioning; at least one of the symptoms is either 1) depressed mood or 2) loss of interest or pleasure
- depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g. feels sad or empty) or observation made by others (e.g. appears tearful)
note: in children and adolescents, can be irritable mood - markedly diminished interest or pleasure in all, or almost all, activities
- significant weight loss when not dieting or weight gain (>5% of body weight in a month), or decrease or increase in appetite nearly every day
- insomnia or hypersomnia nearly every day
- psychomotor agitation or retardation nearly every day
- fatigue or loss of energy nearly every day
- feelings of worthlessness or excessive or inappropriate/delusional guilt
- diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
- recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation
What is a major depressive episode?
- in major depressive disorder affective or mood symptoms include depressed mood and feelings of worthlessness or guilt, cognitive and somatic symptoms but also behavioural symptoms including social withdrawal and agitation
What is manic depression?
- manic episodes greatly elevated mood, creativity, profusion of thought and pressured speech
- may manifest as grandiosity and confidence or anxiety and aggression
- feeling of increased or limitless energy, including reduced need for sleep
- typically highly distractible, irritable, and exhibiting poor judgement
- extremem mania may include disordered (psychotic) thought
What is happening in the brain of people who are depressed?
- abnormally high blood flow abates with resolution of depression, regardless of the treatment (or lack of) associated with remission
- too high when depressed and too low when it goes away
- orbital and medial prefrontal cortex
manic depression
- can be found in people who are highly creative
- e.g. Robert Schumann’s musical compositions and manic depressive episodes
- most prolific during periods of hypomania
Who is John Cade?
- a melbourne doctor (and UniMelb graduate) was conducting research in the 1940s on the effects of uric acid when accidentally discovered the mood stabilising effects of lithium on his guinea pigs
- lithium is an extremely effective drug that is still used to treat manic depression / depression
How has monopolar depression been treated?
- electroconvulsive therapy
- still used today
- still the most effective for SOME people’s depression
- psychotherapy
- antidepressant drugs
- tricyclics (not so common)
- SSRIs NERIs (most commonly prescribed)
- monoamine oxidase inhibitors
Where do drugs interact with neurons?
- drugs that affect the brain and behaviour (other than those affecting its growth or those having a degenerative or neurodegenerative effect) must directly or indirectly affect the excitability of neurons
- interactions with neurotransmission could occur at numerous places in the biochemical pathways related to neurotransmitter synthesis, storage, release, breakdown, re-uptake and postsynaptic receptor interaction
What is the “monoamine hypothesis” of mood disorder?
- point of action seems to be at noradrenaline and serotonin synapses
- tricyclics and reuptake inhibitors act where these chemicals are taken back up into axon terminal
- inhibition of reuptake prolongs neurotransmission - it’s like you’ve released more
- fluoxetine (aka prozac) –> inhibitive action on reuptake allowing more serotonin to persist in synaptic cleft
- monoamine oxidase inhibitors prevent breakdown of serotonin/noradrenaline, second mechanism to maintain concentrations of neurotransmitter in synaptic cleft
- less frequently used
all of these seem to have the function of maintaining concentration of neurotransmitter in synapse
What are antidepressants?
MAO inhibitors
- MAO is the enzyme responsible for the destruction of all monoamines (noradrenaline, dopamine, and serotonin)
MA reuptake inhibitors
- monoamine reuptake (the other mechanism for limiting the action of monoamines at synapses) further supports the idea of impaired monoamine transmission underlying depression
Lithium
- lithium salts are the third category of drugs used to treat depression, particularly manic depression
- their mode of action is not understood but may modulate phosphoinositol second messengers
What are the diffuse modulatory systems of the CNS?
- the consideration of the site of drug action often implcates the diffuse modulatory systems of the central nervous system
- these are:
- a nucleus or cluster of nuclei with relatively few neurons (thousands rather than millions)
- most of the nuclei are in the “central core” of the brain: the brainstem and basal forebrain
- each neuron can influence many (maybe hundreds of thousands) of neurons elsewhere in the brain – this is called a highly divergent projection
- the synapses made by these cells are typically “en passant”
What is the serotonergic system?
- cell bodies all in reticular core of brainstem
- raphe nuclei (midline)
- some project down to spinal cord
- some to cerebellum
- huge projection up to just about all areas of the cerebrum: huge target, 100 billion cells innervated by several 100 thousand cells
What is the noradrenaline system?
- main, small nucleus (locus coeruleus) (brainstem)
- few 100 thousand neurons projecting pretty much everywhere