RELATIONSHIP BETWEEN SELF-REPORT AND INTERVIEWER-RATED LEVELS OF PSYCHOTIC-LIKE
EXPERIENCES (PLEs): A COMPARION OF A CLINICAL vs. COMMUNITY SAMPLE
Joe A Buckby1,2; Alison R Yung1,2; Elizabeth Cosgrave1; Margaret
Ross1,2; Eoin Killackey1,3; Gennady Baksheev1,2
1ORYGEN Youth Health, Melbourne, Australia
2Department of Psychiatry, University of Melbourne, Australia
3Department of Psychology, University of Melbourne, Australia
Background: Psychotic-Like Experiences (PLEs) are predictive of psychosis,
yet are also commonly reported in community studies. It remains unclear why these same
symptoms are endorsed by both people at imminent risk for psychotic disorder and also
among people with no symptomatology or functional impairment. We hypothesised that PLEs,
as measured through questionnaire, would be only moderately related to interview ratings
of PLEs. Further, we hypothesise that there will be a stronger relation between these
methods in clinical vs. community samples.
Methods: Two distinct samples were used in the present study: (1) 150 young
help-seekers (mean age = 17.8 years) referred to a mental health service; (2) 651
adolescents (mean age = 15.8 years) recruited from secondary schools across Melbourne,
Australia. Interview-PLEs were assessed by the Comprehensive Assessment of At-Risk
Mental States (CAARMS) and questionnaire-PLEs by the Community Assessment of Psychic
Experiences (CAPE).
Results: Self-report PLEs were reported by the majority of participants in
both samples (Community: 99.1%, Help-Seekers: 98.6%). In comparison, interview-rated
PLEs were endorsed less frequently (Community: 46.2%, Help-Seekers: 62%). There was a
moderate relationship between interview- and self-report PLEs among help-seekers
(r=.4–.6). However, there was a weaker relationship in the community sample
(r=.2–.4).
Discussion: Self-reported and interview-rated PLEs showed a differential
relationship across the distinct samples investigated in the present study. It may be
that healthy young people are unfamiliar with the constructs tested in measures such as
the CAPE and may frequently misinterpret questions, leading to artificially inflated
prevalences.
STRESS AND HPA AXIS FUNCTIONING IN FIRST-EPISODE PSYCHOSIS: NEUROCOGNITIVE EFFECTS
ON RELATIONAL MEMORY
Felicity Butselaar1,4; Stephen Wood2; Greg Savage1,3; Connie
Markulev4; Yang Yun4; Christina Phassouliotis4; Lisa
Phillips4; Patrick McGorry4; Belinda Garner4
1School of Psychology, Psychiatry and Psychological Medicine, Monash University,
Melbourne, Australia
2Melbourne Neuroscience Centre, The University of Melbourne, Melbourne,
Australia
3Macquarie Centre for Cognitive Science, Macquarie University, Sydney,
Australia
4ORYGEN Research Centre, Department of Psychiatry, The University of Melbourne,
Melbourne, Australia
Increased stress and dysfunction of its neural mechanism, the
hypothalamic-pituitary-adrenal (HPA) axis, is hypothesised to be a vulnerability marker
for the development of psychotic illness and accompanying cognitive impairment. The
brain structure primarily responsible for the regulation of the HPA axis is the
hippocampus. It is highly sensitive to the neurotoxic effects of sustained increased
cortisol levels seen with HPA axis dysfunction, and plausibly, this accounts for
observed deficits in relational memory performance. Nevertheless, there exists a paucity
of prospective longitudinal literature examining these factors in drug naïve patients
during the early acute psychotic phase. Our aim was to determine the role of stress in
the onset and development of first episode psychosis (FEP) and associated memory
impairment. We conducted a comprehensive longitudinal assessment of the possible
predictor relationships between stress, HPA dysfunction, symptoms, and impaired
hippocampal functioning in drug naïve patients at first acute presentation, and again
following three months of treatment. We have examined the associations between
post-dexamethasone plasma cortisol levels, glucocorticoid receptor function and
impairment in cognition and memory performance on a novel relational memory task as a
representation of functional changes within the hippocampus. Results from n = 23 FEP
patients, and follow up data from n = 10 FEP patients following three months of
treatment will be presented along with comparison data from n = 25 baseline and n = 10
follow-up normal controls. Findings from this study will throw light on the origins of
relational memory impairment in first-episode psychosis, and assist in the development
of focused treatment programs.
SOCIAL COGNITIVE SKILLS AND VISUAL SCAN PATHS IN CHILDREN AND YOUNG ADULTS WITH
VELO-CARDIO-FACIAL SYNDROME (22Q11.2 DELETION SYNDROME)
1Priority Research Centre for Brain and Mental Health Research, University of
Newcastle, NSW Australia
2Schizophrenia Research Institute
3Hunter Medical Research Institute
Aims: In the last decade research has found that people with
Velo-Cardio-Facial syndrome (VCFS) have problems with social skills. Little research has
concentrated on investigating the cognitive components underlying social skills. Such
research is important especially since it has been suggested that psychotic symptoms can
arise when people with schizophrenia fail to maintain online representations of their
own and others’ mental states. VCFS constitutes the third highest known risk factor for
schizophrenia. The current study aimed to identify cognitive components underlying the
social problems observed in VCFS.
Methods: In the current pilot study we are investigating social cognition
in young adults with VCFS and healthy controls using Theory of Mind tasks such as a
picture sequencing task and emotion attribution tasks. Visual scanpaths to facial
emotion stimuli were recorded, using Eyelink1000, whilst subjects viewed facial
expression stimuli depicting seven emotions
(happy/sad/neutral/fear/disgust/surprise/anger). Recognition accuracy and Feature/non
feature scanning parameters were recorded concurrently.
Results: We identified differences in how the young adults with VCFS
performed on the mentalising tasks. The scanpath data also suggests that the VCFS group
spend significantly longer looking at the mouth region and less time at the eyes
compared to the control group and were less accurate in identifying the facial
emotions.
Conclusions: People with VCFS have problems with basic social cognitive
functions. The VCFS group don't use optimal strategies when looking at faces and
consequently perform less well when trying to identify facial expressions. This might
have an impact on the social abilities of people with VCFS.
Supported by NH&MRC NHMRC ref 455624
A PROGRESS REPORT ON THE AUSTRALIAN SCHIZOPHRENIA RESEARCH BANK
Vaughan Carr1,2, Carmel Loughland1,2, Stan Catts3, Frans
Henskens4, Assen Jablensky5, Pat Michie1,2, Bryan
Mowry6,7, Chris Pantelis8, Ulrich Schall1,2, Rodney
Scott9
1Schizophrenia Research Institute, Sydney, Australia
2Centre for Brain and Mental Health Research, University of Newcastle,
Australia
3Department of Psychiatry, University of Queensland, Australia
4School of Electrical Engineering and Computer Science, University of Newcastle,
Australia
5Centre for Clinical Research in Neuropsychiatry, University of Western
Australia, Australia
6Queensland Centre for Mental Health Research, University of Queensland,
Australia
7Queensland Institute of Medical Research, Brisbane, Australia
8Melbourne Neuropsychiatry Centre, University of Melbourne, Australia
9Division of Genetics, Hunter Area Pathology Service, University of Newcastle,
Australia
In 2007 the Australian Schizophrenia Research Bank was officially launched and a
recruitment campaign commenced to achieve an initial sample of 2,000 cases of
schizophrenia and 2,000 healthy controls for a nationwide genetic epidemiology study of
schizophrenia. The study involves scientific collaborators in four States and is funded
through a NHMRC Enabling Grant, philanthropic sources and the resources of the
Schizophrenia Research Institute. All participants undergo a comprehensive clinical
assessment using a structured diagnostic interview and symptom ratings, a
neuropsychological test battery and structural MRI scanning; blood is taken for later
genetic studies. This paper presents a limited range of data on the first participants
recruited (N = 322 at the time of writing, 187 cases and 135 controls) one third of whom
have had MRI scans. Some of the challenges involved in a large-scale initiative of this
kind are discussed, including consensus protocol development; quality control issues;
staff recruitment and training; participant sampling and assessment; governance and
access policies and systems; data storage, management and transfer; communications and
operational management challenges. All of these factors are crucial for ensuring the
integrity of the information held in the Bank. By linking reliable and valid clinical,
cognitive, neuroanatomical and genetic information in a large sample of cases and
controls, the Bank has the potential to subdivide the schizophrenia phenotype and
identify aetiologically significant subgroups with characteristic genetic,
neuropsychological, and neuroimaging profiles.
SOCIAL WORKERS BELIEFS ABOUT THE INTERVENTIONS AND LIKELY OUTCOMES FOR SCHIZOPHRENIA
AND DEPRESSION. A COMPARISON WITH THE PUBLIC AND OTHER HEALTH PROFESSIONS
Paloma Cesare
Objective: The main objective was to investigate and compare social workers
beliefs about the interventions and the likely outcomes and prognosis for schizophrenia
and depression with those of psychiatrists, general practitioners, mental health nurses,
clinical psychologists and the general public.
Method: The research used methods employed in previous surveys of
professional and public beliefs. A postal survey of 1010 Australian social workers was
carried out and 267 surveys were distributed via a snowball sampling technique. The
survey was comprised of a vignette describing a person with either depression or
schizophrenia. Respondents rated whether particular medical, psychological and lifestyle
interventions were helpful, harmful or neither.
Results: Social workers had difficulty identifying the correct diagnosis
for the schizophrenia vignette. Social workers supported a wide range of interventions
in the treatment of schizophrenia and depression, but did not endorse medications and
hospital admissions as much as the other health professionals, but endorsed them more
than the general public. Social workers had a clear preference for lifestyle
interventions and endorsed these more than any of the other groups. Social workers were
the most pessimistic of all the groups, including the general public, about the
prognosis for schizophrenia, without professional help.
Conclusions: The research highlights the importance of social workers
receiving adequate education in their undergraduate degrees, to aid in the recognition
and treatment of mental illness, so that people suffering from mental illness receive
satisfactory care.
PRELIMINARY CLIENT AND PROGRAM REVIEW USING THE NEW COMMON DATA SET VARIABLES FOR A
CANADIAN EARLY INTERVENTION IN PSYCHOSIS PROGRAM
Peter Coughlin1, Dr. L. K. Oyewumi2
1Heads Up! Program, Southeastern Ontario District Early Intervention in Psychosis
Program, c/o Religious Hospitallers of Saint Joseph of the Hotel Dieu of Kingston,
Kingston, Ontario, Canada
2Professor of Psychiatry and of Pharmacology & Toxicology, Queen's
University, and Medical Director, Southeastern Ontario District Early Intervention in
Psychosis Program, Kingston, Ontario, Canada
Introduction: Early Intervention Programs (EIP) in Ontario, Canada complete
mandatory Common Data Set (CDS) reporting for the provincial funder (effective 2006–07).
This aggregate data is organized by cohort, i.e. length of client registration with EIP.
Variables are measured at baseline entry to EIP and at reporting period, measuring
change (+/ −) over time. As the data reporting standards and processes are in their
initial years of implementation, interpretation is limited. Preliminary descriptive data
is available at a provincial level (n = 6,042 for March 2007)1 and some variables at program level. The
Southeastern Ontario District Early Intervention in Psychosis Program (SEODEIP) is a
small regional program sponsored by a university hospital and offers services in a rural
region that includes three medium sized cities.
Method: SEODEIP Program uses the CDS demographic, hospitalization and
psychosocial variables to guide service design and evaluation. Data is collected by case
managers using a software application and both aggregate and individual measurement is
available at the clinical and program level.
Results: The presentation will focus upon variables of gender, age,
psychiatric hospitalization, client living arrangements, residence type, employment
status, educational status, highest level education obtained and primary income source.
SEODEIP uses comparators with provincial data, where available. CDS informs case
management, tracks client change and supports program development and communication with
community partners, external bodies.
Conclusion: We use CDS to support clinical and program services. We
anticipate increased reliability of our data and return on the investment of staffing
resources used to report mandatory variables.
AGE-RELATED EFFECTS OF THE SYNTHETIC CANNABINOID, HU210, ON BODY WEIGHT AND
CANNABINOID RECEPTOR DENSITY IN THE RAT BRAIN
Victoria S. Dalton1,2, HongQin Wang1,2, Katerina Zavitsanou1,2
1Schizophrenia Research Institute, Sydney, Australia
2Australian Nuclear Science and Technology Organisation, Sydney,
Australia
Exogenous cannabinoids are known to trigger psychosis in vulnerable individuals,
particularly during adolescence. The aim of this study is to compare the physiological
effects and the underlying adaptive changes in the brain that take place in the
adolescent and adult rat following cannabinoid administration. Adolescent (postnatal day
35) and adult (postnatal day 70) rats were injected with HU210 (25, 50 or 100 µg/kg) or
vehicle for 14 days. Body weight loss was recorded in both groups and cannabinoid
receptor density was quantified in adults using in vitro autoradiography with
[3H] CP55,940. In adults, drug tolerance developed around day four since a
decline in body weight (p < 0.05) was recorded during the first four treatment days
but after this timepoint animals began to gain weight. In contrast, in adolescents body
weight decreased for the first two days of treatment only. In adults, statistically
significant dose dependent reductions in [3H] CP55,940 binding were seen in
cortical, basal ganglia and limbic brain regions examined after chronic administration
of HU210 with overall decreases in binding of 70.3–89.2%, 56.3–85.2% and 41.6–68.6% in
100, 50, 25 µg/kg treatment groups respectively when compared with controls. Binding in
adolescents is yet to be completed however the findings on body weight loss suggest that
adolescent and adult animals react differently to HU210. The endocannabinoid system is
an important regulator of neurotransmitter systems in the brain affected in psychosis.
The adaptive changes that take place therefore following cannabinoid use may play a role
in cannabis-induced psychosis, particularly during adolescence.
PREVALENCE OF PROBLEM GAMBLING IN PEOPLE PRESENTING TO AN ACUTE AREA MENTAL HEALTH
SERVICE
De Castella AR, Chow-Fairhall J, Watkins D, Kulkarni J
Monash Alfred Psychiatry Research Centre, Monash University & Alfred
Hospital, VIC, Australia
Background: Problem Gambling (PG) affect an estimated 2% of the population,
with those affected often suffering from co-morbid problems including mood disorders and
substance abuse. Suicidal behaviour is a common and serious outcome for people with
gambling problems. Understanding the prevalence of problem gambling and suicidality has
important implications for clinicians’ knowledge.
Aims: To identify the prevalence of PG, the types of co-existing mental
disorders and the prevalence of suicidality, in a sample of people presenting to an Area
Mental health Service.
Method: Consecutive presentations of people (N = 848) who were seen either
in the community by The Alfred's Crisis Assessment & Treatment Team or who were
admitted to the Emergency Department of The Alfred and seen by The Alfred's Psychiatry
Triage over a six-month period were screened for suicidal ideas/intent, and problem
gambling.
Results: People with Gambling Problems = 71 (8.4%), (Males = 52, Females =
19). This is four times the reported prevalence rate in the general community. Only half
of those identified with PG had sought help for PG = 37 (52%), (Males = 25, Females =
12). 39.4% of people identified with PG had suicidal ideas or behaviour (N = 71), which
was similar to those presenting without problem gambling (41.4%)
Conclusions: Results of the project highlight that PG is present for a
significant number of people who access Area Mental Health Services. Without concerted
screening, many people with underlying problem gambling would not be detected and would
thus go untreated.
QUALITY OF LIFE ON RISPERDAL CONSTA: BASELINE RESULTS
De Castella AR, Kulkarni J, Fitzgerald PB, Sinclair K, Olsen S, Biffin F, Filia K.
Monash Alfred Psychiatry Research Centre, Monash University & Alfred
Hospital, VIC, Australia
Background: Risperdal Consta is the first depot atypical antipsychotic on
the market. This study follows up 51 people who were commenced on Risperdal Consta over
a two year period to characterise their illness, quality of life and functioning, and to
investigate changes in these parameters over time.
Aims: To measure changes in psychopathology, quality of life, occupational
functioning, and treatment parameters among clients treated with Risperdal Consta.
Method: Demographic and clinical data was collected directly from 51
participants at study entry. Additional information was extracted from their medical
record for the previous two years. Participants were followed-up every 6 months for 2
years, and assessed on a range of QoL and clinical measures. The study is currently in
the follow-up phase.
Results: At baseline, the majority of subjects were males (62.7%), and had
a diagnosis of schizophrenia (72.5%). The overall average age of participants was 39.94
years, with an average duration of illness of 14.1 years. Participants had an average
PANSS score of 65.7 (35–112). Their average overall health state on the EuroQol was
62.71 (range = 2–100, best imaginable health = 100).
Conclusion: The sample enrolled in this prospective two year follow up
study had moderate levels of illness severity at baseline, but had above average self
reported overall health states. Results provide a characterisation of the types of
clients treated with Risperdal Consta within an inner city Area Mental Health
Service.
A COMPREHENSIVE RETROSPECTIVE AUDIT OF THE USE OF RISPERDAL CONSTA IN AN AREA MENTAL
HEALTH SERVICE IN MELBOURNE, AUSTRALIA
De Castella AR, Furtado C, Nicol A, Sinclair K, Williams P, Olsen S, Biffin F,
Fitzgerald PB, Kulkarni J.
Monash Alfred Psychiatry Research Centre, Monash University & Alfred
Hospital, VIC, Australia
Background: Risperdal Consta is the first depot atypical antipsychotic on
the market. Early use of new medications is often a matter of trial and error, until
real world usage data becomes available.
Aims: To investigate how Risperdal Consta has been used during the
1st 12 months after release on the PBS in patients with schizophrenia, and
to describe patient outcomes.
Method: Medical records of all clients initiated on RC during the first 6
months after approval on the PBS were reviewed for 12 months pre RC, and 12 months post
RC. Data captured pre and post RC included; pharmacotherapy, hospitalisations,
adherence, substance use, reason for switch to RC, start dose of RC, location of
initiation, and length of treatment on RC.
Results: 141 files were identified and reviewed. Mean age was 40.4 years.
Two thirds were men. Mean duration of illness was 12 years. 85% had been hospitalised in
the 2 years prior to RC, 29% of clients switched to RC from risperidone (52%), 70% of
clients were initiated on RC while inpatients, 80% of clients had 2 or less dose changes
of RC in the 1st 12 months, more than 30% of clients continued on RC after 12
months, 81.5% of clients received concomitant oral antipsychotics medications during the
1st 12 months, most commonly risperidone (76%), 11.2% of clients were
recorded to have good adherence pre RC compared with 74.2% post RC, most common reason
for discontinuation of RC was inadequate response, most common AP post RC was
clozapine.
Conclusion: This study provides real world data into the use of RC in an
Area Mental Health Service which will help guide clinicians in the use of this
medication in treating patients with schizophrenia.
MIRTAZAPINE ADD-ON THERAPY IN THE TREATMENT OF SCHIZOPHRENIA WITH ATYPICAL
ANTIPSYCHOTICS: A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED CLINICAL TRIAL
Seetal Dodd1, Michael Berk1,2,3, Russell D'Souza4, Harry
Hustig4, Les Koopowitz6, Andrew Monkhouse5, Fiona
Bole4, Suma Sathiya4, Danijela Piskulic4
1Department of Clinical and Biomedical Sciences, University of Melbourne,
Geelong
2Orygen Research Centre, Parkville
3MHRI, Parkville
4Northern Psychiatry Research Centre, Department of Psychiatry, University of
Melbourne
5Glenside Campus, Royal Adelaide Hospital
6Health on Kensington, Leabrook
Background: Negative symptoms are a core part of the phenomenology of
schizophrenia, and are inadequately treated by existing antipsychotics. Some studies
have reported improvement in negative symptoms when antidepressants are administered as
an adjunct to antipsychotics.
Aims: To investigate the efficacy of mirtazapine, adjunctive to
antipsychotics, as treatment for the negative symptoms of schizophrenia.
Method: A 6-week, double-blind, placebo-controlled, randomised trial of
mirtazapine (30 mg/day) or placebo as adjunctive treatment with atypical antipsychotics
was conducted. Outcome measures included the PANSS, CGI, SAS and HAMD.
Results: There were no significant differences between mirtazapine and
placebo treated groups at baseline or from baseline to 6-week endpoint for any of the
outcomes measures. For the PANNS-ve there was a general tendency for patients on
Mirtazapine and those on Placebo to “improve” at both sites with little difference
between the two treatments. Overall, the difference in slopes between Mirtazapine and
Placebo was not significant (p = 0.465).
Conclusion: In this study mirtazapine was not superior to placebo as
adjunctive therapy for negative symptoms of schizophrenia.
A RETROSPECTIVE INVESTIGATION OF HONOS RESULTS IN CLOZAPINE-TREATED PATIENTS
Joanna Fitzsimons1, Tim Lambert2, Seetal Dodd3, Michael
Berk1,3
1Department of Clinical and Biomedical Sciences: Barwon Health, The University of
Melbourne, Geelong, Australia
2Discipline of Psychological Medicine, University of Sydney, Sydney,
Australia
3Community and Mental Health, Barwon Health, Geelong, Australia
While clozapine continues to be the gold standard antipsychotic for treatment refractory
schizophrenia, outcome data most frequently examines psychopathology. The Health of the
Nation Outcome Scale (HoNOS) is a psychosocial measurement tool routinely and easily
utilised by clinicians throughout Australia and measures a variety of outcomes
(behaviour, impairment, symptoms, social) for consumers with mental illness. Few studies
to date have specifically investigated the relationship between clozapine treatment and
HoNOS.
The current study was designed to examine the psychosocial domains measured by HoNOS in
clozapine-treated consumers, in the Barwon Health region, prior to, during and post
clozapine treatment. As part of an ongoing retrospective investigation into the risks
and benefits of clozapine treatment, HoNOS data was collated from consumers who were
treated with clozapine (n = 390) in the Barwon Health region from 1997 to 2008. A total
of 4659 HoNOS measurements were obtained (M = 12 measurements per consumer, range:
1–51). HoNOS results were allocated into one of three groups: pre clozapine treatment,
during clozapine treatment or post clozapine treatment, and then further in to either
inpatient or outpatient results. Further results and the implications of these
investigations will be discussed.
‘ABOUT HELEN’ – PSYCHOSIS AND PREGNANCY (A CASE REPORT)
H Gilbert1,2, J Kulkarni1,2, C Gurvich1,2
1Monash Alfred Psychiatry Research Centre, Alfred Hospital, Melbourne,
Australia
2School of Psychology, Psychiatry and Psychological Medicine, Monash University,
Melbourne, Australia
Introduction: The desire to reproduce is both a powerful urge and a basic
human right for women, regardless of mental health status. Currently, mental illness is
treated with antipsychotic medication, however research is limited regarding the effect
of this medication upon fetal development and maternal health. The challenge for
clinicians, and women in this vulnerable population group, is to balance the risk to the
mother's mental health and wellbeing, against any possible risk of fetal abnormalities
and developmental problems in the infant.
Aims: To follow the pathway of Helen's pregnancy, delivery and first
postnatal year, as she learns to cope with her mental illness and accept that her baby
may be put into care.
Method: A case report approach is used to highlight Helen's journey during
her pregnancy and for one year postpartum. Appropriate information is gathered along
this timeline, including demographic, medical, psychiatric, medication and obstetric
history, as well as information on general health and wellbeing for both mother and
baby.
Results: Helen's symptoms were exacerbated throughout her pregnancy, during
which time she was medicated with Clozapine. Her baby developed fetal abnormalities and
Helen was deemed unfit to provide the necessary skills to care for her baby.
Discussion: The combination of poor psychosocial history, existing
involvement with child protection agencies, psychiatric diagnoses and admissions,
medications and substance abuse, present many issues affecting outcomes for both mother
and baby during the perinatal period.
Acknowledgements: This research is supported by AstraZeneca, Janssen-Cilag,
Mayne Pharmaceuticals and the Australian Rotary Health Research Fund.
‘Imaging genetics’ in schizophrenia and bipolar disorder: Evaluating shared
cognitive endophenotypes.
Melissa J. Green1,2,3, Thomas W. Weickert1,3,4, Cynthia Shannon
Weickert1,3,4, Philip B. Mitchell1,2, Peter R.
Schofield4
1School of Psychiatry, University of New South Wales, Sydney, Australia
2Black Dog Institute, Prince of Wales Hospital, Randwick, Australia
3Schizophrenia Research Institute, Darlinghurst, Australia
4Prince of Wales Medical Research Institute, Randwick, Australia
Introduction: To evaluate emerging evidence from the field of ‘imaging
genetics’ with regard to the hypothesis that shared genetic susceptibility for bipolar
disorder (BD) and schizophrenia (SCZ) may be associated with common neuropsychological
and social cognitive impairments.
Methods: We review evidence from integrative investigations of the
association between candidate susceptibility genes and cognitive endophenotypes for
schizophrenia and bipolar disorder, utilising functional imaging techniques to more
closely approximate the neurophysiological systems associated with gene action.
Results: Genes implicated in the aetiology of schizophrenia and bipolar
disorder are associated with cognitive processes mediated by frontal and temporal brain
systems (including working memory and verbal memory). For example, reliable associations
between prefrontal brain activity, executive function, and polymorphisms on the catechol
O-Methyltransferase (COMT) gene have been consistently reported in both healthy and
patient samples. Similarly, there is growing evidence for polymorphisms on the Brain
Derived Neurotrophic Factor (BDNF) gene in association with memory in schizophrenia and
bipolar disorder. Relatively less attention has been given to the potential
endophenotypic status of social cognitive processes, despite evidence from health
participants for the contribution of prefrontal and temporal brain regions to these
skills. However, preliminary findings suggest associations with BDNF and COMT
polymorphisms and social cognitive processes should be further explored.
Conclusion: Neuropsychological and social cognitive processes provide a
plausible target for investigation of the shared genetic basis of schizophrenia and
bipolar disorder. The elucidation of genotypic markers of cognitive function may provide
important predictors of pharmacological treatment response to facilitate personalized
treatment of psychosis.
LOWERED SELF-ESTEEM IN SCHIZOPHRENIA: THE ROLE OF AUDITORY HALLUCINATIONS AND
PERCEIVED STIGMA
Groot C1, Rossell S2
1The University of Melbourne, Department of Psychiatry
2Monash University
The relationship between stigma, self-esteem and auditory hallucinations (AH) is of
recent interest in schizophrenia research. Relevant authors purport that low self-esteem
is causal in the experience and severity of current AH. However, this conclusion may be
premature. The current research further examined the relationship between stigma,
self-esteem and AH. It was hypothesised that the perceived stigma associated with one's
experience of AH reduces self-esteem. 56 patients with a diagnosis of schizophrenia or
schizo-affective disorder and 44 healthy controls participated in the study. Assessment
of AH was performed with the Scale for the Assessment of Positive Symptoms (SAPS). The
patient group was divided by AH status, i.e., current AH (n = 21); past history of AH (n
= 15); and those having never experienced AH (n = 20). Examination of cognitive styles
was performed using Rosenberg's Self Esteem Questionnaire (RSE). The experience of AH
significantly correlated with lower self-esteem. Thus, both past voice hearers and
current voice hearers had lower scores on the RSE than patients who had never heard a
voice and healthy controls. This reduction in self-esteem was not related to the
frequency or severity of the voices. This suggests that current self-esteem is adversely
affected by the experience of AH; whether past or present. Contrary to previous
conclusions, this finding lends credence to the hypothesis that patients’ perceived
stigma and stereotyped beliefs about mental illness (here, one's experience of AH) may
influence the observed reduction of self-esteem. Given these findings, CBT strategies
for AH should target perceived stigma, stereotyped beliefs and reduced self-esteem.
ESTROGEN AND COGNITION IN WOMEN WITH SCHIZOPHRENIA
Gurvich C, Mu L, Gilbert H, De Castella A, Kulkarni J
The Alfred Psychiatry Research Centre, The Alfred and Monash University School
of Psychology, Psychiatry and Psychological Medicine, Melbourne, Australia
Background: Estrogen receptors have been found in several brain areas
involved in cognition. The relationship between estrogen and cognition has been
investigated via exploratory studies of cognition and circulating estrogen, as well as
epidemiological and experimental studies that have examined cognitive enhancing efficacy
of estrogen therapy in women across their lifespan. There is also some evidence for a
positive effect of estradiol on cognitive function in women with schizophrenia, although
findings are limited and inconclusive.
Aim: The current studies aimed to investigate cognitive performance in
women with schizophrenia before and after adjunctive estrogen therapy.
Methods: Women with a diagnosis of schizophrenia participated in one of two
double-blind, randomised controlled trials of adjunctive estrogen: i) 17 women of
child-bearing age received adjunctive transdermal estradiol (100mcg/day adjunctive
transdermal estradiol, 200mcg/day adjunctive transdermal estradiol, or adjunctive
transdermal placebo) for 8 weeks and ii) 24 postmenopausal women received adjunctive
placebo; adjunctive raloxifene (a selective estrogen receptor modulator 60mg); or
adjunctive HRT for 12 weeks. Cognitive functioning was assessed at baseline and trial
end.
Results: Preliminary findings indicated an improvement in verbal memory and
attention for women receiving estrogen treatment.
Conclusion: Adjunctive estrogen may have the potential to enhance cognitive
functioning, in relation to attention and verbal memory, for women with
schizophrenia.
EVestG: A Diagnostic Measure for Schizophrenia
Saman Haghgooie1, Brian J. Lithgow1, Caroline Gurvich1,2, and Jayashri
Kulkarni1,2
1Monash University, Melbourne, Australia
2The Alfred Psychiatry Research Centre, The Alfred Hospital and Monash,
University School of Psychology, Psychiatry and Psychological Medicine, Melbourne,
Australia
Introduction: Schizophrenia is a severe mental illness associated with
multipleneuropathological, neurochemical and genetic abnormalities. The benefits of a
validated, quantitative diagnosistic tool are well established. Electrovestibulography
(EVestGTM) is a new technique, similar to electrocochleography (ECOG), that can detect
and record neural activity generated by the vestibular system. Rather than the auditory
stimulus used in ECOG, EVestGTM uses a vestibular stimulus, whereby the vestibular
system is stimulated by passively tilting a participant seated in a special hydraulic
and instrumented chair programmed to follow a smooth motion profile.
Method: EVestGTM responses were compared for a small group of schizophrenia
patients (n = 4) and age matched healthy controls (n = 10). Background activity was
compared to dynamic measures during acceleration and deceleration phases of the
tilt.
Results: Preliminary results show a significant difference between the
responses in the control and schizophrenia groups, whereby the schizophrenia patients
appear not only to exhibit an overall decreased EVestG signal amplitude but a suppressed
dynamic response.
Conclusion: While an increased sample size is required to validate these
findings, preliminary findings suggest that EVestGTM provides a novel measure of
vestibular output that identifies differences between schizophrenia patients and healthy
controls. EVestGTM may have potential diagnostic benefits in neurological and
psychiatric populations.
ACTIONS OF ANTIPSYCHOTIC DRUGS ON THE EGFR-ACTIVATED ERK/MAPK SIGNALING
PATHWAY
Louise Hilton, Avril Pereira, Suresh Sundram
Mental Health Research Institute, Melbourne, Australia
Schizophrenia is a debilitating disease occurring in 1% of the world's population. To
date, the pathology of the disease is poorly understood. Recent genetic studies have
identified genes and chromosomal loci with strong association to schizophrenia, and of
these one of importance is neuregulin-1. Neuregulin-1 is involved in the activation of
the epidermal growth factor receptor (EGFR) leading to downstream signaling pathways
including the extracellular signal regulated kinase/mitogen activated protein kinase
(ERK/MAPK) cascade. This pathway regulates synaptic proliferation and synaptic
plasticity, two processes involved in the pathology of schizophrenia.
Previous work in our laboratory has examined antipsychotic drugs (APD) and their effects
on the ERK/MAPK signaling pathway. Although several APD decreased ERK activation in
primary cortical neurons within 10 min of treatment, clozapine was unique in its ability
to stimulate activation of ERK1/2 with prolonged treatment. By using the EGFR inhibitor,
AG148, the clozapine-induced ERK1/2 activation was shown to be a direct result of
recruitment of the EGFR. To elucidate the mechanism behind EGFR activation and to
identify any G-protein coupled receptors involved in the process, we are currently
generating cell lines expressing the EGFR family members. We are also examining the
effect of each APD on the ERK/MAPK pathway in H4 human neuroglioma cells. If the actions
of each APD on the EGFR signaling to ERK1/2 can be determined it will open up the
possibility of utilising this system for the development of additional therapeutics to
treat schizophrenia.
VOXEL-BASED MORPHOMETRY EVALUATING GRAY MATTER ASYMMETRY IN PATIENTS WITH
SCHIZOPHRENIA
Yasuhiro Kawasaki1,4, Michio Suzuki1,4, Tutomu Takahashi1,4, Tomiki
Sumiyoshi1,4, Philip K. McGuire2, Msayoshi
Kurachi3,4
1Department of Neuropsychiatry, University of Toyama Graduate School of Medicine
and Pharmaceutical Sciences, Toyama, Japan
2Section of Neuroimaging, Division of Psychological Medicine, Institute of
Psychiatry, London, United Kingdom
3Department of Psychiatric Early Intervention, University of Toyama Graduate
School of Medicine and Pharmaceutical Sciences, Toyama, Japan
4CREST, JST, Tokyo, Japan
Methods: Voxel-based morphometry to evaluate gray matter asymmetry was
carried out using magnetic resonance images from a total of 120 right-handed subjects.
They comprised four groups of 30 subjects, i.e. male schizophrenia, female
schizophrenia, male control, and female control. In order to examine gray matter
asymmetry we generated images of the lateralization index.
Results: The analysis within each of four groups revealed a consistent
pattern of gray matter asymmetry over all groups. However group comparison between all
patients and all healthy subjects showed significant difference in the cerebral
lateralization in the pars triangularis and planum temporale. Frequency distributions of
the lateralization index showed a skew toward rightward asymmetry in the pars
trianglaris and a reduction in leftward asymmetry in the planum temporale in patients
relative to controls.
Discussion: A disturbance of cerebral asymmetry in schizophrenia was
suggested to be present in language-related regions, which may reflect a perturbation in
the lateralization process underlying left cerebral dominance for language.
THE NATIONAL REGISTER OF ANTIPSYCHOTIC MEDICATION IN PREGNANCY (NRAMP)
J Kulkarni1,2, H Gilbert1,2, N Marston1,2, C Gurvich1,2,
K McCauley2
1Monash Alfred Psychiatry Research Centre, Alfred Hospital, Melbourne,
Australia
2School of Psychology, Psychiatry and Psychological Medicine, Monash University,
Melbourne, Australia
Introduction: Current data on antipsychotic use in pregnancy is
limited.
Aims: Establishment of The National Register of Antipsychotic Medication in
Pregnancy (NRAMP) will provide evidence-based clinical guidelines for the best use of
antipsychotic medication during pregnancy and for one year postpartum.
Method: NRAMP is an Australia-wide study involving female participants with
a history of mental illness, who take antipsychotic medication and become pregnant.
Information is collected via telephone and/or face to face interviews during pregnancy,
following delivery, and for the first year postpartum. Information includes
demographics, medical, psychiatric, medication and obstetric history, and information on
general health and wellbeing for both mother and baby.
Results: This study is current and ongoing. Results to date will be
presented in terms of medications and mother/baby outcomes at various time points:
antenatal, post-delivery and for one year postpartum.
Discussion: The collection of on-going data, and the resulting guidelines,
have the potential to provide regular contemporary updates to clinical treating teams
for evidence-based management of women in this vulnerable population group. We plan to
fill a void in mental health services where currently there is a distinct lack of
information available to treating clinicians, with regard to providing safe and timely
care for women who take antipsychotic medication and become pregnant. We hope this
initiative will also improve the quality of life for those who live daily with mental
illness, both now and into the future.
Acknowledgements: This study is supported by AstraZeneca, Janssen-Cilag,
Mayne Pharmaceuticals and the Australian Rotary Health Research Fund.
SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) – A POTENTIAL TREATMENT FOR THE
PSYCHOTIC SYMPTOMS OF SCHIZOPHRENIA?
Kulkarni J1, Gavrilidis E1, Gurvich C,1 De Castella
A1, Fitzgerald P1, Gilbert H1 Davis S2
1Monash Alfred Psychiatry Research Centre, The Alfred Hospital and the School of
Psychology, Psychiatry and Psychological Medicine
2Department of Medicine, Alfred Hospital, Faculty of Medicine, Nursing and Health
Sciences, Department of Obstetrics and Gynaecology, Faculty of Medicine, Nursing and
Health Sciences
Introduction: Several contemporary investigators have reported promising
findings using adjunctive hormones in the treatment of psychosis and depressive
symptoms, as well as the prevention of cognitive decline. To overcome the potential
risks of breast/endometrial cancer and thromboembolic events associated with long term,
unopposed estrogen treatment, Selective Estrogen Receptor Modulators (SERMs), such as
raloxifene, were developed. Our pilot study demonstrated an improvement in aspects of
cognition in post-menopausal women with schizophrenia who received adjunctive raloxifene
60mg/day. The current study examined the efficacy of a higher dose of raloxifene
(120mg/day) in the treatment of psychopathology in postmenopausal women with
schizophrenia. Cognitive functioning and the impact on the hypothalamo-pituitary-gonadal
axis were also investigated.
Method: The study employed a 12 week, double-blind, randomised,
placebo-controlled, adjunctive treatment trial design. Post-menopausal women with a
diagnosis of schizophrenia or schizoaffective disorder were invited to participate and
randomised to receive adjunctive raloxifene 120mg/day or adjunctive placebo.
Psychopathology, cognitive function and hormone assays were measured fortnightly.
Results: Preliminary findings will be presented.
Discussion: While the findings of our pilot study indicated an improvement
in aspects of cognition (verbal recognition memory, psychomotor speed and inhibitory
control), changes in psychopathology were not observed with a dose of 60mg/day
raloxifene. The current study will extend these findings using an increased dose of
raloxifene of 120mg/day.
TAMOXIFEN – A POTENTIAL TREATMENT FOR WOMEN IN THE MANIC PHASE OF BIPOLAR AFFECTIVE
DISORDER?
Kulkarni J1, Mu L1, Gurvich C1, De Castella A1,
Fitzgerald P1, Davis S2
1Monash Alfred Psychiatry Research Centre, The Alfred Hospital and the School of
Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne
Australia
2Department of Medicine, Alfred Hospital, Monash University, Melbourne,
Australia
Background: Bipolar Affective Disorder (BPAD) is an illness with high
morbidity and mortality. Lithium and other mood stabilisers are the main treatments for
BPAD, despite little being known about their mechanisms of action. Recent attempts to
elucidate the biochemical actions of these drugs have focussed on the Protein Kinase C
(PKC) pathways. Another PKC inhibitor hypothesised to be effective in the treatment of
mania is tamoxifen, a selective estrogen receptor modulator with estrogen receptor
antagonist actions in the CNS.
Aims: The aim of the current study was to compare the effectiveness of two
adjunctive antiestrogen agents (tamoxifen and progesterone) to placebo in the treatment
of acute mania.
Method: 51 women in the manic phase of BPAD or schizoaffective disorder
were included in this 28-day, three-arm (40mg/day oral tamoxifen or 20mg/day oral
progesterone or oral placebo) double-blind, placebo controlled, adjunctive study. All
patients also received a mood stabiliser as the baseline treatment. Manic, psychotic and
depressive symptoms were measured weekly using the CARS-M, PANSS and MADRS rating scales
respectively, as were estrogen, progesterone, and gonadotropin levels.
Results: All groups improved over time with respect to symptoms of mania
and psychopathology. The tamoxifen group showed a pattern of greater improvement at days
14 and 28.
Conclusion: The results suggest that tamoxifen may be a useful adjunctive
treatment of acute manic symptoms in women with BPAD.
A TALE OF TWO CANNABINOIDS: BEHAVIOURAL EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL AND
CANNABIDIOL IN SCHIZOPHRENIA-RELEVANT PARADIGMS
Leonora Long1,2,3, Jonathon Arnold1,4, Tim Karl1,2,3
1Schizophrenia Research Institute, Sydney, Australia
2Garvan Institute of Medical Research, Sydney, Australia
3Prince of Wales Medical Research Institute, Sydney, Australia
4Department of Pharmacology, University of Sydney, Sydney, Australia
Cannabis use doubles the risk of developing schizophrenia. While
Δ9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive
cannabis constituent, the non-psychoactive plant cannabinoid cannabidiol (CBD) may have
anxiolytic and antipsychotic potential. We investigated the profile of these two
cannabinoids in a battery of schizophrenia-relevant behavioural tests in mice. Adult
male C57/BL6 mice were given 21 daily injections of vehicle, Δ9-THC (0.3, 1,
3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Testing was performed on treatment days 1
and days 15–21 to assess acute and chronic effects. Δ9-THC produced the
classical behavioural ‘tetrad’ (hypolocomotion, analgesia, sedation and hypothermia)
typical of cannabinoid CB1 receptor agonists, while CBD had no effect on
these behaviours. Δ9-THC (0.3 and 10 mg/kg) and CBD (5 and 50 mg/kg) both
increased prepulse inhibition after acute treatment but not after chronic treatment.
Chronic CBD (50 mg/kg) increased the time mice spent in the centre of an open field,
indicating an anxiolytic effect. Importantly, CBD also reduced locomotor activity
following dexamphetamine challenge (5 mg/kg) on day 21 of treatment, indicating an
antipsychotic-like action. This demonstration of the anxiolytic and antipsychotic-like
effects of cannabidiol in mice supports earlier findings from acute studies in rats and
provides the first behavioural data from chronic cannabidiol administration. Further
work will investigate the impact of chronic Δ9-THC and CBD treatment on
dexamphetamine-induced expression of the immediate early gene product c-fos.
Furthermore, we will examine behavioural and neurochemical effects of these cannabinoids
in our Nrg1 HET genetic mouse model of schizophrenia.
DO SEMANTIC DEFICITS UNDERLIE DELUSIONS?
Erica Neill, Susan L. Rossell
Alfred Psychiatry Research Centre, Monash University, VIC, Australia
Background: Semantic memory deficits (SMD) have been demonstrated to be a
core dysfunction in schizophrenia. Some authors have suggested that SMD may explain the
development of some psychotic symptoms, particularly thought disorder. Delusions have
also shown a relationship with SMD but have been less well studied; this study
investigates the relationship between SMD and the presence and severity of
delusions.
Methods: Participants with schizophrenia were compared on a battery of
tasks designed to assess semantic memory. Accuracy and reaction time to these tasks was
correlated with the presence of delusions.
Results: The results demonstrated that delusions are associated with SMD.
Delusions correlated with semantic memory tasks that examined language production,
concept comprehension, and semantic priming. There were no correlations with thought
disorder on these tasks.
Conclusions: There is evidence to suggest that delusional thinking is
associated with SMD. Accurate semantic processing and the formation of semantic memories
allows for culturally accepted interpretations of our environment. SMD suggest faulty
processing of real world information, knowledge and language, which may lead to the
development of delusional thinking.
SUICIDE AMONGST YOUNG PEOPLE WITH FIRST-EPISODE PSYCHOSIS: AN 8–10 YEAR FOLLOW-UP
STUDY.
Robinson J1, Harris M2, Cotton S1
1Orygen Research Centre
2QCMHR, University of Queensland
Background: Whilst much research has focused upon suicide among people with
schizophrenia, less is known about suicidality among young people with first-episode
psychosis (FEP).
Aims: 1. Estimate the suicide rate among young people with FEP within 8–10
years following commencement of treatment 2. Examine risk factors for suicide 3.
Describe the timing of suicide.
Methods: This study linked an existing dataset (FEPOS) with the National
Coroners Information System (NCIS). The FEPOS dataset contains clinical information
collected via file audit on a cohort of 661 people who entered treatment at the Early
Psychosis Prevention and Intervention Centre (EPPIC) between 1/1/1998–31/12/2000. The
NCIS records death data from July 2002. NCIS records were supplemented with data from
the Victorian State Coroner's Office.
Results: Of the 661 patients, 17 died during the follow up period. Nearly
two thirds of deaths were suicides (64.7%, n=11; 1.66%). The majority
of patients who died were male (95.1%, n=16); six had a diagnosis of
schizophrenia. Death was associated with male gender and a suicide attempt during
treatment. Three people died during treatment and the remaining 14 died following
discharge. No pattern with regard to timing of death was evident.
Discussion: This study confirmed previous findings that this group is at
high risk of suicide. Male gender and previous suicide attempt were the only variables
associated with suicide suggesting that a focus of future research could involve
developing and testing interventions for young people with FEP who attempt suicide.
PSYCHOTIC-LIKE EXPERIENCES IN A COMMUNITY SAMPLE OF AUSTRALIAN ADOLESCENTS:
ASSOCIATIONS WITH DEPRESSION AND FUNCTIONING
Jaymee E Ryan1,2, Kathryn Baker1, Elizabeth M Cosgrave1, Joe A
Buckby1,2, Gennady N Baksheev1,2, Margaret Ross1,2,
Alison R Yung1,2
1Orygen Youth Health Research Centre, Melbourne, Australia
2University of Melbourne, Melbourne, Australia
Introduction: Psychotic-like experiences (PLEs) are a risk factor for the
development of psychotic disorders among clinical samples. Conversely, PLEs are commonly
reported in community samples. Some PLEs are associated with psychological problems,
therefore, it was important to determine which PLEs are risk factors for psychotic
disorders. The aim of the study was to investigate the frequency and characteristics of
PLEs in a community sample of adolescents and to determine whether subtypes of PLEs were
associated with distress, depression, and functioning.
Method: A community-based sample of Year 10 students aged 15–16 years
(n=875) completed a battery of questionnaires. PLEs were assessed by
the Community Assessment of Psychic Experiences (CAPE), depressive symptomatology was
assessed by The Centre for Epidemiologic Studies Depression Scale (CES-D), and
psychosocial functioning by the Revised Multidimensional Assessment of Functioning Scale
(RMAFS).
Results: PLEs were common in the present sample, with the majority of
participants endorsing one CAPE item at least ‘sometimes’ in their lifetime (99.1%,
n=867). Self-reported depression and functioning were significantly
correlated with total CAPE scores (r = .54 and −.42 respectively),
however, these associations varied across specific subtypes of PLEs.
Conclusion: The present research confirms that PLEs are common among a
community sample of adolescents. PLEs were associated with depression and poorer
functioning, and this association was stronger for some subtypes of PLEs. This indicates
that some subtypes of PLEs may be associated with a greater risk of transition into a
psychotic disorder and that others may be non-distressing or ‘benign’.
MODELLING DISEASE FREQUENCY MEASURES IN SCHIZOPHRENIA EPIDEMIOLOGY
Saha S1, Barendregt J2, Vos T2, Whiteford H1,3,
McGrath J1,3,4
1Queensland Centre For Mental Health Research, Wacol, Australia
2Centre for Burden of Disease and Cost-Effectiveness, Herston, Australia
3Department of Psychiatry, The University of Queensland, St Lucia,
Australia
4Queensland Brain Institute, The University of Queensland, St Lucia,
Australia
Background: Recent systematic reviews have compiled estimates related to
the incidence, prevalence and mortality associated with schizophrenia. The aims of this
study were (a) to model various frequency measures, (b) to examine the consistency of
published versus modelled estimates, and (c) to explore the relative change in
prevalence estimates after adjustments were made to incidence, remission, and mortality
estimates.
Methods: We identified studies that provided matched incidence and
prevalence estimates. We applied the DisMod software program to model incidence from
observed prevalence and vice versa. The accuracy of the modelled data was compared to
the published data using Mann-Whitney tests. Finally, we conducted several ‘thought
experiments’ to explore the impact of changing the incidence, remission, and mortality
rates on prevalence estimates.
Results: We identified 24 matched-pairs of incidence and prevalence
estimates. The distributions of modelled versus published estimates were significantly
different. In 20 pairs, DisMod calculated modelled prevalence estimates that were higher
than published estimates, while modelled incidence estimates were lower than published
estimates in 21 pairs. In the majority of pairs, the difference between published and
modelled estimates was greater than 50%. With respect to the ‘thought experiments’, a
25% reduction in mortality was associated with a 5–7% increase in prevalence, while 25%
reduction in incidence or remission rates resulted in 18–23% and 1.2–2.4% decrease in
prevalence estimates, respectively.
Conclusion: The consistency between published incidence and prevalence
estimates of schizophrenia is poor. Models can help interrogate these inconsistencies
and provide insights into the dynamics of schizophrenia epidemiology.
LIFETIME HISTORY OF SUBSTANCE USE PREDICTS TRANSITION TO PSYCHOSIS IN ULTRA-HIGH
RISK INDIVIDUALS
M.R. Schäfer1, K. Papageorgiou1, J. Becker1, P.D.
McGorry2, G.P. Amminger1,2
1Department of Child- and Adolescent Psychiatry, Medical University of Vienna,
Austria
2ORYGEN Research Centre (incorporating EPPIC), University of Melbourne,
Australia
Background: The relationship between use of illicit substances and poor
clinical outcomes is well established in schizophrenia. Very few studies examined the
role of substance use in the prodromal phase of psychosis. We examined substance use as
predictor for transition to psychosis in ultra-high-risk (UHR) individuals with
subthreshold symptoms.
Methods: The study sample comprised 81 UHR individuals (according to
criteria of Yung et al., 1998) (mean age = 16.4, SD = 2.1 years) who participated in a
RCT of omega-3 fatty acids vs. placebo (ClinicalTrials.gov number, NCT00396643).
Substance use was assessed at baseline using the SCID for DSM-IV. Baseline
psychopathology measures included the PANSS. Conversion to psychosis was operationally
defined using cut-off points on the PANSS (4 or more on hallucinations, 4 or more on
delusions and 5 or more on conceptual disorganisation), the frequency of symptoms (at
least several times a week), and their duration (more than 1 week). Cox regression
analysis was used with adjustments for the effects of treatment, age, sex, positive
symptoms, and negative symptoms to investigate the predictive validity of substance use
for psychosis status 12 months after baseline.
Results: 13 of 81 (16.0%) individuals made a transition to psychosis within
the follow-up period. Cox regression analysis revealed lifetime history of substance
abuse as independent significant predictor of transition to psychosis in UHR individuals
(p < 0.05); more severe negative symptoms at baseline (p < 0.05), and being in the
placebo group (p < 0.02), also independently predicted psychosis. In contrast,
substance use at study entry was not found associated with the outcome of interest.
Conclusions: The findings suggest lifetime history of illicit substance use
as an important independent prognostic factor in UHR individuals.
Acknowledgement: Acknowledgement: Supported by Stanley Medical Research
Institute Grant 03-T315
USING THE COMPREHENSIVE ASSESSMENT OF AT-RISK MENTAL STATES (CAARMS) TO IDENTIFY
YOUNG PEOPLE AT ULTRA-HIGH RISK OF DEVELOPING PSYCHOSIS: EVALUATION OF TRAINING
WORKSHOPS WITH MENTAL HEALTH SERVICES
MB Simmons1,2, B Nelson1,2, AR Yung1,2, JA Buckby1,2, L
O'Dwyer3, SM Francey1, S Leicester1, S
Bapat3, PD McGorry1,2
1ORYGEN Research Centre, Melbourne, Australia
2Department of Psychiatry, The University of Melbourne, Melbourne,
Australia
3EPPIC Statewide Services, ORYGEN Youth Health, Melbourne, Australia
Overview: The most common way to identify individuals at risk of developing
psychosis is the ultra high risk (UHR) approach. UHR criteria are assessed using the
Comprehensive Assessment of At Risk Mental States (CAARMS), a specialised instrument
developed at the Personal Assessment and Crisis Evaluation Clinic. A CAARMS training DVD
and workbook package was recently developed in order to assist with UHR identification.
This study reports the outcome of training workshops held with mental health
professionals using this package. The aim was to investigate whether the workshops
increased participants’ confidence and ability to accurately identify UHR cases and
distinguish these from non-UHR and first-episode psychosis (FEP) cases.
Method: 137 mental health workers participated in the training sessions
across eight sites. Training involved four modules: theoretical background; rating
written vignettes for UHR, non-UHR or FEP status; viewing and discussing the CAARMS
Training DVD; and re-rating matched written vignettes for UHR, non-UHR or FEP
status.
Results: Confidence in identifying UHR cases and using the CAARMS increased
as a result of the workshop. Participants’ ability to correctly identify UHR-positive
cases did not improve. This may have been the result of a ceiling effect due to the
baseline ability to identify UHR-positive cases being high. However, there was a trend
for participants’ ability to correctly identify UHR-negative cases to improve.
Conclusions: UHR training workshops are a valuable means of increasing
mental health workers’ confidence in identifying UHR patients. Future training with
experienced mental health professionals should focus on the correct identification of
UHR-negative cases.
THE PREVALENCE OF METABOLIC SYNDROME IN CHRONIC AND TREATMENT RESISTANT
SCHIZOPHRENIA AND ITS INCIDENCE IN THE FIRST THREE MONTHS OF CLOZAPINE TREATMENT
Sundram S, Bandara J, Wragg A, Aklagi H, Lohdi R, Sathiya S
Northern Psychiatry Research Centre, Melbourne, Australia
Introduction: Physical health of long-term psychiatric patients is commonly
overlooked. Metabolic syndrome (MS) affects about one quarter of the general adult
population, is increasing in prevalence and is associated with increased risks of
developing diabetes mellitus and cardiovascular disease. Patients with schizophrenia and
related disorders (SSD) have an almost doubled prevalence of MS compared to the general
population
Methods: Consented patients from a psychiatric rehabilitation service,
including patients recently commenced on Clozapine, were studied. In addition to
demographic and clinical data, BMI, BP and abdominal girth, fasting blood glucose,
fasting serum insulin and lipids were measured. Demographic, biological and biochemical
parameters will be assessed using analysis of variance and correlational analyses.
Result: 70 patients were assessed in this study with mean age of 38.11 year
(between 20 and 66 year old). 67 percent of them were diagnosed with schizophrenia, 8.6
percent with schizoaffective disorder and 4.3 percent with bipolar affective disorder.
Diabetes has been diagnosed in 7.1 percent of population study and 4.3 percent with
hypercholesterolemia. Mean BMI is 31.10. Fasting blood sugar range between 4 mmol/l and
16 mmol/l with mean value of 5.67 mmol/l. incidence of MS during first three months of
clozapine treatment seems significantly high at the present phase of study.
Conclusion: Many studies have determined that the prevalence of metabolic
syndrome among SSD patients is higher than the general population, however there is
limited Australian data. Although environmental factors such as poverty, homelessness
and poor nutrition interact with and may predispose to MS, there is evidence to suggest
that patients with schizophrenia are liable to elevated rates of glucose intolerance and
diabetes, independent of treatment.
CANNABINOID EFFECTS ON 5HT1A RECEPTOR DENSITY AND D2-RELATED FUNCTIONALITY IN THE
ADULT RAT BRAIN
Katerina Zavitsanou1,2, Vu Nguyen1, Hongqin Wang1, Victoria
Dalton1,2
1Australian Nuclear Science and Technology Organisation, Sydney,
Australia
2Schizophrenia Research Institute, Sydney, Australia
Cannabinoids have been shown to interact with neurotransmitter systems implicated in
psychosis such as serotonin and dopamine. However, the exact mechanisms of such
interactions are not fully understood especially during adolescence a critical period
for both the development of psychosis and for initiation to substance abuse. In the
present study, we measured serotonin 5HT1A receptor density and dopamine D2 receptor
functionality in the brain of male rats treated with the synthetic cannabinoid HU210
(25,50 or 100ug/kg, ip) for 14 days or received a vehicle for 13 days and an acute dose
of HU210 on day 14. 5HT1A receptor density was measured on brain sections using
[3H]8-OH-DPAT whereas D2 receptor functionality was examined by measuring
activation of GTP-binding proteins by the D2 agonist (R(−)-Propylnorapomorphine,(NPA).
5HT1A receptor density was significantly increased in hippocampal regions CA1 (28%, p =
0.028), CA2 (31%, p = 0.024) and dentate gyrus (20%, p = 0.001) of rats treated with the
100ug/kg of HU210 for 14 days compared to vehicle treated controls. Similarly, the
stimulation of GTP binding proteins by NPA was significantly increased in the caudate
nucleus (12.3%, p = 0.01) and cortical layers I–III (19.6%, p < 0.001) and V–VI
(24.3%, p < 0.001) of rats in the same treatment group compared to controls.
Interestingly, the acute dose of HU210 resulted in a significant increase in NPA
stimulation of GTP binding in the caudate nucleus only (17.4%, p < 0.001). The
present results may have implications for understanding the mechanisms by which cannabis
may trigger psychosis in vulnerable individuals and for treating cannabis dependent
individuals.
Footnotes
1Common Data Set – Mental Health (CDS-MH) Management Reports — 2007/08 Q2.
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