Noradrenergic and serotonergic function in posttraumatic stress disorder.
BACKGROUND
Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine.


METHODS
Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times.


RESULTS
Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks.


CONCLUSIONS
These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.
Southwick
S M
SM
Clinical Neurosciences Division, Veterans Affairs Medical Center, West Haven, Conn, USA.
Krystal
J H
JH
Bremner
J D
JD
Morgan
C A
CA
Nicolaou
A L
AL
Nagy
L M
LM
Johnson
D R
DR
Heninger
G R
GR
Charney
D S
DS
D000328:Adult; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016584:Panic Disorder / Q000139:chemically induced; D010879:Piperazines / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*; D015016:Yohimbine / Q000494:pharmacology
D010879:Piperazines; D015016:Yohimbine; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine; D009638:Norepinephrine