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Levy D.L.,Psychology Research Laboratory | Sereno A.B.,University of Houston | Gooding D.C.,University of Wisconsin - Madison | O'Driscoll G.A.,McGill University
Current Topics in Behavioral Neurosciences | Year: 2010

Eye tracking dysfunction (ETD) is one of the most widely replicated behavioral deficits in schizophrenia and is over-represented in clinically unaffected first-degree relatives of schizophrenia patients. Here, we provide an overview of research relevant to the characterization and pathophysiology of this impairment. Deficits are most robust in the maintenance phase of pursuit, particularly during the tracking of predictable target movement. Impairments are also found in pursuit initiation and correlate with performance on tests of motion processing, implicating early sensory processing of motion signals. Taken together, the evidence suggests that ETD involves higher-order structures, including the frontal eye fields, which adjust the gain of the pursuit response to visual and anticipated target movement, as well as early parts of the pursuit pathway, including motion areas (the middle temporal area and the adjacent medial superior temporal area). Broader application of localizing behavioral paradigms in patient and family studies would be advantageous for refining the eye tracking phenotype for genetic studies. © Springer-Verlag Berlin Heidelberg 2010.

Morgan C.J.,University of Alabama at Birmingham | Lenzenweger M.F.,Binghamton University State University of New York | Rubin D.B.,Harvard University | Levy D.L.,Psychology Research Laboratory
Statistics in Medicine | Year: 2014

A number of mixture modeling approaches assume both normality and independent observations. However, these two assumptions are at odds with the reality of many data sets, which are often characterized by an abundance of zero-valued or highly skewed observations as well as observations from biologically related (i.e., non-independent) subjects. We present here a finite mixture model with a zero-inflated Poisson regression component that may be applied to both types of data. This flexible approach allows the use of covariates to model both the Poisson mean and rate of zero inflation and can incorporate random effects to accommodate non-independent observations. We demonstrate the utility of this approach by applying these models to a candidate endophenotype for schizophrenia, but the same methods are applicable to other types of data characterized by zero inflation and non-independence. © 2014 John Wiley & Sons, Ltd.

Need A.C.,Duke University | McEvoy J.P.,Duke University | Gennarelli M.,Genetic Unit | Gennarelli M.,University of Brescia | And 19 more authors.
American Journal of Human Genetics | Year: 2012

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics.

Pagnini F.,University of Milan | Simmons Z.,Pennsylvania State University | Corbo M.,NEuroMuscular Omnicentre NEMO | Molinari E.,University of Milan | Molinari E.,Psychology Research Laboratory
Amyotrophic Lateral Sclerosis | Year: 2012

The literature on psychological aspects of amyotrophic lateral sclerosis (ALS) has explored quality of life, depression, anxiety, spirituality, hopelessness, and other constructs in an attempt to understand the patient's grief and other psychological responses to the disease. However, there is a lack of research on the efficacy of psychological interventions. We believe it is important to develop 'best practices' for the improvement of quality of life and the reduction of psychological distress related to ALS. © 2012 Informa Healthcare.

Capodagllo P.,Research Laboratory in Biomechanics and Rehabilitation | Lafortuna C.,CNR Institute of Molecular Bioimaging and Physiology | Petroni M.L.,University of San Marino | Salvadori A.,Pneumological Rehabilitation Unit | And 4 more authors.
European Journal of Physical and Rehabilitation Medicine | Year: 2013

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to- date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.

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