Jennifer R. Fanning

Serotonin Augmentation Reduces Response to Attack in Aggressive Individuals

We tested the theory that central serotonin (5-hydroxytryptamine, or 5-HT) activity regulates aggression by modulating response to provocation. Eighty men and women (40 with and 40 without a history of aggression) were randomly assigned to receive either 40 mg of paroxetine (to acutely augment serotonergic activity) or a placebo, administered using double-blind procedures. Aggression was assessed during a competitive reaction time game with a fictitious opponent. Shocks were selected by the participant and opponent before each trial, with the loser on each trial receiving the shock set by the other player. Provocation was manipulated by having the opponent select increasingly intense shocks for the participant and eventually an ostensibly severe shock toward the end of the trials. Aggression was measured by the number of severe shocks set by the participant for the opponent. As predicted, aggressive responding after provocation was attenuated by augmentation of serotonin in individuals with a pronounced history of aggression.

Suicidality among older male veterans in the United States: results from the National Health and Resilience in Veterans Study.

Older men have a higher rate of suicide than the general population, but little is known about the prevalence and correlates of suicidality among older male veterans. In this study, we evaluated the prevalence, and risk and protective factors associated with current suicidal ideation (SI) and past suicide attempt (SA) in a contemporary, nationally representative sample of older male veterans. We analyzed data from 1962 male veterans aged 60 or older who participated in the National Health and Resilience Veterans Survey (NHRVS) between October and December 2011. Bivariate analyses and multivariate logistic regression were used to evaluate risk and protective factors associated with current SI and past SA in the full sample, and separately among combat and non-combat veterans. Six percent of the sample reported past 2-week SI, and combat veterans were more likely to contemplate suicide (9.2%) than non-combat (4.0%) veterans. Lifetime SA was reported by 2.6% of respondents. Major depression and physical health difficulties were the strongest risk factors for SI in combat veterans, while generalized anxiety disorder (GAD) was the strongest risk factor for SI in non-combat veterans. Posttraumatic stress disorder (PTSD) was independently associated with SI in both groups of veterans, and social connectedness was negatively related to SI in both groups. These results suggest that a significant proportion of older male veterans in the United States contemplates suicide, with higher rates of SI among combat than non-combat veterans. Interventions designed to mitigate psychological distress and physical difficulties, and to promote social connectedness may help mitigate suicidality risk in this population.

Effects of alcohol on tests of executive functioning in men and women: a dose response examination.

Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohols effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075%, and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the GoStop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the GoStop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely attributable to alcohols interference with prefrontal cortex function. Although it is well established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the GoStop, a visual stop-signal task.

Self-Focused Attention Reduces Self-Injurious Behavior in Alcohol-Intoxicated Men

Both chronic alcohol use and acute intoxication are risk factors for self-aggression (i.e., intentional self-injury) across the spectrum of lethality. Studies designed to identify a cause-and-effect relation between alcohol intoxication and self-aggression, or the factors that facilitate or mitigate this effect, are rare due to the inherent difficulty of studying self-injurious behavior experimentally. In this study, we experimentally demonstrate that alcohol intoxication leads to heightened self-injurious behavior, and that enhanced self-focused attention (self-awareness) attenuates this effect. Specifically, 40 men consumed either alcohol (mean Blood Alcohol Concentration [BAC] = .10) or a veridical control drink, and then completed a laboratory task designed to assess self-injurious behavior. Self-focused attention was experimentally enhanced in half the participants in each drink condition. Results support the notion that prevention and intervention programs designed to reduce intentional self-injurious behaviors should include components that address alcohol misuse and self-awareness.

Social cognitive deficits in schizophrenia and their relationship to clinical and functional status

While research on social cognitive impairments in schizophrenia is quickly growing, relatively little is still known about the severity and correlates of these impairments. The few studies that have examined this issue suggest that social cognitive impairments may be positively related to psychiatric symptoms and negatively related to functioning. In the current analyses of 119 stable outpatients with schizophrenia spectrum diagnoses, we sought to further characterize the nature of social cognitive impairments in schizophrenia. Specifically, we examined (1) social cognitive impairments on four different social cognitive tasks including measures of emotional processing and Theory of Mind and (2) the demographic, symptom and functional correlates of these impairments. For three of the four social cognitive tasks examined, the majority of participants performed 1 or more S.D. worse than healthy controls, with variability in the degree of impairment across tasks. Contrary to expectation, correlations between social cognitive performance on each of the four tasks and clinical and functional features were few and weak, and for the most part did not replicate the previously reported relationship of social cognition to severity of symptoms or current functional status.

Emotional intelligence and impulsive aggression in Intermittent Explosive Disorder

Emotional intelligence (EI) relates to ones ability to recognize and understand emotional information and then, to use it for planning and self-management. Given evidence of abnormalities of emotional processing in impulsively aggressive individuals, we hypothesized that EI would be reduced in subjects with Intermittent Explosive Disorder (IED: n = 43) compared with healthy (n = 44) and psychiatric (n = 44) controls. The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) was used to assess both Experiential EI and Strategic EI. Strategic, but not Experiential, EI was lower in IED compared with control subjects. These differences were not accounted for demographic characteristics, cognitive intelligence, or the presence of clinical syndromes or personality disorder. In contrast, the relationship between IED and Strategic EI was fully accounted for by a dimension of hostile cognition defined by hostile attribution and hostile automatic thoughts. Interventions targeted at improving Strategic EI and reducing hostile cognition will be key to reducing aggressive behavior in individuals with IED.

COMT Associations with Disordered Gambling and Drinking Measures

AbstractDisordered gambling and alcohol dependence are influenced by unique and shared genetic factors. Although the evidence is mixed, some research has linked catechol-O-methyltransferase (COMT) rs4680 (or COMT Val158Met) to the development of gambling or drinking problems; however, no molecular genetic study has jointly examined gambling and drinking problems. Furthermore, the majority of past studies examined gambling or drinking problems using a case–control design. The purpose of the current study was to examine associations of COMT rs4680 with dimensionally and categorically measured gambling and drinking problems in a nonclinical sample (139 Caucasian adults). The current study found that COMT rs4680 was related to both dimensionally and categorically measured gambling and drinking problems. It appears that the COMT Met/Met genotype may be a genetic risk factor that contributes to the development of both gambling and drinking problems.

Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects

Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects.

Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects

Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression.

Serotonin (5-HT) augmentation reduces provoked aggression associated with primary psychopathy traits

Psychopathy has long been associated with aggressive behavior; however, the neurochemical underpinnings of this relationship are poorly understood. Serotonin (5-HT) neurotransmitter system abnormalities have been associated with provoked aggression in general. In addition, 5-HT dysregulation has been linked to empathy, a trait that is lacking in individuals who score high on primary psychopathy. The purpose of this study was to determine if 5-HT modulates the relationship between psychopathic traits and aggression. Participants (N = 47) completed a self-report measure of psychopathy and were then administered either 40 mg paroxetine (acutely augmenting 5-HT) or placebo. Aggression was assessed during a competitive reaction-time game in which electric shocks were exchanged with an increasingly provocative fictitious opponent. Results indicated that primary psychopathy (but not secondary psychopathy) was related to aggressive responding to provocation. Moreover, 5-HT augmentation attenuated this effect, supporting the notion that aggressive responding associated with primary psychopathic traits may be due in part to 5-HT dysregulation.