Increased serotonin-2 and B-adrenergic receptor binding in frontal cortex of suicide victims
A statistically significant 28% increase in the mean (+/- SD) number of serotonin2 receptors (127.8 +/- 13.4 vs 99.6 +/- 11.1 fmol/mg of protein) and a 73% increase in beta-adrenergic receptor binding (14.5 +/- 1.5 vs 8.4 +/- 1.5 fmol/mg) was found in the frontal cortices of violent suicide victims compared with matched controls. No significant differences were found in the number of serotonin1 binding sites (109.5 +/- 13.4 vs 99.9 +/- 8.8 fmol/mg). We have previously reported a reduced density of presynaptic tritiated imipramine binding sites on serotonergic nerve terminals in the frontal cortices of suicide victims. These data support the hypothesis that suicide completed by violent methods is associated with reduced presynaptic serotonergic activity that has generated compensatory upregulation of the postsynaptic serotonin2 receptor sites. The increase observed in beta-adrenergic binding suggests that there may also be a concomitant reduction in presynaptic noradrenergic activity associated with suicide. If antidepressant pharmacotherapies specifically downregulate cortical beta-adrenergic and/or serotonin2 receptors in depressed subjects, as has been demonstrated in animal studies, and since these effects would be in the opposite direction of the receptor changes found in suicide victims, they may account for the therapeutic action of antidepressants on suicidal behavior and depressive disorders.
Available from: Aki Takahashi
- "Genetic approach—Platelet 5-HT 2A receptor binding is increased in patients with personality disorders and in a psychiatric population with greater lifetime aggression scores (Coccaro et al. 1997; McBride et al. 1994). Positive correlation between impulsive physical aggression and 5-HT 2A receptor expressions in orbitofrontal cortex has been reported using PET (Rosell et al. 2010) and a similar finding was reported in a postmortem study of suicide victims (Mann et al. 1986; Oquendo et al. 2006). However, another PET study reported opposite changes in 5-HT 2A receptor expression (Meyer et al. 2008). "
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ABSTRACT: Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT(1A) receptor) can often result in inconsistent results on aggression, due to "phasic" effects of pharmacological agents versus "trait"-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT(1A) and 5-HT(1B)) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene-environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT (e.g., MAOA) determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT(1B), 5-HT transporter, Pet1, MAOA) or indirectly [e.g., BDNF, neuronal nitric oxide (nNOS), αCaMKII, Neuropeptide Y]. The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior.
Available from: PubMed Central
- "An early study29 found increased β-adrenergic receptor binding in the frontal cortex of suicide victims. More recently, post-mortem and functional imaging studies in the prefrontal cortex of depressed suicide victims have shown altered density and sensitivity of α2A-adrenoceptors which modulate NE release.30–32 "
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ABSTRACT: Depression is one of the most common psychological diseases with significant potential morbidity and mortality. Although the underlying pathophysiology of depression has not been clearly defined, preclinical and clinical evidence suggest disturbances in serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmission in the central nervous system. Virtually all currently available antidepressants act on one or more of the following mechanisms: inhibition of reuptake of 5-HT or NE (and DA), antagonism of inhibitory presynaptic 5-HT or NE receptors, or inhibition of monoamine oxidase. All of these mechanisms result in an enhanced neurotransmission of 5-HT and/or NE. Evidence for the involvement of NE in depression is abundant, and recent studies on neuronal pathways and symptoms highlight the specific role of NE in this disorder. NE plays a determinant role in executive functioning regulating cognition, motivation, and intellect, which are fundamental in social relationships. Social dysfunction is possibly one of the most important factors affecting the quality of life in depressed patients.
Available from: ncbi.nlm.nih.gov
- "One of the earliest studies determining β-adrenergic receptors in the postmortem brain of suicide victims was reported by Meyerson et al. (1982) who found a trend toward an increase in β-adrenergic receptor binding in the cortical tissues obtained from suicide victims compared with control subjects. Mann et al. (1986) found a significant increase in β-adrenergic receptor binding in the frontal cortex of suicide victims compared with control subjects. This was supported by another group (Arango et al 1990), which observed a significant increase in the B max of β-adrenergic receptors in the outer layers of the grey matter in suicide victims compared with control subjects. "
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