Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression

Psychiatry Service-Mount Sinai School of Medicine and the Bronx VA Medical Center, 130 West Kingsbridge Road, PO Box 1168, Bronx, NY 10468, USA.
Psychopharmacology (Impact Factor: 3.88). 12/2004; 176(3-4):451-8. DOI: 10.1007/s00213-004-1913-8
Source: PubMed

ABSTRACT Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment.
The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET.
Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas.
Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified.
These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.

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    • "Cortical dysfunction has been implicated as a possible anatomical correlate of certain acts of aggressive behavior (e.g., Brower and Price, 2001; Davidson et al., 2000; Hoptman et al., 2002) and has been speculated to be a core feature underlying SZ illness (e.g., Barch et al., 2001; Lewis, 2012). Damage to the prefrontal cortical area, for example, has been hypothesized to be associated with heightened aggression, emotional outbursts, disorganization, and impulsive, risk-taking and aggressive behavior (Raine et al., 1998; New et al., 2004). Since cortical dysfunction is believed to underlie aggression as well as contribute to SZ illness, examination of cognition and aggression in SZ may be seen as a natural experiment aimed at examining a common denominator implicated in both. "
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    Schizophrenia Research: Cognition 09/2014; Volume 1:101-111. DOI:10.1016/j.scog.2014.06.001
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    • "Similarly to the time-frame of the antidepressant effects of these agents, their antiaggressive potential is generally observed only following prolonged treatment (2-3 weeks), likely as a result of neuroplastic adaptive mechanisms resulting in receptor desensitization or synaptic remodelling. Chronic SSRI administration has been shown to restore the metabolic activity of the PFC (New et al., 2004), suggesting that the reduction in aggression induced by these compounds may depend on the integrity of the prefrontal function, which is essential for impulse control as well as emotional appraisal of social contexts. In support of this possibility, Troisi and colleagues (Troisi et al., 1995) documented that, in a subset of patients affected by mental retardation and epilepsy, chronic treatment with fluoxetine led to enhanced, rather than reduced aggressiveness. "
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    Neuroscience 02/2013; 236:160-185. DOI:10.1016/j.neuroscience.2013.01.015 · 3.36 Impact Factor
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    • "Clinically, chronic treatment (i.e. >3 weeks) with selective serotonin reuptake inhibitors (SSRIs) has been shown to reduce aggressive outbursts and violent behavior in psychiatric patients (Barkan et al. 2006; Blader 2006; Bond 2005; Coccaro and Kavoussi 1997; New et al. 2004; Reist et al. 2003; Walsh and Dinan 2001). However, SSRIs have occasionally been reported to increase the incidence of aggressive and suicidal behavior, and the causes of these paradoxical effects remain unknown (Spigset 1999; Troisi et al. 1995). "
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