d,l-fenfluramine Response in Impulsive Personality Disorder Assessed with [18F]fluorodeoxyglucose Positron Emission Tomography

Abstract

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered

Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge in Major Depressive Disorder with and without Borderline Personality Disorder

“…We did not find a difference in the orbitofrontal cortical area between depressed patients with BPD and MDD without BPD in contrast to findings from both lesion (Butter et al, 1970;Grafman et al, 1996;Heinrichs, 1989;Raleigh et al, 1979) and neuroimaging studies (De La Fuente et al, 1997;Goyer et al, 1994;New et al, 2002New et al, , 2004Siever et al, 1999) that suggest a role for the orbitofrontal cortex in impulsive aggression. Our sample of depressed women with BPD did not differ significantly in terms of clinical measures of aggression and impulsivity from the depressed women without BPD (see Table 1).…”

“…BPD patients are reported to have decreased response to FEN when compared to controls in left middle and superior temporal gyrus , left inferior parietal lobe (BA 40), and left caudate body (Soloff et al, 2000). Similarly, impulsive aggressive patients have decreased regional metabolism in the right superior parietal cortex following FEN challenge compared with healthy volunteers (Siever et al, 1999). These two results are in contrast to ours.…”

“…In agreement with our findings, most studies of BPD found low relative glucose metabolism and regional cerebral blood flow (rCBF) in the anterior cingulate gyrus at rest (De La Fuente et al, 1997;Goyer et al, 1994). PET studies report that FEN responses are blunted in the orbitofrontal cortex and anterior cingulate gyrus (Siever et al, 1999) in impulsive aggressive subjects compared to healthy controls, as are m-CPP responses (New et al, 2002), although not all studies agree (Soloff et al, 2000). Moreover, a treatment study assessing decreases in aggressive behavior after a 12 week course of fluoxetine found that changes in cingulate and orbitofrontal glucose metabolism were correlated to clinical improvement, further supporting the importance of serotonergic function in these regions and the regulation of impulsive aggression (New et al, 2004).…”

“…One study using FDG found no differences in temporal glucose metabolism in subjects with BPD compared to healthy volunteers (De La Fuente et al, 1994). Similarly, a study using a FEN challenge design (Siever et al, 1999) has shown that impulsive aggressive patients have no differences in temporal rCMRglu compared to normal controls after placebo administration. However, also using a FEN challenge approach, Soloff et al (2000) found that borderline patients showed greater rCMRglu in the left superior temporal gyrus after placebo compared to normal controls, as was the case in our study.…”

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

“…This is consistent with reported blunted metabolic and neuroendocrine responses to 5-HT 2C R agonist m-(chlorophenyl) piperazine (mCPP) and to fenfluramine (which effects 'net' serotonergic activity) in patients who have made suicide attempts and/or showed a pattern of impulsive/aggression, a trait that is highly correlated with suicide. [38][39][40] The mechanism by which this variation in serotonergic function influences suicidal behavior remains to be elucidated.…”