Mission Statement
The purpose of our study is to learn more about the functioning of adolescent
and young adult offspring and siblings of patients with psychotic disorders.
There exists scientific evidence that psychotic disorder can run families;
however, it is not clearly understood how this happens. Because the illness
typically begins in early adulthood, we examine adolescent and young adult
members of such families in order to see if we can understand why some
people in a family go on to develop the illness and others do not. We
expect that at least 90% of these children will never develop the illness,
but how they perform on some of the tests in this study might help us
understand how the illness works so that we can design better treatments
for it.
The three major aims of the study are:
- To identify predictors of social dysfunction and psychopathology in
adolescent children and siblings of patients who have a psychotic disorder. - To better describe the neural substrate of psychotic disorders prior
to the onset of psychosis and lay the foundation for work that will examine
if neurodegeneration occurs after illness onset. - To establish the infrastructure required to monitor adolescents at
risk for psychosis so that future proposals can select adolescents at
risk for psychotic disorders for prevention protocols.
History of Program
For the past ten years, with funding from an NIMH Merit Award, we have
been testing hypotheses about neurobiologic manifestations of schizotaxia
(the predisposition to schizophrenia) among schizophrenic patients and the
nonpsychotic relatives of schizophrenic patients. Our work-showing that
schizotaxia is associated with negative symptoms, neuropsychological dysfunction
and structural brain abnormalities-converges with data from other centers
to show that schizotaxia is a subtle brain disorder affecting about 20 to
50 percent of the nonpsychotic relatives of schizophrenic patients. The
data collected during prior funding periods have allowed us to demonstrate
a) neuropsychological deficits in schizophrenic patients and their relatives,
b) gender differences in the expression of these deficits, c) stability
of these deficits over time, d) structural brain abnormalities in patients
and relatives, e) functional MRI abnormalities in patients and relatives,
f) how the psychometric features of neuropsychological tests make them useful
for assessing phenotypes in genetic linkage studies of schizophrenia, g)
neuropsychological deficits and structural and functional brain abnormalities
in adolescents at high risk for schizophrenia. We have decided to pursue
three major aims in this continuation proposal that will help us better
understand the neural substrates of schizotaxia and how they lead to schizophrenia.
First, we will identify predictors of social dysfunction and psychopathology
in adolescent children of schizophrenic patients. Second, we will better
describe the neural substrate of schizophrenia prior to onset of psychosis
and lay the foundation for work that will examine if neurodegeneration occurs
before or after illness onset. Third, we will establish the infrastructure
required to monitor adolescent at risk for psychosis so that future proposals
can select adolescents at risk for schizophrenia for prevention protocols.
To accomplish these aims, we will assess 150 adolescent children of schizophrenic
patients (ACSZ) and 150 normal controls with neuropsychological, psychosis
proneness, psychosocial functioning, and family adversity measures. All
controls and ACSZ will also be evaluated with magnetic resonance imaging.
All 300 subjects will be monitored for adverse outcomes at six-month intervals.
Given the wide age range for the onset of schizophrenia, we plan to follow
this sample for many years. Thus, we will also lay the foundation for future
proposals that will monitor the incidence of psychosis in this sample through
young adulthood. This will eventually allow us to assess 1) the predictive
validity of schizotaxia measures and environmental adversity for subsequent
psychosis and 2) longitudinal changes in neuropsychological functioning
and brain structure and function in subjects who do and do not become psychotic.
Achievement of the second goal will help clarify which brain abnormalities
in schizophrenic patients can be attributed to neurodevelopmental events
prior to onset and which are due to neurodegeneration after onset.
Research Participation
To qualify for participation the patient must have a diagnosis of
Schizophrenia
Schizoaffective Disorder
Major Depression with Psychotic Features or
Bipolar Disorder with Psychotic Features
AND have
siblings or children ages 13 to 25
The Patient will be asked to
- consent to give the study staff permission to contact specified family members
- participate in a
2-3 hr. interview and/or
- provide a medical records release form
and - The patient will be compensated $50
The Sibling or Child will be asked to
- Complete tests of memory and attention & interviews regarding feelings and thoughts (approximately 6 hrs.)
- Have an MRI (1 ½ hrs.)
- Have follow up contact by phone every 6 mos. (for approximately 20 minutes)
- Repeat tests, interviews and MRI at 2 years
The Sibling or Child will be compensated $100 for each set of tests and interviews, $100 for each MRI, and $25 for follow up calls
The Parent/Caregiver will be asked to
- Complete family environment interview (approximately 3 hours)
- Have follow-up contact by phone every 6 months (for approximately 30 minutes)
- The Parent/Caregiver will be compensated
$40 for the family interview and $35 for follow up calls
Faculty/Staff
Principal Investigator
Ming T. Tsuang, M.D., Ph.D.
Stanley Cobb Professor of Psychiatry
Investigators
Stephen V. Faraone, Ph.D.
Associate Professor of Psychology
Larry J. Seidman, Ph.D.
Associate Professor of Psychology
Bill Stone, Ph.D.
Assistant Professor of Psychology
Investigators at MGH
Verne Caviness, Jr., M.D., D.Phil.
Nikos Makris, M.D., Ph.D.
Bruce Fischl, Ph.D.
Project Manager
Lisa Gabel, BA
Phone: (617) 626-9502
email: [email protected]
Research Assistants
Sharon White, BA
Phone: (617) 626-9501
Virna Merino, MS
Phone: (617) 626-9786
Nicole Peace, BA
Contact information
Lisa Gabel
Massachusetts Mental Health Center
74 Fenwood Road
Boston, MA 02115
Phone: (617) 626-9502
Fax: (617) 734-7915
E-mail: [email protected]
Publications
- Cloninger CR, Kaufmann CA, Faraone SV, Malaspina D, Svrakic DM, Harkavy-Friedman
J, Suarez BK, Matise TC, Shore D, Lee H, Hampe CL, Wynne D, Drain C,
Markel PD, Zambuto CT, Schmitt K, Tsuang MT. Genome-wide search for
schizophrenia susceptibility loci: the NIMH Genetics Initiative and
Millennium Consortium. American Journal of Medical Genetics (Neuropsychiatric
Genetics) 1998; 81: 275-281. - Faraone SV, Matise T, Svrakic D, Pepple J, Malaspina D, Suarez B,
Hampe C, Zambuto CT, Schmitt K, Meyer J, Markel P, Lee H, Harkavy Friedman
J, Kaufmann C, Cloninger CR, Tsuang MT. Genome scan of European-American
schizophrenia pedigrees: results of the NIMH Genetics Initiative and
Millennium Consortium. American Journal of Medical Genetics (Neuropsychiatric
Genetics) 1998; 81: 290-295. - Goldstein JM, Seidman LJ, Goodman JM, Koren D, Lee H, Weintraub S,
Tsuang MT. Are there sex differences in neuropsychological functions
among schizophrenic patients? Results from a case-control study. American
Journal of Psychiatry 1998; 155:1358-1364. - Kaufmann CA, Suarez B, Malaspina D, Pepple J, Svrakic D, Markel PD,
Meyer J, Zambuto CT, Schmitt K, Matise TC, Harkavy-Friedman JM, Hampe
C, Lee H, Shore D, Wynne D, Faraone SV, Tsuang MT, Cloninger CR. NIMH
genetics initiative Millennium schizophrenia consortium: linkage analysis
of African-American pedigrees. American Journal of Medical Genetics
(Neuropsychiatric Genetics) 1998; 81: 282-289. - Koren D, Seidman LJ, Harrison RH, Lyons MJ, Kremen WS, Caplan BB,
Goldstein JM, Faraone SV, Tsuang MT. Factor structure of the Wisconsin
Card Sorting Test: Dimensions of deficit in schizophrenia. Neuropsychology
1998; 12: 289-302. - Kremen WS, Buka SL, Seidman LJ, Goldstein JM, Koren D, Tsuang MT.
IQ decline during childhood and adult psychotic symptoms in a community
sample: A 19-year longitudinal study. American Journal of Psychiatry
1998; 155: 672-677. - Kremen WS, Faraone SV, Seidman LJ, Pepple JR, Tsuang MT. Neuropsychological
risk indicators for schizophrenia: A preliminary study of female relatives
of schizophrenic and bipolar probands. Psychiatry Research 1998; 79:
227-240. - Kremen WS, Faraone SV, Toomey R, Seidman LJ, Tsuang MT. Sex differences
in self-reported schizotypal traits in relatives of schizophrenic patients.
Schizophrenia Research 1998; 34:27-37. - Leonard S, Gault J, Moore T, Hopkins J, Tobinsion M, Olincy A, Adler
LE, Cloninger CR, Kaufmann C, Tsuang MT, Faraone SV, Malaspina D, Svrakic
D, Freedman R. Further investigation of a chromosome 15 locus in schizophrenia:
Analysis of affected sibpairs from the NIMH Genetics Initiative. American
Journal of Medical Genetics (Neuropsychiatric Genetics) 1998; 81: 308-312. - Seidman LJ, Breiter H, Goodman JM, Goldstein JM, Woodruff P, O’Craven
K, Savoy R, Tsuang MT, Rosen BR. A functional magnetic resonance imaging
study of auditory vigilance with low and high information processing
demands. Neuropsychology 1998; 12: 505-518. - Seidman LJ, Stone WS, Jones R, Harrison RH, Mirsky AF. Comparative
effects of schizophrenia and temporal lobe epilepsy on memory. Journal
of the International Neuropsychology Society 1998; 4: 342-352. - Seidman LJ, Van-Manen KJ, Gamser DM, Turner WM, Faraone SV, Goldstein
JM, Tsuang MT. Effects of increasing processing load on vigilance in
schizophrenia and in adults with attentional and learning disorders.
Schizophrenia Research 1998; 34:101-112. - Toomey R, Faraone SV, Seidman LJ, Kremen WS, Pepple JR, Tsuang MT.
Association of neuropsychological vulnerability markers in relatives
of schizophrenic patients. Schizophrenia Research 1998; 31: 89-98. - Toomey R, Faraone SV, Simpson JC, Tsuang MT. Negative, positive, and
disorganized symptom dimensions in schizophrenia, major depression,
and bipolar disorder. J Nerv Ment Dis 1998; 186: 470-6. - Tsuang MT, Faraone SV. The concept of target features in schizophrenia
research. Acta Psychiatrica Scandinavica 1998; 97: 1-10. - Tsuang MT, Stone WS, Faraone SV. Overview for treatment for schizotypal
and schizoid personality disorders: present and future. NOOS Aggiornamenti
in Psichiatria 1998; 3. - Tsuang MT, Stone WS, Faraone SV. Schizophrenia: epidemiology and genetic
studies. Epidemiology and Genetics of Schizophrenia 1998; 1-52. - Faraone SV, Meyer J, Matise T, Svrakic D, Pepple J, Malaspina D, Suarez
B, Hampe C, Chan G, Aelony A, Schmitt K, Markel P, Lee H, Harkevy-Friedman
J, Kaufmann CA, Cloninger CR, Tsuang MT. Suggestive linkage of chromosome
10p to schizophrenia not due to transmission ratio distortion. American
Journal of Medical Genetics (Neuropsychiatric Genetics) 1999; 88: 607-608. - Faraone SV, Seidman LJ, Kremen WS, Toomey R, Pepple JR, Tsuang MT.
Neuropsychological functioning among the nonpsychotic relatives of schizophrenic
patients: A four-year follow-up study. Journal of Abnormal Psychology
1999; 108:176-181. - Faraone SV, Tsuang D, Tsuang MT. Genetics of Mental Disorders: A Guide
for Students, Clinicians, and Researchers 1999. New York, NY: Guilford. - Faraone SV, Tsuang D, Tsuang MT. Psychiatric Genetics: A Guide for
Mental Health Professionals 1999. New York, NY: Guilford. - Goldstein JM, Goodman JM, Seidman LJ, Kennedy DN, Makris N, Lee H,
Tourville J, Caviness VS, Faraone SV, Tsuang MT. Cortical abnormalities
in schizophrenia identified by structural magnetic resonance imaging.
Archives of General Psychiatry 1999; 56: 537-547. - Seidman LJ, Faraone SV, Goldstein JM, Goodman JM, Kremen WS, Toomey
R, Tourville J, Kennedy D, Makris N, Caviness VS, Tsuang MT. Thalamic
and amygdala-hippocampal volume reductions in first degree relatives
of schizophrenic patients: An MRI-based morphometric analysis. Biological
Psychiatry 1999; 46: 941-954. - Toomey R, Seidman LJ, Lyons MJ, Faraone SV, Tsuang MT. Poor perception
of nonverbal social–emotional cues in relatives of schizophrenic
patients. Schizophrenia Research 1999; 40:121-130. - Tsuang MT, Faraone SV. The concept of target features in schizophrenia
research. Acta Psychiatrica Scandinavica Supplement 1999; 395: 2-11. - Tsuang MT, Faraone SV, Green AI. Schizophrenia and other psychotic
disorders. In J. Armand M. Nicholi (Ed.), The Harvard Guide to Psychiatry
1999. Cambridge, MA: Harvard University Press. - Tsuang MT, Seidman LJ, Faraone SV. New approaches to the genetics
of schizophrenia: Neuropsychological and neuroimaging studies of nonpsychotic
first degree relatives of people with schizophrenia. In: Gattaz WF,
Hafner H, eds. The Fourth Symposium on the Search for the Causes of
Schizophrenia .Vol. IV. (Balance of the Century). Berlin: Springer,
1999: 191-207. - Tsuang MT, Stone WS, Faraone SV. Schizophrenia: A review of genetic
studies. Harvard Review of Psychiatry 1999; 7: 185-207. - Tsuang MT, Stone WS, Seidman LJ, Faraone SV, Zimmet S, Wojcik J, Green
AI. Treatment of nonpsychotic relatives of patients with schizophrenia:
Four case studies. Biological Psychiatry 1999; 45: 1412-1418. - Buka SL, Goldstein JM, Seidman LJ, Tsuang, M.T. Maternal recall of
pregnancy history: Accuracy and bias in schizophrenia research. Schizophrenia
Bulletin 2000; 26:335-350. - Faraone SV, Seidman LJ, Kremen WS, Toomey R, Pepple JR, Tsuang, M.T.
Neuropsychological functioning among the nonpsychotic relatives of schizophrenic
patients: The effect of genetic loading. Biological Psychiatry 2000;
48:120-126. - Fucetola R, Seidman LJ, Kremen WS, Faraone SV, Goldstein JM, Tsuang
MT. Age and neuropsychological function in schizophrenia: A decline
in executive functions compared to normal volunteers. Biological Psychiatry
2000; 48:137-146. - Goldstein JM, Seidman LJ, Buka SL, Horton N, Donatelli J, Rieder RO,
Tsuang, M.T. Impact of genetic vulnerability and chronic exposure to
hypoxia on overall intelligence by age 7 in offspring at high risk for
schizophrenia compared with affective psychosis. Schizophrenia Bulletin
2000; 26:323-334. - Kremen WS, Seidman LJ, Faraone SV, Toomey R, Tsuang MT. The question
of neuropsychologically normal schizophrenia. Journal of Abnormal Psychology
2000; 109:743-752. - Lyons MJ, Huppert J, Toomey R, Harley RJG, Eisen S, True W, Faraone
SV, Tsuang MT. Lifetime prevalence of mood and anxiety disorders in
twin pairs discordant for schizophrenia. Twin Research 2000; 3: 28-32. - Seidman LJ, Buka SL, Goldstein JM, Horton N, Rieder RO, Donatelli
J, Tsuang MT. The relationship of obstetrical complications to cognitive
functioning at age 7 in the New England Cohorts of the National Collaborative
Perinatal Project. Schizophrenia Bulletin 2000; 26:309-321. - Tsuang MT, Faraone SV. The frustrating search for schizophrenia genes.
American Journal of Medical Genetics 2000; 97: 1-3. - Tsuang MT, Faraone SV. The Future of Psychiatric Genetics. Current
Psychiatry Reports 2000; 2: 133- 136. - Tsuang MT, Stone WS, Faraone SV. Towards reformulating the diagnosis
of schizophrenia. American Journal of Psychiatry 2000; 147: 1041-1050. - Tsuang MT, Stone WS, Faraone SV. Towards the prevention of schizophrenia.
Biological Psychiatry 2000; 48: 349-356. - Faraone SV, Green AI, Seidman LJ, Tsuang M.T. “Schizotaxia”:
Clinical implications and a new direction for research. Schizophrenia
Bulletin 2001; 27:1-18. - Freedman R, Leonard S, Gault JM, Hopkins J, Cloninger CR, Kaufmann
CA, Tsuang MT, Faraone SV, Malaspina D, Svrakic DM, Sanders A, Gejman
P. Linkage disequilibrium for schizophrenia at the chromosome 15q13-14
locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).
American Journal of Medical Genetics (Neuropsychiatric Genetics) 2001;
105: 20-2. - Freedman R, Leonard S, Olincy A, Kaufmann CA, Malaspina D, Cloninger
CR, Svrakic D, Faraone SV, Tsuang MT. Evidence for the multigenic inheritance
of schizophrenia. American Journal of Medical Genetics (Neuropsychiatric
Genetics) 2001; 105: 794-800. - Goldstein JM, Seidman LJ, Horton NJ, Makris N, Kennedy DN, Caviness
VS, Faraone SV, Tsuang MT. Normal sexual dimorphism of the adult human
brain assessed by in-vivo magnetic resonance imaging. Cerebral Cortex
2001; 11: 490-497. - Kremen WS, Seidman LJ, Faraone SV, Tsuang MT. IQ and neuropsychological
profiles in patients with schizophrenia and normal volunteers. Biological
Psychiatry 2001; 50: 453-462. - Malaspina D, Goetz RR, Friedman JH, Kaufmann CA, Faraone SV, Tsuang
M, Cloninger CR, Nurnberger JI, Blehar MC. Traumatic Brain Injury and
Schizophrenia in Members of Schizophrenia and Bipolar Disorder Pedigrees.
American Journal of Psychiatry 2001; 158: 440-446. - Rosas HD, Goodman J, Chen YI, Jenkins BG, Kennedy DN, Makris N, Patti
MS, Seidman LJ, Beal MF, Koroshetz WJ. Striatal volume loss in HD as
measured by MRI and the influence of CAG repeat. Neurology 2001; 57:
1025-1028. - Smoller JW, Rosenbaum JF, Biederman J, Susswein LS, Kennedy J, Kagan
J, Snidman N, Laird N, Tsuang MT, Faraone SV, Schwarz A, Slaugenhaupt
SA. Genetic association analysis of behavioral inhibition using candidate
loci from mouse models. American Journal of Medical Genetics (Neuropsychiatric
Genetics) 2001; 105: 226-235. - Stone WS, Faraone SV, Seidman LJ, Green AI, Wojcik J, Tsuang MT. Concurrent
validation of schizotaxia: A pilot study. Biological Psychiatry 2001;
50:434-440. - Tsuang DW, Faraone SV, Tsuang MT. Genetic counseling for psychiatric
disorders. Current Psychiatry Reports 2001; 3: 138-143. - Tsuang MT, Stone WS, Faraone SV. Genes, environment and schizophrenia.
Br J Psychiatry 2001; 178: S18-24. - Faraone SV, Tsuang DW, Tsuang MT. Methods in psychiatric genetics
(2nd Edition). In M. T. Tsuang & M. Tohen (Eds.), Textbook in Psychiatric
Epidemiology 2002. New York: Wiley-Liss. - Goldstein JM, Seidman LJ, O’Brien L, Horton NJ, Kennedy DN,
Makris N, Caviness VS, Faraone SV, Tsuang MT. Impact of normal sexual
dimorphism on sex differences in structural brain abnormalities in schizophrenia
assessed by magnetic resonance imaging. Archives of General Psychiatry
2002; 59:154-164. - Seidman LJ, Faraone SV, Goldstein JM, Kremen WS, Horton NJ, Makris
N, Toomey R, Kennedy D, Caviness VS, Tsuang MT. Left hippocampal volume
as a vulnerability indicator for schizophrenia: An MRI morphometric
study of non-psychotic first degree relatives. Archives of General Psychiatry
2002; 59: 839-849. - Seidman LJ, Kremen WS, Koren D, Faraone SV, Goldstein JM, Tsuang MT.
A comparative profile analysis of neuropsychological functioning in
patients with schizophrenia and bipolar psychoses. Schizophrenia Research
2002; 53: 31-44. - Tsuang DW, Faraone SV, Tsuang MT. Implications of Psychiatric Genetics
and the Use of Genetic Counseling. Directions in Psychiatry 2002; 22:
155-164. - Tsuang MT, Stone WS, Faraone SV. Understanding predisposition to schizophrenia:
toward intervention and prevention. Canadian Journal of Psychiatry 2002;
47: 518-526. - Tsuang MT, Stone WS, Tarbox SI, Faraone SV. An integration of schizophrenia
with schizotypy: identification of schizotaxia and implications for
research on treatment and prevention. Schizophrenia Research 2002; 54:
169-175. - Wilcox MA, Faraone SV, Su J, Van Eerdewegh P, Tsuang MT. Genome scan
of three quantitative traits in schizophrenia pedigrees. Biol Psychiatry
2002; 52: 847-854. - Kremen WS, Seidman LJ, Faraone SV, Tsuang MT. Is there disproportionate
impairment in semantic or phonemic fluency in schizophrenia? Journal
of the International Neuropsychological Society 2003; 9: 79-88. - Cirillo M, Seidman LJ. Verbal declarative memory dysfunction in schizophrenia:
From clinical assessment to genetics and brain mechanisms. Neuropsychology
Review, (In Press). - Faraone SV, Seidman LJ, Kennedy D, Makris N, Caviness VS, Kremen WS,
Goldstein JM, Toomey R, Tsuang MT. Structural brain abnormalities among
relatives of patients with schizophrenia: Implications for linkage studies.
Schizophrenia Research (In Press). - Kalinowski AG, Weinstein CS, Seidman LJ. Organizational and retrieval
deficits on the Rey–Osterrieth complex figure in schizophrenia.
In: Knight J, Kaplan EF, eds. The Rey–Osterrieth Handbook. Odessa,
FL: Psychological Assessment Resources, (In Press) - Seidman LJ, Lanca M, Kremen WS, Faraone SV, Tsuang MT. Organizational
and visual memory deficits in schizophrenia and bipolar psychoses using
the Rey-Osterrieth Complex Figure:Effects of duration of illness. Journal
of Clinical and Experimental Neuropsychology (In Press). - Seidman LJ, Wencel HE. Genetically mediated brain abnormalities in
schizophrenia. Current Psychiatry Reports, (In Press). - Seidman LJ, Wencel HE, McDonald C, Murray R, Tsuang MT. Neuroimaging
studies of non-psychotic first degree relatives of people with schizophrenia:
Towards a neurobiology of vulnerability to schizophrenia (“schizotaxia”).
In Stone WS, Faraone SV, Tsuang MT, eds. Early Clinical Intervention
and Prevention in Schizophrenia. Totowa, NJ; The Humana Press, Inc.
(In Press). - Stone WS, Seidman LJ, Woijcik J, Green A. Glucose effects on cognition
in schizophrenia. Schizophrenia Research (In Press).
Related Links
Directions to MRI
http://www.martinos.org/NewFiles/directions.html#Anchor-37516
NIMH information about:
Bipolar Disorder
http://www.nimh.nih.gov/publicat/bipolar.cfm
Depression
http://www.nimh.nih.gov/publicat/depression.cfm#intro