W11 - Students

O1 The role of routine foetal anomaly ultrasound scans in detecting autism in

utero.

Ms Lois Salter, Medical student, University of Edinburgh; Dr Andrew Stanfield, Psychiatry

consultant, Royal Edinburgh Hospital; Dr Jane Walker, Consultant in Obstetric Radiology,

Royal Infirmary Edinburgh; Prof Anne O’Hare, Consultant in Community and Child

Health, Community and Child Health Edinburgh

Aims and hypothesis: We set out to investigate if autism is detectable in utero, by

comparing measurable foetal data of children who later developed autism and controls

using Foetal Anomaly Scans (FAS) at around twenty weeks gestation. As previous

studies have identified larger head circumferences (HC) in autistic children at birth, we

hypothesise the same will be true in utero.

Background: Previous research suggests that autism may be detectable from infancy.

An imbalance in foetal growth in autism has also previously been observed. The FAS

conducted routinely in the Lothians since December 2008 offer a window into the foetal

development of all children, including those later diagnosed with autism.

Methods: we used retrospective FAS of children identified as later developing autism and

extracted head circumference (HC), cerebellar diameter (CD), ventricular atrial width

(VAW), abdominal circumference (AC) and femur length (FL) from the scans.

Demographic data such as maternal age was controlled for. We compared 36 autistic

children’s scans with 108 controls.

Results: There was a significant interaction of group between HC, CD, FL and AC and

gestational age, suggesting that the autistic children were growing at a faster rate during

this period of foetal development (18-24 weeks). No significant VAW effects were found

as expected.

Conclusions: These results suggest that children with autism grow at a different rate to

controls in the beginning of the 2nd trimester; notably, both their brains and bodies

appear to grow faster at this stage. Autism may thus be detectable much earlier in

development, allowing for targeted early detection and treatment of the condition.

Supported by a grant from the Patrick Wild Centre Seedcorn Fund, University of

Edinburgh

Category: Research

O2 BASH: Badmouthing, Attitudes and Stigmatisation in Healthcare

Dr Damien Brown, Medical student, Barts & The London School of Medicine and

Dentistry; Dr Rhodri David, Psychiatry consultant, East London NHS Foundation Trust;

Ms Melanie Smuk, Statistician, Centre for Psychiatry, Barts and The London School of

Medicine and Dentistry; Prof Ania Korszun, Professor of Psychiatry and Education, Barts

and The London School of Medicine and Dentistry

Aims and hypothesis

To explore the prevalence and nature of medical students’ experience of “bashing”•

different medical specialties, including psychiatry, and whether this influences students’

career choices.

Background

Specialty “bashing” is defined as “distinctly negative feedback and comments directed by

members of one medical specialty toward other specialties. To improve the current

under-recruitment into psychiatry, it is important to identify and combat contributory

factors. “Bashing” of certain specialties has been previously cited as a reason for not

choosing careers in those specialties.

Methods

In a nationwide on-line survey, medical students at all stages of the undergraduate

course were asked to rank specialties that they perceive to attract most negative

comments (rank 1) to the fewest (rank 8); whether they had witnessed negative

comments about specialties; and the effect of this on their own career choice.

Results

Questionnaires were completed by 960 medical students from 13 Medical Schools.

General Practice and Psychiatry were reported to attract significantly (p=0.001) more

negative comments (mean ranks 2.20 and 2.29 respectively) than other specialties

(Obstetrics & Gynaecology 5.13, Surgery 4.55, Cardiorespiratory 6.37, Anaesthetics

5.08, Radiology 4.04, Emergency medicine 6.35). Perception of negative comments

significantly increased with year of study (p=0.001). Twenty seven percent of students

reported that experience of “bashing” had caused them to change their career choices.

Seventy two percent of students agreed that “bashing” will always be part of medicine,

and 74% of medical students endorsed an unspoken hierarchy of specialties in medicine.

Conclusion

Psychiatry and GP attract more negative comments than other medical specialties,

contributing to a medical school culture in which some specialities are considered more

worthy and prestigious than others. This has an effect on a quarter of students steering

them away from their chosen specialties. More needs to be done in medical school

curricula to challenge this unofficial framework that stigmatizes psychiatry.

Category: Education and Training

O3 Family-Based and Case-Control Association Studies of AKT1 and TCF4 Gene

Polymorphisms in Cognitive Functions in Schizophrenia

Ms Tze Jen Chow, PhD student, Department of Biomedical Engineering, Faculty of

Engineering and Science, Universiti Tunku Abdul Rahman, Jalan Genting Kelang,

Setapak, 53300 Kuala Lumpur, Malaysia; Dr Shiau Foon Tee, PhD student, Department

of Chemical Engineering, Faculty of Engineering and Science, Universiti Tunku Abdul

Rahman, Jalan Genting Kelang, Setapak, 53300 Kuala Lumpur, Malaysia; Dr Siew Yim

Loh, , Department of Rehabilitation Medicine, Faculty of Medicine, University Malaya,

Kuala Lumpur, Malaysia; Dr Pek Yee Tang, , Department of Biomedical Engineering,

Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Jalan Genting

Kelang, Setapak, 53300 Kuala Lumpur, Malaysia

AIMS AND HYPOTHESIS: This study aims to examine the relationship of the gene

variants with neurocognitive phenotypes in schizophrenia.

BACKGROUND: AKT1 and TCF4 are candidate genes for schizophrenia and have been

implicated to involve in cognitive functions including working memory and executive

functions.

METHODS: We recruited 11 multiplex family samples (n=24), including 11 proband and

their affected relatives. Independent samples consist of 207 unrelated patients

diagnosed with undifferentiated and disorganised schizophrenic subtype and 207 control

subjects. Cognitive functions of the familial patients were assessed using Trail Making

Test-A for cognitive processing speed and Trail Making Test-B for executive functioning.

Seven single nucleotide polymorphisms from AKT1 and six from TCF4 gene were

genotyped. The relationship of cognitive functions with the variants was examined using

the familial samples. We then further examined the association by comparing the

unrelated patients and controls.

RESULTS: Rs3730358 (P =0.045), rs2498784 (P =0.040) and rs3803300 (P =0.030)

were found significant in Trail Making Test-A in familial study, while Trail Making Test-B

reported none. This suggests AKT1 variants might exert greater effect on cognitive

processing speed compared to executive functioning. On the contrary, TCF4 reported no

significant relation with Test-A, but rs10401120 was found to have significant (P =0.007)

effect on Test-B. When variants were tested in unrelated patients and controls,

rs10401120 (P =0.007 x 10-21) and rs17512836 (P =0.0008) showed significant

difference in allele and genotype frequency.

CONCLUSIONS: Patients with family history of schizophrenia might experience greater

deficit in cognitive performance than those without a family history. Our analysis

suggests an association between the AKT1 gene with cognitive processing speed and

TCF4 gene with executive functioning in schizophrenia.

This work is funded by Malaysia Toray Science Foundation Science & Technology

Research Grant (12/G46)

Category: Research

O4 A reinforcement reward learning paradigm in bipolar 1 disorder and healthy

siblings.

Dr Jess Sussmann, PhD student, University of Edinburgh; Dr Liana Romaniuk, Medical

student, University of Edinburgh; Dr Heather Whalley, Research Fellow, University of

Edinburgh; Prof Stephen Lawrie, Psychiatry consultant, University of Edinburgh; Prof

Jeremy Hall, Psychiatry consultant, University of Cardiff; Prof Andrew McIntosh,

Psychiatry consultant, University of Edinburgh

Aims and Hypothesis

Abnormalities of reward processing and decision-making are core features of bipolar

disorder (BD). These processes are closely linked with fronto-striatal and midbrain

dopaminergic pathways. We sought to test whether dysfunctions of these pathways were

present in BD and investigated their unaffected relatives to assess genetic liability.

Background

Decision-making involves learning about ones environment and uncovering causal links

between ones behaviour and likelihood of obtaining rewards. Through our knowledge of

motivational and reward value neural circuitry we can explore how decision-making

impairments in psychiatric disorders are manifest in the brain.</p>

Methods

Sample: Twenty-one bipolar I patients each with their unaffected sibling, were compared

to 22 healthy age and gender-matched controls using an instrumental reward learning

task during event-related functional MRI.

Analyses: Two a priori region of interest analyses; i) ventral striatum (VS)/ midbrain and

ii) prefrontal cortex (dlPFC, vmPFC, mOFC) were employed and modelled using a Q

learning reinforcement algorithm to generate trial by trial sequences of prediction errors

and stimulus values for each participant. Extracted data from hypothesised regions were

analysed to account for related sibling pairs and symptom scores (HAM-D, YMRS).

Results

Prediction error associated VS increases in activation were observed in patients

compared to controls. Decreased prefrontal activations were seen in patients in

association with value encoding compared to controls and correlated with depression

scores. Activations in siblings were intermediate for both measures.

Conclusions

These results suggest reward learning circuitry is altered in BD with intermediate

changes seen in BD relatives. Prediction error associated increased VS activity,

demonstrating a dysregulated representation of prediction error in the striatum, and

decreased PFC activity associated with the value encoding of reward in a region linked

with decision-making, reward planning and action, may be intermediate phenotypes of

BD. These findings confirm reinforcement reward learning abnormalities and offer an

explanation for vulnerability to the core features of BD.

Category: Research

O5 Mitochondrial protein expression in white blood cells as a potential

biomarker for Alzheimers disease

Dr Manraj S Bhamra, FY Doctor, Queen Elizabeth Hospital, Birmingham; Dr Joanna

Riddoch-Contreras, Post Doctorate Researcher, Institute of Psychiatry, King\'s

College London, London

AIMS AND HYPOTHESIS

To determine human mitochondrial protein expression in white blood cells (WBC), as a

potential biomarker for Alzheimer’s disease (AD).

BACKGROUND

AD is a progressive age-related neurodegenerative disorder affecting approximately 34

million people worldwide, a figure which is expected to quadruple by 2050. Definitive

diagnosis still relies on a post-mortem brain examination, and neurodegenerative and

cognitive changes begin years before clinical manifestations. The field is therefore in

critical need of a reliable biomarker to aid in early diagnosis and identification of

preclinical disease.

Mitochondrial dysfunction is considered detrimental to cellular and metabolic

homeostasis, and has been identified as an early pathological feature in AD, particularly

in neurons most vulnerable to degeneration. Similar changes have been found in

peripheral blood cells, such as platelets and WBC. Recent gene expression analysis in the

same lab has revealed significant downregulation of mitochondrial gene expression in

WBC of mild cognitive impairment subjects (MCI, a prodromal stage of AD) and AD

patients compared to elderly controls.

METHODS

WBC were extracted from 17 AD, 11 MCI and 20 healthy age matched elderly controls. A

bead based multiplex panel assay simultaneously detected changes in mitochondrial

protein complexes I-V and NNT in these patients using a 96 well plate format. Samples

were analysed using the Luminex xMAP detection system.

RESULTS

We found a significant downregulation of complex I, II and IV protein expression in WBC

in AD samples compared to controls. The most striking difference was a decrease in

complex 2 in MCI and AD (p=0.007) compared to controls.

CONCLUSIONS

Alterations in mitochondrial oxidative phosphorylation occur in AD, with evidence to

suggest this also occurs early on in MCI. These results implicate WBC mitochondrial

protein expression as a potential diagnostic and prognostic biomarker of AD, and suggest

the utility of a blood-based biomarker. These results have facilitated an expansion of the

project in which we aim to further evaluate and extend our analysis in WBC and post-

mortem brain samples using a greater number of subjects, with the overall aim of

developing a peripheral biomarker for early AD.

Category: Research

O6 Smoking and Risk of Postpartum Psychosis in Women with Bipolar Disorder

Dr Holly Morgan, FY Doctor; Ms Arianna Di Florio, Clinical Research Fellow, Institute of

Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine;

Prof Ian Jones, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff

University School of Medicine

Aims and Hypothesis:

1- To test the hypothesis that medical co-morbidities are associated with episodes of

postpartum psychosis (PP) in bipolar women.

2 - To test the hypothesis that smoking is inversely associated with episodes of PP in

bipolar women, consistent with findings for pre-eclampsia, another pregnancy-related

disorder, and in contrast to other mental disorders.

3 - To test whether any associations are specific for PP or if they extend to postpartum

bipolar depression.

Background:

For every 1,000 births, 100-150 women will suffer from a postpartum psychiatric

episode. The majority of these will be postnatal depression (PND), but 1-2 per 1000

women will develop PP. PP is an important condition to recognise as, if left undiagnosed,

it can lead to significant morbidity and even mortality in the form of suicide and

infanticide. Many risk factors have been identified including bipolar disorder and family

history, but so far no link to smoking has been reported.

Methods:

Information about pregnancy, childbirth, medical co-morbidities and smoking history

were gathered retrospectively for 662 parous women with DSM-IV bipolar I disorder by

interview and case-note review. Women who had experienced PP and those who had not

were compared. SPSS software was used to assess results for significance. Analyses

were controlled for a number of clinical and socio-economic confounders.

Results:

No significant differences were seen between the groups in co-morbidities. There was a

negative association between smoking and PP (OR: 0.36, 95%CI 0.246- 0.517)

Category: Research