Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.

Background: Chronic alcohol use results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic-pituitary-adrenal axis responses, high stress-induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol-related stress arousal changes and that alpha-1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake.

Disordered Aggression and Violence in the United States.

Objective: To determine the prevalence and correlates of DSM-5 intermittent explosive disorder and related aggressive disorders in the United States.

Methods: Community survey data (collected between 2001-2004) from the National Comorbidity Survey-Replication (NCS-R) and Adolescent Supplement (NCS-AS) involving 10,148 adolescents and 9,282 adults, respectively, were reanalyzed with recurrent aggressive behavior defined as 3 serious aggressive outbursts in any given year. In addition to prevalence, assessments of aggression severity, property damage, injury to others, intimate partner assault, utilization of guns and weapons to threaten, and treatment utilization for recurrent aggressive behavior were also assessed.

5-HT agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study.

Rationale: Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsive aggression do not respond adequately to selective serotonin reuptake inhibitors and may require treatment with a direct 5-HT agonist.

Objectives: To test the hypothesis that pretreatment with the selective 5-HT2c agonist, lorcaserin, can reduce aggressive responding in impulsively aggressive individuals.

Stress-related suppression of peripheral cytokines predicts future relapse in alcohol-dependent individuals with and without subclinical depression.

Chronic alcohol abuse and depressive symptoms are both associated with peripheral cytokine changes. Despite this, cytokine adaptations have not been assessed in co-morbid populations or prospectively as predictors of relapse. We examine cytokine responses to stress in alcohol-dependent individuals and social drinkers, both with and without subclinical depression.

Lesions causing hallucinations localize to one common brain network.

The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connected brain network.

Role of the kynurenine pathway and the endocannabinoid system as modulators of inflammation and personality traits.

Background: Kynurenine pathway metabolites and endocannabinoids both exert potent regulatory effects on the immune system, but the relationship between these molecules is unknown. The role of these immunobiological mediators in emotionality and personality traits is not previously characterized.

Methods: Interleukin-6 (IL-6), 2-arachidonoylglycerol (2-AG) and picolinic acid (PIC) were measured in the plasma of physically healthy individuals who had history of mood, anxiety, and personality disorders (n = 96) or who had no history of any psychiatric disorder (n = 56) by DSM-5 Criteria.

Psychiatric comorbidity in Intermittent Explosive Disorder.

This study examined aspects of psychiatry comorbidity in Intermittent Explosive Disorder (IED) in order to explore the validity of IED in the context of other psychiatric disorders. Data from the National Comorbidity Study - Revised (NCS-R: n = 9,282 adults) and its Adolescent Supplement (NCS-AS: n = 10,148 adolescents) and a large clinical research data set (n = 1640) were analyzed in this study. Mean number of comorbid disorders among current IED participants was similar to that among other Non-IED disorders and comorbidity of IED with Non-IED disorders was similar to comorbidity among Non-IED disorders.

Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans.

Rationale: The catechol-O-methyl transferase (COMT) enzyme has been implicated in determining dopaminergic tone and the effects of delta-9-tetrahydrocannabinol (THC) in the human brain.

Objective: This study was designed to evaluate the effect of (1) a functional polymorphism and (2) acute pharmacological inhibition of COMT on the acute response to THC in humans.

Methods: Sub-study I: The effect of intravenous (IV) THC (0.

Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis.

Rationale: Δ-9-Tetrahydrocannabinol (Δ-9-THC) produces psychotomimetic effects in humans. However, the role of dopamine signaling in producing such effects is unclear. We hypothesized that dopaminergic antagonism would reduce the psychotomimetic effect of Δ-9-THC.

Social desirability, deceptive reporting, and awareness of problematic aggression in intermittent explosive disorder compared with non-aggressive healthy and psychiatric controls.

Individuals with DSM-5 Intermittent Explosive Disorder (IED) are often suspected of minimizing the nature of their recurrent, problematic, impulsive aggressive behavior due to the social undesirability of these behaviors. Our first study involved 400 study participants categorized as Healthy Controls (HC), Psychiatric Controls (PC) and as having IED and included the Crowne-Marlowe Social Desirability Scale (SDS), the Lie Scale from the Eysenck Personality Questionnaire-Revised (EPQ-R Lie), and the Readiness to Change (Anger) Questionnaire (RTC). IED study participants had lower SDS and lower EPQ-R Lie scores, while having higher RTC scores, compared with both HC and PC study participants.

Comorbidity of personality disorder with intermittent explosive disorder.

There is ambiguity in how recurrent anger and aggression are accounted for by psychiatric nosology. One area of uncertainty is the extent to which Intermittent Explosive Disorder (IED) overlaps with and is distinct from Personality Disorder (PD). Accordingly, we conducted a study of individuals with IED and PD in order to understand the nature of comorbidity relationships seen across these two areas of psychopathology.

Examining the Relationship Between Neurosteroids, Cognition, and Menopause With Neuroimaging Methods.

Purpose Of Review: Previous literature has shown inconsistent findings regarding the effects of neurosteroids on the brain in postmenopausal women. The goal of this paper is to examine how and whether advances in neuroimaging have helped elucidate the relationship between the withdrawal of and/or treatment with neurosteroids and cognition at menopause.

Recent Findings: Neuroimaging techniques such as structural and functional MRI have been used in recent studies to examine the relationship between neurosteroids and brain structure and functioning.

Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause.

Objective: Cancer-related cognitive impairment (CRCI) is commonly reported following the administration of cancer treatment. Current longitudinal studies, primarily in women with breast cancer, suggest that up to 35% to 60% of patients exhibit persistent CRCI (pCRCI) following completion of chemotherapy. Complaints of subjective cognitive decline (SCD) are also commonly reported by women during and following the menopause transition in noncancer patients.

DSM-5 intermittent explosive disorder: Relationship with Disruptive Mood Dysregulation Disorder.

Objective: This study was designed to estimate how many adults with DSM-5 Intermittent Explosive Disorder (IED) would also meet diagnostic criteria for Disruptive Mood Dysregulation Disorder (DMDD). This was done by examining how many individuals with IED would meet the DMDD criterion of being persistently angry in between impulsive aggressive outbursts.

Methods: The first one-hundred study participants diagnosed with DSM-5 IED in our clinical research program were included in this study.

The Psychiatric Consequences of Cannabinoids.

With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function.

Circulating endocannabinoids and affect regulation in human subjects.

The endocannabinoid (EC) system influences a wide variety of neurobiological processes including affect and emotionality as well as other neuropsychiatric functions. In this study we examined the relationship of circulating endocannabinoids [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] with affect and emotionality in 175 individuals with (n = 115) and without (n = 60) mood, anxiety, and/or personality disorders. Circulating AEA levels displayed a modest, though statistically significant, inverse relationship with a composite measure of affect regulation (β = - 0.

Mild Traumatic Brain Injury and Aggression, Impulsivity, and History of Other- and Self-Directed Aggression.

Mild traumatic brain injury (mTBI) is highly prevalent, with an estimated occurrence in the United States of more than 1.3 million per year. While one consequence of mTBI is impulsive aggressive behavior, very few studies have examined the relationship between history of mTBI and aggressive behavior in impulsively aggressive individuals.

Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population.

Background: Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations.

Reduced frontal grey matter, life history of aggression, and underlying genetic influence.

Physically healthy, adult, same-sexed twins (n = 287) from a population-based twin cohort underwent high-resolution magnetic resonance imaging (MRI) to identify fronto-limbic brain regions significantly associated with lifetime history of aggression. MRI scans used a 3D magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence, for voxel-based morphometry (VBM) and history of aggressive behavior was assessed using the Life History of Aggression measure. Aggression had modest, inverse associations with grey matter volume (GMV) in medial prefrontal cortex (mPFC, b = -0.

Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis.

Background: Intermittent explosive disorder is defined as a recurrent, problematic, and impulsive aggression that affects 3% to 4% of the US population. While behavioral genetic studies report a substantial degree of genetic influence on aggression and impulsivity, epigenetic mechanisms underlying aggression and intermittent explosive disorder are not well known.

Methods: The sample included 44 subjects (22 with a DSM-5 diagnosis of intermittent explosive disorder and 22 comparable subjects without intermittent explosive disorder).

Identification and regulation of emotions in adults of varying weight statuses.

Comparing individuals of varying weight statuses on their identification and regulation of emotions may increase our understanding of mechanisms that drive excess weight gain and highlight more precise weight regulation targets. In Study I ( N = 1333), adults with obesity had reduced self-reported attention to and repair of emotions compared to adults with overweight or normal weight. In Study II ( N = 85), adults with obesity had deficits in assessor-administrated tasks of strategic emotional intelligence (i.

Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.

Advances in cancer treatment are producing a growing number of cancer survivors; therefore, issues surrounding quality of life during and following cancer treatment have become increasingly important. Chemotherapy-related cognitive impairment (CRCI) is a problem that is commonly reported following the administration of chemotherapy treatment in patients with cancer. Research suggests that CRCI can persist for months to years after completing treatment, which has implications for the trajectory of normal and pathologic cognitive aging for the growing number of long-term cancer survivors.