MATERIALS AND METHODS
Participants
People with schizophrenia. From the 478 potential patients across
Australia (either responding to a national television program on
schizophrenia research or recruited from local clinics) who were screened
for participation in this study, 149 were excluded, 221 declined and 10
were lost to follow-up after completing the telephone screen, leaving a
total of 98 patients with schizophrenia or schizoaffective disorder being
recruited into two sites: either Neuroscience Research Australia, Randwick,
New South Wales, Australia (27 females and 49 males) or the Northern
Adelaide Local Health Network Mental Health Service, Adelaide, South
Australia, Australia (11 females and 11 males). All participants were
between 18 and 51 years of age and had been receiving antipsychotics for
at least 1 year before entering the study (see Supplementary Table 1 for
the frequency of people receiving each antipsychotic medication at entry
into the trial and the parallel group analysis). A diagnosis of schizophrenia
or schizoaffective disorder was determined using the Structured Clinical
Interview for Diagnostic and Statistical Manual IV-TR Axis I Disorders47 by a
clinician trained in administration of the SCID which was confirmed
independently by another clinician. Patients with a concurrent Axis I
psychiatric diagnosis, a history of substance abuse or dependence (within
the past 5 years), head injuries with loss of consciousness, seizures, central
nervous system infection, untreated diabetes or hypertension, mental
retardation or contraindications to the administration of raloxifene were
excluded. Women were excluded if they were currently pregnant or were
receiving hormone therapy and refused alternate forms of birth control.
See Figure 1 for the CONSORT diagram.
Healthy comparison group. A group of healthy adults were also recruited
for a one-time assessment to provide a baseline comparison group.
Exclusion criteria consisted of a personal history of or a first-degree relative
with a DSM-IV Axis I psychiatric diagnosis, history of substance abuse or
dependence (within the past 5 years), head injuries with loss of consciousness,
seizures, central nervous system infection, untreated diabetes or
hypertension or mental retardation. Eighty-seven healthy adults (41 females
and 46 males) between 20 and 50 years of age met criteria for entry into the
comparison group. Nineteen of the total healthy controls were recruited
from Adelaide and 68 were recruited from the Sydney area.
All participants provided informed written consent before entering the
study, which was conducted under protocols approved by the University of
New South Wales (07/121 and 09/187), South Eastern Sydney and Illawarra
Area Health Service (07-259) Human Research Ethics Committees and the
Queen Elizabeth Hospital Ethics and Human Research Committee, Adelaide
(2010188). The trial was registered with the Australian and New Zealand
Clinical Trials Registry, registration number: ACTRN12608000461392, with
the primary and secondary outcomes of cognitive (immediate and delayed
story recall, working memory and verbal fluency) and symptoms measures
(positive and negative symptoms), respectively.