Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients.

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines and has been suggested to be a risk factor in vascular disorders, e.g., diabetic vascular complications. The primary aim of the present study was to investigate if serum SSAO activity is associated with clinical parameters in non-small cell lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a correlation between SSAO activity and the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).Thirty-three patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO were observed in all patients. Serum SSAO activity was not statistically associated with survival (p = 0.35). A highly significant statistical correlation was found between SSAO activity and VEGF (p < 0.0001). No significant correlation between SSAO and bFGF was observed. We conclude that SSAO was not associated with survival in patients with NSCLC. However, a strong correlation between serum SSAO activity and the angiogenic factor VEGF was found that might implicate new aspects of the mechanisms controlling angiogenesis.

Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia.

A functional polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been related to negative affect and amygdala activity. We studied amygdala activation during social anxiety provocation in relation to affective ratings and 5-HTT genetic variation. [H2(15)O]positron emission tomography was used to estimate amygdala blood flow during private and public speaking (baseline and anxiety conditions) in 17 patients with social phobia. Genotyping identified patients with long and short alleles in the promoter region of the 5-HTT. Individuals with one or two copies of the short allele exhibited significantly increased levels of anxiety-related traits, state anxiety, and enhanced right amygdala responding to anxiety provocation, compared with subjects homozygous for the long allele. Thus, 5-HTT genetic variation was associated with symptom severity and amygdala excitability in social phobia.

Transcription factor AP-2beta genotype associated with anxiety-related personality traits in women. A replication study.

Attempts to link transmitter system genes to certain aspects of personality have been performed. Several monoamine-related gene variants have been investigated. We previously reported an association between a transcription factor activating protein-2beta (AP-2beta) variant and anxiety-related personality traits as estimated by Karolinska Scales of Personality (KSP). To confirm this reported association, we have, in the present study, analysed an enlarged group of healthy volunteers (n = 370) with regard to AP-2beta genotype and personality traits. For estimation of personality traits, individuals completed 5 different personality questionnaires, i.e. Swedish Universities Scales of Personality (SSP), Health-Relevant 5- Factor Personality Inventory (HP5i), Temperament and Character Inventory, the Revised NEO Personality Inventory and KSP. In contrast to men, women having two long AP-2beta alleles displayed lower scores for muscular tension (KSP; F = 10.65, p = 0.0013), somatic trait anxiety (SSP; F = 7.18, p = 0.0081), trait irritability (SSP; F = 4.51, p = 0.032), mistrust (SSP; F = 4.01, p = 0.0468) and negative affectivity (HP5i; F = 10.20, p = 0.0017) than women with at least one short allele. The data presented in this study, together with our previously published data, suggest that AP-2beta intron 2 genotype is associated with low levels of anxiety-related personality traits in women. Hence, these data further suggest the human AP-2beta gene as a novel candidate gene in personality.

Overexpression of semicarbazide-sensitive amine oxidase in smooth muscle cells leads to an abnormal structure of the aortic elastic laminas.

Elevated semicarbazide-sensitive amine oxidase (SSAO) activity has been observed in several human conditions, eg, diabetes, and it has been speculated that SSAO contributes to the development of vasculopathies associated with this disease. To investigate in vivo consequences of elevated expression of SSAO in vascular tissues, we have developed a transgenic model for overexpression of human SSAO in mice. A smooth muscle-specific promoter, smooth muscle alpha-actin promoter 8 (SMP8) was used. Transgenic expression of human SSAO in tissues with a high content of smooth muscle cells was confirmed by Northern blot analysis. Enzymatic analysis of homogenates from transgenic tissues showed elevated levels of SSAO activity compared to non-transgenic littermates. Furthermore, when plasma SSAO activity was analyzed, much higher activity was detected compared to plasma from control mice, indicating that plasma SSAO may originate from smooth muscle cells. Histopathological evaluation of aorta and renal artery from transgenic mice revealed an abnormal structure of the elastin tissue. Instead of the regularly folded elastic laminae normally found in tunica media of sacrificed mice, the elastic laminae were straight and unfolded with irregularly arranged elastic fibers, forming tangled webs, between the intercalating elastic laminae. These alterations of the elastin structures suggest that overexpression of SSAO has led to a reduced elasticity of the arteries. Moreover, the mean femoral arterial pressure of the SMP8 SSAO transgenic mice was significantly lower in comparison to non-transgenic littermates. This suggests that the transgenic mice have a defect in their ability to regulate blood pressure.

The serotonin 2A -1438 G/A receptor polymorphism in a group of Swedish male criminals.

Studies have shown that genetic components to some extent underlie behavioral disorders such as impulsive aggression and violence, and that central serotonergic mechanisms are involved in the development of such behavior. In the present study, we analyzed a polymorphism in the gene encoding the serotonin 2A receptor (5-HT2A -1438 G/A) in a group of Swedish criminals (n=97) and in a group of healthy Swedish blood donors (n=202). The 5-HT2A -1438 GG genotype was lower in the criminal group than in the control group (P=0.034). In accordance with previous results, no associations were found between the 5-HT2A -1438 G/A polymorphism and personality as measured by Karolinska Scales of Personality. Neither were there any associations between the studied polymorphism and the type of crime committed.

Platelet monoamine oxidase activity in a nonhuman primate model of type 2 excessive alcohol consumption.

OBJECTIVE: Low platelet monoamine oxidase (MAO) activity is associated with "type 2 alcoholism." MAO activity is also affected by cigarette smoking. Since most alcoholics are smokers, it is difficult to evaluate the possible effect of platelet MAO activity on alcoholism independently of the effects of smoking. The authors investigated the relationship between platelet MAO activity and excessive alcohol consumption in rhesus macaques. METHOD: Platelet MAO activity and CSF metabolite concentrations were measured. The authors also investigated level of voluntary alcohol intake and social dominance rank. RESULTS: Subjects with low platelet MAO activity consumed alcohol to excess, had low CSF 5-hydroxyindoleacetic acid concentrations, and were less competent socially. CONCLUSIONS: These findings show that nonhuman primates that exhibit type 2-like alcohol features display low platelet MAO activity and support the notion that platelet MAO activity is a biologic marker for central serotonergic activity. The results also challenge the hypothesis that low platelet MAO activity in type 2 alcoholism is simply an artifact of smoking.

Low platelet monoamine oxidase activity in Swedish imprisoned criminal offenders.

Numerous studies report a connection between low platelet monoamine oxidase activity (trbc MAO) and personality traits such as impulsiveness and sensation seeking. Generally, criminal offenders constitute a group of individuals that are high in such temperamental characteristics. In this study, we investigated trbc MAO activity in imprisoned criminal offenders and in controls where the confounding factor of smoking was under control. Radiometric MAO assays were performed in 99 male criminal offenders and in 60 non-criminal volunteers. Offenders had significantly lower trbc MAO activity than controls, i.e., 8.8 +/- 3.0 nmol/10(10) platelets/mm and 11.3 +/- 5.1, respectively (p<0.0001). When only smoking individuals were included in the analysis, the difference in trbc MAO was still statistically significant (p<0.05). Based on these data, we suggest that trbc MAO is related to mechanisms predisposing for development of specific personality characteristics that in turn increase vulnerability for criminal behaviour. The results also suggest that low trbc MAO activity in criminal offenders is not an artefact of cigarette smoking.

Risk factors for the neurohumoral alterations underlying personality disturbances.

Numerous studies have shown that MAO-B activity in platelets correlates with specific personality characteristics such as sensation seeking and impulsiveness. Low levels of platelet MAO as well as the personality traits associated with these low levels have been associated with type 2 alcoholism, recurrent criminality and antisocial violent behavior. Platelet MAO has a high degree of heritability and regulation of MAOB gene expression seems to explain most of the inter-individual differences in activity. The transcription factor family AP-2 is an important regulatory factor for neural gene expression and neural development, especially in midbrain structures, including the monoaminergic nuclei. In man, the gene encoding AP-2beta contains a polymorphic region in the second intron, consisting of a variable number of tandem repeats [CAAA](4-5). The long AP-2beta allele has previously been associated with specific personality traits as well as with binge-eating disorder characterized by an impulsive temperament. We have shown that males and females homozygous for the long AP-2beta allele display significantly lower platelet MAO activity compared to subjects with one or two short alleles. Thus, we find it likely that the personality disturbances previously linked to low platelet MAO activity could be associated with the presence of two long alleles of the AP-2beta gene. We suggest that the molecular mechanisms underlying the association between platelet MAO and vulnerability, e.g. substance abuse, may involve specific transcription factors that regulate the expression of midbrain monoamine structures as well as that of platelet MAO.

A regulatory monoamine oxidase a promoter polymorphism and personality traits.

Monoamine oxidase type A (MAOA) has been implicated to be part of mechanisms underlying human temperament and psychiatric disorders. We hypothesised that a functional polymorphism in the 5' untranslated region of the MAOA gene is associated with specific personality traits. In 371 healthy Caucasians, we estimated personality traits by the use of the Karolinska Scales of Personality (KSP), Scandinavian Universities Scales of Personality, Health-Relevant 5-Factor Personality inventory, Temperament and Character Inventory and the revised NEO Personality Inventory. In the same subjects, we analysed the genotype of a polymorphic region consisting of a variable number of a 30-bp repeat sequence located approximately 1.2 kb upstream of the MAOA gene. After correction for multiple testing, no statistically significant differences between MAOA genotype and personality were observed in men (n = 206) nor in women (n = 165). We conclude that the structure of this MAOA promoter region does not have a large impact on the expression of personality characteristics in the present Swedish population.

Personality traits and platelet monoamine oxidase activity in a Swedish male criminal population.

BACKGROUND: A Swedish male criminal population was grouped into personality disorder subgroups and investigated with regard to personality traits and platelet monoamine oxidase (MAO) activity. The main aim of the study was to examine the possibility of a risk factor combination by having low platelet MAO activity as well as belonging to a certain diagnostic DSM-IV axis I (drug abuse in the present series) and/or II subgroup. METHODS: Personality disorders were grouped into clusters according to the cluster system used in DSM-IV axis II. The prisoners were grouped into five subgroups and each subject completed the Karolinska Scales of Personality self-report questionnaire. The comparison group for the personality data comprised 51 non-criminal males from a longitudinal Swedish project. Platelet MAO activity was assessed for the criminals as well as for a control group including 60 non-criminal healthy male Caucasians. For testing the existence of syndromes, a configuration frequency analysis (CFA) was used. RESULTS: The results showed low scores on the socialisation and high scores on the sensation seeking-related traits impulsiveness and monotony avoidance, and the somatic anxiety-related muscular tension in the criminals with any DSM-IV mental disorder, however most markedly in cluster AB and cluster B subjects. In addition, cluster AB subjects had significantly lower platelet MAO activity than controls. Two significant 'types' were found among the criminals: one was characterised by low platelet MAO activity, cluster B personality diagnosis as well as drug abuse disorder diagnosis; and the other by a pattern of normal platelet MAO activity, no cluster B personality disorder and no drug abuse disorder diagnosis. CONCLUSION: The aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour.