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PubMed1997

Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22.

Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 (theta = 0.01, alpha = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at theta = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding.

Bipolar Disorder↗
PubMed1993

Communication styles of children of mothers with affective disorders, chronic medical illness, and normal controls: a contextual perspective.

Research has demonstrated impaired parent-child relationships in families with affective disorders. The present study examines the association of children's interactional style during a direct conflict-solving task to both the mother's interactional style and the child's diagnostic status. The sample includes 63 children, ages 8 to 16, of mothers with affective disorders, chronic medical illness, and normal controls. Children's dominant coping style profile (CS) (autonomous, neutral, or critical) was related to their mother's affective style (AS) (benign or negative). Affective disorder in the child at 6-month followup was associated with a critical CS profile at intake, while the child's nonaffective symptomatology was unrelated to CS. Findings indicate that children's affective disturbance is linked to interpersonal deficits in affectively charged situations. Results suggest that the child's CS is more strongly predicted by maternal AS than by either the child's or the mother's diagnostic status.

Adaptation, Psychological↗
PubMed2003

Identification and mapping of genetic loci affecting the free-threshing habit and spike compactness in wheat ( Triticum aestivum L.).

Recombinant inbred lines of the International Triticeae Mapping Initiative (ITMI) mapping population were used to localize genetic loci that affect traits related to the free-threshing habit (percent threshability, glume tenacity, and spike fragility) and to spike morphology (spike length, spikelet number, and spike compactness) of wheat ( Triticum aestivum L.). The ITMI population was planted in three environments during 1999 and 2000, and phenotypic and genotypic data were used for composite interval mapping. Two quantitative trait loci (QTL) that consistently affected threshability-associated traits were localized on chromosomes 2D and 5A. Coincident QTL on the short arm of 2D explained 44% of the variation in threshability, 17% of the variation in glume tenacity, and 42% of the variation in rachis fragility. QTL on chromosomes 2D probably represent the effect of Tg, a gene for tenacious glumes. Coincident QTL on the long arm of 5A explained 21% and 10% of the variation in glume tenacity and rachis fragility, respectively. QTL on 5A are believed to represent the effect of Q. Overall, free-threshing-related characteristics were predominantly affected by Tg and to a lesser extent by Q. Other QTL that were significantly associated with threshability-related traits in at least one environment were localized on chromosomes 2A, 2B, 6A, 6D, and 7B. Four QTL on chromosomes 1B, 4A, 6A, and 7A consistently affected spike characteristics. Coincident QTL on the short arm of chromosome 1B explained 18% and 7% of the variation in spike length and spike compactness, respectively. QTL on the long arm of 4A explained 11%, 14%, and 12% of the variation in spike length, spike compactness, and spikelet number, respectively. A QTL on the short arm of 6A explained 27% of the phenotypic variance for spike compactness, while a QTL on the long arm of 7A explained 18% of the variation in spikelet number. QTL on chromosomes 1B and 6A appear to affect spike dimensions by modulating rachis internode length, while QTL on chromosomes 4A and 7A do so by affecting the formation of spikelets. Other QTL that were significantly associated with spike morphology-related traits, in at least one environment, were localized on chromosomes 2B, 3A, 3D, 4D, and 5A.

Chromosome Mapping↗
PubMed2003

Interaction between mother's and father's affection as a risk factor for anxiety and depression symptoms--evidence for increased risk in adults who rate their father as having been more affectionate than their mother.

BACKGROUND: Retrospective reports of low care from either parent are found to be associated with increased risk for anxiety and depression in adulthood. Furthermore, fathers are generally reported as having been less caring than mothers, which raises the issue of whether greater care from fathers across the whole population would benefit mental health. METHODS: A community survey was carried out in Canberra, Australia, with 2404 adults aged 20-24 and 2530 aged 40-44. Respondents retrospectively reported on affection shown by their parents and on other aspects of family functioning. These data were analysed in relation to risk for anxiety and depressive symptoms and neuroticism. RESULTS: Retrospective reporting of greater affection from both fathers and mothers was generally associated with fewer anxiety and depression symptoms and lower neuroticism. However, there was a significant interaction effect, such that mental health was worse in families where the father was reported to show a higher level of affection but the mother a lower level. Such families were found to have a range of problems, including higher rates of emotional problems in the parents, conflict in the home, parental separation or divorce, and parental mistreatment. These family problems accounted for much of the interaction effect observed. CONCLUSIONS: Greater affection from the father is not always associated with lower risk for anxiety and depression. Where the father is more affectionate than the mother there tends to be increased family problems and increased risk. It is possible that family problems lead fathers to show increased affection to their children or mothers to show reduced affection.

Adult↗
PubMed2004

Effect of the antidepressant nefazodone on the density of cells expressing mu-opioid receptors in discrete brain areas processing sensory and affective dimensions of pain.

RATIONALE: The principal use of antidepressants is in the treatment of depression and affective disorders. Antidepressants have also been used as an adjuvant to analgesics in pain treatment. However, in chronic treatment, their antinociceptive and antidepressive effects coexist simultaneously. Antidepressants can interact with the opioid system, which is also involved in regulating nociceptive processing and affective state. Chronic antidepressants could act by increasing mu-opioid receptor expression in many brain areas involved in the regulation of nociception and affective state. OBJECTIVES: The aim of this study was to evaluate the antinociceptive and antidepressant-like effects and the possible variations in mu-opioid receptor expression induced by a chronic nefazodone treatment in brain areas related to pain and affective state. METHODS: Wistar rats were chronically treated with nefazodone (10 and 25 mg/kg IP, twice a day, for 14 days). Twelve hours after the last day 14 dose of nefazodone, a tail-flick test was performed. After the administration of a daily dose of nefazodone, Porsolt's test was carried out 12 h after last dose. Two hours after completion of 14 days treatment, other animals were processed for mu-opioid receptor immunocytochemistry using polyclonal antisera raised in rabbits. Several brain regions were analyzed: the frontal and cingulate cortex, the dorsal raphe nucleus and the periaqueductal gray. RESULTS: Chronic nefazodone treatment induced a significant increase in tail-flick latency and a significant decrease in immobility time at total doses of 20 and 50 mg/kg per day ( P<0.05). In treated animals, the density of neural cells immunostained for mu-opioid receptor in the frontal and cingulate cortices, dorsal raphe nucleus and periaqueductal gray had increased after chronic nefazodone compared to controls. CONCLUSION: Therefore, chronic nefazodone induces antinociceptive and antidepressant-like effects in rats and increases mu-opioid receptor expression in brain areas related to pain and affective state. These results suggest that antidepressants could be effective on somatic and affective dimensions of pain and this action could be related to its influence on the opioid system.

Animals↗
PubMed2005

Giant cell tumors of the knee: subchondral bone integrity affects the outcome.

From January 1992 to July 2001, we treated 38 patients with giant cell tumour in the knee region. Seventeen tumours were located in the distal femur and 21 in the proximal tibia . Twenty patients were classified as Campanacci grade II, 15 as grade III, and three as grade I. Patients' mean age was 34.5 (19-65) years, and the mean follow-up was 52 (24-134) months. Operative procedures were chosen according to the extent of bone and soft-tissue involvement. In 28 patients, intralesional curettage and bone grafting was performed and in ten patients a wide resection. We defined subchondral bone of the knee to be affected when the distance to the tumour was less than 3 mm. We then measured the area of affected subchondral bone radiographically using plain radiographs, CT, and MRI. In patients initially treated with curettage and bone grafting, the mean area of initially affected subchondral bone was 18.6 (0-81)%. The mean Enneking functional score at follow-up was 88 (66.6-100). There was a linear trend showing that the larger the area of affected subchondral bone, the worse the functional score. Among patients initially treated with wide resection, the mean area of affected subchondral bone was 68.2 (41-100)%. There was, however, no significant association between affected subchondral bone area and functional score.

Adult↗
PubMed2006

Does familial non-medullary thyroid cancer adversely affect survival?

BACKGROUND: Familial non-medullary thyroid cancer (FNMTC) is associated with a higher rate of multifocality and a higher recurrence rate than sporadic thyroid cancer. However, the effect of FNMTC on life expectancy is unknown. MATERIAL AND METHODS: Using data from our FNMTC database, we calculated life expectancy and survival rates after diagnosis of FNMTC and compared the results with the rates for unaffected family members and for the standard US population. Overall life expectancy and survival rates were calculated using the Kaplan-Meier method. We compared patients from families with 2 affected members with patients from families with > or = 3 affected members. We also compared patients diagnosed in a known familial setting (index cases and subsequent cases) with patients diagnosed before the familial setting was recognized. RESULTS: There were 139 affected patients with 757 unaffected family members. The mean age at diagnosis was 40.8 +/- 13.9 years and the mean follow-up time was 9.4 +/- 11.7 years. Ten patients died of thyroid cancer during follow-up. The life expectancy of patients with FNMTC was similar to that of their unaffected family members. Survival was significantly shorter for patients with 3 or more affected family members, for patients diagnosed before the familial setting was recognized, and for patients with anaplastic cancer. CONCLUSIONS: Our results suggest that FNMTC may be more aggressive than sporadic thyroid cancer, particularly in families with 3 or more affected members. However, when recognized and treated appropriately, it does not significantly shorten the overall life expectancy of the affected patients.

Adenocarcinoma, Follicular↗
PubMed2005

Identification of deletions and duplications of the DMD gene in affected males and carrier females by multiple ligation probe amplification (MLPA).

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused in the majority of cases by deletions of the DMD gene and are readily detectable in affected males by multiplex polymerase chain reaction (PCR). However, different approaches must be used for the identification of female carriers, in which deletions are not detectable by PCR, because of the presence of a normal X chromosome. In this study, we used the multiple ligation probe amplification (MLPA) tool for the identification of female carriers of DMD deletions or duplications in 12 families with a single affected male, 10 of which were previously diagnosed as carriers of a DMD rearrangement, and the remaining two as having an unknown disease-causing mutation. In all the investigated affected males, MLPA analysis confirmed the presence of a DMD rearrangement, and in six of them allowed the refinement of the breakpoints. In 12 female relatives of the affected patients, MLPA analysis showed a DMD deletion or duplication, confirming their carrier status. Two of these were the mother and the sister of a patient whose disease-causing mutation was not known. MLPA analysis thus proved to be an useful tool for the analysis of both affected males and females carriers of DMD rearrangements in cases in which the disease-causing mutation in the affected male was not known, providing useful information for the genetic counselling of the family.

Chromosomes, Human, X↗
PubMed1997

Genetic variation of the 5-HT2A receptor gene and bipolar affective disorder.

Abnormalities of the serotonergic system have classically been associated with the origin of affective disorders through the biochemical action of therapeutic agents and their role in affective and perceptual states. In the present study, we hypothesized that genetic variation in the 5-hydroxytryptamine (serotonin) type 2A (5-HT2A) receptor gene (HTR2A) might have an effect on the aetiology of bipolar affective disorder. Four different polymorphisms in the HTR2A gene were studied in 88 patients with bipolar affective disorder and 113 healthy controls, all of Spanish origin. No significant association was observed between any of the four polymorphisms at the HTR2A locus, whether tested individually or as haplotypes, and bipolar affective disorder. The lack of association suggests that HTR2A is not a major risk factor for bipolar affective disorder.

Bipolar Disorder↗
PubMed1998

Breast cancer risk assessment: use of complete pedigree information and the effect of misspecified ages at diagnosis of affected relatives.

Reliable risk estimates for hereditary breast cancer are important for the genetic counseling of women who have one or more first- and/or second-degree relatives affected by the disease. If no mutation analysis of known high-penetrance breast cancer genes is performed, risk estimation is often based on published reference tables. These tables express a woman's age-specific risk of breast cancer as a function of the ages at diagnosis of one or two affected relatives with different degrees of relationship to the counselee. However, unaffected relatives are not taken into account when these estimates are derived. We report here the extent to which risk estimation is influenced by the number and ages of any unaffected relatives and by the exact genealogical relationship between the proband and affected relative rather than merely the degree. Additionally, we describe the sensitivity of risk estimates when ages at diagnosis of affected relatives are misspecified because of inaccurate information supplied by the counselee. We determined a proband's probability of being a carrier of a highly penetrant breast cancer susceptibility gene, such as BRCA1 or BRCA2, by likelihood calculations that take into account information from the entire pedigree. This genetic risk was used to estimate a phenotypic lifetime breast cancer risk, which was compared with the risks derived from the published reference tables. We demonstrate numerically that the tabulated values tend to over-estimate the probands risk and that the extent of over-estimation depends greatly on the number and ages of unaffected relatives. The validity of the relatives ages at diagnosis can affect risk predictions considerably in small families with two or three affected relatives. Furthermore, the magnitude of the estimated breast cancer risks depends upon the assumed genetic model and can therefore vary appreciably when different penetrance estimates are used.

Adult↗
PubMed1985

The role of the anterior hypothalamus in affective defense behavior elicited from the ventromedial hypothalamus of the cat.

In the preceding paper a hypothalamic circuit subserving feline affective defense behavior was described. This circuit included an ascending component from the ventromedial nucleus to the anterior hypothalamus and a descending component from the anterior hypothalamus to the midbrain central gray substance. The present study was undertaken to test the hypothesis that the anterior hypothalamus plays a central role in the organization of this functional pathway. In the first part of this study, dual stimulation methods were utilized to demonstrate that concurrent stimulation of the ventromedial hypothalamus facilitates the occurrence of affective defense responses elicited from the anterior hypothalamus. In the second part of the study, lesions placed in the anterior hypothalamus significantly increased the latency and threshold current for affective defense responses elicited from the ventromedial hypothalamus. [14C]2-deoxyglucose autoradiography confirmed the fact that anterior hypothalamic lesions effective in blocking affective defense were placed in regions where the vast majority of ventromedial hypothalamic fibers terminate. In contrast, lesions which had little or no effect upon the latency or threshold for affective defense elicited from the ventromedial hypothalamus appeared to leave intact the connections from the ventromedial to the anterior hypothalamus. These findings are consistent with the proposed intrahypothalamic anatomical substrate subserving affective defense behavior described in the preceding paper.

Aggression↗
PubMedDate not supplied

Age at onset in bipolar-related major affective illness: clinical and genetic implications.

Age-of-onset data were collected on 142 bipolar probands (61 males, 81 females) and 110 siblings. After correcting for demographic factors the age at illness onset did not distinguish bipolar from unipolar siblings or siblings from probands. This indicates that in a subset of pedigree data, bipolar and unipolar affective disorders may be different phenotypic manifestations of the same underlying disorder. A total of 43% of affected individuals gave evidence of illness before age 30 and 11% were ill as adolescents. Also 2% were affected prior to age 15. The data indicate that affective illness is not uncommon in adolescence and may occur as a childhood disorder. Estimation of the age-of-onset probability distribution was obtained by incorporating demographic factors (survivorship data) into the observed ages at onset of affected individuals. A square-root normal curve fits the age-of-onset probability density function. The implications for morbid risk prediction and genetic analysis of affective disorders were discussed.

Adolescent↗
PubMed1985

Somatosensory evoked potentials over the non-affected hemisphere in patients with unilateral cerebrovascular lesions.

Changes in somatosensory evoked potentials (SEPs) over the non-affected hemisphere in 61 patients with unilateral cerebrovascular lesions were studied using age-matched controls. The latencies showed no significant differences when compared to controls. In cerebral infarctions produced by occlusion of the perforating artery in the middle cerebral artery (MCA), the amplitudes over the non-affected hemisphere decreased in the acute phases, but did not change in the chronic phases in comparison with the controls; whereas in cerebral infarctions produced by occlusion of the cortical artery in the MCA, the amplitudes over the non-affected hemisphere increased in the chronic phases compared to controls. The amplitudes over the non-affected hemisphere in intracerebral hemorrhages (ICH) increased in the chronic phases in comparison with the controls, but in the acute phases, they showed no change in the cortical artery group nor in ICH. The increases in the amplitudes were more prominent in patients with than in patients without sensory impairment. These data suggest that the affected hemisphere gives rise to high amplitude SEPs over the non-affected hemisphere.

Acute Disease↗
PubMed1989

Perceptual asymmetry in schizophrenia and affective disorder: implications from a right hemisphere task.

The patterns of perceptual asymmetry exhibited by normal, schizophrenic, and affectively-disordered subjects on a dichotic tonal discrimination task, were compared. Affectively-disordered subjects' performances differed significantly from those of normal subjects, with normals demonstrating the expected left ear advantage, and affectively-disordered subjects showing no lateral advantage. The performance of the schizophrenic subjects fell between those of the normal and affective groups along a laterality continuum, with paranoid schizophrenic subjects tending to show a larger left ear advantage than non-paranoid schizophrenic subjects. The results do not support the hypothesis that schizophrenic subjects inappropriately transfer processing of right hemisphere stimuli to the left hemisphere, but do suggest that subgroup distinctions may be relevant to hypotheses of lateralized dysfunction in schizophrenia. Further, the performance of the affective group supports previous findings of right hemisphere abnormalities in affective disorder.

Adolescent↗
PubMedDate not supplied

Cardiovascular risk factors in affective disorder.

100 patients with affective disorder (unipolar affective disorder and bipolar affective disorder) were evaluated for evidence of increased risk for the major cardiovascular risk factors including hypertension, hypercholesterolemia, obesity, and cigarette use. Unipolar affective disorder patients showed no evidence of increased cardiovascular risk compared to population controls. Bipolar affective disorder patients displayed increased systolic blood pressure, definite hypertension, and use of cigarettes. These findings are consistent with a link between affective disorders and excess cardiovascular mortality.

Adult↗
PubMedDate not supplied

Neurofunctional assessment of lateralized hemispheric asymmetries in affective illness.

Performances of 59 affective patients, 59 schizophrenics and 59 normal controls on the Quality Extinction Test (QET), which has been proven to be valuable for detecting abnormal hemisphere functioning in neurological and psychiatric patients, are presented. Frequencies of the left and right extinctions of the affective patients did not exceed those of normal controls. Compared to schizophrenics, fewer affective patients had left and right extinctions and the number of these extinctions was significantly lower in affective patients. These results would indicate that affective patients do not differ from controls relative to lateralized cerebral malfunctioning as measured by the QET. The differences between affective and schizophrenic patients' QET performances may be explained by differences in the course and chronicity of the disease.

Adult↗
PubMedDate not supplied

Affective disorder in childhood: separating the familial component of risk from individual characteristics of children.

In studying the risk of affective disorder in children, the investigator must deal with the problem that there are two possible units of analysis: the child and the family. An analysis based on children must take account of the intercorrelation within a sibship to produce correct results, while a family-based analysis makes it difficult to investigate individual characteristics of children that help determine the net risk. A two-stage iterative approach to this problem is proposed, yielding estimates of the effect of family-based factors (parental illness, family social class, marital status of parents) and individual factors (age and sex of child, previous non-affective illness). This technique is applied to a sample of 275 children from 143 families representing a wide range of familial risk for affective disorder. The final family-based model (predicting at least one child with affective disorder in the sibship) indicates a six-fold increase in risk to the child associated with maternal affective disorder (P less than 0.001), a three-fold increase in risk associated with paternal affective disorder (P less than 0.05) and divorce or separation of the biological parents, and a suggestion of increased risk in the highest social class (P = 0.06). The excess sibship risk, due to child factors age, prior anxiety disorder, and prior childhood diagnosis, contributed significantly to the family prediction (P less than 0.001).

Anxiety Disorders↗
PubMed1985

Therapeutic responses to tricyclic antidepressants and related drugs in non-affective disorder patient populations.

Although therapeutic responsiveness to tricyclic antidepressants has been primarily associated with the affective disorders, clinical investigations in the last decade have suggested that non-affective disorders such as panic disorder, obsessive-compulsive disorder, anxiety disorder, bulimia, enuresis, migraine, and the chronic pain syndrome may also respond to tricyclics and other antidepressants. This therapeutic responsiveness may sometimes be related to improvement in secondary depressive symptoms, but may also clearly occur in the absence of secondary depression; in particular, improvement in the core symptoms of at least some of these disorders may occur without a change in mood. Furthermore, many patients with these disorders display psychobiologic abnormalities that show many similarities, but also some differences, compared to those observed in patients with affective disorders, despite the frequent absence of affective symptoms. While an improvement in subclinical or "masked" depression remains one hypothesis linking tricyclic responsiveness and shared biological abnormalities in this diverse group of diagnostic entities, an alternative hypothesis (the "ven disorder" hypothesis) is presented, suggesting the possibility that tricyclic and other antidepressant-responding patients have a core disorder with common psychobiologic abnormalities but multiple clinical and diagnostic presentations. An alternative hypothesis (the "shotgun" hypothesis) suggests that the multiple actions of tricyclics (e.g. on adrenergic receptors vs. muscarinic receptors vs. serotonin system changes) may each be differentially important in the therapeutic outcome in patients with specific or predominant problems in one or another of these areas. An examination of both the similarities and differences among the non-affective, tricyclic-responsive disorders and the affective disorders may provide clues about the important psychobiologic elements in these disorders, and to the mode of action of tricyclic antidepressants and related drugs across the psychiatric disorder spectrum.

Anorexia Nervosa↗