Candidate gene associations with mood disorder, cognitive vulnerability, and fronto-limbic volumes.

BACKGROUND: Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function: ANK3 (rs10994336), BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191). AIMS: The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto-limbic regions implicated in affect regulation. METHODS AND MATERIALS: Participants included 128 individuals with bipolar disorder (33% male, Mean age = 38.5), 48 with major depressive disorder (29% male, Mean age = 40.4), and 149 healthy controls (35% male, Mean age = 36.5). Genotypes were determined by 5'-fluorogenic exonuclease assays (TaqMan®). Fronto-limbic volumes were obtained from high resolution brain images using Freesurfer. Chi-square analyses, bivariate correlations, and mediational models examined relationships between genetic variants, mood diagnoses, cognitive measures, and brain volumes. RESULTS: Carriers of the minor BDNF and ANK3 alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients (P = 0.047). CACNA1C minor allele carriers had larger bilateral caudate, insula, globus pallidus, frontal pole, and nucleus accumbens volumes (smallest r = 0.13, P = 0.043), and increased IQ (r = 0.18, P < 0.001). CACNA1C associations with brain volumes and IQ were independent; larger fronto-limbic volumes did not mediate increased IQ. Other candidate variants were not significantly associated with diagnoses, cognition, or fronto-limbic volumes. DISCUSSION AND CONCLUSIONS: CACNA1C may be associated with biological systems altered in mood disorder. Increases in fronto-limbic volumes and cognitive ability associated with CACNA1C minor allele genotypes are congruent with findings in healthy samples and may be a marker for increased risk for neuropsychiatric phenotypes. Even larger multimodal studies are needed to quantify the magnitude and specificity of genetic-imaging-cognition-symptom relationships.

A transitional care service for elderly chronic disease patients at risk of readmission.

BACKGROUND: Multiple hospital admissions, especially those related to chronic disease, represent a particular challenge to the acute health care sector in Australia. OBJECTIVE: To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care. DESIGN: A quasi-experimental controlled trial. SETTING: A large tertiary metropolitan teaching hospital. PARTICIPANTS: 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities. INTERVENTION: Implementation of a chronic disease management model of transitional care aimed at improving patient management and reducing readmissions to acute care. MAIN OUTCOME MEASURES: Readmission rates and emergency department presentation rates at 3-and 6-month follow up. Secondary outcome measures include quality of life, discharge destination, and primary health care service utilisation. RESULTS: There was no difference in readmission rates, emergency department presentation rates, quality of life, discharge destination or primary health care service utilisation. The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors, the difficulty of influencing readmission rates, and local system issues. CONCLUSION: The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research methodologies.