Omega-3 Dietary Supplements in Schizophrenia

This study looks to investigate whether patients with schizophrenia for 2 years or less may
benefit from omega-3 supplements. The main hypothesis to be tested in this study is that
white matter integrity assessed with diffusion tensor imaging (DTI) and erythrocyte membrane
omega-3 concentration may provide the means for identifying patients most likely to derive
clinical benefit from omega-3 supplementation.

To test this hypothesis the investigators will enroll 58 patients with recent-onset
schizophrenia into a 16-week long randomized double blind placebo-controlled study of
risperidone versus risperidone plus omega-3 supplementation. Study assessments after consent
will include a baseline MRI and an MRI at the final visit, blood-work, clinical interviews
to assess symptoms, and medical assessments for side effects. DTI exams and peripheral
omega-3 concentration will be obtained prior to the initiation of treatment and the primary
outcome measure will be the total Brief Psychiatric Rating Scale Score.

Specific aims are:

- To examine the efficacy of omega-3 fatty acids as an adjuvant agent in the treatment of
patients with recent-onset schizophrenia. The investigators hypothesize that patients
treated with omega-3 fatty acids will demonstrate greater Brief Psychiatric Rating
Scale (BPRS) reductions compared to the placebo group.

- To identify whether pre-treatment fractional anisotropy (FA) assessed by DTI predicts
which patients will derive clinical benefit from omega-3 fatty acids. The investigators
hypothesize that patients with lower fractional anisotropy will derive greater clinical
benefit from omega-3 fatty acid supplementation.

- To identify whether pre-treatment peripheral omega-3 fatty acid concentrations predict
which patients will derive clinical benefit from omega-3 fatty acids. The investigators
hypothesize that patients with lower peripheral omega-3 fatty acid concentrations will
derive greater clinical benefit from omega-3 fatty acid supplementation.

Inclusion Criteria:

- Current DSM-IV-defined diagnosis of schizophrenia, schizophreniform, schizoaffective
disorder, psychosis NOS or Bipolar I as assessed using the Structured Clinical
Interview for Axis I DSM-IV Disorders;

- Does not DSM-IV criteria for a current substance-induced psychotic disorder, a
psychotic disorder due to a general medical condition, delusional disorder, brief
psychotic disorder, shared psychotic disorder, or a mood disorder with psychotic
features;

- current positive symptoms rated more than 4 (moderate) on one of these BPRS items:
conceptual disorganization, grandiosity, hallucinatory behavior, and unusual thought
content;

- is in a early phase of illness as defined by having taken antipsychotic medications
for a cumulative lifetime period of 2 years or less;

- age 15 to 40;

- competent and willing to sign informed consent; and

- for women, negative pregnancy test and agreement to use a medically accepted birth
control method.

Exclusion Criteria:

- serious neurological or endocrine disorder or any medical condition or treatment
known to affect the brain;

- any medical condition which requires treatment with a medication with psychotropic
effects;

- significant risk of suicidal or homicidal behavior;

- cognitive or language limitations, or any other factor that would preclude subjects
providing informed consent;

- medical contraindications to treatment with risperidone (e.g. neuroleptic malignant
syndrome with prior risperidone exposure), omega-3 supplements (e.g. bleeding
disorder, seafood allergies) or placebo capsules (e.g. allergies to capsule
components);

- contraindications to MRI imaging (e.g. presence of a pacemaker);

- lack of response to a prior adequate trial of risperidone;

- taking omega-3 supplements within the past 8 weeks, and

- requires treatment with an antidepressant or mood stabilizing medication.