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PubMed2005

No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.

The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.

Bipolar Disorder↗
PubMed2005

The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history.

BACKGROUND: This article is the first report of the Irish Affected Sib Pair Study of Alcohol Dependence, whose goal is to detect the genomic location of susceptibility loci for alcohol dependence (AD). This article describes phenotypic characteristics of the probands, siblings, and parents included in the sample and examines agreement among different sources of diagnostic information, including the validity of family history (FH) assessment. METHODS: Structured diagnostic interviews were conducted with 1414 individuals from 591 families ascertained in Ireland. AD was assessed among 1201 probands and affected siblings with use of the Semi-Structured Assessment for the Genetics of Alcoholism and among 213 parents with use of a modified version of the Structured Clinical Interview for DSM. Probands and siblings were also assessed for drinking history, comorbid disorders, and other clinical characteristics. FH reports based on FH-Research Diagnostic Criteria were obtained for 1113 of these individuals as well as for 3652 first-degree relatives who were not interviewed. RESULTS: Sample characteristics confirm the severity of AD among the affected individuals. Agreement between FH ratings and diagnoses based on direct interviews was high for both parent-offspring and sibling-sibling comparisons (e.g., positive and negative predictive values > 80% for a range of cutoffs). Agreement among individuals about their family members was also high for a single item (1 month or more of drinking problems, tetrachoric r = 0.86-0.98), the total number of DSM-IV AD symptoms (polychoric r = 0.86-0.96), and classifications based on a range of cutoffs (kappa = 0.75-0.80). Use of multiple informants improved classification accuracy only slightly (6-10%). CONCLUSIONS: The authors successfully collected data for a large sample of affected sibling pairs for molecular genetic analysis of AD. Individuals with AD were able to provide accurate evaluations of alcoholism symptoms in their parents and adult siblings. A single screening item performed nearly as well as the full scale. Collecting information from multiple informants may not be cost effective for the gain in predictive accuracy. FH information collected from affected informants can be a valuable source of diagnostic information for family studies of alcoholism.

Adult↗
PubMed2006

Affective context-induced modulation of the error-related negativity.

The error-related negativity putatively reflects the activity of performance-monitoring processes influenced by motivational factors, and is overactive in certain anxiety states, suggesting that affective factors affect its generation. We examined the effects of emotionally arousing and neutral task-irrelevant backgrounds on the error-related negativity to determine whether an affective context 'mismatch' alters error-related neural processing. Event-related potentials were acquired while healthy participants performed a modified Eriksen flanker task wherein flanker stimuli were superimposed on neutral, pleasant, and unpleasant pictures. The error-related negativity varied as a function of picture valence, peaking both earlier and larger in the context of pleasant backgrounds than neutral or unpleasant backgrounds. Findings support the hypothesis that affective factors influence the error-related negativity, potentially reflecting an affective mismatch associated with performance monitoring.

Adult↗
PubMed2007

The genetics of bipolar affective disorder.

PURPOSE OF REVIEW: Molecular genetic studies of bipolar affective disorder are beginning to show some positive and reproducible findings. The most relevant of these will be reviewed. RECENT FINDINGS: Obtaining consistent findings from whole genome scans has been hampered by small sample sizes and phenotypic heterogeneity. Recently, there have been concerted efforts to overcome these problems by combining data for meta-analysis. What has become increasingly clear is that several regions that are likely to contain genes contributing to bipolar affective disorder are also relevant to schizophrenia, a finding supported by recent twin data. Studies to date have implicated the D-amino acid oxidase activator complex (also known as G72/G30), disrupted in schizophrenia-1 and neuregulin, and have pointed to several promising linkage regions in which the genes have not yet been identified. In addition, there is some evidence to support the involvement of genetic variants in catechol-o-methyl transferase and brain-derived neurotrophic factor in the aetiology of bipolar affective disorder. SUMMARY: Molecular genetic research in bipolar affective disorder may lead to the development of new diagnostic paradigms for classifying the psychoses and affective states. In addition, determining the functional significance of the susceptibility genes will pave the way for enhanced diagnostic accuracy and improved treatments.

Amino Acid Oxidoreductases↗
PubMed2001

Partial dissociation of PrP(Sc) deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats.

The diagnosis of transmissible spongiform encephalopathies (TSEs) depends on the detection of vacuolation in brain sections taken from affected individuals and/or the identification of the disease-associated isoform of the PrP (prion) protein (PrP(Sc)). During the course of an investigation, goats clinically affected following experimental infection with three different sources of TSE (SSBP/1, CH1641 and BSE) developed widespread vacuolar degeneration in the brain. With BSE, PrP(Sc) was clearly recognized in affected goat brain by immunocytochemistry (icc) and Western blotting, but in contrast the experimental scrapie sources SSBP/1 and CH1641 showed almost no or very little PrP(Sc) by icc. Western blot analysis of PrP(Sc) from BSE-affected and SSBP/1-affected goat brain showed that the protein was present in brain affected by both TSE sources, but could not be used to determine how much protein was present. It became clear that PrP(Sc) and vacuolation could be partially dissociated following challenge with two of the three TSE sources. Subtle differences in glycosylation patterns between BSE- and SSBP/1-associated PrP protein isoforms could also be recognized, although these experimentally generated results should not be regarded as a BSE/scrapie differential test. However, our study warns that the reliance on PrP(Sc) determination by icc alone as a means by which to diagnose TSE infection may generate false negative results.

Animals↗
PubMed2004

Prion protein gene polymorphisms in healthy and scrapie-affected Spanish sheep.

The Rasa Aragonesa sheep is the second most important Spanish breed after the Merino breed. Reported here is the prion protein (PrP) haplotype frequency distribution for scrapie-related codons (136, 154 and 171) and a sequencing study of the complete PrP gene open reading frame for this breed and six other closely related breeds. The study includes four scrapie-affected sheep flocks belonging to Rasa Aragonesa and Rasa Navarra breeds. Thirty-eight scrapie-affected sheep, 502 healthy sheep from scrapie-affected flocks and 905 sheep from a breed survey were genotyped. The most frequent PrP haplotype in both scrapie and healthy flocks was ARQ, which was found at significantly higher frequency in scrapie-affected sheep. The susceptibility-associated VRQ haplotype was found at low frequencies in six out of eight breeds, but was not present in the 38 scrapie-affected sheep. The resistance-associated ARR haplotype was found in all breeds except one (Ojinegra) at frequencies >or=14 %. Fourteen amino acid polymorphisms were detected in these Spanish sheep, including the known amino acid substitutions at codons 112, 136, 141, 143, 154, 171 and 176, and new polymorphisms at codons 101 (Q-->R), 151 (R-->G), 151 (R-->H), 172 (Y-->D) and 175 (Q-->E). Most of the novel polymorphic codons show frequencies lower than 5 %.

Animals↗
PubMed2004

Fifteen-year follow-up of ICD-10 schizoaffective disorders compared with schizophrenia and affective disorders.

OBJECTIVE: The nosological status of schizoaffective disorders is still unclear. The aim of the present study was to compare ICD-10 schizoaffective disorders to schizophrenia and affective disorders with respect to the clinical picture and the long-term outcome. METHOD: Two hundred and forty-one first-admitted inpatients from the years 1980-1982 who fulfilled the ICD-10 criteria for schizophrenia, schizoaffective or affective disorders were included. Patients were examined at the time of first hospitalization and then followed-up after 15 years. RESULTS: With respect to the clinical picture at the time of first hospitalization ICD-10 schizoaffective disorders were distinguishable from both schizophrenia and affective disorders. However, with respect to the long-term outcome ICD-10 schizoaffective disorders had a prognosis similar to that of affective disorders. CONCLUSION: Differing prognosis implies that schizoaffective disorders should be distinguished from schizophrenia and suggests their subcategorization under affective disorders.

Adult↗
PubMed1994

Polymorphism analysis of the prion gene in BSE-affected and unaffected cattle.

Polymerase chain reaction (PCR) primers designed to amplify the octapeptide repeat region of the bovine prion gene were used to test the association of genotypes with bovine spongiform encephalitis (BSE) in 56 BSE-affected and 177 unaffected animals. Three alleles (A,B,C) were detected as single-strand conformation polymorphisms (SSCPs) and two alleles (1,2--representing six or five copies of the octapeptide repeat respectively) were detected as amplified double-strand fragment length polymorphisms (AMFLPs). Observed genotypes of SSCPs and AMFLPs were analysed by chi-square. The SSCP genotypes of nuclear family members of animals with BSE and BSE-affected animals were different (P < 0.001, P < 0.01) from unrelated animals of the same breed without BSE. No genotypic differences were found between the BSE-affected animals and their relatives (P > 0.469). No AMFLP genotypic differences were detected between BSE-affected animals, their relatives, unrelated animals of the same breed or animals of different breeds (P > 0.05). These data suggest that BSE-affected animals and their relatives are more likely to have the AA SSCP genotype than unrelated animals of the same breed or animals of different breeds.

Alleles↗
PubMed2005

Self-care in diabetes: model of factors affecting self-care.

AIMS AND OBJECTIVES: The aim of this paper is to explore self-care in diabetes and to present a model of factors that affect self-care according to reviewed literature. BACKGROUND: Self-care in diabetes is crucial to keep the disease under control. Self-care consists at least four aspects: (i) self-monitoring of blood glucose, (ii) variation of nutrition to daily needs, (iii) insulin dose adjustments to actual needs and (iv) taking exercise regularly. It is known that diverse factors influence self-care such as knowledge, physical skills and emotional aspects and self-efficacy which have been listed as being of high importance. METHODS: The searched databases were ProQuest, PsycINFO and Medline from 1995 to 2002. The search terms were "self-care" or "self-management" coexisting with diabetes and "self-efficacy". The search was limited to English and adults with type 1 diabetes. RESULTS: The main components of the model clarify how knowledge, physical skills and emotional factors as well as self-efficacy influence self-care which again affects metabolic control. Flexible self-care indicates high level of self-care when patients are able to care for and manage the disease in a responsible and flexible way that does not affect their life extensively, resulting in adequate glycosylated haemoglobin value. Self-efficacy is a strong predictor of flexible self-care and affects metabolic control through increased perceived ability to conduct self-care. CONCLUSIONS: The review illuminated that benefits of self-care should be emphasized and knowledge of the Diabetes Complication and Control Trial results can contribute to better self-care. However, factors affecting flexible self-care still require better identification. RELEVANCE TO CLINICAL PRACTICE: The review emphasizes and adds to the topic, that in daily practice health care practitioners must assess diabetes-related knowledge, physical skills and emotional factors in combination with self-efficacy and the four self-care areas. The effects of self-monitoring of blood glucose needs better clarifications as it is now regarded the cornerstone of flexible self-care.

Blood Glucose Self-Monitoring↗
PubMed1992

Urinary protein analysis in cardiomyopathy-affected and healthy cattle by SDS-polyacrylamide gel electrophoresis.

Urinary proteins of cardiomyopathy (CMP)-affected (n = 31) and of healthy cattle (n = 35) were analyzed by a combination of SDS-polyacrylamide gel electrophoresis and silver stain. The following results were obtained: 1) Out of the various urinary proteins found in CMP-affected and healthy cattle, IgG, Tf, Alb, alpha 1-acid GP, Apo A1, IgG heavy and light chain could be identified. 2) In CMP-affected cattle, all the proteins mentioned above were detected in increased amounts in the urine. The quantities of Alb, Tf, and IgG were especially large. 3) In the case of CMP, the permeability of the glomerular filter was highly increased for large serum proteins. The tubular protein reabsorption of small proteins was less altered by the disease. 4) Although the electrophoretic pattern of the urinary proteins was abnormal in all the examined CMP-affected animals, the urinary protein concentrations were increased (> 230 mg/l) in only 42% of the cases. Consequently, the urinary protein concentration is not a reliable parameter for detecting renal diseases. 5) For both CMP-affected and healthy cattle the urinary protein pattern depended neither on the urine sampling technique (catheterization, spontaneous urine) nor on the reproductive stage.

Animals↗
PubMed2004

Central blockade of muscarinic cholinergic receptors disrupts affective and attentional set-shifting.

Impairments in multiple aspects of attentional and executive function follow damage to cholinergic neurons in the central nervous system. Affective and attentional set-shifting represent two aspects of executive function controlled by different sectors of the prefrontal cortex. The involvement of cholinergic neural mechanisms in these aspects of executive function has not been specified. To determine whether central muscarinic cholinergic receptors were involved in affective and/or attentional set-shifting, we tested rats on a series of discrimination learning problems, which included affective (reversal learning) and attentional set (extradimensional shift)-shifting components, under the systemic influence of scopolamine, a muscarinic antagonist. Scopolamine impaired both reversal learning and extradimensional shifting, but was without effect on learning new discrimination problems that did not require an affective or attentional shift. Systemic administration of methylscopolamine, which does not cross the blood-brain barrier, did not impair affective or attentional set-shifting, indicating that the scopolamine effects were centrally mediated. These data implicate muscarinic receptors in the central nervous system in the control of executive function. Taken together with other recent data, they may also suggest an important role for cholinergic receptors outside of the neocortex in regulating these aspects of attention and executive function.

Animals↗
PubMed1976

Ages of death of children with Huntington's chorea and of their affected parents.

Bird et al. (1974) noted an interesting 'anticipation' phenomenon in Huntington's Chorea occurring in patients who inherited the gene from their father. More extensive samples from 165 pedigrees in the Low Countries permitted us to show that most of this apparent 'anticipation' is an artifact due to sampling biases related to the year of birth categories of the affected parents. When these biases were excluded no differences exist between the ages of death of affected mothers and their affected children, but a small difference of approximately two years remains between affected fathers and their affected children. This is explainable by the observation that juvenile cases of Huntington's Chorea usually have inherited the abnormality from their father.

Adolescent↗
PubMed1991

Using a dummy quantitative variable to deal with multiple affection categories in genetic linkage analysis.

Some diseases which have a genetic contribution to aetiology do not demonstrate a clear correspondence between genotype and phenotype. A variety of different clinical syndromes may be thought to reflect the action of a gene, but the probability of affection conditional on genotype may vary between these different diagnostic categories. The normal approach of repeating linkage analyses several times using different diagnoses to define individuals as affected loses power in two ways: multiple testing must be allowed for, and the distinction between more and less extreme forms of affection is lost. It is shown that for fully dominant or recessive autosomal diseases it is straightforward to assign a quantitative value to each diagnostic category to obtain the desired ratio of the likelihoods of affection conditional on the three possible genotypes. The increased power provided by using this quantitative value in linkage analysis is demonstrated by application to simulated pedigrees containing cases of bipolar and unipolar affective disorder.

Bipolar Disorder↗
PubMed1992

An observational study of the affective concomitants of mastery in infants.

The hypothesis that attempts at motor mastery were accompanied by positive affective responses was tested in an observational study of 9-11-month old infants in a daycare setting. Five infants were observed as they attempted three age-appropriate motor tasks--pulling to stand, standing with support, and taking steps with support. Positive affective responses included smiling, babbling, and laughing. The five infants were observed for a total of 82 hours. The proportion of positive affective behaviors associated with practicing new motor tasks was compared to the proportion associated with well-practiced tasks. The hypothesis that more positive affective behaviors would be associated with attempts at mastering the new motor tasks was confirmed. There was no diminution in the association between the new motor tasks and positive affect as the infants continued to practice and master the three motor tasks. The results are discussed in terms of individual differences in mastery motivation and the often suggested continuity between early mastery motivation and later competencies.

Child↗
PubMed1997

Sleep problems in children of affectively ill mothers.

The objective of the study was to determine whether the frequency and severity of sleep problems were greater in children of affectively ill mothers than in children of control mothers. Sleep problems were studied in children of mothers with a diagnosis of unipolar (N = 38) and bipolar (N = 23) affective illness and children of mothers with no current or past psychiatric diagnosis (N = 24). Mothers' reports on the Child Behavior Checklist (CBCL) were obtained three times, 4 years apart, on sibling pairs (ages 1.5-3.5 and 5-8 years, respectively, at first assessment). In addition, on the third assessment, the Diagnostic Interview for Children and Adolescents was filled out by mothers and children. In both siblings, sleep problems, as assessed through the CBCL, were more frequent and severe in children of affectively ill mothers. In younger siblings, the persistence of sleep problems was more frequent in children of affectively ill mothers. Co-occurrence of sleep problems among siblings was more frequent in children of affectively ill mothers than in those of control mothers.

Adult↗
PubMed1992

Characterization of neutral proteinases from Alzheimer-affected and control brain specimens: identification of calcium-dependent metalloproteinases from the hippocampus.

Three neutral proteinases from human hippocampal tissue have been identified and partially characterized using substrate gel electrophoresis. The proteinases showed activity when gelatin was used as the substrate, but had no detectable activity against casein. Based on the results of inhibition studies and the calcium requirements, it was concluded that the activities were due to calcium-dependent metalloproteinases. The apparent molecular weights were 130,000 (MP-130), 100,000 (MP-100), and 70,000 (MP-70). Half-maximal activities were observed with 20 microM Ca2+ for MP-130, 40 microM Ca2+ for MP-100, and 800 microM Ca2+ for MP-70. In the presence of Ca2+, Zn2+ reestablished the activities of the three metalloproteinases at a lower concentration than did either Co2+ or Mn2+. One millimolar Al3+ inhibited 67% of the MP-70 activity, but did not affect the MP-100 and MP-130 activities. An analysis of Alzheimer-affected hippocampal and control samples showed that the specific activity (in units per milligram of sodium dodecyl sulfate-soluble protein) of MP-70 varied less than the activities of MP-100 and MP-130 between the two groups. Although p-amino-phenylmercuric acetate (p-APMA) increased the activities of MP-70 by 70% in both groups of specimens, the resulting activities from Alzheimer samples were greater than those from control samples (p less than 0.01). A wide range of MP-100 specific activity was observed in both groups, and its mean activity was higher in Alzheimer-affected samples (p less than 0.05). Treatment with p-APMA increased the activity of MP-100 only 25% in both groups of tissue samples. MP-130 activity was detected predominantly in Alzheimer-affected hippocampal specimens, and treatment with p-APMA failed to increase its activity in both the control and the Alzheimer-affected specimens. The results demonstrate an elevated level of metalloproteinase activities, capable of degrading tissue matrix components, in the hippocampus from postmortem Alzheimer patients.

Aged↗
PubMed1997

Knowledge generation for the HIV-affected family.

PURPOSE: To examine the current literature about HIV-affected families in regard to knowledge development and priorities for future research. SIGNIFICANCE: The current view of HIV focuses largely on HIV-infected individuals. There is a paucity of relevant research and a need to make explicit the priorities for knowledge generation about HIV-affected families. SCOPE: HIV family literature, 1980-1996, was reviewed and categorized and serves as the context for presenting future priorities for knowledge generation about HIV-affected families. Priorities identified were designing and testing family-level services; determining epidemiology of the phenomenon of HIV family caregiving; who gives care and why, what caregivers do, the outcomes of caregiving, quality of family care, and relationships CONCLUSIONS: A critical need is to address in-depth the problems that have limited knowledge development about HIV-affected families. This explication of issues and questions to understand HIV-affected families can stimulate future research.

Caregivers↗
PubMed1978

Life events and primary affective illness.

Life events at the onset of primary affective illness were assessed in 183 patients with primary affective disorder who were attending a research lithium clinic. About 50% of patients recalled significant life events in the 3-month interval preceding their initial affective episode. Family history data of those patients who reported life events were not significantly different from those who did not report life events at onset. Furthermore, there were no significant differences among patients classified as bipolar or unipolar regarding reporting of life events at onset of illness. These data suggest that the delineation of a subgroup of patients with "reactive" primary affective illness is not supported by a decreased familial load for affective disorder in their relatives.

Adult↗