The National Alliance for Research on Schizophrenia
and Depression is providing more than $500,000 in 2004 to
nine Johns Hopkins University researchers to study causes
and treatments for mental illness.
NARSAD, the largest donor-supported organization in
the world devoted exclusively to funding scientific
research on psychiatric disorders, is awarding one
Distinguished Investigator Award (one year/$100,000) and
eight two-year Young Investigator awards ($60,000) to the
Hopkins community.
The scientific leadership of NARSAD, the Scientific
Council, reviewed more than 1,000 grant applications to
select these current awards.
"The research NARSAD is supporting with these grants
represents all phases of the leading edge of research on
the human brain and mental disorders," says the council's
president, Herbert Pardes, who also is president and CEO of
New York-Presbyterian Hospital and professor of psychiatry
at Columbia University College of Physicians and Surgeons,
as well as the former vice president for health sciences of
Columbia University and former director of the National
Institute of Mental Health.
"Not long ago, people were looking for a single gene
for each mental illness," Pardes says, "but today, as our
research grants show, there is a multiplicity of genes
functioning in complex relationships at the core of each of
the characteristic mental illnesses. The research we are
funding aims to understand this complexity and then to
treat it."
Christopher Ross, professor, SOM, received a
Distinguished Investigator Award to develop models for
schizophrenia and other psychiatric diseases focusing on
the DISC-1 gene, mutations in which can cause a rare form
of schizophrenia. He plans to develop mouse models related
to mutant DISC-1 using lentiviral expression methods. Using
neuropathologic analyses and behavioral studies, he
predicts that mutant DISC-1 will produce abnormal neuronal
development resulting in abnormal neuronal morphology in
the cerebral cortex, hippocampus and possibly other
forebrain regions.
The Young Investigator Awards are as follows.
Susan E. Holmes, assistant professor, SOM, plans to
screen a sample of individuals with schizophrenia and
bipolar disorder for three of the seven genes in the
so-called "14-3-3" family of proteins, which has been
associated with both conditions. Several lines of genetic
evidence show these genes may have a strong association
with these diseases.
Francis M. Mondimore, assistant professor, SOM, will
evaluate data from several hundred families who have
participated in genetic studies to identify family members
with chronic depression. She will then analyze the data to
determine whether periods of chronic depression run in some
families and not others. She will also perform genetic (or
linkage) analysis to find the location of the genes
responsible for putting individuals at risk for developing
chronic depression. Mondimore hopes to determine if chronic
depression is a marker for a genetic subtype of affective
disorders such as unipolar and bipolar depression.
Jennifer L. Payne, assistant professor, SOM, aims to
test whether women with mood disorders who experience
hormonally triggered depressions have an underlying genetic
vulnerability that differs from women with mood disorders
who do not experience such depressions. These studies may
lead to an identification of women at risk for hormonally
triggered depressions and to new treatments for them.
Akira Sawa, assistant professor, SOM, aims to
engineer
transgenic mice expressing mutant DISC1 and wild-type
DISC1, hoping these mice will be the first good genetic
animal model of schizophrenia. Sawa predicts that once
these mice are successfully produced, they will be
important tools for studying schizophrenia pathogenesis and
for evaluating new therapeutics.
Shanthini Sockanathan, assistant professor, SOM,
notes
that studies have shown that the regions of the brain
affected in people with schizophrenia also usually contain
retinoic acid, a key molecule involved in developmental
processes within the central nervous system. He therefore
will investigate whether disrupting retinoic acid signaling
will mimic abnormalities seen in schizophrenia. He will
genetically disrupt retinoid signaling in mice embryos and
examine the outcomes of the disturbances at certain points
in brain development.
Virginia L. Willour, instructor, SOM, notes that the
only genome scan for obsessive-compulsive disorder that has
been published to date identified one candidate region for
a gene on chromosome 9p24 that met criteria for suggestive
significance. Now, the Hopkins OCD Family study has
collected DNA samples from 50 OCD pedigrees containing at
least one pair of affected siblings, resulting in 59
independent OCD sib pairs. In the proposal, Willour aims to
genotype the 50 Hopkins pedigrees using microsatellite
markers on 9p24. If the 9p24 finding is not replicated,
then two other suitable candidate genes, such as
brain-derived neurotrophic factor or
catechol-o-methyltransferase, will be chosen.
Sarah H. Ying, assistant professor, SOM, proposes
studying whether dysfunction in the cerebellum alone can
result in neuropsychological and psychiatric disorders.
Ying suggests that the role of cerebellar dysfunction may
be demonstrated in spinocerebellar ataxia type 6, an
inherited condition primarily affecting the cerebellum. A
study of affect and executive function in patients with the
disorder is currently under way. In the planned project,
Ying aims to use novel MRI processing techniques to
visualize details of the cerebellum. The methods will then
allow Ying to query the structural basis of affective and
executive dysfunction, an important feature of psychiatric
conditions, in the SCA6 disease model.
Peter P. Zandi, assistant professor, SPH, proposes to
combine data from several family-based studies to generate
one of the largest datasets for genetic investigations of
bipolar disorder, which probably involves multiple genes in
its pathophysiology. While many current approaches use
genetic analysis based on single-gene methodologies with
certain genes contributing a minor amount to the disease,
Zandi hypothesizes his method will overcome these
limitations in identifying many susceptibility genes.
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