Familial Schizophrenia and Spectrum Personality Disorders
Condition: Schizophrenia
MeSH terms: Schizophrenia; Personality Disorders
Study type: Observational

Summary: 
      We propose to recruit 150 case families (i.e., families with a schizophrenia proband), 150
      control families, and 45 control subjects who exhibit schizophrenia spectrum personality
      symptoms in the absence of a family history of schizophrenia. Participants will undergo a
      number of clinical, electrophysiological, perceptual, and cognitive assessments. These data
      will be used to identify phenotypes likely to be associated with genetic risk for
      schizophrenia, and to determine how these phenotypes aggregate in families. Some of the
      analyses will focus on examining associations between candidate genes and these alternative
      phenotypes. Thus if we are not able to recruit relatives we may still collect these
      phenotypic data in probands and their genetic sample for future genotype/phenotype
      association studies. Testing procedures require a 10-12 hour time commitment and testing will
      be completed over 2 or more days. Participants will be asked to give a blood (or saliva if
      difficult to obtain blood sample for instance because of fear of blood draws), which will be
      stored for future genetic analyses.
    

Detailed description: 
      Specific aims of the proposed study are:

        1. To test the hypothesis that abnormalities in predictive pursuit, antisaccade
           performance, working memory, visual attention (CPT), sensory gating (PPI and P50) and
           other measures of information processing mark the liability for schizophrenia. Secondly,
           we will examine the pattern of familial aggregation of these measures to determine
           whether observed deficits are likely to reflect genetic and/or environmental effects.
           The hypothesis will be supported if (a) the frequency of these neurophysiological
           deficits is higher in relatives of schizophrenic probands than in relatives of control
           probands; (b) the prevalence of neurophysiological abnormalities is higher in case
           relatives with SSP symptoms than in nonSSP case relatives; (c) risk is increased among
           case relatives of "affected" probands vs. case relatives of "unaffected" probands (i.e.,
           risk in relatives of case probands who exhibit an abnormality vs. relatives of case
           probands who do not).

        2. To test the hypothesis that some physiological deficits reflect a common underlying
           phenotype, while others mark independent aspects of disease risk. To test this
           hypothesis (a) we will examine correlation matrices (adjusted for within family
           correlation) for neurophysiological assessments among case relatives and control
           relatives. Factor structures in the two groups will be examined using exploratory factor
           analyses, followed by confirmatory factor analyses using validation samples of
           case/control relatives. Confirmatory Factor Analyses (CFA) will also be used to
           determine how factor solutions based on case/control relatives fit the data of case
           probands. (b) Factor scores for correlated measures will be derived and the familial
           risk for composite measures of neurophysiological functioning estimated using the
           methods described in Specific Aim 1. (c) Secondary within family analyses will be
           performed to estimate the heritability of derived factor scores and to determine whether
           patterns of familial correlations suggest a genetic or environmental cause.

        3. To evaluate whether particular domains of psychopathology are marked by different
           putative phenotypic markers. We will specifically test the hypotheses that predictive
           pursuit, working memory, and sensory gating measures are more strongly associated with
           positive psychotic symptoms, while smooth pursuit initiation and processing speed
           measures are more strongly associated with primary negative symptoms. The relationships
           between clinical domains and other measures or clusters will be examined in an
           exploratory hypothesis-generating framework.

        4. We propose to collect blood samples (or rarely saliva sample) from each participant to
           be stored for future association studies, as well as formal linkage analyses using
           phenotypes identified in specific aims 1 and 2.

        5. We plan to examine how nicotine dependence may run in families and to examine if
           patterns of nicotine use may be related to a family history of schizophrenia.
           Participants will be asked about their smoking history and current smoking habits.
           Current smokers will be asked more specific questions about their smoking behaviors to
           estimate level of current nicotine dependence. It is hoped that this information will
           give us clues about why so many individuals with schizophrenia smoke.
    

Observational model: Family-Based
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        University of Maryland, Baltimore: Enrolling by Invitation
      
Biospecimen description: 
      Blood sample for DNA extraction
    
Keywords: Schizophrenia; Genetics; Eyetracking