Learned irrelevance and associative learning is attenuated in individuals at risk for psychosis but not in asymptomatic first-degree relatives of schizophrenia patients: translational state markers of psychosis?

Learned irrelevance (LIrr) refers to a form of selective learning that develops as a result of prior noncorrelated exposures of the predicted and predictor stimuli. In learning situations that depend on the associative link between the predicted and predictor stimuli, LIrr is expressed as a retardation of learning. It represents a form of modulation of learning by selective attention. Given the relevance of selective attention impairment to both positive and cognitive schizophrenia symptoms, the question remains whether LIrr impairment represents a state (relating to symptom manifestation) or trait (relating to schizophrenia endophenotypes) marker of human psychosis. We examined this by evaluating the expression of LIrr in an associative learning paradigm in (1) asymptomatic first-degree relatives of schizophrenia patients (SZ-relatives) and in (2) individuals exhibiting prodromal signs of psychosis ("ultrahigh risk" [UHR] patients) in each case relative to demographically matched healthy control subjects. There was no evidence for aberrant LIrr in SZ-relatives, but LIrr as well as associative learning were attenuated in UHR patients. It is concluded that LIrr deficiency in conjunction with a learning impairment might be a useful state marker predictive of psychotic state but a relatively weak link to a potential schizophrenia endophenotype.

A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer

First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in prostate-specific antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.

Premorbid IQ in patients with functional psychosis and their first-degree relatives

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC +) and those who had not (OC -). Both OC + and OC - schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC + patients and their relatives. Relatives of OC + schizophrenic patients had significantly higher IQ than relatives of OC - schizophrenic patients. (C) 2000 Elsevier Science B.V. All rights reserved.

First Degree Bestowed

The first graduate, John Auld, receives his convocation hood from (?) during the first ever Convocation held at Brock in 1967. Chancellor R. L. Hearn stands in front of John Auld.

First-Degree Discrimination in a Competitive Setting: Pricing and Quality Choice

The paper investigates competition in price schedules among vertically differentiated dupolists. First order price discrimination is the unique Nash equilibrium of a sequential game in which firms determine first whether or not to commit to a uniform price, and then simultaneously choose either a single price of a price schedule. Whether the profits earned by both firms are larger or smaller under discrimination than under uniform pricing depends on the quality gap between firms, and on the disparity of consumer preferences. Firms engaged in first degree discrimination choose quality levels that are optimal from a welfare perspective. The paper also reflects on implications of these findings for pricing policies of an incumbent threatened by entry.

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/µU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Impaired top-down modulation of saccadic latencies in patients with schizophrenia but not in first-degree relatives

Impaired eye movements have a long history in schizophrenia research and meet the criteria of a reliable biomarker. However, the effects of cognitive load and task difficulty on saccadic latencies (SL) are less understood. Recent studies showed that SL are strongly task dependent: SL are decreased in tasks with higher cognitive demand, and increased in tasks with lower cognitive demand. The present study investigates SL modulation in patients with schizophrenia and their first-degree relatives. A group of 13 patients suffering from ICD-10 schizophrenia, 10 first-degree relatives, and 24 control subjects performed two different types of visual tasks: a color task and a Landolt ring orientation task. We used video-based oculography to measure SL. We found that patients exhibited a similar unspecific SL pattern in the two different tasks, whereas controls and relatives exhibited 20–26% shorter average latencies in the orientation task (higher cognitive demand) compared to the color task (lower cognitive demand). Also, classification performance using support vector machines suggests that relatives should be assigned to the healthy controls and not to the patient group. Therefore, visual processing of different content does not modulate SL in patients with schizophrenia, but modulates SL in the relatives and healthy controls. The results reflect a specific oculomotor attentional dysfunction in patients with schizophrenia that is a potential state marker, possibly caused by impaired top-down disinhibition of the superior colliculus by frontal/prefrontal areas such as the frontal eye fields.

Incidence of breast cancer in first-degree female relatives of men with newly diagnosed prostate cancer

Prostate cancer is the most common incident cancer and the second leading cause of death in men in the United States. Although numerous attempts have been made to identify risk factors associated with prostate cancer, the results have been inconsistent and conflicting. The only established risk factors are age and ethnicity. A positive family history of prostate cancer has also been shown to increase the risk two- to three-fold among close relatives.^ There are several similarities between breast and prostate cancer that make the relationship between the two of interest. (1) Histologically, both cancers are predominantly adenocarcinomas, (2) both organs have a sexual and/or reproductive role, (3) both cancers occur in hormone-responsive tissue, (4) therapy often consists of hormonal manipulation, (5) worldwide distribution patterns of prostate and breast cancer are positively correlated.^ A family history study was conducted to evaluate the aggregation of prostate cancer and co-aggregation of breast cancer in 149 patients referred to The University of Texas, M.D. Anderson Cancer Center with newly diagnosed prostate cancer. All patients were white, less than 75 years of age at diagnosis and permanent residents of the United States. Through a personal interview with the proband, family histories were collected on 1,128 first-degree relatives. Cancer diagnoses were verified through medical records or death certificate. Standardized incidence ratios were calculated using a computer program by Monson incorporating data from Connecticut Tumor Registry.^ In this study, familial aggregation of prostate cancer was verified only among the brothers, not among fathers. Although a statistically significant excess of breast cancer was not found, the increased point estimates in mothers, sisters and daughters are consistent with a co-aggregation hypothesis. Rather surprising was the finding of a seven-fold increased risk of prostate cancer and a three-fold increased risk of breast cancer among siblings in the presence of a maternal history of any cancer. Larger family history studies including high risk (African-Americans) and lower-risk groups (Hispanics) and incorporating molecular genetic evaluations should be conducted to determine if genetic differences play a role in the differential incidence rates across ethnic groups. ^