Biological basis of anxiety and depression Flashcards
When is anxiety considered a disorder?
When it is excessive enough to lead to atypical and maladaptive irrational behaviours plus personal distress as a result
What is the underlying problem in anxiety disorders?
In animals anxiety is helpful because survival is regularly threatened in the wild
For humans, however, in addition to actual challenges/threats triggering the stress response, anticipations of homeostatic challenge is sufficient i.e. the stimulus doesn’t even have to be real to produce the widespread effects
How can the elevated plus maze be used to model anxiety?
Plus shaped maze with two pairs of arms, two of which are open and two which have opaque walls
Rodents spend less time in open arms, venturing out only once or twice out of curiosity
Spending less time in the open is the manifestation of an anxiogenic effect, while spending more time there demonstrates an anxiolytic effect
When GABA antagonists administered, see anxiogenic response and time spent in open arms decreases further, while benzodiazepines (which enhance GABA) produce anxiolytic effect
This shows us GABA involved in anxiety
How can “open field” be used to model anxiety?
A large brightly lit square - rodents prefer staying near the edge for the majority of the time. Anxiogenic effects demonstrated by even less venturing into middle
Diazepam produces anxiolytic effects i.e. spend more time in middle
Further support for GABA
What neurotransmitter imbalances are thought to be implicated in anxiety (physiological state)?
Reduced GABA activity produces heightened anxiety, so drugs which enhance GABA function are anxiolytic
Serotonin also thought to be involved - lesions to 5HT system or inhibition of synthesis produces same effect as benzodiazepines i.e. reduced anxiety
What is interesting about drugs in the context of anxiety?
Benzodiazepines have been shown to be effective, but drugs which act DIRECTLY on GABA receptors don’t seem to have same effect - suggest that benzodiazepines probably don’t directly affect GABA systems but potentially have more of a modulatory effect on the brain, maybe indirectly on the receptors e.g. by upregulating them
What NT imbalance is thought to be involved in anxiety disorders?
Especially in panic attacks, noradrenaline function is increased
Antidepressants affect NA can prove effective - “switching off” NA by activating autoreceptors with clonidine is effective in some cases
How is serotonin implicated in anxiety disorders?
Effectiveness of tricyclic antidepressants and SSRIs for panic attacks and OCD
What are drugs for anxiety disorder like?
Generally fairly slow onset of therapeutic action, thought to act through long-term adaptive effect e.g. downregulating receptors
Pharmacological effect in brain only takes a couple of hours but therapeutic effects not seen until later
To what extent does treating anxiety SYMPTOMS help in anxiety disorders?
Anxiety disorders are self-perpetuating problems - stimulus triggers initial anxiety symptoms, but then anxiety can develop regarding these symptoms which leads to more anxiety and associated symptoms such as avoidance etc
Treating anxiety can help break this cycle, and preventing extreme anxiety symptoms can stoop anxiety from becoming maladaptive
For example, B-blockers work on CVS not anxiety directly, but reduce cardiovascular symptoms of panic and in this way we could avoid full panic attacks
What are two main ways in which anxiety symptoms can be reduced?
Alcohol - oldest anxiolytic drug, essentially a sedative and not specific to anxiety; short term, with risks of dependence and rebound (acute i.e. hangovers, or chronic withdrawal)
Benzodiazepines - Diazepam (Valium), profound sedatives, muscle relaxants and anti-convulsants; anxiolytic dose is not sedative, therapeutic index high so difficult to overdose and reduced risk of abuse potential
What is the therapeutic index for a drug?
Dose range between min dose required for desired effect and dose at which effects start to get toxic - barbiturates, for example, have a low index so doses need to be very carefully controlled for fear of causing death!
What is the main treatment for anxiety disorders?
Antidepressants with serotonergic or noradrenergic action - SSRIs are particularly good for social phobias, panic, GAD and PTSD - require higher dose for anxiolytic effect than required for antidepressant action
What has been suggested regarding the involvement of serotonin in anxiety disorders?
We don’t know whether there are abnormalities in serotonergic function or whether the therapeutic effect of drugs like SSRIs utilise serotonin’s widespread modulatory action over many other NT systems, and work by counteracting dysregulation of other transmitter systems
What are the treatment options for GAD?
Benzodiazepines, tricyclics if comorbid depression
CBT, interpersonal therapy, stress management
