Schizophrenia
Conditions
Keywords
schizophrenia
Brief summary
Schizophrenia has long been known to be an illness with significant evidence for a genetic predisposition. The purpose of this study is to determine the genetic abnormalities that cause childhood and adult onset schizophrenia.
Detailed description
It is known from genetic linkage and gene expression studies that the alpha 7 nicotinic receptor gene is abnormally expressed in people with schizophrenia. The immediate objectives of this proposal support the long-term objectives of a comprehensive description of the pathophysiology of schizophrenia and new drug treatments by carefully defining the physiological genotype-phenotype relationship for a single candidate gene. Subjects and family members with a mental illness or who appear to have a mental illness will be asked to undergo an interview, perform some mental tests and have a blood, urine, and saliva sample taken one time.
Interventions
OTHERDiagnostic
Diagnostic evaluation for schizophrenia. Schizophrenia includes schizophrenia and schizoaffective disorder.
Sponsors
VA Office of Research and Development
Study design
Observational model
FAMILY_BASED
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* Individuals thought to have schizophrenia or schizoaffective disorder, be the parent of such an individual, or be in the matched control group of unrelated individuals not thought to have schizophrenia or schizoaffective disorder
Exclusion criteria
* Unable to give informed consent; * Psychotic disorder judged to be secondary to substance abuse, psychotic disorder that appears to be secondary to a known medical or neurological disorder, or severe mental retardation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genetic Linkage | ten years | Log of the Odds for Linkage, a standard genetic analysis metric. The number shown as a result is from a polymorphism in the promoter of the gene for the alpha7 nicotinic receptor on chromosome. Its presence in the individuals in this study, considering all three groups in one analysis, is compared to what of P50 sensory gating. P50 is a Positive wave in scalp-recorded auditory evoked potential that occurs 50 msec after the sound stimulus. P50 sensory gating is the decrement in this wave to the second of repeated sounds. The log of the odds is the common logarithm of the ratio of the odds that the gene polymorphism and P50 sensory gating are associated versus the odds that they are both distributed in the individuals at random. It is similar to the more common chi squared. |
| Heritability Coefficient | 5 years | h squared which ranges from 0 to 1. This number is similar to the more standard Pearson's correlation coefficient, except that the variable, in this case P50 sensory gating, is correlated across the statuses: schizophrenia proband (has the illness), schizophrenia relative (not ill but relative of someone who is), or control (not ill and has no known ill relative, P50 is a Positive wave in scalp-recorded auditory evoked potential that occurs 50 msec after the sound stimulus. P50 sensory gating is the decrement in this wave to the second of repeated sounds. |
| Log of the ODDS of Linkage | 1 day | Log of the ODDS ratio of Linkage divided by the ODDS of no linkage from a maximum likelihood analysis conducted using the statistical program LINKAGE |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Schizophrenia Probands Persons who meet DSM-IV criteria for schizophrenia or schizoaffective disorder | 179 |
| Schizophrenia Relatives Persons who are first degree relatives of persons in Arm 1 | 179 |
| Controls Persons who are not related to persons in Arm 2 and do not have schizophrenia themselves. | 180 |
| Total | 538 |
Baseline characteristics
| Characteristic | Schizophrenia Probands | Schizophrenia Relatives | Controls | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 179 Participants | 179 Participants | 180 Participants | 538 Participants |
| Age, Continuous | 42 years | 41 years | 42 years | 42 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 23 Participants | 28 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 156 Participants | 152 Participants | 466 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 41 Participants | 40 Participants | 121 Participants |
| Race (NIH/OMB) More than one race | 33 Participants | 33 Participants | 34 Participants | 100 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants | 30 Participants | 31 Participants | 91 Participants |
| Race (NIH/OMB) White | 61 Participants | 60 Participants | 60 Participants | 181 Participants |
| Region of Enrollment United States | 179 participants | 179 participants | 180 participants | 538 participants |
| Sensory gating ratio | 68 percent STANDARD_DEVIATION 12 | 49 percent STANDARD_DEVIATION 16 | 34 percent STANDARD_DEVIATION 9 | 58 percent STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 97 Participants | 85 Participants | 93 Participants | 275 Participants |
| Sex: Female, Male Male | 82 Participants | 94 Participants | 87 Participants | 263 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 179 | 0 / 179 | 0 / 179 |
| serious Total, serious adverse events | 0 / 179 | 0 / 179 | 0 / 179 |
Outcome results
Primary
Genetic Linkage
Log of the Odds for Linkage, a standard genetic analysis metric. The number shown as a result is from a polymorphism in the promoter of the gene for the alpha7 nicotinic receptor on chromosome. Its presence in the individuals in this study, considering all three groups in one analysis, is compared to what of P50 sensory gating. P50 is a Positive wave in scalp-recorded auditory evoked potential that occurs 50 msec after the sound stimulus. P50 sensory gating is the decrement in this wave to the second of repeated sounds. The log of the odds is the common logarithm of the ratio of the odds that the gene polymorphism and P50 sensory gating are associated versus the odds that they are both distributed in the individuals at random. It is similar to the more common chi squared.
Time frame: ten years
Population: People with schizophrenia and their relatives in families and controls as members of single families were used to establish the log of the odds ratio.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Genetic Linkage | 5.2 log (odds ratio) |
p-value: <0.001Simulation
Primary
Heritability Coefficient
h squared which ranges from 0 to 1. This number is similar to the more standard Pearson's correlation coefficient, except that the variable, in this case P50 sensory gating, is correlated across the statuses: schizophrenia proband (has the illness), schizophrenia relative (not ill but relative of someone who is), or control (not ill and has no known ill relative, P50 is a Positive wave in scalp-recorded auditory evoked potential that occurs 50 msec after the sound stimulus. P50 sensory gating is the decrement in this wave to the second of repeated sounds.
Time frame: 5 years
Population: Schizophrenia probands and relatives and controls.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Heritability Coefficient | 0.5 coefficient |
| Schizophrenia Relatives | Heritability Coefficient | 0.5 coefficient |
| Controls | Heritability Coefficient | 0.1 coefficient |
Comparison: The coefficient of segregation versus no segregation of the P50 sensory gating percent in families with schizophrenia.p-value: 0.001Firsher's transform r to Z
Primary
Log of the ODDS of Linkage
Log of the ODDS ratio of Linkage divided by the ODDS of no linkage from a maximum likelihood analysis conducted using the statistical program LINKAGE
Time frame: 1 day
Population: Probands with schizophrenia, their relatives, and controls. The log of the odds ratio summarizes data from the entire study population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Log of the ODDS of Linkage | 5.2 units on a log scale |
| Schizophrenia Relatives | Log of the ODDS of Linkage | 5.2 units on a log scale |
| Controls | Log of the ODDS of Linkage | 1 units on a log scale |