Prospective observational cohort (n=20) assessing neurobiological effects of intranasal ketamine in adolescents and adults with Bipolar Disorder — Fear of Harm phenotype; off-dose and 2–3 h post-dose neuroimaging/EEG comparisons.
Aim 1: Evaluate whether individuals with Bipolar Disorder — Fear of Harm phenotype show enhanced amygdala fMRI responses to fearful stimuli, increased resting temporal beta/gamma EEG activity, and blunted posterior insula cold responses when partially withdrawn from ketamine, with normalization after intranasal ketamine.
Aim 2: Test whether ketamine alters functional connectivity of the amygdala and insula with hypothalamus, thalamus, hippocampus and vmPFC in ways that correlate with pre–post clinical change.
Aim 3: Determine whether low-dose medicinal intranasal ketamine is associated with morphometric abnormalities seen in high-dose recreational users by scanning participants on long-term treatment.
Participants on a stable intranasal ketamine regimen; tested one or two days beyond their usual administration date and again 2–3 hours after dosing.
Customary prescribed intranasal dose; will not exceed 300 mg per dosing interval; participants delay dose by 2 days for off-dose assessment