Testosterone enhances risk tolerance without altering motor impulsivity in male rats.

Anabolic-androgenic steroids (AAS) increase impulsive and uncontrolled aggressive ('roid rage) in humans and enhance agonistic behavior in animals. However, the underlying mechanisms for AAS-induced aggression remain unclear. Potential contributing elements include an increase risk-taking and/or motor impulsivity due to AAS. This study addressed the effects of chronic high-dose testosterone on risk tolerance using a risky decision-making task (RDT) and motor impulsivity with a go/no-go task in operant chambers. Male Long-Evans rats were treated for at least 4 weeks with testosterone (7.5mg/kg) or vehicle beginning in late adolescence. Testosterone was used because it is popular among human AAS users. In RDT testing, one lever was paired with delivery of a small "safe" food reward, while the other was paired with a large "risky" reward associated with an increasing risk of footshock (0%, 25%, 50%, 75%, 100%) in successive test blocks. Three shock intensities were used: 1.0, 1.2, and 1.4mA/kg. As shock intensity and risk of shock increased, preference for the lever signifying a large reward significantly declined for both vehicle- and testosterone-treated rats (p<0.05). There was also a significant effect of drug (p<0.05), where testosterone-treated rats showed greater preference for the large reward, compared to vehicle-treated controls. Increased preference for the large reward, despite risk of footshock, is consistent with increased risk tolerance. In go/no-go testing, rats were trained to press a single lever if the go cue was presented (stimulus light) or to refrain from pressing during the no-go cue (tone). There was no effect of testosterone on pre-cue responses, or performance in go and no-go trials. These results suggest that AAS may increase risk-tolerance without altering motor impulsivity.

Impulsivity is associated with uric acid: evidence from humans and mice.

BACKGROUND: The ability to control impulses varies greatly, and difficulty with impulse control can have severe consequences; in the extreme, it is the defining feature of many psychiatric disorders. Evidence from disparate lines of research suggests that uric acid is elevated in psychiatric disorders characterized by high impulsivity, such as attention-deficit/hyperactivity disorder and bipolar disorder. The present research tests the hypothesis that impulsivity is associated with higher uric acid in humans and mice. METHODS: Using two longitudinal, nonclinical community samples (total n = 6883), we tested whether there is an association between uric acid and normal variation in trait impulsivity measured with the Revised NEO Personality Inventory. We also examined the effect of uric acid on behavior by comparing wild-type mice, which naturally have low levels of uric acid, with mice genetically modified to accumulate high levels of uric acid. RESULTS: In both human samples, the emotional aspects of trait impulsivity, specifically impulsiveness and excitement seeking, were associated with higher levels of uric acid concurrently and when uric acid was measured 3 to 5 years later. Consistent with the human data, the genetically modified mice displayed significantly more exploratory and novelty-seeking behavior than the wild-type mice. CONCLUSIONS: Higher uric acid was associated with impulsivity in both humans and mice. The identification of biological markers of impulsivity may lead to a better understanding of the physiological mechanisms involved in impulsivity and may suggest potential targets for therapeutic intervention.

The effect of acute tryptophan depletion on mood and impulsivity in polydrug ecstasy users.

RATIONALE: Several studies suggest users of 3,4-methylenedioxymethamphetamine (ecstasy) have low levels of serotonin. Low serotonin may make them susceptible to lowered mood. OBJECTIVE: This work aims to study the acute effects on mood and impulsivity of lowering serotonin levels with acute tryptophan depletion in polydrug ecstasy users and to determine whether effects were different in men and women. METHODS: In a double-blind cross-over study, participants who had used ecstasy at least 25 times (n = 13) and nonuser controls (n = 17) received a tryptophan-deficient amino acid mixture and a control amino acid mixture containing tryptophan, at least 1 week apart. Mood was measured using the profile of mood states, and impulsivity was measured with the Go/No-Go task. RESULTS: The main result shows that a lowering of mood after acute tryptophan depletion occurred only in female polydrug ecstasy users (n = 7), relative to controls (n = 9). Results from the Go/No-Go task suggested that impulsivity was not increased by acute tryptophan depletion in polydrug ecstasy users. LIMITATION: The group sizes were small, when males and females were considered separately. CONCLUSIONS: Women polydrug ecstasy users appear to be more susceptible than men to the effects of lowered serotonin levels. If use of ecstasy alone or in conjunction with other drugs causes progressive damage of serotonin neurons, women polydrug ecstasy users may become susceptible to clinical depression.

Personality traits and leptin.

OBJECTIVE: Personality traits related to high neuroticism and low conscientiousness are consistently associated with obesity. Hormones implicated in appetite and metabolism, such as leptin, may also be related to personality and may contribute to the association between these traits and obesity. The present research examined the association between leptin and Five Factor Model personality traits. METHODS: A total of 5214 participants (58% women; mean [standard deviation] age = 44.42 [15.93] years; range, 18-94 years) from the SardiNIA project completed the Revised NEO Personality Inventory, a comprehensive measure of personality traits, and their blood samples were assayed for leptin. RESULTS: As expected, lower conscientiousness was associated with higher circulating levels of leptin (r = -0.05, p < .001), even after controlling for body mass index, waist circumference, or inflammatory markers (r = -0.05, p < .001). Neuroticism, in contrast, was unrelated to leptin (r = 0.01, p = .31). CONCLUSIONS: Individuals who are impulsive and lack discipline (low conscientiousness) may develop leptin resistance, which could be one factor that contributes to obesity, whereas the relation between a proneness to anxiety and depression (high neuroticism) and obesity may be mediated through other physiological and/or behavioral pathways.

Norepinephrine and impulsivity: effects of acute yohimbine.

RATIONALE: Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. OBJECTIVE: We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity. METHODS: Subjects were 23 healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and axis I or II disorder. Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0.4 mg/kg oral yohimbine or placebo in a randomized, counterbalanced design. Metabolites of norepinephrine [3-methoxy-4-hydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA)] and dopamine [homovanillic acid (HVA)] were measured by high-pressure liquid chromatography with electrochemical detection. Rapid-response impulsivity was measured by commission errors and reaction times on the immediate memory task (IMT), a continuous performance test designed to measure impulsivity and attention. RESULTS: Yohimbine increased plasma MHPG and VMA but not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse rate. On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates. Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance. CONCLUSIONS: These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls. Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive behavior.

Activation of the cholinergic anti-inflammatory system in peripheral blood mononuclear cells from patients with borderline personality disorder.

A case-control study including patients (n = 20) with Borderline Personality Disorder (BPD) and healthy controls (n = 33) was carried out. To avoid interferences of other clinical conditions on biological findings, patients were free of current major depressive episodes or substance dependence disorders, and had no life history of schizophrenia, bipolar or neuropsychiatric disorders. Patients were free of medication for at least two weeks at the time of the study. Studies carried out in peripheral mononuclear blood cells and plasma evidence a systemic inflammatory condition in unstable-impulsive BPD patients. Specifically, a significant increase in some intracellular components of two main pro-inflammatory pathways such as iNOS and COX-2, as well as an increase in the plasma levels of the inflammatory cytokine IL1ß. Interestingly, patients have an increase in the protein expression of the anti-inflammatory subtype of nicotinic receptor α7nAChR. This finding may reflect a possible mechanism trying to maintain intracellular inflammation pathways under control. All together, these results describe an imbalanced, pro-inflammatory and oxidant phenotype in BPD patients independent of plasma cotinine levels. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways have interesting potential as biological markers for BPD and other generalized impulsive syndromes, specially data obtained with α7nAChR and its lack of correlation with plasma levels of nicotine metabolites. Their pharmacological modulation with receptor modulators can be a promising therapeutic target to take into account in mental health conditions associated with inflammatory or oxido/nitrosative consequences. Also, identifying at-risk individuals would be of importance for early detection and intervention in adolescent subjects before they present severe behavioural problems.

Effects of blood lead and cadmium levels on the functioning of children with behaviour disorders in the family environment.

INTRODUCTION AND OBJECTIVE: The developing brain of a child is extremely prone to damage resulting from exposure to harmful environmental factors, e.g. heavy metals. Intoxication of children's organisms with lead and cadmium affects their intellectual development. Even a relatively small amount of this metal in children's blood can lead to developmental dysfunctions. The aim of this study was to analyse the correlation between blood lead and cadmium levels in children with behaviour disorders and their functioning in the home. MATERIAL AND METHODS: This survey-based study was conducted among 78 families with children diagnosed as having behaviour disorders. It was performed using the ADHD-Rating Scale-IV. To determine lead and cadmium levels the laboratory procedure was based on Stoppler and Brandt's method. RESULTS: The mean blood lead level was 19.71 µg/l and the mean blood cadmium level was 0.215 µg/l. Higher blood lead levels in children correlates positively with incidences of hyperactive and impulsive behaviour in the home, as assessed by parents (p=0.048). Statistically significant effects of cadmium on children's behaviour were not noticed. CONCLUSIONS: The effect of lead on the developing organism of a child has such behavioural consequences as attention disorders, hyperactivity and impulsive behaviour which, in turn, may interfere with children's functioning in the home. A negative effect of cadmium on the functioning of children with behaviour disorders in the home was not proved.

Lower levels of cannabinoid 1 receptor mRNA in female eating disorder patients: association with wrist cutting as impulsive self-injurious behavior.

The cannabinoid 1 (CB 1) receptor as the primary mediator of the endocannabinoid (EC) system was found to play a role in eating disorders (EDs), depression, anxiety, and suicidal behavior. The CB 1 receptor is assumed to play a crucial role in the central reward circuitry with impact on body weight and personality traits like novelty-seeking behavior. In a previous study we found higher levels of CB 1 receptor mRNA in patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared to healthy control women (HCW). The aim of the present study was to investigate the possible influence of the EC and the CB 1 receptor system on wrist cutting as self-injurious behavior (SIB) in women with EDs (n=43; AN: n=20; BN: n=23). Nine ED patients with repetitive wrist cutting (AN, n=4; BN, n=5) were compared to 34 ED patients without wrist cutting and 26 HCW. Levels of CB 1 receptor mRNA were determined in peripheral blood samples using quantitative real-time PCR. ED patients with self-injurious wrist cutting exhibited significantly lower CB 1 receptor mRNA levels compared with ED patients without wrist cutting and HCW. No significant differences were found between ED patients without a history of wrist cutting and HCW. Furthermore, a negative association was detected between CB 1 receptor mRNA levels and Beck Depression Inventory (BDI) scores. To our knowledge, this is the first study reporting a down-regulation of CB 1 receptor mRNA in patients with EDs and wrist cutting as SIB. Due to the small sample size, our results should be regarded as preliminary and further studies are warranted to reveal the underlying mechanisms.

The effects of acute tryptophan depletion on costly information sampling: impulsivity or aversive processing?

RATIONALE: The neurotransmitter serotonin (5-HT) has been implicated in both aversive processing and impulsivity. Reconciling these accounts, recent studies have demonstrated that 5-HT is important for punishment-induced behavioural inhibition. These studies focused on situations where actions lead directly to punishments. However, decision-making often involves making tradeoffs between small 'local' costs and larger 'global' losses. OBJECTIVE: We aimed to distinguish whether 5-HT promotes avoidance of local losses, global losses, or both, in contrast to an overall effect on reflection impulsivity. We further examined the influence of individual differences in sub-clinical depression, anxiety and impulsivity on global and local loss avoidance. METHODS: Healthy volunteers (N = 21) underwent an acute tryptophan depletion procedure in a double-blind, placebo-controlled crossover design. We measured global and local loss avoidance in a decision-making task where subjects could sample information at a small cost to avoid making incorrect decisions, which resulted in large losses. RESULTS: Tryptophan depletion removed the suppressive effects of small local costs on information sampling behaviour. Sub-clinical depressive symptoms produced effects on information sampling similar to (but independent from) those of tryptophan depletion. Dispositional anxiety was related to global loss avoidance. However, trait impulsivity was unrelated to information sampling. CONCLUSIONS: The current findings are consistent with recent theoretical work that characterises 5-HT as pruning a tree of potential decisions, eliminating options expected to lead to aversive outcomes. Our results extend this account by proposing that 5-HT promotes reflexive avoidance of relatively immediate aversive outcomes, potentially at the expense of more globally construed future losses.

Salivary cortisol levels in Parkinson's disease and its correlation to risk behaviour.

OBJECTIVE: To investigate salivary cortisol samples in patients with Parkinson's disease (PD) with and without impulsive compulsive behaviours (ICB) during a risk task. METHODS: Salivary cortisol levels were measured in 13 PD patients without ICB (PD-ICB) and in 15 PD patients with ICB (PD+ICB) before, after medication and throughout the day, and were compared with results with 14 healthy controls. All participants also performed a gambling task to assess risk taking behaviour. RESULTS: Significantly higher diurnal cortisol levels were found in the PD-ICB group compared with healthy controls but no differences were seen between the PD+ICB and the control group. Increased cortisol levels were significantly correlated with increased risk taking in PD+ICB patients but no interaction was found in the PD-ICB group. CONCLUSIONS: The findings are in keeping with previous studies which have linked low cortisol levels with antisocial behaviour. The higher cortisol levels during the risk task in the PD+ICB group are consistent with reports in pathological gamblers during gambling and addicts during drug abuse. The results support the hypothesis that cortisol plays an important role in risk taking in ICBs.

High impulsivity predicting vulnerability to cocaine addiction in rats: some relationship with novelty preference but not novelty reactivity, anxiety or stress.

RATIONALE: Impulsivity is a vulnerability marker for drug addiction in which other behavioural traits such as anxiety and novelty seeking ('sensation seeking') are also widely present. However, inter-relationships between impulsivity, novelty seeking and anxiety traits are poorly understood. OBJECTIVE: The objective of this paper was to investigate the contribution of novelty seeking and anxiety traits to the expression of behavioural impulsivity in rats. METHODS: Rats were screened on the five-choice serial reaction time task (5-CSRTT) for spontaneously high impulsivity (SHI) and low impulsivity (SLI) and subsequently tested for novelty reactivity and preference, assessed by open-field locomotor activity (OF), novelty place preference (NPP), and novel object recognition (OR). Anxiety was assessed on the elevated plus maze (EPM) both prior to and following the administration of the anxiolytic drug diazepam, and by blood corticosterone levels following forced novelty exposure. Finally, the effects of diazepam on impulsivity and visual attention were assessed in SHI and SLI rats. RESULTS: SHI rats were significantly faster to enter an open arm on the EPM and exhibited preference for novelty in the OR and NPP tests, unlike SLI rats. However, there was no dimensional relationship between impulsivity and either novelty-seeking behaviour, anxiety levels, OF activity or novelty-induced changes in blood corticosterone levels. By contrast, diazepam (0.3-3 mg/kg), whilst not significantly increasing or decreasing impulsivity in SHI and SLI rats, did reduce the contrast in impulsivity between these two groups of animals. CONCLUSIONS: This investigation indicates that behavioural impulsivity in rats on the 5-CSRTT, which predicts vulnerability for cocaine addiction, is distinct from anxiety, novelty reactivity and novelty-induced stress responses, and thus has relevance for the aetiology of drug addiction.

Growth hormone responses to GABAB receptor challenge with baclofen and impulsivity in healthy control and personality disorder subjects.

BACKGROUND: The role of abnormal GABAergic neural transmission in impulsive aggression is not well understood. We have previously shown that central levels of GABA are positively correlated with impulsivity in adult humans with and without personality disorder. An important regulator of GABAergic function is the GABA(B) receptor, a presynaptic autoreceptor and heteroreceptor. GABA(B) receptor sensitivity may be tested by measuring the growth hormone response to the receptor-agonist baclofen. The purpose of this investigation is to test the hypothesis that dimensional measures of impulsivity and impulsive aggression are negatively correlated with growth hormone response. METHODS: Twenty healthy volunteers (without Axis I or II disorder) and 20 personality-disordered subjects (meeting DSM-IV general criteria for personality disorder) underwent challenge with 20 mg baclofen administered orally, followed by a time series of blood samples for measure of growth hormone response analyzed by repeated measures ANOVA. RESULTS: An expected significant effect for drug and drug × time interaction verified that baclofen caused a surge in growth hormone level. There was no effect of group (healthy volunteer or personality disorder) or interaction with group on the time series or peak growth hormone response. As hypothesized, peak growth hormone response was negatively correlated with impulsivity as measured by the Barratt Impulsivity Scale (BIS-11; r = -0.39, n = 37, p < 0.02). The relationship remained significant when examining the healthy volunteer and personality disorder groups separately, indicating that the relationship with impulsivity was not merely due to the presence or absence of personality disorder. The relationship with impulsive aggression was only at a trend level of significance. CONCLUSION: The magnitude of growth hormone response to baclofen, an index of GABA(B) receptor function, was negatively correlated with a dimensional measure impulsivity, but not related to the categorical diagnosis of personality disorder. Further work is necessary to understand how GABAergic dysfunction may play a role in impulsive aggression.

Androgen levels and anger and impulsivity measures as predictors of physical, verbal and indirect aggression in boys and girls.

Previous studies indicate that androgen levels and certain psychological characteristics such as anger and impulsivity are related to the development and maintenance of aggression. Further studies are required to analyze the potential predictor role of the interaction of said factors on aggressive behavior. 90 nine-year-old children (44 boys and 46 girls) were assessed in relation to their levels of physical, verbal and indirect aggression, using a peer-rating technique. Testosterone and androstenedione levels were analyzed using an enzymoimmunoassay technique in saliva samples. Anger (state and trait) and anger control were measured using the STAXI-NA, and impulsivity was measured through the MFF-20. A General Linear Model revealed that sex was the best predictor for aggression measures, with boys scoring higher than girls in physical, verbal and indirect aggression; after sex, testosterone was found to be the best predictor (in a positive sense) of all three types of aggressive behavior studied. In addition to observing a main effect of androstenedione on physical and verbal aggression, a 'state anger*androstenedione' interaction was found to predict these types of aggression, with androstenedione acting as a moderator (inhibitor) of the effects of anger on these behaviors; also, a 'state anger*testosterone' interaction was found to predict verbal aggression. The results support the idea that, after sex, androgens constitute a biological marker to be taken into consideration in relation to individual differences in aggressive behavior. It is possible that at the age of 9, testosterone tends to increase aggression, while androstenedione tends to moderate (inhibit) the effects of anger on aggression.

Association of polymorphisms of the serotonergic pathways with clinical traits of impulsive-aggression and suicidality in adolescents: a multi-center study.

OBJECTIVES: Suicidal behaviour runs in families. This study evaluated association between common polymorphisms in the serotonergic and adrenergic candidate genes (HTR2A, 5HTTLPR, and MAOA) and suicidality, psychopathology and aggression in adolescents. METHODS: Four groups of adolescents were included: Suicidal (N=35) and non-suicidal (N=30) psychiatric inpatients, suicide attempters admitted to three psychiatric emergency rooms (N=51) and a community-based control group (N=95). All were genotyped and underwent psychological assessment for relevant endophenotypes and plasma serotonin content (p5HT) was measured. RESULTS: Homozygosity for the T allele of the HTR2A 102T/C polymorphism was associated with lower impulsivity (P=0.03) and aggression (P=0.01) compared to TC carriers. Low activity MAOA genotypes were associated with suicidality (P=0.04). No association was found between p5HT level and the examined polymorphisms. CONCLUSIONS: Our findings are in line with the associations described in adult suicidal population. Further studies are needed to evaluate the gene ? environmental interactions in larger samples in an attempt to clarify the possible role of genetic factors in pediatric suicidal and impulsive-aggressive behaviour.

The function of hypothalamus-pituitary-adrenal axis in children with ADHD.

OBJECTIVE: To explore the relationship between hypothalamus-pituitary-adrenal (HPA) axis and Attention Deficit Hyperactivity Disorder (ADHD) in non-stress states. METHOD: 128 male children with ADHD aged between 6 and 14 years old were recruited, while 30 healthy male children were chosen as a control group. The diagnostic material was based on DSM-IV. The included ADHD children were further classified into the three sub-groups: ADHD-predominantly inattention type (ADHD-I) (n=44), ADHD-predominantly hyperactive impulsive type (ADHD-HI) (n=32), and ADHD-combined type (ADHD-C) (n=52). The levels of cortisol and adrenocorticotropin hormone (ACTH) were evaluated by the automatic particle enzyme immunoassay and electrochemiluminescence respectively per morning (8:00 am). Intelligence test was assessed by the Raven's Standard Progressive Matrices. RESULTS: The children with ADHD had significantly lower intelligence quotient (IQ) (84.5±11.3) in contrast to the control group (98.6±12.4, P<0.01), although the lower level of IQ in ADHD-C group (79.2±10.7) was also found when compared with other two sub-groups [ADHD-I (85.6±10.4) and ADHD-HI (91.3±12.6)]. In addition, no significant difference between the ADHD-HI group and the control group regarding the level of IQ were revealed. The level of cortisol in the ADHD group (226.47±129.12 nmol/L) was significantly lower than that of the control group (384.53±141.43 nmol/L, P<0.001). The level of cortisol of the ADHD-HI group (154.36±71.62 nmol/L) was significantly lower than that of other two groups [ADHD-I group (219.42±117.66 nmol/L) (P<0.01) and ADHD-C group (258.30±136.39 nmol/L) (P<0.01)]. There were no significant differences in the ACTH level either between the ADHD and the control group (P>0.05), or between sub-groups in ADHD (P>0.05). CONCLUSION: In the non-stress states, the existence of dysfunction of the HPA axis (lower plasma cortisol) in children with ADHD might be due to the under-reactivity of the HPA axis ; the low plasma cortisol level might contribute less to the outcomes of cognitive behavior of ADHD children and instead more closely relate to the core domains of attention deficit, hyperactivity and impulsive behavior of ADHD patients.

Low cholesterol is a risk factor for attentional impulsivity in patients with mood symptoms.

This study examined the relationship between cholesterol levels and impulsivity in a large sample of patients with mood symptoms. Three hundred and one patients with mood, anxiety, and personality disorders completed a battery of psychometric scales including the Barratt Impulsiveness Scale-Version 11 (BIS-11) and the Profile of Mood States (POMS). On the same day of psychometric assessment, blood samples were analyzed for total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). Statistical analysis controlling for the confounding effects of age, gender, diagnosis, and current mood symptoms showed that lower TC levels were associated with increased attentional impulsivity. There was a weak linear correlation between TC and attentional impulsivity across the entire range of TC levels (110-295mg/dL) but a highly significant difference between participants with TC levels lower than 165mg/dL and the rest of the sample. The current study adds to the growing body of evidence pointing to the association between serum cholesterol and mental health. Considering that attentional impulsivity is a demonstrated risk factor for suicide, patients presenting with low cholesterol and mood symptoms may warrant increased clinical attention and surveillance.

[The effect of lead and cadmium on the lipid profile and psychosocial functioning of children with developmental disorders]. / Wplyw olowiu i kadmu na profil lipidowy i funkcjonowanie psychospoleczne u dzieci z zaburzeniami rozwoju.

INTRODUCTION: Impulsiveness, hyperactivity, and attention deficit are the most frequent neurocognitive disorders of childhood. Leaving aside the putative role of environmental and nutritive factors, the etiology and pathogenesis of these disorders remains unknown. The aim of this study was to examine the relationship between the concentration of lead, cadmium, and polyunsaturated fatty acids, and functioning of the child with developmental disorders. MATERIAL AND METHODS: The study enrolled 78 children with behavioral disorders. The mean age of the children was eight years. Standardized tools were used: Manfred Cierpka Family Assessment Measures, Children's Health Questionnaire Parent Form-28, and ADHD-Rating Scale-IV. Concentrations of lead and cadmium in venous blood, lipid profile, and the percentage of some omega-3 and omega-6 fatty acids in the erythrocyte membrane were measured. RESULTS: A correlation between higher levels of lead in blood of the child and impulsive and hyperactive behaviors at home was observed. Concentrations of cadmium correlated with increased incidence of attention deficit at school. Analysis of the health profile revealed that lead and cadmium correlate with some of the elements that make up the image of a properly functioning child. Reduced levels of AA and EPA positively correlated with the incidence of hyperactive and impulsive behaviors. Reduced levels of GLA impaired the acceptance of norms and values. Levels of EPA and DHA had an impact on the overall state of health of the child, as well as on physical activity and feeling of loneliness. CONCLUSIONS: 1. Developmental disorders at school and difficulties in functioning at home may be the consequence of dysfunctions caused by lead and cadmium. 2. Deficiencies of AA, GLA, DHA, and EPA fatty acids or a disorder of their metabolism affect the behavior of the child in the form of hyperactivity, impulsiveness, and attention deficit.

Cortisol responses to ipsapirone challenge correlate with aggression, while basal cortisol levels correlate with impulsivity, in personality disorder and healthy volunteer subjects.

BACKGROUND: This study was performed to test the hypothesis that 5-HT-1a receptors, as assessed by the cortisol (post-synaptic) and temperature (pre-synaptic) responses to the 5-HT-1a agonist, Ipsapirone (IPSAP), play a role in the regulation of impulsive aggressive behavior in human subjects. METHODS: Fifty-two healthy subjects (28 with Personality Disorder: PD; 24 Healthy Volunteers: HV) underwent acute challenge with the selective 5-HT-1a agonist, ipsaprione (IPSAP: .3 mg/kg po). Residual Peak Delta Cortisol (ΔCORT[IPSAP]-R; after removal of Basal CORT and IPSAP plasma levels) was used as the primary 5-HT-1a post-synaptic receptor variable. Residual Nadir Delta Temperature (ΔTEMP[IPSAP]-R; after removal of Basal TEMP) was used as the primary 5-HT-1a somatodendritic (pre-synaptic) receptor variable. Measures of trait aggression included the Aggression scales of the Buss-Durkee Hostility Inventory (BDHI) and the Life History of Aggression (LHA); trait impulsivity was assessed with the Impulsivity scale of the Eysenck Personality Questionnaire (EPQ-II). RESULTS: Correlations between ΔCORT[IPSAP]-R responses and BDHI Aggression scores varied by group. Specifically, BDHI Aggression correlated inversely with ΔCORT[IPSAP]-R values in PD subjects but directly in HV subjects. While EPQ-II Impulsivity did not correlate with ΔCORT[IPSAP]-R responses, this measure of impulsivity correlated directly with Basal CORT levels in all subjects. ΔTEMP[IPSAP]-R responses did not correlate with measures of trait aggression or trait impulsivity. CONCLUSION: Physiologic responses of 5-HT-1a post-synaptic receptors may be reduced as a function of trait aggression, but not impulsivity, in PD subjects. In contrast, pre-synaptic 5-HT-1a receptors may not play a role in the regulation of aggression or impulsivity in human subjects.

Negative association between plasma cortisol levels and aggression in a high-risk community sample of adolescents.

In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.

The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity.

RATIONALE: Platelet monoamine oxidase (MAO) activity is associated with impulsivity in clinical samples. Recently, a functional promoter polymorphism of neuronal nitric oxide synthase (NOS1) termed NOS1 ex1f-VNTR was found to have an effect on impulsivity-related traits and resulting psychopathology. OBJECTIVE: The study aims to explore the effect of both platelet MAO activity and NOS1 ex1f-VNTR genotype on impulsivity in a population-derived sample. METHODS: This study was on a non-clinical sample of adult male subjects, previously used to investigate the effect of platelet MAO activity on impulsivity-related behaviour (Paaver et al., Psychopharmacology 186:32-40, 2006). Six hundred thirty-seven male subjects were genotyped for the NOS1 ex1f-VNTR promoter polymorphism. Impulsivity was self-reported. Effects of age and smoking, known to affect platelet MAO activity, were controlled for. RESULTS: No main effect of either NOS1 genotype or platelet MAO activity was present. However, significant interactions were found between effects of the NOS1 genotype and platelet MAO activity on impulsivity measures. Impulsivity and in particular the aspects of adaptive impulsivity (e.g. fast decision-making and excitement-seeking behaviour) were higher in subjects with the NOS1 ex1f-VNTR short/short genotype if they belonged to the platelet MAO medium activity (interquartile) range. CONCLUSIONS: This study supports evidence for higher impulsivity in the NOS1 short/short genotype subjects and further suggests that this is present in the subset of subjects who have close to average platelet MAO activity.