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Type 1 (classical) cadherins including FAT1 serve
as a guide for the migration and positioning of neurons during their
development, processes thought to be involved in the development of
schizophrenia and bipolar disorder. Thus,
making FAT1 a candidate gene for schizophrenia and bipolar disorder. Current
studies primarily focused on the role of type 1 cadherins and FAT in cancer.
However, numerous studies demonstrate FAT’s possible contribution in the
development of mental illnesses. Certain Reports have regarded FAT as a
susceptibility gene for bipolar disorder; significantly associated to bipolar
disorder. On the other hand, negative results
were noted as well. Cumulative evidence suggest that schizophrenia and
bipolar disorder may share many risk genes, however only few evidence for
cadherins has been found.

This study was the first study conducted that focused on a possible
role of FAT on the response to psychotropic medications.
The main purpose of this study is
to inspect possible effects of a set of markers in the FAT on the ef?cacy and
tolerability of aripiprazole (an atypical antipsychotic) in treating
schizophrenic patients. Initially to enlarge the ?ndings detected
in bipolar patients to schizophrenia patients, Pae et
al. (2010) preliminarily examined the potential in?uence of a set of SNPs
in FAT gene, selected based on earlier ?ndings (rs2306987, rs2306990, rs2637777
and rs2304865), on clinical and safety outcomes in a sample of schizophrenic Korean
patients treated with aripiprazole. 87 out of 177 screened schizophrenia
inpatients or outpatients were included into the intent-to-treat sample. Included patients had inefficiently controlled symptoms and/or bad
toleration for current antipsychotic medications. Patients were randomly assigned
to three different switching conditions to aripiprazole (10mg) by (1) concurrent
discontinuation of current antipsychotic, (2) gradual lessening of current
antipsychotic over 4 weeks, half dose after the ?rst 2 weeks or (3) gradual reduction
off current antipsychotic over 4 weeks after maintenance of current dose for 2
weeks. Patients were then monitored for 12 weeks to evaluate the tolerability
and ef?cacy of distinct switching tactics. (Rescue medications
(medicine intended to relieve symptoms immediately) of benzodiazepines
(less than 4mg per day of diazepam or equivalent) and antiparkinsonian were
allowed in the occurrence of severe extrapyramidal symptoms, but not for use of
prophylactics (medicine intended to prevent disease). There were no signi?cant distinctions
noted in the number of benzodiazepines’ users and the dosage administered was
found among the three groups.

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Ef?cacy
was assessed using the Clinical Global Impression Severity and Improvement
Scale (CGI-S; CGI-I), an efficient research rating instrument suitable for all
psychiatric disorders that provides an overall
clinician-determined summary measure including knowledge of the patient’s
history, psychosocial circumstances, symptoms, behavior, and the impact of the
symptoms on the patient’s ability to function. Other measures of outcome employed were the Brief Psychiatric
Rating Scale (BPRS) a rating scale used to
measure psychiatric symptoms such as depression, anxiety,
hallucinations and unusual behavior, and
the Schedule for the Assessment of Negative Symptoms (SANS), an assessment tool designed to identify 20 negative symptoms of
schizophrenia which are numerically graded on a scale from 0 to 5. Side
effects were evaluated by the Simpson–Angus Scale for Extrapyramidal Symptoms
(SAS) , A 10-item testing instrument-range of scores 0-40
(increased scores indicate increased severity) used to evaluate drug-related extrapyramidal syndromes., the Barnes Akathisia Scale (BAS), a rating scale that assesses the severity of drug-induced akathisia,
and the Abnormal Involuntary Movement Scale (AIMS), a rating scale that
measures an involuntary movement disorder called tardive dyskinesia (TD)
that sometimes develops as a side effect of long-term r treatment with antipsychotics.
Multivariate analysis of covariance (MANCOVA) (a statistical technique
that assesses for statistical differences on multiple continuous
dependent variables by an independent grouping variable, while controlling the
third covariate variable) was used to test the SNPs effect on ef?cacy
and safety indexes. Haplotype analysis was performed. Haploview 3.2 was
utilized to create a linkage disequilibrium map and to test for Hardy–Weinberg
equilibrium (HWE), a theorem stating that allele and
genotype frequencies in a population remain constant from a generation to
another in the absence of other evolutionary influences. The “R” statistical environment, package ‘haplo.score’, was executed to make tests for
associations using multimarker haplotypes in order to compare clinical and
safety scores at every haplotype evaluation point.

The results of the study showed that FAT
variants and clinical or safety assessments were not related. No signi?cant difference was observed for side effects. No signi?cant
association with clinical and safety scores was demonstrated at any time with
the Haplotype analysis. The data also suggests no association between
investigated alleles and genotypes in FAT and response to aripiprazole. Thus, suggesting that FAT gene does not have a
role in the response to aripiprazole in schizophrenia patients.  However, more experimentation and research on
this study is required because this study carries a number of limitations 

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