Neurotransmitter abnormality

Selasa, 12 Januari 2010

Studies have repeatedly demonstrated that the metabolites of serotonin are altered amongst those who have attempted suicide (Asberg et al. 1976) or manifest externally-directed aggression (Coccaro 1998). Those who display impulsive aggression consistently show blunted neuro-endocrinal responses to agents that enhance serotonergic activities (Coccaro et al. 1996). It seems that impulsiveness, autoaggression, and outwardly-directed aggression are all associated with dysfunctions of the serotonergic system indicated by low 5-hydroxyindoleaceticacid levels in lumbar cerebro-spinal fluid (CSF) (Linnoila and Virkkunen 1992) and blunted neuroendocrine responses to fenfluramine (O’Keane et al. 1992; Herpertz et al. 1995; Cleare et al. 1996).

There is some degree of cortical localization of these abnormalities to areas involved in inhibiting limbic aggression in the orbital-frontal cortex, ventralmedial
cortex and cingulate cortex which show decreased activation in response to serotonergic probes (Siever et al. 1999; New et al. 2002). Reduced serotonergic modulation of these inhibitory areas may result in the disinhibition of aggression. It is consistent with this assumption that selective serotonin re-uptake inhibitors (SSRIs) appear effective in reducing impulsive aggression independent of depression when used in higher doses and/or for longer durations ( Markovitz et al. 1991; Coccaro et al. 1997). The study of 5HT synthesis capacity using PET in medication-free BPD subjects (Leyton et al. 2001) provided evidence of reduced 5HT synthesis capacity in cortico-striatal sites, including the medio-frontal gyrus, anterior cingulated gyrus, superior temporal gyrus, and corpus striatum. Notably, the indication of 5HT synthesis capacity correlated with impulsivity scores.

There is some evidence of enhanced dopaminergic activity in association with psychotic-like thinking in PD, particularly schizotypal PD. Increased dopamine concentrations have been found in the CSF of schizotypal patients (Siever et al. 1999) including BPD patients with co-morbid schizotypal presentations. Psychotic symptoms are induced by amphetamines (a dopamine agonist) in BPD patients (Schulz et al. 1988). These findings are consistent with clinical reports that amphetamines benefit BPD patients with psychotic symptoms. Noradrenergic abnormalities have been noted in BPD associated with risk taking and sensation seeking.