Familial Schizophrenia and Spectrum Personality Disorders
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Schizophrenia, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 16 - 58 |
| Updated: | 3/6/2019 |
| Start Date: | July 2004 |
| End Date: | December 2019 |
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.
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.
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.
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.
Inclusion Criteria:
- All male and female participants must be age 16 and above.
- Case probands will include individuals who meet DSM-IV criteria for schizophrenia or
Research Diagnostic Criteria (RDC) for schizoaffective disorder.
- Control probands will include individuals matched with case probands with respect to
age, gender, and county of residence who do not meet DSM-IV criteria for schizophrenia
or other psychotic disorders.
- Case and control relatives will include all available and age-eligible first-degree
relatives of identified case and control probands. Exception to this criterion will
occur if we identify a schizophrenia proband family of large pedigree willing to
participate, then we will include several generations of relatives (second, third or
more degree) for subsequent linkage studies in a subgroup of our sample.
- SSP controls will include individuals recruited from the community who exhibit
schizophrenia spectrum personality (SSP) traits in the absence of a personal or family
history of psychotic illness.
Exclusion Criteria:
- Subjects under 16 years of age will be excluded.
- Subjects with serious medical, neuro-ophthalmological or neurological illness (e.g.,
cancer,seizure disorders,encephalopathy), current substance abuse or extensive history
or drug dependence will be excluded, with the exception of subjects participating for
clinical interview and blood sample only.
- Subjects with mental retardation will be excluded.
- Control probands and SSP controls who meet DSM-IV criteria for a psychotic illness, or
have a family history of psychotic illness will be excluded.
- Schizophrenic patients who are judged to be incompetent to provide voluntary informed
consent based on the ESC evaluation
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