سوخت و ساز بدن زیرلایه انرژی در میان مجرمان الکلی خشن با داشتن اختلال شخصیت ضد اجتماعی

Abstract A large proportion of violent offences in Western countries are attributable to antisocial personality disorder (APD). Several studies have shown abnormal lipid, carbohydrate and low cerebrospinal fluid (CSF) monoamine metabolite levels in habitually violent alcoholic offenders with APD, but it is not clear how these biochemical abnormalities are related to each other in this disorder. We aimed to study energy substrate metabolism among habitually violent offenders with APD. Insulin sensitivity (euglycemic insulin clamp), basal energy expenditure (indirect calorimetry), and CSF 5-hydroxyindoleacetic acid (5-HIAA) measurements were performed on 96 habitually violent antisocial male alcoholic offenders and on 40 normal male controls. Habitually violent, incarcerated offenders with APD had significantly lower non-oxidative glucose metabolism, basal glucagon, and free fatty acids when compared with normal controls, but glucose oxidation and CSF 5-HIAA did not differ markedly between these groups. The effect sizes for lower non-oxidative glucose metabolism among incarcerated and non-incarcerated APD subjects were 0.73 and 0.51, respectively, when compared with controls, indicating that this finding was not explained by incarceration. Habitually violent offenders with APD have markedly lower glucagon and non-oxidative glucose metabolism when compared with healthy controls, and these findings were more strongly associated with habitual violent offending than low CSF 5-HIAA levels, a well-established marker for impulsive violent behavior. Follow-up studies are needed to confirm if abnormal glucose and lipid metabolism can be used to predict violent offending over the course of the APD offender's life span.

Introduction A large proportion of violent offences in industrialized countries are attributable to antisocial personality disorder (APD) associated with early onset alcoholism (Cloninger, 1987). In Finland, for example, offenders with APD are responsible for up to 80% of the most severe habitual, impulsive violence (Tiihonen and Hakola, 1994 and Eronen et al., 1996). In countries where more premeditated violence occurs, such as violence associated with organized crime, such figures can differ, but it is obvious that APD is the most important psychiatric diagnosis associated with severe violent crimes. A recent study showed that among 23,000 prisoners in Western countries about 47% had APD, although not all of them were habitually violent offenders (Fazel and Danesh, 2002). As a result, societies suffer from enormous financial losses due to conduct disorder and APD because of institutional and other costs (Brand and Price, 2000 and Scott et al., 2001). Low brain serotonin turnover as indicated by low CSF 5-HIAA (Virkkunen et al., 1989 and Virkkunen et al., 1996), low blood glucose nadir in the glucose tolerance test (Virkkunen et al., 1989), and low CSF MHPG (methoxy-hydroxy-phenylglycol) (Virkkunen et al., 1996) have been used as predictors of violent crimes among impulsive, habitually violent alcoholic offenders, who generally have APD. In addition, these offenders usually have early-onset alcoholism, known as type 2 alcoholism (Cloninger, 1987, Cloninger et al., 1981 and Sigvardsson et al., 1996). Several studies suggest that habitually violent offenders often have low serum cholesterol levels (Virkkunen, 1979, Virkkunen, 1983, Freedman et al., 1995, New et al., 1999, Buydens-Branchey et al., 2000, Golomb et al., 2000 and Repo-Tiihonen et al., 2002), which suggests that they may also have alterations in their lipid metabolism. According to a recent large study of a community cohort (Golomb et al., 2000), low total cholesterol concentrations are associated with violence in the general population. Brain imaging studies strongly suggest that impulsive aggressive behavior is associated with decreased glucose uptake in prefrontal cortex (Bufkin and Luttrell, 2005). Given that previous studies have indicated abnormalities in carbohydrate and lipid metabolism, as well as in brain glucose uptake among habitually violent offenders with APD, there is a need to clarify the underlying mechanisms behind abnormal glucose metabolism with standardized methods. We used the euglycemic insulin clamp method to study energy substrate metabolism among habitual violent offenders with APD and healthy control subjects.

Results 3.1. Biochemical and metabolic variables The demographic, biological and biochemical characteristics of the participants at baseline are shown in Table 2. The groups were comparable for most measures. However, basal S-glucagon and S-FFA concentrations were substantially lower in the P-APD subjects than in controls. Smaller differences were observed between groups in S-HDL-cholesterol, S-triglycerides and S-GT. Table 2. Demographic and biological variables at baseline Subjects P-APD (n = 67) F-APD (n = 29) Controls (n = 40) P Age, y 33.2 (11.2) 39.0 (8.1) 33.7 (8.7) 0.01 (KW) Weight, kg 78.5 (12.0) 80.5 (14.2) 80.5 (11.3) 0.67 (F2, 133 = 0.40) Height, cm 177.5 (5.6) 177.0 (6.1) 179.7 (6.8) 0.12 (F2, 133 = 2.17) Body mass index (kg/m2) 24.7 (3.6) 25.7 (4.2) 24.9 (3.0) 0.49 (F2, 133 = 0.71) FFM, kg 63.6 (7.6) 65.2 (9.7) 64.9 (8.1) 0.57 (F2, 133 = 0.56) Fat % 18.6 (5.5) 18.6 (6.0) 19.2 (3.7) 0.41 (KW) Waist / hip ratio 0.92 (0.06) 0.95 (0.07) 0.92 (0.06) 0.06 (F2, 132 = 2.82) Biochemical variables S-glucose, mmol/l 4.0 (0.5) 4.2 (0.4) 3.9 (0.5) 0.04 (F2, 123 = 3.43) S-insulin, mU/l 11.7 (7.7) 12.6 (7.8) 9.1 (5.3) 0.01 (KW) S-C-peptide, ug/l 1.9 (0.7) 1.9 (0.8) 1.7 (1.0) 0.06 (KW) S-glucagon, ng/l 54.6 (25.1)a 63.1 (29.8) 74.5 (30.3) 0.002 (F2, 120 = 6.85) S-FFA, mmol/l 0.44 (0.26)a 0.67 (0.50) 0.62 (0.28) < 0.001 (KW) S-cholesterol, mmol/l 4.8 (1.1) 5.3 (1.6) 4.7 (0.8) 0.35 (KW) S-HDL-cholesterol, mmol/l 1.1 (0.2)a 1.3 (0.5) 1.3 (0.3) 0.01 (KW) S-LDL-cholesterol, mmol/l 3.1 (1.0) 2.9 (1.3) 2.8 (0.8) 0.31 (F2, 115 = 1.18) S-triglycerides, mmol/l 1.3 (0.7) 2.0 (1.5)a 1.2 (0.8) 0.001 (KW) S-GT, U/l 65.8 (116.0)a 64.3 (91.3)a 27.2 (24.4) 0.002 (KW) CSF-5HIAAb Pmol/l 67.2 (25.0) 60.0 (24.4) 69.3 (25.6) 0.41 (F2, 77 = 0.91) Data are given as mean (± S.D.). P-APD are habitually violent male antisocial personality disorder offenders in prison; F-APDs are habitually violent male antisocial personality disorder offenders already free from prison; and Controls are age matched healthy males. Group effects were analyzed by analysis of variance with Bonferroni multiple-comparison test. The Kruskall-Wallis (KW) one-way ANOVA on ranks was used for variables having asymetric distributions where a logarithm transformation could not be used (Kruskall–Wallis Multiple-Comparison z-Value Test). P value indicates the significance for any difference between groups. All subjects gave blood samples but, due technical reasons, the data from all subjects were not available for all variables. Results on S-Glucagon were obtained from 62 subjects in P-APD group, 25 subjects in F-APD group and 36 subjects in control group, and results on S-FFA from all except one P-APD subject. a Indicates P < 0.01 compared with control mean. b Results were obtained from 26 subjects in P-APD group, 21 subjects in F-APD group and 33 subjects in control group (due to refusals of lumbar puncture). Table options Table 3 shows the results of substrate oxidation during the euglycemic insulin clamp. Nonoxidative glucose metabolism during the third hour of the insulin clamp was significantly lower in P-APD subjects than in controls (effect size 0.73) (Table 3). When age and BMI were used as a covariate, the significance of the difference (F2, 131 = 8.38; P < 0.001) did not change. Moreover, when both groups of APD subjects (F- and P-APDs) were combined, the difference between APDs and controls remained significant (F1, 133 = 12.73; P < 0.001), indicating that this finding was typical for all APD offenders. Lipid oxidation appeared to be lower and respiratory quotient higher among incarcerated APD subjects, compared to crime-free subjects with APD. The CSF 5-HIAA levels were slightly lower among P-APD and F-APD subjects when compared with controls (effect size 0.08–0.37), but these differences were not statistically significant. Table 3. Metabolic variables Subjects P-APD (n = 67) F-APD (n = 29) Controls (n = 40) P Total glucose disposal 8.95 (3.02) 8.96 (3.12) 10.59 (3.40) 0.02 (F2, 133 = 3.82) Basal glucose oxidation 2.21 (0.92)a 1.67 (1.09) 1.80 (0.60) 0.006 (KW) Stimulated glucose oxidation 4.46 (0.79) 4.03 (1.92) 4.20 (1.05) 0.01 (KW) Non-oxidative glucose disposal 4.49 (2.71)b 5.14 (2.47) 6.49 (2.80) 0.001 (F2, 132 = 6.94) Basal lipid oxidation 0.83 (0.37) a 1.26 (0.45) 0.98 (0.28) < 0.001 (KW) Stimulated lipid oxidation 0.18 (0.26) a 0.57 (0.42) 0.28 (0.37) < 0.001 (KW) Basal energy expenditure 19.18 (1.77) 20.32 (2.69) 19.22 (1.42) 0.07 (KW) Stimulated energy expenditure 20.74 (1.81) 21.57 (2.18) 21.13 (1.99) 0.16 (F2, 133 = 1.84) Respiratory quotient 0h 0.85 (0.07)a 0.80 (0.05) 0.82 (0.05) < 0.001 (KW) Respiratory quotient 3h 0.98 (0.05)a 0.92 (0.06) 0.96 (0.05) < 0.001 (F2, 133 = 14.08) Data are given as mean (± S.D.). P-APD are habitually violent male antisocial personality disorder offenders in prison; F-APDs are habitually violent male antisocial personality disorder offenders already free from prison; and Controls are age matched healthy males. Group effects were analyzed by analysis of variance with Bonferroni multiple-comparison test. The Kruskall–Wallis (KW) one-way ANOVA on ranks was used for variables having asymetric distributions where a logarithm transformation could not be used (Kruskall–Wallis Multiple-Comparison z-Value Test). P value indicates the significance for any difference between groups. Data were not available from one F-APD subject for non-oxidative glucose disposal (due to technical reasons). The unit of glucose and lipid metabolism is mg/kg.min and the unit of energy expenditure cal/kg.min. a P < 0.01 compared with F-APDs. b P < 0.001 compared with control mean (effect size 0.73). The effect size for difference in NOG3h among F-APD vs. controls was 0.51 (F1, 66 = 4.24, P = 0.043; with Bonferroni correction P = 0.129). Table options 3.2. Correlations for time spent outside of prison When all differing metabolic factors in violent offender groups were used as dependent factors, and Spearman rank correlations were examined in F-APD subjects, time spent outside of prison (“months in freedom”) correlated negatively with stimulated glucose oxidation (Spearman r = − 0.54, P = 0.004) and respiratory quotient 3 h (Spearman r = − 0.49, P = 0.009). This finding also correlated with stimulated lipid oxidation (Spearman r = 0.48; P = 0.010), but not with non-oxidative glucose disposal (r = − 0.19; P = 0.34). No statistically significant correlations were observed between the time outside of prison and basal glucose oxidation (r = − 0.32; P = 0.098), respiratory quotient 0 h (r = − 0.12; P = 0.55), or basal lipid oxidation (r = − 0.01; P = 0.94). In a partial correlation analysis, where the linear effect of age was controlled by regression, results in the F-APD group did not change much concerning stimulated glucose oxidation (Spearman Pair-Wise Deletion r = − 0.53, n = 26, P = 0.006), respiratory quotient 3h (r = − 0.48, n = 28, P = 0.012), stimulated lipid oxidation (r = 0.47, n = 28, P = 0.014), or non-oxidative glucose disposal (r = − 0.16, n = 27, P = 0.44). Thus, increased age could not explain the association between glucose and lipid oxidation values vs. the ability to stay crime-free. This metabolism trait of higher lipid and lower glucose oxidations was associated with a better outcome, with less criminality and violence. In a partial correlation analysis (2-tailed) controlled for age, the positive correlation between CSF-5-HIAA vs. the time outside of prison approached statistical significance (r = 0.39, n = 21, P = 0.085).