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

Department of Psychiatry, Columbia University, College of Physicians & Surgeons, New York, NY, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 07/2005; 30(6):1163-72. DOI: 10.1038/sj.npp.1300689
Source: PubMed


Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.

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Available from: Kevin M Malone, Jun 19, 2014
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    • "Also, the site of the present IMPC deactivation is next to the site of deactivation imposed by fenfluramine in BA 32 in depressed subjects, in whom Kegeles et al. (2003) described a correlation between greater metabolic suppression and acute mood improvement during the challenge. In a study of depressed patients with and without borderline personality disorder, fenfluramine affected the metabolism in BA 11, 21, and 40 in a manner that depended on the presence of the personality disorder (Oquendo et al., 2005). Thus, in the IMPC, monoaminergic reactivity correlates with personality disorder and depression. "
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    • "In the PFC, volume loss and lower resting metabolism has been found in the ACC (de la Fuente et al., 1997; Hazlett et al., 2005; Tebartz van Elst et al., 2003) and OFC (Lange et al., 2005; Soloff et al., 2003; Tebartz van Elst et al., 2003) and decreased N-acetylaspartate, a measure of neuronal integrity, in dorsolateral PFC (Tebartz van Elst et al., 2001). Measures of local serotonergic function also show deficits in the ACC (Frankle et al., 2005; Leyton et al., 2001; New et al., 2002, 2004; Oquendo et al., 2005; Siever et al., 1999) and OFC (Soloff, Meltzer, Greer, Constantine, & Kelly, 2000) of BPD patients. Volume loss and lower resting metabolism has also been found in both hippocampus and amygdala, which are often measured as one contiguous complex (Brambilla et al., 2004; Driessen et al., 2000; Juengling et al., 2003; Rusch et al., 2003; Schmahl, Vermetten, Elizinga , & Bremner, 2003; Tebartz van Elst et al., 2003). "
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