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The prevalence of migraine in patients with bipolar and unipolar affective disorders.

There is a well-known association between migraine and affective disorders, but the information is sparse concerning the prevalence of migraine in subgroups of the affective disorders. The present study was undertaken to investigate the prevalence of migraine in unipolar depressive, bipolar I and bipolar II disorders. Patients with major affective disorders (n = 62), consecutively admitted to an open psychiatric ward, were examined with a semi-structured interview based on DSM-IV diagnostic criteria, combined with separate criteria for affective temperaments. Diagnosis of unipolar and bipolar I disorders followed the DSM-IV criteria, while bipolar II disorder encompassed patients with either discrete hypomanic episodes or a cyclothymic temperament. Migraine was diagnosed according to IHS-criteria. Symptoms of migraine were found to be common in these patients, both in those with unipolar depression (46% prevalence of migraine) and in those with bipolar disorders (44% prevalence). Among the bipolar patients there was, however, a striking difference between the two diagnostic subgroups, with a prevalence of 77% in the bipolar II group compared with 14% in the bipolar I group (P = 0.001). These results support the contention that bipolar I and II are biologically separate disorders and point to the possibility of using the association of bipolar II disorder with migraine to study both the pathophysiology and the genetics of this affective disorder.

Adult↗

On the power of affected relative pair designs for linkage studies.

Using the recurrence risk ratio (lambda), Risch (1990b) indicated that affected pairs of distant relatives are preferable to affected sib-pairs for linkage analysis when lambda is large and the mode of inheritance is additive. By using the optimum test for affected sib-pairs instead of the test used by Risch (1990b), the range of values of lambda for which the affected sib-pair design has larger or smaller power than other pairs is clarified. Risch's conclusion remains true when lambdaO > 2.5, however, sib-pairs have larger power for lower values. As affected sib-pairs occur smore frequently than other relative pairs, when ascertainment costs are non-negligible, they may be the most cost-effective relative pairs to use.

Genetic Linkage↗

Inflammatory bowel disease in 67 families each with three or more affected first-degree relatives.

BACKGROUND & AIMS: Some families have multiple members with inflammatory bowel disease (IBD). Do clinical features of familial differ from sporadic cases? Is there concordance between affected family members? Do environmental factors affect familial clustering? METHODS: In 67 families, each with three or more first-degree relatives with IBD, the 213 affected family members were interviewed, and their case records were reviewed. RESULTS: The clinical manifestations of familial cases did not differ from IBD reported in a large series. There was concordance for type of disease (P < 0.001) but not greater than expected concordance for age at diagnosis, site and extent of disease, or transmural aggressiveness of Crohn's disease. A significant association between smoking with Crohn's disease and non-smoking with ulcerative colitis was found (P < 0.001), even in families with both disorders. The intervals between diagnosis of successive family cases varied so greatly that a single etiologic factor with a constant latent period seems to be unlikely. When IBD affected successive generations, parents were diagnosed at a later age than the children (P < 0.001) and after the child in 12 of 49 cases. CONCLUSIONS: Analysis has not identified any clinically significant differences between familial and sporadic cases of IBD. Tobacco smoking affects disease type in familial cases.

Adolescent↗

Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders.

The therapeutic effects of carbamazepine (CBZ) were evaluated in 103 patients with affective disorders, 54 with schizophrenic disorders, and 26 with schizoaffective disorders by a multi-institutional open study. The rate of marked and moderate improvement was 72.8% in affective disorders, 54.6% in schizophrenic disorders, and 61.5% in schizoaffective disorders. Symptom items of the Clinical Psychopharmacology Research Group rating scale for mania showed significant improvement in the patients with affective disorders as well as in those of the other two groups. In the Brief Psychiatric Rating Scale as applied to patients with schizophrenic or schizoaffective disorders, symptom items related to affect and emotion showed significant improvement. The antimanic efficacy of CBZ was also noted in many poor responders to lithium. Side-effects were observed in 82 patients (44.8%), and abnormal laboratory findings in 37 patients (44.8%), and abnormal laboratory findings in 37 patients. The present study seems to confirm the usefulness of CBZ for the treatment of affective disorders and in some cases, of schizophrenic and schizoaffective disorders.

Adult↗

Erythrocyte lithium transport during lithium treatment in patients with affective disorders.

Erythrocyte lithium transport mechanisms--lithium-sodium countertransport (LSC), lithium-potassium cotransport (LPC) and passive lithium efflux (PLE)--were measured in 46 patients with bipolar affective disorder on prophylactic lithium therapy and in 20 healthy control subjects. Maximal velocity of LSC measured at saturating intracellular lithium concentration was lower in the patients than in the controls; this may concur with previous reports on possible links between impaired activity of LSC and bipolar affective illness. When measured at therapeutic lithium concentration, LSC was 4 times lower and Km for LSC was 5 times higher in lithium-treated affective patients than in control subjects. The in vivo erythrocyte:plasma lithium ratio was inversely correlated with LSC in lithium-treated patients; higher ratios were found in females than in males. No differences were found between affective patients and control subjects in other erythrocyte lithium transport measurements. The values for lithium transport were not related to age, duration of lithium therapy, concomitant neuroleptic treatment, hypertension or obesity. Lower activity of LSC was found in patients with lithium-induced thyroid enlargement than in the other patients. The results obtained are discussed in the light of contemporary findings concerning erythrocyte lithium transport mechanisms in affective disorders and other conditions.

Adult↗

The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal.

The negative affective symptoms of opiate withdrawal powerfully motivate drug-seeking behavior and may trigger relapse to heroin abuse. To date, no medications exist that effectively relieve the negative affective symptoms of opiate withdrawal. The corticotropin-releasing factor (CRF) system has been hypothesized to mediate the motivational effects of drug dependence. The CRF signal is transmitted by two distinct receptors named CRF receptor-1 (CRF1) and CRF2. Here we report that genetic disruption of CRF1 receptor pathways in mice eliminates the negative affective states of opiate withdrawal. In particular, neither CRF1 receptor heterozygous (CRF1+/-) nor homozygous (CRF1-/-) null mutant mice avoided environmental cues repeatedly paired with the early phase of opiate withdrawal. These results were not due to altered associative learning processes because CRF1+/- and CRF1-/- mice displayed reliable, conditioned place aversions to environmental cues paired with the kappa-opioid receptor agonist U-50,488H. We also examined the impact of CRF1 receptor-deficiency upon opiate withdrawal-induced dynorphin activity in the nucleus accumbens, a brain molecular mechanism thought to underlie the negative affective states of drug withdrawal. Consistent with the behavioral indices, we found that, during the early phase of opiate withdrawal, neither CRF1+/- nor CRF1-/- showed increased dynorphin mRNA levels in the nucleus accumbens. This study reveals a cardinal role for CRF/CRF1 receptor pathways in the negative affective states of opiate withdrawal and suggests therapeutic strategies for the treatment of opiate addiction.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

The Wsh and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in Wsh and Ph mutant mice.

The receptor tyrosine kinases (RTKs) c-kit and platelet-derived growth factor receptor alpha chain (PDG-FRa) are encoded at the white spotting (W) and patch (Ph) loci on mouse chromosome 5. While W mutations affect melanogenesis, gametogenesis, and hematopoiesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. W-sash (Wsh) is an expression mutation and blocks c-kit expression in certain cell types and enhances c-kit expression in others, including at sites important for early melanogenesis. We have determined the effect of Ph on c-kit expression during embryogenesis in Ph heterozygotes. Immunohistochemical analysis revealed enhanced c-kit expression in several cell types, including sites important for early melanogenesis. We propose that in both Wsh and Ph mutant mice c-kit misexpression affects early melanogenesis and is responsible for the pigment deficiency. Moreover, we have defined the organization of the RTKs in the W/Ph region on chromosome 5 and characterized the Wsh mutation by using pulsed-field gel electrophoresis. Whereas the order of the RTK genes was determined as Pdgfra-c-kit-flk1, analysis of the Wsh mutation revealed that the c-kit and Pdgfra genes are unlinked in Wsh, presumably because of an inversion of a small segment of chromosome 5. The Ph mutation consists of a deletion including Pdgfra and the 3' deletion endpoint of Ph lies between Pdgfra and c-kit. Therefore, positive 5' upstream elements controlling c-kit expression in mast cells and some other cell types are affected by the Wsh mutation and negative elements are affected by both the Wsh and the Ph mutation.

Animals↗

Screening the yeast "disruptome" for mutants affecting resistance to the immunosuppressive drug, mycophenolic acid.

The immunosuppressive drug mycophenolic acid (MPA) is a potent and specific inhibitor of IMP dehydrogenase, the first committed step of GMP synthesis. A screen for yeast genes affecting MPA sensitivity, when overexpressed, allowed us to identify two genes, IMD2 and TPO1, encoding a homologue of IMP dehydrogenase and a vacuolar pump, respectively. In parallel, 4787 yeast strains, each carrying an identified knock-out mutation, were tested for growth in the presence of MPA, allowing identification of 100 new genes affecting MPA resistance when disrupted. Disturbance of several cellular processes, such as ergosterol biosynthesis, vacuole biogenesis, or glycosylation impaired the natural capacity of yeast to resist MPA, although most of the highly sensitive mutants affected the transcription machinery (19 mutants). Expression of TPO1 and/or IMD2 was strongly affected in 16 such transcription mutants suggesting that low expression of these genes could contribute to MPA sensitivity. Interestingly, the spt3, spt8, and spt20 mutants behaved differently than other Spt-Ada-Gcn5-acetyltransferase (SAGA) mutants. Indeed, in these three mutants, as in previously characterized transcription elongation mutants, IMD2 expression was only affected in the presence of MPA, thus suggesting a possible role for some SAGA subunits in transcription elongation.

Blotting, Northern↗

A preliminary investigation of affective and cognitive response to erotic stimulation in men before and after sex therapy.

Affective and cognitive responses to erotic stimulation were studied in sexually dysfunctional men before and after treatment in a sex therapy program. A comparison group of functional men was studied over the same time interval. A pool of 34 Likert-scaled items assessing various cognitions, affects, and perceptions was administered during baseline and following two erotic audiotapes and a self-generated sexual fantasy. To focus on global response patterns rather than individual item responses, five aggregate indices (sexual arousal, physicality, sensuality, negative affect, positive affect) were derived using a strategy that combined face-validity and reliability analysis. Cluster analysis was employed as an auxiliary technique to confirm the coherence of these groupings. All five indices differentiated dysfunctional men from controls, and further, three indices (physicality, sensuality, sexual arousal) showed significant variation across types of erotic stimulation. Correlations among the five indices, as well as with penile response, revealed two trends that differentiated dysfunctional men from controls during the pretest, but that diminished following sex therapy in the dysfunctional men. Future investigations might further rely on multiple-item indices as described here. Such measures may provide a more integrated view of sexual response in the laboratory and lead to greater understanding of affective and perceptual differences between functional and dysfunctional men.

Adult↗

Disturbances in affective communication following brain injury.

PRIMARY OBJECTIVE: Disturbances in affect expression and perception are often clinically observed in brain injured patients during the acute stages of recovery. This study examined whether such disturbances are related to the acute nature of the injury or specific type of injury in patients with stroke (CVA) versus traumatic brain injury (TBI). RESEARCH DESIGN: Retrospective cohort of patients seen for inpatient rehabilitation following brain injury. PROCEDURES: Participants were 27 CVA and 27 TBI patients. Their performance was compared to 27 normal controls on the BNI Screen for Higher Cerebral Functions. OUTCOMES AND RESULTS: While both patient groups performed significantly worse than the control group on affect expression, perception and spontaneity (p<0.01), the CVA group performed significantly worse than the TBI group (p<0.01) on affect perception. Results of this study document disturbances in affect in brain injured patients and highlight the importance of assessing affect during early recovery.

Adult↗

Service providers' perception of affective influences on decision-making about treatments for chronic pain.

PURPOSE: Service providers working with people who have complex health problems like chronic pain are considered at particular risk from the heavy emotional content of these interactions (frustration, guilt, hostility). For the good of service users and in the interests of healthcare workers' own health it is important for them to employ reflective practice acknowledging these issues. Service providers are inculcated to negate the affective domain of their practice despite the growing awareness that wellbeing can no longer be envisioned as a linear (cause and effect) process divorced from socio-cultural influences and attendant values and beliefs. The aim of this report is to examine to what degree service users (SU) and service providers (SP) believe their decisions about treatment importance are influenced by self-image and emotion. DESIGN: These results are extrapolated from a larger study based on a postal questionnaire that went to members of the Pain Society (UK Chapter of IASP) and service users belonging to chronic pain support groups in the North-West of England. The question of interest in this report asked participants to identify their level of agreement with statements about how four themes influence their decision-making about whether a treatment is important. The themes (coherence, purposiveness, self-image and affect) arise from Chapman's model of consciousness and pain. RESULTS: Only 20.5% of service providers rated the influence of self-image (what someone like me would think) as 3 (mostly) or 4 (completely). Service provider rating for the influence of affect (how this treatment makes me feel) were similarly low with only 19.4% of respondents selecting a rating of 3 or 4. In marked contrast, 73.3% of the service users selected self-image and 92.9% selected affect as a strong influence. CONCLUSION: Service providers felt that affect and self-image had little influence on their decision-making. However, there is growing evidence in the literature to suggest that it is not possible, nor preferable, to divorce emotion from the clinical encounter.

Adult↗

Affective tasks elicit material-specific memory effects in temporal lobectomy patients.

Eighteen patients who had undergone a right (9) or left (9) temporal lobectomy (RTL, LTL) including removal of the amygdala and hippocampus were evaluated. Sixteen male and sixteen female undergraduate subjects were evaluated for normative comparison. All subjects were administered Verbal (words) and Visual (faces) paired associates tasks. The present study sought to evaluate material-specific memory after temporal lobectomy, and to compare affective versus neutral memory as well. Thus, there were 4 tasks: Verbal Affective, Verbal Neutral, Visual Affective, and Visual Neutral. The material-specific effects of better Verbal memory performance by the RTL subjects compared to the LTL subjects and better Visual memory performance by the LTL subjects than the RTL subjects were only significant for the Affective tasks, and not the Neutral tasks. Perhaps adding an affective dimension to the material-specific memory tasks engaged the amygdala in addition to the other structures known to be important in memory. A strong interpretaion of the present data is made difficult by task differences and the low average IQ and possible reorganization of function that may have occurred in the patient sample.

Adult↗

Arsenic groundwater contamination and sufferings of people in North 24-Parganas, one of the nine arsenic affected districts of West Bengal, India.

To understand the magnitude of the arsenic calamity in West Bengal, a detailed study spanning 7 years was made in North 24-Parganas, one of the nine arsenic affected districts. Area and population of North 24-Parganas district are 4093.82 sq. km and 7.3 million, respectively. Fourty eight thousand and thirty water samples were analyzed from hand tubewells of North 24-Parganas in use for drinking, cooking and 29.2% of the tubewells were found to have arsenic above 50 microg/L, the maximum permissible limit of World Health Organization (WHO) and 52.8% have arsenic above 10 microg/L, WHO recommended value of arsenic in drinking water. Out of the 22 blocks of North 24-Parganas, in 20 blocks arsenic has been found above the maximum permissible limit and so far in 16 blocks people have been identified as suffering from arsenical skin lesions. From the generated data, it is estimated that about 2.0 million and 1.0 million people are drinking arsenic contaminated water above 10 microg/L and 50 microg/L level, respectively in North 24-Parganas alone. So far, in our preliminary study 33,000 people have been examined at random from arsenic affected villages in North 24-Parganas and 2274 people have been registered with arsenical skin lesions. Extrapolation of the available data indicates about 0.1 million people may be suffering from arsenical skin lesions from North 24-Parganas alone. A sum of 21,000 hair, nail, and urine samples analyses from arsenic affected villages show 56%, 80%, and 87% people have arsenic in biological specimen more than normal/toxic (hair) level, respectively. Thus, many may be subclinically affected. Due to use of arsenic contaminated groundwater for agricultural irrigation, rice and vegetable are getting arsenic contaminated. Hence there is an additional arsenic burden from food chain. People from arsenic affected villages are also suffering from arsenical neuropathy. A followup study indicates that many of the victims suffering from severe arsenical skin lesions for several years are now suffering from cancer or have already died of cancer.

Adult↗

Simple, robust linkage tests for affected sibs.

Parametric-linkage analysis applied to large pedigrees with many affected individuals has helped in the identification of highly penetrant genes; but, for diseases lacking a clear Mendelian inheritance pattern or caused by several genes of low to moderate penetrance, a more robust strategy is nonparametric analysis applied to small sets of affected relatives, such as affected sib pairs. Here we show that the robustness of affected-sib-pair tests is related to the shape of the constraint set for the sibs' identity-by-descent (IBD) probabilities. We also derive a set of constraints for the IBD probabilities of affected sib triples and use common features of the shapes of the two constrain sets to introduce new nonparametric tests (called "minmax" tests) that are more robust than those in current use. Asymptotic-power computations support the robustness of the proposed minmax tests.

Automation↗

Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family.

A family with a (1;11)(q42;q14.3) translocation significantly linked to a clinical phenotype that includes schizophrenia and affective disorders is described. This translocation generates a LOD score of 3.6 when the disease phenotype is restricted to schizophrenia, of 4.5 when the disease phenotype is restricted to affective disorders, of 7.1 when relatives with recurrent major depression, with bipolar disorder, or with schizophrenia are all classed as affected. This evidence for linkage is among the strongest reported for a psychiatric disorder. Family members showed no distinctive features by which the psychiatric phenotype could be distinguished from unrelated cases of either schizophrenia or affective disorders, and no physical, neurological, or dysmorphic conditions co-occurred with psychiatric symptoms. Translocation carriers and noncarriers had the same mean intelligence quotient. Translocation carriers were similar to subjects with schizophrenia and different from noncarriers and controls, in showing a significant reduction in the amplitude of the P300 event-related potential (ERP). Furthermore, P300 amplitude reduction and latency prolongation were measured in some carriers of the translocation who had no psychiatric symptoms-a pattern found in other families with multiple members with schizophrenia, in which amplitude of and latency of P300 appear to be trait markers of risk. The results of karyotypic, clinical, and ERP investigations of this family suggest that the recently described genes DISC1 and DISC2, which are directly disrupted by the breakpoint on chromosome 1, may have a role in the development of a disease phenotype that includes schizophrenia as well as unipolar and bipolar affective disorders.

Adolescent↗

Excess of twins among affected sibling pairs with autism: implications for the etiology of autism.

It is widely accepted that genes play a role in the etiology of autism. Evidence for this derives, in part, from twin data. However, despite converging evidence from gene-mapping studies, aspects of the genetic contribution remain obscure. In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ. Of 166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) were twin pairs. Deviation from expected values was statistically significant (P<10(-6) for all twins); in a similarly ascertained sample of individuals with type I diabetes, there was no deviation from expected values. We demonstrate that to ascribe the excess of twins with autism solely to ascertainment bias would require very large ascertainment factors; for example, affected twin pairs would need to be, on average, approximately 10 times more likely to be ascertained than affected non-twin sib pairs (or 7 times more likely if "stoppage" plays a role). Either risk factors (related to twinning or to fetal development) or other factors (genetic or nongenetic) in the parents may contribute to autism.

Autistic Disorder↗

Disclosure of personal medical information: differences among parents and affected adults for genetic and nongenetic conditions.

Protecting the confidentiality of medical information has been an issue of great interest in the fields of bioethics, public policy, and law. Few empirical studies have addressed patient experiences and attitudes toward disclosure of private medical information in multiple contexts such as health insurance, employment, and the family. Furthermore, it is unclear whether differences exist in experiences and attitudes about privacy between those living with a serious medical condition versus those who have a child with a medical condition. The study sought to determine whether attitudes and experiences related to medical privacy and confidentiality differ between affected adults and parents of affected children. Interviews were conducted with 296 adults and parents of children with sickle cell disease (SCD), cystic fibrosis (CF), or diabetes mellitus (DM). This cross-sectional study collected data regarding their experiences, attitudes, and beliefs concerning medical privacy and confidentiality. Multinomial logistic regression analysis was conducted on quantitative data. Qualitative analysis was conducted on data from open-ended response items. Parents disclose their child's diagnosis to others more often than affected adults disclose their own disease status. Parents are less likely than affected adults to regret their disclosure, to hope others do not find out, to have been pressured to share information, and to be asked about their disease by employers. Affected adults express greater concern about disclosure, a greater prevalence and greater fear of discrimination, and experience greater pressure from family members to disclose. Clinicians and researchers working with these populations should consider these differences in privacy and disclosure. Further study is necessary to examine the implications of these differences in attitudes and experiences concerning insurance, employment, and social interactions among persons with these conditions.

Adult↗

The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively.

The CCR4 transcriptional regulatory complex consisting of CCR4, CAF1, DBF2 and other unidentified factors is one of several groups of proteins that affect gene expression. Using mass spectrometry, we have identified the 195, 185 and 116 kDa species which are part of the CCR4 complex. The 195 and 185 kDa proteins were found to be NOT1 and the 116 kDa species was identical to NOT3. NOT1, 2, 3 and 4 proteins are part of a regulatory complex that negatively affects transcription. All four NOT proteins were found to co-immunoprecipitate with CCR4 and CAF1, and NOT1 co-purified with CCR4 and CAF1 through three chromatographic steps in a complex estimated to be 1.2x10(6) Da in size. Mutations in the NOT genes affected many of the same genes and processes that are affected by defects in the CCR4 complex components, including reduction in ADH2 derepression, defective cell wall integrity and increased sensitivity to monoand divalent ions. Similarly, ccr4, caf1 and dbf2 alleles negatively regulated FUS1-lacZ expression, as do defects in the NOT genes. These results indicate that the NOT proteins are physically and functionally part of the CCR4 complex which forms a unique and novel complex that affects transcription both positively and negatively.

Alleles↗