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Background: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting., Methods: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults., Results: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism., Conclusions: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Patients presenting with an oncology emergency should be assessed and treated promptly to address symptoms, preserve function, and maintain quality of life. In some circumstances, this requires treatment of patients on weekends. The primary objective of this study was to review the delivery of urgent radiotherapy (RT) at our institution to determine the proportion of courses with a documented indication for which weekend RT could be justified based on comparison with published literature., Methods: Patients undergoing RT on weekends (January 2009-July 2009) were reviewed retrospectively for demographics, disease site, functional status, and documented reason for after-hours treatment. Data were obtained from both the electronic and paper medical records and input into an Excel spreadsheet after being anonymized. Summary statistics were calculated. A literature search was conducted to supplement the Alberta Health Services Palliative Radiotherapy clinical practice guidelines, which included review of relevant publications from the Standards and Guidelines Evidence database., Results: A total of 108 patients (73 males, 35 females) received RT to 132 sites over this period, primarily on both Saturday and Sunday (87.8%). Of these, 37.9% had a lung primary, 97.0% were treated with palliative intent, and 46.2% received spine RT. On average, 18.9 weekend treatment courses took place each month (range, 2-12). 67.1% had a planned anteroposterior field arrangement, and the dose-fractionation schedule was 2000 cGy in five fractions in the majority (68.9%). Based on the reason documented for emergency RT, 72.1% of all after-hours treatments could be justified by comparison to published literature., Conclusions: Given resource and technical considerations, delivery of RT during weekends requires specific clinical justification. Presently at our center, decision to institute after-hours RT is at the discretion of the treating radiation oncologist. The majority of indications for weekend treatment of these patients could be justified based on published evidence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Schizophrenia is commonly considered a neurodevelopmental disorder. Our aim was to determine whether the proton magnetic resonance spectroscopic (1H-MRS) changes seen in adults with schizophrenia are displayed in children at risk for developing schizophrenia., Methods: Children with symptoms of schizophrenia-spectrum disorders (n = 16; mean age = 132 months) and a comparison group (n = 12; mean age 130 months) took part in a 1H-MRS study of the left frontal lobe. Areas of peaks from N-acetylaspartate (NAA), choline (Cho), and creatine (Cre) were determined and ratios of NAA/Cre and Cho/Cre calculated and compared between groups., Results: The mean ratio of NAA/Cre was significantly lower in schizophrenia-spectrum subjects than the comparison group (1.67 vs. 1.92; p < .05). Medication status did not affect results in schizophrenia-spectrum subjects., Conclusions: Our findings suggest that the metabolic changes associated with adult schizophrenia are observed in children with some or all of the symptoms of schizophrenia, supporting a neurodevelopmental theory for schizophrenia.

Objective: This initial report, from an ongoing study, examines whether children who have symptoms of schizophrenia spectrum disorder display neuropsychological or neuroanatomic abnormalities similar to those seen in adults with schizophrenia., Method: Experimental subjects were 12 children between 8 and 12 years of age who displayed symptoms of early-onset schizophrenia or schizotypal personality disorder, as assessed through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The experimental subjects were compared with 13 controls on neuropsychological test performance, magnetic resonance imaging measurements, and proton magnetic resonance spectroscopy results., Results: Findings from the first phase of this project reveal significant overall group differences for several morphometric magnetic resonance imaging measurements and all neuropsychological measures. Differences between the groups were found for amygdala volume, mesial temporal volume, callosal area, and anatomic asymmetry. Magnetic resonance spectroscopy data showed a trend toward group differences., Conclusions: These findings support a neurodevelopmental model of schizophrenia which postulates that environmentally or genetically programmed events in utero disrupt the establishment of fundamental aspects of brain structure and function.

Several lines of inquiry provide converging evidence for a critical role for the right cerebral hemisphere in negative affective experiences. This research includes the assessment of affective consequences of both focal cerebral lesions and pharmacological inactivation of one or the other hemisphere, as well as experimental and physiological techniques assessing differential hemispheric activation. The specific nature of right hemispheric involvement is conceptualized as a tendency to become activated by aversive experiences, and once activated, to process stimuli in a manner consistent with the right hemisphere's more negative affective tone. A theory of right hemisphere involvement in depressive affect is presented in detail and its relevance to clinical phenomena, e.g., the co-occurrence of depression and pain, and sex differences in depression, is examined, as is congruence with cognitive theories of depression.