CSF testosterone: relationship to aggression, impulsivity, and venturesomeness in adult males with personality disorder

OBJECTIVE: Studies of various species suggest that testosterone, assayed in various compartments, is correlated with aggression and possibly related behaviors. The objective of this study was to assess the relationship between cerebrospinal fluid testosterone (CSF TEST) and measures of aggression, impulsivity, and venturesomeness in male personality disordered subjects and test the hypothesis that CSF TEST would correlate directly with each measure in this group. METHODS: Lumbar CSF for morning basal levels of testosterone were obtained from 31 male subjects with personality disorder. Aggression was assessed dimensionally through the use of the life history of aggression (LHA) assessment, and categorically by the research diagnosis of intermittent explosive disorder. Impulsiveness and venturesomeness were assessed using the Eysenck personality questionnaire - II (EPQ-II). RESULTS: CSF TEST did not correlate with measures of aggression or impulsivity but did correlate directly with venturesomeness (r = .42, p = .021). Adjusting for age and height modestly reduced the magnitude and statistical significance of this correlation. CONCLUSIONS: In contrast to some published studies, CSF TEST was not found to have a significant relationship with aggression. The presence of a modest correlation between CSF TEST and venturesomeness, but not impulsivity, in male personality-disordered subjects suggests a possible relationship between CSF TEST and a type of sensation-seeking that involves consideration of the consequences of action taken.     

The role of impulsivity, sensation seeking and aggression in the relationship between childhood AD/HD symptom and antisocial behavior in adolescence

The aim of the study was to test the mediator role of impulsivity, sensation seeking, and proactive and reactive aggression on the relationship between childhood Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and antisocial behavior in a sample of 729 Italian high school students. Although significant mediation effects were observed for impulsivity and sensation seeking, a complete mediation effect was observed only for proactive aggression. The results of this study confirm and extend previous findings suggesting that selected personality traits may represent risk factors for developing antisocial behavior in adolescence/adulthood in subjects with a history of ADHD.     

Substance use disorders: Relationship with intermittent explosive disorder and with aggression,anger, and impulsivity

BackgroundA relationship between substance use and aggression has been noted for decades. While substance use appears to be associated with an increased risk of aggressive behavior, no study has yet reported on the pattern of comorbidity and temporal relationship between impulsive aggression (i.e., intermittent explosive disorder) and substance use disorders (SUD), specifically.MethodsTo specify these relationships, we examined DSM-5 diagnosis data from diagnostic interviews of 1355 adults who met one of five non-overlapping diagnostic subgroups: those with intermittent explosive disorder (IED; n = 339), those with SUD (n = 136), IED+SUD (n = 280), adults with psychiatric disorders but no SUD or IED (n = 320), and healthy Controls: HC, n = 282).ResultsOccurrence of lifetime SUD was elevated in IED vs. all Non-IED subjects (Odds Ratio: 3.61 [95% CI: 2.82–4.63]) and onset of IED preceded SUD in 80% of comorbid IED+SUD cases. Examination of the severity of impulsive aggression and SUD revealed that IED increased SUD severity but the presence of SUD did not increase severity of IED core features, including aggression, anger, or impulsivity.ConclusionsSubjects with IED are at increased risk of developing substance use disorder, compared to those without IED. This suggests that history of recurrent, problematic, impulsive aggression is a risk factor for the later development of SUD rather than the reverse. Thus, effective treatment of impulsive aggression, before the onset of substance misuse, may prevent or delay the development of SUD in young individuals.     

Cerebrospinal fluid concentrations of free GABA in schizophrenia: No changes after haloperidol treatment

Summary The concentrations of free GABA were determined in the cerebrospinal fluid of 19 paranoid schizophrenic patients before and after 3 weeks on haloperidol treatment. No significant effect of the neuroleptic treatment on the CSF free GABA concentrations was detected. Furthermore, no correlations were found between changes in GABA concentrations and psychopathological improvement on the Brief Psychiatric Rating Scale. These negative findings are at variance with earlier reports of increased or decreased CSF GABA concentrations after neuroleptics and suggest that subtle changes of the amino acid concentrations in the brain might not be faithfully reflected in the concentrations of its free fraction in the cerebrospinal fluid.     

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.     

On the role of impulsivity and decision-making in suicidal behavior

Suicide risk constitutes a complex set of interacting demographic, clinical, psychobiological and environmental variables. Impulsivity is a long-known risk factor for suicide attempts. However, research based on clearer conceptual refinement in this area is imperative. One emerging field of study is that of decision-making. Impulsivity involves a failure of higher-order control, including decision-making. Using standardized operational definitions that take into consideration relevant aspects of impulsivity, including state- and trait-components and a deeper understanding of the process of decision-making in the suicidal mind, we may come a step closer to understanding suicidality and winning the fight in this scourge of human suffering.     

Free and conjugated GABA in human cerebrospinal fluid: Effect of degenerative neurologic diseases and isoniazid

gamma-Aminobutyric acid (GABA) was measured in CSF as such and following acid hydrolysis by the ion-exchange/fluorometric method. The conjugated GABA level was obtained by subtracting the free GABA level from the total GABA level. Results showed that at room temperature, while the free GABA level increased, the level of conjugated GABA decreased in a linear fashion during the first 24 h (r = -0.974; P less than 0.001). Aging and CSF conjugated GABA levels were inversely correlated (r = -0.613; P less than 0.05). Unlike free GABA levels, the levels of conjugated GABA were not altered in Huntington's disease, Parkinson's disease, cerebellar ataxias, dementias, epilepsy and multiple sclerosis compared to controls. In patients with Huntington's disease, on administration of isoniazid at 900 mg/day, along with pyridoxine at 100 mg/day, a 4-fold increase of both free (P less than 0.005) and conjugated GABA (P less than 0.0025) was seen. The results indicate that while total GABAergic peptides are not altered in several of the neurologic diseases studied, drugs such as isoniazid and/or pyridoxine can significantly elevate both free and conjugated GABA levels in human CSF.     

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.     

Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of serotonin, were measured in relation to aggression, impulsivity, and social functioning in 29 children and adolescents with disruptive behavior disorders. The cerebrospinal fluid 5-hydroxyindoleacetic acid level was low compared with that of age-, sex-, and race-matched patients with obsessive-compulsive disorder. Within the disruptive group, significant negative correlations with age-corrected 5-hydroxyindoleacetic acid level were seen for the child's report of aggression toward people and the expressed emotionality of the child toward his or her mother; other correlations of age-corrected 5-hydroxyindoleacetic acid level with measures of aggression were in the expected negative direction but did not reach statistical significance. Impulsivity per se and socioenvironmental factors were not significantly related to cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.     

Cerebrospinal fluid GABA levels in chronic migraine with and without depression

Psychiatric comorbidity is one of the key elements in chronic migraine (CM) management. Depression is particularly common in these patients, occurring in up to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA) levels may be decreased in animal models of depression. Also, clinical studies have reported low level in mood disorder patients for both plasma and cerebrospinal fluid (CSF) GABA. We hypothesized that low GABA levels in the brain might be related to the depression associated with CM. We studied 14 chronic migraine patients, with or without depression, compared to age-and sex-matched controls. CSF GABA levels were measured by HPLC. CSF GABA levels showed significant lower levels in depressed patients than those without depression. No difference was found when comparing patients versus controls. A GABA deficiency may be the underlying mechanism of depression in CM. Hence, preventive therapies modulating GABA neurotransmission could be used in CM associated with depression.     

Sex,aggression and impulse control: An integrative account

There is evidence that the male sex and a personality style characterized by low self-control/high impulsivity and a propensity for negative emotionality increase the risk for impulsive aggressive, antisocial and criminal behavior. This article aims at identifying neurobiological factors underlying this association. It is concluded that the neurobiological correlates of impulsive aggression act through their effects on the ability to modulate impulsive expression more generally, and that sex-related differences in the neurobiological correlates of impulse control and emotion regulation mediate sex differences in direct aggression. A model is proposed that relates impulse control and its neurobiological correlates to sex differences in direct aggression.     

Catechol-o-methyltransferase gene modulation on suicidal behavior and personality traits: review, meta-analysis and association study

Suicide is one of the leading causes of death among young adults. Both genetic and personality factors plausibly have a role on suicidal behavior. We focused on the catechol-O-methyltransferase gene (COMT) and we performed: a review of studies investigating the association between COMT and both suicidal behavior and personality; a meta-analysis of studies investigating the association between suicidal behavior and COMT rs4680 polymorphism; an association study investigating the link between seven COMT polymorphisms (rs737865, rs5844402, rs5993883, rs4680, rs4633, rs165599 and rs9332377) and both personality traits and suicidal behavior. For the review and the meta-analysis we performed an electronic search to identify studies focused on the association between COMT and both suicidal behavior and personality. The sample of the association study was composed of three groups: 289 German healthy controls, 111 German suicide attempters and 70 Italian mood disorder patients. From the review, the meta-analysis and the association study no relationship emerged between COMT and suicidal behavior. Nevertheless, from both review and association study several links were found between COMT and personality traits. In particular, in the association study we found a significant correlation between rs4633 and Reward Dependence (Temperament and Character Inventory). As secondary results we found an association between rs737865 and Angry Reaction (State-Trait Anger Expression Inventory) and between rs9332377 and Irritability (Questionnaire for Measuring Factors of Aggression). Our findings suggested that COMT variants may not be directly implicated in suicidal behavior, however evidence of a COMT role in the modulation of personality traits has been found.     

Cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid: reciprocal relationships with impulsive aggression in human subjects

While the relationship between cerebrospinal fluid 5-HIAA (CSF 5-HIAA) and aggression is typically reported as inverse, studies of some groups of aggressive individuals demonstrate a positive (or no) relationship, between these two variables. It is possible that simultaneous examination of both CSF 5-HIAA and CSF homovanillic acid (HVA), which co-vary in human subjects may clarify differences in reported findings in different groups of aggressive individuals. CSF 5-HIAA and CSF HVA concentrations were simultaneously examined in 60 healthy human subjects (40 with personality disorder and 20 healthy controls) and were correlated with measures of aggression and impulsivity. CSF 5-HIAA concentrations correlated positively, and CSF HVA concentrations correlated inversely, with a composite measure of impulsive aggression in all subjects as well as in the personality disordered subjects. The CSF 5-HIAA findings are consistent with those demonstrating reduced post-synaptic 5-HT receptor responsiveness to 5-HT agent challenge and suggest differences in the pathophysiology between different groups of subjects with aggressive behavior, particularly with regard to severity of aggressive behavior.     

GABA Levels in Cerebrospinal Fluid of Patients with Epilepsy

Abstract: The lumbar cerebrospinal fluid (CSF) γ-aminobutyric acid (GABA) levels were measured in 27 patients with epilepsy, another three epileptic patients with status epilepticus and three epileptic patients with chronic cerebellar ataxia. The mean lumbar CSF GABA levels of the 27 patients with epilepsy were not significantly different from those of normal controls. Six of these 27 patients who had daily partial complex and partial motor seizures showed significantly low CSF GABA levels as did the six other patients, three each with status epilepticus and chronic cerebellar ataxia. These findings suggest that some epileptic patients have impaired brain GABAergic neurons.     

Inter-relationship between different platelet measures of 5-HT and their relationship to aggression in human subjects

The objective of this study was to explore the inter-relationship of three platelet measures of serotonergic function (5-HT): 5-HT Transporter Binding, 5-HT-2 Receptor Binding and 5-HT Content and to explore their inter-relationship with measures of aggression and impulsivity. 58 male subjects with personality disorder were studied. Numbers of platelet 5-HT Transporter and 5-HT-2 Receptor sites were assessed by examining the Bmax of ³H-Paroxetine Binding and the Bmax of ¹²⁵I-LSD Binding to the blood platelet; 5-HT Content was assessed by measuring the amount of 5-HT in the platelet material. Life history of aggression was assessed by Life History of Aggression. Impulsivity was assessed by the Impulsivity Scale of the Eysenck Personality Questionnaire-II. Platelet 5-HT Transporter Binding correlated with both 5-HT-2 Receptor Binding and 5-HT Content; the latter two variables did not correlate with each other. Only Platelet 5-HT Transporter binding correlated significantly with LHA Aggression. These data suggest that while Platelet 5-HT Transporter binding correlates with both 5-HT-2 Receptor Binding and with 5-HT Content, that only 5-HT Transporter Binding represents a correlate of aggression in male personality disordered subjects.     

Cerebrospinal fluid tau levels in Alzheimer's disease are elevated when compared with vascular dementia but do not correlate with measures of cerebral atrophy

Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset.     

History of suicide attempt in male substance-dependent inpatients and relationship to borderline personality features, anger, hostility and aggression

The aim of this study was to investigate the relationship between severity of borderline personality features and history of suicide attempt (HSA) in male substance-dependent inpatients and the effect of anger, hostility and aggression on this relationship. Further, the effect of some variables that may be related to suicide and/or borderline personality, such as age at inception of regular substance use, substance of dependence (alcohol/drug), depression, and both state and trait anxiety, were controlled. Participants were 200 consecutively admitted male substance-dependent inpatients. Patients were investigated with the Borderline Personality Inventory (BPI), the Buss-Perry Aggression Questionnaire (AQ), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Among substance-dependent inpatients, 33.0% (n = 66) were identified as the group with HSA. Mean scores employment status, marital status and duration of education did not differ between groups, whereas current age and age at onset of regular substance use were lower in group with HSA. Mean scores of BPI, AQ and its subscales (anger, hostility and physical/verbal aggression), BDI and STAI were higher in the HSA group. In addition, the rates of drug dependency and borderline personality disorder were higher in this group. The severity of borderline personality symptoms was highly correlated with subscales of the AQ, depression and anxiety, whereas it was negatively correlated with age at onset of regular substance use. The severity of anger and borderline personality features predicted HSA in the logistic regression model. Results suggest that, to reduce the risk of suicide attempt among substance-dependent patients, the feeling of anger must be the target of evaluation and treatment among those with borderline personality features.     

Modeling the relationship between affective lability, impulsivity, and suicidal behavior in patients with borderline personality disorder

This article reviews the concept of affective lability and suggests that new models are needed to characterize the relationship between affective states such as affective lability, impulsivity, and suicidal behavior. The association of affective lability, impulsivity, and suicidal behavior is most relevant to understanding the risk of suicide in individuals with borderline personality disorder. The relationship between affective lability and suicide might be explained as 1) a form of bipolarity, 2) a form of impulse dyscontrol, 3) a quantitative disorder of affect, or 4) an environmental reactivity. Our opinion of the relevant literature suggests that a quantitative disorder of affect accompanied by the inability to control these affects are the essential components leading to the risk of suicidal behavior. Characterizing the dyscontrol and high intensity of affect leads to a reconceptualization of depression in patients with borderline personality disorder and to a re-examination of the causal chain of events leading to suicidal behavior. The implications for clinical practice resulting from the proposed model are discussed.