SUMMARY
Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as the mammalian skull is a challenge because of the sheer ...complexity of the factors involved. We hypothesize that even in this complex system, the expression of phenotypic variation is structured by the interaction of a few key developmental processes. To test this hypothesis, we created a highly variable sample of crania using four mouse mutants and their wild‐type controls from similar genetic backgrounds with developmental perturbations to particular cranial regions. Using geometric morphometric methods we compared patterns of size, shape, and integration in the sample within and between the basicranium, neurocranium, and face. The results highlight regular and predictable patterns of covariation among regions of the skull that presumably reflect the epigenetic influences of the genetic perturbations in the sample. Covariation between relative widths of adjoining regions is the most dominant factor, but there are other significant axes of covariation such as the relationship between neurocranial size and basicranial flexion. Although there are other sources of variation related to developmental perturbations not analyzed in this study, the patterns of covariation created by the epigenetic interactions evident in this sample may underlie larger scale evolutionary patterns in mammalian craniofacial form.
OBJECTIVES:
To identify attitudes that influence patient help‐seeking behavior and aspects of treatment that influence patient preferences for management of depression.
DESIGN:
Three focus group ...discussions (two patient groups stratified by race and one professional group). Questions addressed experience with depression, help‐seeking behaviors, treatment preferences, and perceived barriers to mental health care.
SETTING:
Academic medical center.
PATIENTS/PARTICIPANTS:
Eight black patients and eight white patients with depression; seven health care professionals (four physicians and three social workers).
MEASUREMENTS AND MAIN RESULTS:
Discussions were audiotaped, transcribed, and reviewed independently by two investigators to identify and group distinct comments into categories with specific themes. Differences were adjudicated by a third investigator. Comments within categories were then checked for relevance and consistency by a health services researcher and a psychiatrist. More than 90% of the 806 comments could be grouped into one of 16 categories. Black patients raised more concerns than white patients regarding spirituality and stigma. Patients made more comments than professionals regarding the impact of spirituality, social support systems, coping strategies, life experiences, patient‐provider relationships, and attributes of specific treatments. They discussed the role these factors played in their help‐seeking behavior and adherence to treatment.
CONCLUSIONS:
In‐depth focus group discussions with depressed patients can provide valuable and unique information about patient experiences and concerns regarding treatment for depression. Clinicians, researchers, and policymakers need to incorporate the range of factors identified by patients into their decision making for individuals with depression.
KEY WORDS: depression; patient attitudes; patient preferences; patient‐centered care.
OBJECTIVE: This study described the characteristics of users of Internet-based depression support groups and assessed whether use predicts change in depression symptoms and social support. METHOD: ...Users (N=103) of these groups were recruited into the study cohort and followed prospectively. Demographic characteristics, support group use, depression care, score on the Medical Outcomes Study Social Support Survey, and score on the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were assessed by Internet survey at baseline, 6 months, and 12 months. RESULTS: Users' demographic characteristics included median age of 40 years, 78.6% women, and 56.3% unmarried. Most (86.4%) were currently depressed (CES-D Scale score >22). Over 50% of participants heavily used the support group (5 or more hours in 2 weeks), and 37.9% preferred online communication to face-to-face counseling. Social support scores were low, compared with those from other studies of primary care patients with depression. The overall follow-up rate was 81.6% at 6 or 12 months. During follow-up, 72.6% of responders still participated in the online group; 81.0% were still receiving face-to-face depression care. Heavy users of the Internet groups were more likely to have resolution of depression (CES-D Scale score ≤22) during follow-up than less frequent users, after adjustment for age, gender, employment, and baseline CES-D Scale score with logistic regression. Social support scores did not change during follow-up. CONCLUSIONS: Users had high depression severity scores, were socially isolated, and perceived considerable benefit from the group. Internet depression support groups warrant continued research regarding supplementation of face-to-face depression care.
Fatigue is a common, non-specific, subjective symptom associated with several medical and psychiatric illnesses. The purpose of this investigation was to explore further the epidemiology of ...unexplained fatigue in the general population and the relationship between fatigue and depression.
The design was a prospective population-based study. Subjects included community-dwelling adults who were participants of the Baltimore sample of the Epidemiologic Catchment Area Program in 1981 and who were reinterviewed 13 years later. Lay interviewers using the Diagnostic Interview Schedule interviewed subjects.
Number of somatization symptoms and history of a dysphoric episode at baseline were the two strongest predictors of both new onset of fatigue as well as recurrent/chronic fatigue over the 13-year follow-up interval. In addition, individuals who reported a history of unexplained fatigue at baseline as well as during the follow-up, were at markedly increased risk for new onset major depression as compared to those who never reported such fatigue, (RR = 28.4, 95% CI) (11.7, 68.0). Similarly, respondents who developed new fatigue or had remitted fatigue after 1981 were also at increased risk for developing major depression.
Somatization was the strongest predictor of both new and chronic fatigue with unknown cause. In addition, fatigue was both predictive and a consequence of the depression syndrome.
To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease ...(LOPD).
We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the < or =50 age at onset (AAO) category.
The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (chi(2) = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO < or =50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases.
The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.
Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine ...leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.
There is suggestive evidence that depression increases risk of myocardial infarction (MI), but there are no prospective studies in which the measure of depression corresponds to clinical criteria. ...This study examines prospectively whether a major depressive episode increases the risk of incident MI and evaluates the role of psychotropic medication use in this relationship.
The study is based on a follow-up of the Baltimore cohort of the Epidemiologic Catchment Area Study, a survey of psychiatric disorders in the general population. A history of major depressive episode, dysphoria (2 weeks of sadness), and psychotropic medication use were assessed in 1981, and self-reported MI was assessed in 1994. Sixty-four MIs were reported among 1551 respondents free of heart trouble in 1981. Compared with respondents with no history of dysphoria, the odds ratio for MI associated with a history of dysphoria was 2.07 (95% CI, 1.16 to 3.71), and the odds ratio associated with a history of major depressive episode was 4.54 (95% CI, 1.65 to 12.44), independent of coronary risk factors. In multivariate models, use of barbiturates, meprobamates, phenothiazines, and lithium was associated with an increased risk of MI, whereas use of tricyclic antidepressants and benzodiazepines was not. Among individuals with no history of dysphoria, only lithium use was significantly associated with MI.
These data suggest that a history of dysphoria and a major depressive episode increase the risk of MI. The association between psychotropic medication use and MI is probably a reflection of the primary relationship between depression and MI.
Objective The objective of this study was to determine the minimum threshold level at which maximum anatomic prolapse predicts bothersome pelvic floor symptoms. Study Design We performed a ...cross-sectional study of women older than 40 years undergoing gynecologic and urogynecologic examinations using Pelvic Organ Prolapse Quantification (POP-Q) examinations to assess support and Pelvic Floor Distress Inventory questionnaires to assess symptoms. Across the spectrum of prolapse severity, we calculated receiver operating characteristic (ROC) curves and areas under the curves (AUCs) for each symptom. Results Of 296 participants, age was 56.3 ± 11.2 years, and 233 (79%) were white. POP-Q stage was 0 in 39 (13%), 1 in 136 (46%), 2 in 89 (30%), and 3 in 33 (11%). ROC analysis for each symptom revealed an AUC of 0.89 for bulging/protrusion; 0.81 for splinting to void; 0.55-0.62 for other prolapse and urinary symptoms; and 0.48-0.56 for bowel symptoms. Using a threshold of 0.5 cm distal to the hymen, the sensitivity (69%) and specificity (97%) were high for protrusion symptoms but poor for most other symptoms considered. Conclusion Vaginal descensus 0.5 cm distal to the hymen accurately predicts bulging/protrusion symptoms; however, we could not identify a threshold of prolapse severity that predicted other pelvic floor symptoms.
Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF ...and HTML versions of the article.
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