biology of anxiety notes

More notes from NEI. These are simply my notes from some of Stahl's Brainstorms bits on anxiety circuits.

• The same malfunctioning circuits are likely involved in anxiety and worry related symptoms in an array of anxiety disorders. So perhaps rather than lumping as psychiatrists have been doing since the time of DSMs -- it is time to deconstruct anxiety disorders into individual symptoms.
• When fear is provoked, the amygdala becomes active in both those with anxiety disorders and those without.
• It has been hypothesized that anxiety disorders involve inappropriate timing/amount of firing from the otherwise normal circuit. For example, the circuit could be chronically overactive in generalized anxiety disorder or have its flood gates open during panic attacks.
• Similarly, malfunctioning in the cortico-striato-thalamic loops (loops right back to cortex) can be helpful leading to meticulous planning or might go over the top and lead to excessive worry or even obsessive compulsive disorder.
• Benzodiazepines impact GABAergic neurotransmission to increase neuronal inhibition.
• Some inputs to the amygdala come from sensory thalamus and are rapid and almost reflective, causing fast fear reactions without thought.
• Other amygdala inputs travel to prefrontal cortex, sensory cortex or hippocampus for pondering first before determining level of anxiety.
• Inputs to amygdala often use Glutamate to "ring the alarm."
• This glutamate release can be slowed by GABA from cortical interneurons and hippocampus as well as Serotonin from the Raphe nucleus.
• Also GABA interneurons and serotonergic nerve terminals in the amygdala itself act as brakes on amygdala fear output.
• Perhaps cognitive-behavioral therapy enhances cortical inhibitory tone by reprogramming neurons as they are desensitized and deconditioned to triggers.
• The fear response includes motor response (Periaqueductal Gray Area leading to fight/flight or freezing), endocrine response (cortisol response via hypothalamus), respiratory (hyperventialation from brainstem respiratory centers and cardiovascular (tachycardia and increased blood pressure via norepinephrine from locus ceruleus.
• How neurons work: sodium enters the neuron via voltage sensitive sodium channel. Sodium's entry changes the voltage across the membrane. When the voltage change is sensed by voltage sensitive calcium channels, calcium then can enter too. Calcium's entrance triggers neurotransmitter release from synaptic vesicles. If this process is excessive it can lead to seizure, anxiety, or pain.
• The alpha 2 delta ligands act at the level of the voltage sensitive calcium channel to slow this process. Alpha 2 delta ligands (like pregabalin and gabapentin) bind selectively and tightly to the alpha 2 delta subunit of the voltage sensitive calcium channel. When the alpha 2 delta ligands bind to the alpha 2 delta subunit, calcium flow slows which then slows neurotransmitter release. This may have anxiolytic impacts as well as the better known anticonvulsant and neuropathic pain-allieviating ones.