Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding.

Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 04/1997; 16(3):211-6.
Source: PubMed


The purpose of this study was to examine the relationship between platelet 5-HT2A receptor binding and aggressive behavior. 125I-LSD Bmax and Kd values were measured for 22 subjects meeting DMS-III-R criteria for one or more personality disorders and 12 healthy volunteer subjects. Aggression and impulsivity were assessed using the Buss-Durkee Hostility Inventory (BDHI) Assault scale, Life History of Aggression (LHA) scale, and the Barratt-11 Impulsiveness scale (BIS-11). Bmax and Kd values did not differ between personality disordered subjects and healthy volunteers. However, both Bmax and Kd values correlated positively with BDHI Assault scores in personality-disordered subjects but not in healthy volunteer subjects. These results suggest that assaultiveness in personality-disordered subjects may covary with increasing numbers, but decreasing affinity, of platelet 5-HT2A receptor sites labeled by 125I-LSD.

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    • "Aggression is often categorised as either 'premeditated' (predatory , instrumental) or 'impulsive' (reactive, affective) (Meloy, 2006; Siever, 2008). Insufficient serotonergic facilitation of 'top-down' control including the 5-hydroxytryptamine 2A receptors (Coccaro et al., 1997; Krakowski et al., 2006) and 5-HT 2C receptors (Winstanley et al., 2004), catecholaminergic stimulation, the gamma aminobutyric acid (GABA)-glutaminergic system (Lieving et al., 2008) and pathology in neuropeptide systems (Coccaro et al., 1998; Kirsch et al., 2005; Coccaro et al., 2007a,b; Hermans et al., 2008; Ditzen et al., 2009) may contribute to this. Heredity contributes substantially to impulsive aggression (Beitchman et al., 2006; Marks et al., 2007; Mann et al., 2009). "
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    ABSTRACT: Cross-sectional studies have reported an association between lipids and serotonin levels and aggression, but a literature search revealed a paucity of prospective studies. Subjects of the present naturalistic study were 254 of all (489) involuntary and voluntary acutely admitted patients to a psychiatric hospital during 1year. Serum lipids and platelet serotonin at admission were prospectively compared with recorded intra-institutional and 1-year post-discharge violence and self-harm. Total cholesterol had a significant negative relationship to inpatient suicidal behaviour and inpatient violent behaviour and to 3-month post-discharge violent behaviour. Triglycerides were a significant marker of inpatient self-mutilation and of self-mutilation in combination with suicidal behaviour at 3 and 12 months of follow-up. High-density lipoprotein (HDL) had a significant negative relationship to violence at 12-months, and to repeated violence in seven patients with two or more admissions. The post-discharge relationships between total cholesterol and violence and between triglycerides and self-harm remained significant even when controlling for other possible explanatory variables in a multivariate model. Results did not change after controlling for current medication at admission. There was no association between platelet serotonin and violence or self-harm. Future research may examine if lipid measurements add incremental validity to established clinical risk assessment procedures of violent and self-harm behaviour.
    Psychiatry Research 04/2011; 186(2-3):293-9. DOI:10.1016/j.psychres.2010.07.029 · 2.47 Impact Factor
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    • "They often result in undesirable consequences" [7]. Impulsivity has been linked strongly to outbreaks of aggression in adults (here considered as overt impulsive behavioral aggression) that are associated with increased 5-HT2a platelet receptor binding (Bmax and Kd), decreased 5-HT1a postmortem binding and low serotonin (5-HT) activity [8-10]. While some studies have failed to find the same relationship of low 5-HT activity with aggression in children [11-13] many others do report an inverse relationship [14-16] sensitive to pharmacotherapy [17]. "
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    ABSTRACT: Background Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC). Methods Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach. Results In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described. Discussion A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.
    Behavioral and Brain Functions 11/2008; 4(1). DOI:10.1186/1744-9081-4-48 · 1.97 Impact Factor
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    • "A large quantity of studies was published. In particular, platelet serotonin 2A receptor sites have been found associated with impulsivity and aggression in a Positron Emission Tomography (PET) study (Coccaro et al., 1997). Moreover, rs6311 was found to be associated with impulsive traits in alcohol dependents, measured with the Baratt Impulsiveness Scale (BIS) (Preuss et al., 2001). "
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    ABSTRACT: Temperamental traits, the most basic part of personality, have been largely correlated with neurotransmitter systems and are under genetic control. Among serotonin candidates, the 2A receptor (5-HT(2A)) received considerable attention. We analyzed four SNPs (rs643627, rs594242, rs6311 and rs6313) in the 5-HT(2A) gene and their association with personality traits, as measured with the Temperament and Character Inventory (TCI). The sample was composed of three sub-groups: two German sub-samples, consisting of a healthy group of 289 subjects (42.6% males, mean age: 45.2+/-14.9) and a psychiatric patient group of 111 suicide attempters (38.7% males, mean age: 39.2+/-13.6), and an Italian sub-sample, composed of 60 mood disorder patients (35.0% males, mean age: 44.0+/-14.8). Controlling for sex, age and educational level, the SNPs were not strongly associated with personality dimensions. Only the rs594242 showed an association with Self-Directedness (p=0.003) in the German sample, while rs6313 was marginally associated with Novelty Seeking (p=0.01) in the Italian sample. We conclude that 5-HT(2A) SNPs may marginally modulate personality traits but further studies are required.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2007; 31(6):1275-81. DOI:10.1016/j.pnpbp.2007.05.008 · 3.69 Impact Factor
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