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The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis
- A. Hargreaves, R. Anney, C. O'Dushlaine, K. K. Nicodemus, Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Wellcome Trust Case Control Consortium 2, M. Gill, A. Corvin, D. Morris, Gary Donohoe
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- Journal:
- Psychological Medicine / Volume 44 / Issue 10 / July 2014
- Published online by Cambridge University Press:
- 28 November 2013, pp. 2177-2187
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Background
Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.
MethodIn total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.
ResultsIncreased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1–3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.
ConclusionsThese data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.
Forelimb kinematics of the flat walk and fox trot of the Missouri Fox Trotter
- M C Nicodemus, K Slater
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- Journal:
- Comparative Exercise Physiology / Volume 6 / Issue 4 / November 2009
- Published online by Cambridge University Press:
- 11 February 2010, pp. 149-156
- Print publication:
- November 2009
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While temporal variable measurements have assisted in objectively defining and distinguishing between four-beat stepping gaits performed by gaited horses, kinematic research describing joint motion of the gaited horse is limited. The objective of this study was to measure the temporal variables and the forelimb kinematics of the flat walk and fox trot of the Missouri Fox Trotter (MFT) to provide a more comprehensive description of these gaits and to assist in distinguishing between them. Reflective markers placed along the lateral aspect of the right forelimb and the zygomatic process of the temporal bone were tracked at 60 Hz as eight MFTs were ridden at a flat walk and fox trot for ten strides. Student's paired t-tests were performed to compare means of analysed parameters between gaits on finding that the fox trot was a faster stepping gait (fox trot velocity: 3.17 ± 0.03 m s− 1, flat walk velocity: 1.75 ± 0.06 m s− 1) with a shorter stride duration (fox trot: 0.63 ± 0.03 s, flat walk: 1.17 ± 0.06 s) and greater stride frequency (fox trot: 1.59 ± 0.09 strides s− 1, flat walk: 0.09 ± 0.04 strides s− 1) than the flat walk (P < 0.05). Both gaits were performed with similar stride length (fox trot: 2.0 ± 0.03 m, flat walk: 1.95 ± 0.05 m), but the fox trot had an irregular rhythm with diagonal couplets (diagonal advanced placement: 0.10 ± 0.01 s, lateral advanced placement: 0.23 ± 0.02 s). Vertical head excursions, protraction/retraction angles and joint angle-time curves for the shoulder, elbow, carpus and forelimb fetlock were similar between gaits. Shoulder peak flexion of the fox trot occurred later in the stride (fox trot: 38 ± 5%, flat walk: 20 ± 3%; P < 0.05), but the timing of the other peak flexion and extension joint angles were similar between gaits. The fox trotting carpus flexed more (fox trot: 136 ± 3°, flat walk: 147 ± 4°) than the carpus of the flat walk (P < 0.05), but the other peak flexion and extension joint angles were comparable between gaits. Measured temporal and kinematic variables assisted in defining the fox trot and flat walk and differences between variables can be applied in distinguishing between the two gaits.