Impact of Primary Disease Site of Involvement by Early-Stage Follicular Lymphoma on Patient Outcomes.

Introduction: Follicular lymphoma is a common non-Hodgkin lymphoma that can start in a diverse array of tissues throughout the body. While the majority of patients may be able to live many years with this disease, cure remains very difficult to achieve.

Objective: We sought to investigate the impact of follicular lymphoma primary disease site in early-stage disease on patient outcomes using a large national database.

Early life adversity and increased antisocial and depressive tendencies in young adults with family histories of alcohol and other substance use disorders: Findings from the Family Health Patterns project.

Background: Individuals with a family history of alcohol and other substance use disorders (FH+) are several times more likely to develop alcohol problems compared to individuals with no such family histories (FH-). Here we sought to evaluate associations of early life adversity (ELA) with two key risk-related FH+ phenotypic characteristics: increased antisocial and depressive tendencies.

Methods: We examined data from 1187 FH+ and FH- young adults (average age 23.

Addiction resistance to alcohol: What about heavy drinkers who avoid alcohol problems?

Background: Some individuals are resistant to alcohol use disorders despite high levels of intake. Addiction Resistance (AR) measures the disparity between alcohol consumption and alcohol use disorder (AUD) symptoms, such that some persons exhibit few (AUD) symptoms despite higher intake. The validity of the concept and the factors contributing to AR are not well understood.

Working memory reflects vulnerability to early life adversity as a risk factor for substance use disorder in the FKBP5 cortisol cochaperone polymorphism, rs9296158.

Early life adversity (ELA) negatively affects health behaviors in adulthood, but pathways from ELA exposure to behavioral outcomes are poorly understood. ELA in childhood and adolescence may translate into adult outcomes by way of modified glucocorticoid signaling. The cortisol cotransporter, FKBP5 has a G-to-A substitution (rs9296158) that hinders cortisol trafficking within target cells, and this impaired glucocorticoid signaling may shape the long-term response to ELA.

Early-Life Adversity and Blunted Stress Reactivity as Predictors of Alcohol and Drug use in Persons With COMT (rs4680) Val158Met Genotypes.

Background: Risk for alcoholism may be enhanced by exposure to early-life adversity (ELA) in persons with genetic vulnerabilities. We examined ELA in the presence of a common variant of the gene for the enzyme catechol-O-methyltransferase (COMT, Val158Met, rs4680) in relation to cortisol reactivity, the onset of early drinking, and experimentation with drugs.

Methods: Saliva cortisol reactivity to speech and mental arithmetic stress was measured in 480 healthy young adults (23.

Cortisol stress reactivity in women, diurnal variations, and hormonal contraceptives: studies from the Family Health Patterns Project.

Women have smaller cortisol responses to psychological stress than men do, and women taking hormonal contraceptives (HC+) have smaller responses than HC- women. Cortisol secretion undergoes substantial diurnal variation, with elevated levels in the morning and lower levels in the afternoon, and these variations are accompanied by differences in response to acute stress. However, the impact of HC use on these diurnal relationships has not been examined.

Early life adversity and increased delay discounting: Findings from the Family Health Patterns project.

Increased discounting (devaluing) of delayed rewards is associated with nearly all types of substance use disorders (SUDs) and is also present in individuals with family histories of SUDs. Early life adversity (ELA) likely contributes to these findings as it is common in both individuals with SUDs and their children and is linked to increased delay discounting and other neurocognitive impairments in human and animal studies. Here we examined data from 1192 healthy young adults (average age 23.

Blunted stress reactivity reveals vulnerability to early life adversity in young adults with a family history of alcoholism.

Background And Aims: People with blunted stress reactivity have poor impulse control and also show increased risk for alcoholism. Exposure to early life adversity (ELA) contributes to blunted reactivity, but individual differences in susceptibility to ELA are not well understood. This study aimed to determine whether exposure to ELA has a greater impact on stress reactivity in young adults with a family history of alcoholism (FH+) compared with young adults with no family history of alcoholism (FH-).

Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project.

Early life adversity (ELA) contributes to behavioral impulsivity along with risk for substance use disorders, both accompanied by blunted stress-axis reactivity. However, the biological contributors to blunted stress reactivity are not known. We took advantage of the fact that women have significant opioid inhibition of cortisol output by using the opioid antagonist, naltrexone, to unmask opioid interactions due to ELA.

Defining the phenotype of young adults with family histories of alcohol and other substance use disorders: Studies from the family health patterns project.

Individuals with a family history of alcohol and other drug use disorders (FH+) are at increased risk for developing substance use disorders themselves relative to those with no such histories (FH-). Here we sought to identify key characteristics associated with FH+ status and alcohol and other drug use disorder status in a large cohort of FH+ and FH- young adults. We conducted principal component analyses on demographic, temperament, and cognitive measures differentiating 506 FH+ and 528 FH- young adults.

Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress.

Objective: Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers.

Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project.

Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling.

Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.

Differences in stress reactivity may affect long-term health outcomes, but there is little information on how these differences arise. The stress axis is regulated by, in part, the endogenous opioid, beta-endorphin, acting on mu-opioid receptors. Persons carrying one or two copies of the G allele of the mu-opioid receptor gene (OPRM1 A118G) may have higher receptor binding for beta-endorphin compared with AA homozygotes that may contribute to individual differences in cortisol reactivity to stress, leading to a relative blunting of cortisol stress reactivity in G allele genotypes.

Risk factors for alcoholism in the Oklahoma Family Health Patterns project: impact of early life adversity and family history on affect regulation and personality.

Aim: This study examined the impact of early lifetime adversity (ELA) on affect regulation and personality in persons with family history (FH+) and without (FH-) a family history of alcoholism. We examined the impact of early life adversity in healthy young adults, 18-30 years of age enrolled in a long-term study on risk for alcohol and other substance abuse.

Methods: ELA was assessed by a composite score of low socioeconomic status and personal experience of physical or sexual abuse and/or separation from parents before age 16, resulting in a score of 0, 1-2, or >3 adverse events.

Anomalous temporoparietal activity in individuals with a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.

Background: Individuals with a family history of alcoholism (FH+) are at enhanced risk of developing alcohol or other substance use disorders relative to those with no family history (FH-). Alcoholics and FH+ subjects have greater interference scores on the Stroop color-word task, suggesting these impairments may be a component of the cognitive phenotype of at-risk individuals.

Methods: In this study, we examined whole-brain activations in 24 FH+ and 28 FH- young adults performing the counting Stroop task, a variant of the Stroop task adapted for neuroimaging studies.

Differential impact of serotonin transporter activity on temperament and behavior in persons with a family history of alcoholism in the Oklahoma Family Health Patterns Project.

Background: Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+).

Methods: We tested 314 healthy young adults (23.

Hormonal contraceptive use diminishes salivary cortisol response to psychosocial stress and naltrexone in healthy women.

The use of hormonal contraception (HC) may affect salivary cortisol levels at rest and in response to a pharmacological or stress challenge. Therefore, the current study used a secondary data analysis to investigate the effect of HC on salivary cortisol levels in response to the mu-opioid receptor antagonist naltrexone and a psychosocial stressor, and also across the diurnal curve. Two hundred and nine women (n=72 using hormonal contraception; HC+) completed a two-session stress response study that consisted of a stress day, in which they were exposed to public speaking and mental arithmetic, and a rest day, in which unstimulated cortisol levels were measured to assess the diurnal rhythm.

Early life adversity contributes to impaired cognition and impulsive behavior: studies from the Oklahoma Family Health Patterns Project.

Background: Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism.

Methods: We tested 386 healthy young adults (18 to 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop color-word task, and a delay discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards.

Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.

Naltrexone evokes a cortisol response through its blockade of central opioid receptors on the hypothalamic-pituitary-adrenocortical axis (HPA). The magnitude of this cortisol response may be useful as a probe for central opioid activity in different groups of subjects. Accordingly, the present study examined the effect of opioid blockade on the HPA in 70 women and 58 men with (N=41) and without (N=87) a family history of alcoholism, using a randomized, placebo-controlled, double blind administration of oral naltrexone (50mg).

Lifetime adversity leads to blunted stress axis reactivity: studies from the Oklahoma Family Health Patterns Project.

Background: Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease; however, little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity.

Methods: We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory.