Abstract
Keynote address 1
The Connectome: What’s in it for Psychiatry?
Professor Edward Bullmore
University of Cambridge and GlaxoSmithKline, Cambridge, UK
In the last few years there has been rapidly increasing interest and investment in the idea that we can understand the network organization of the human brain – in other words, the connectome. In this talk, I will describe some of the work that we and others have done using the mathematical theory of graphs as simple models of complex networks, to measure the topology and spatial properties of human brain networks derived from neuroimaging data. It has been found that human brain networks are normally small-world, modular networks with a number of highly connected hubs. To that extent the human brain is similar to many other complex networks, ranging from the nervous system of the worm C elegans to the North American airline network. The human brain network is also economically wired, a property shared in common with other spatially embedded complex systems, such as high performance computer chips. But what does this mean for psychiatry? I will focus on how connectomics has begun to elucidate network abnormalities in people with schizophrenia, shedding new light on models of psychosis as a dysconnectivity disorder. I will also address some of the recent work using network analysis to understand the disease process in Alzheimer’s disease and consider how this way of thinking about brain organization could be useful in the discovery of new drugs for central nervous system disorders. I will conclude that the future is bright for connectomics in psychiatry although a number of big questions and opportunities remain to be addressed.
Keynote address 2
The Many Faces of Bipolar Spectrum Disorders
Ulrik Fredrik Malt
Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital – Rikshospitalet, Norway Bipolar spectrum disorders (Bip-SD: bipolar I, II, III, cyclothymia and sub-threshold disorders) often present with depressive and hypomanic or manic symptoms. However, psychiatric and behavioural manifestations of Bip-SD may differ from this stereotype. Episodic profound existential anxiety is particularly common and may be the most prominent symptom with higher anxiety than depression questionnaire and rating scales scores (e.g. SCL-90; HAD). Other patients may be referred with diagnoses such as alcohol abuse, intermittent explosive disorder, ADHD, OCD, anorexia nervosa or social phobia. Psychosomatic symptoms including hypochondria or chronic fatigue syndrome may also be the reason for consulting health care. However, Bip-SD are highly genetic disorders (heritability 80% +) affecting all bodily functions (e.g. immunology, hormones, autonomic nervous system and biological rhythms). Molecular findings include functional alterations in cell membrane, mitochondria, intracellular signal systems and neuroplasticity. Alterations are often found in functional assessments (e.g. neuropsychology, fMRI, PET, EEG and ERP). Bip-SD is also associated with increased prevalence of some somatic disorders (e.g. cardiovascular disorders and symptoms such as angina pectoris, hypertension and tachycardia; gastrointestinal disorders such as ulcer, gastritis and IBS; diabetes type II; arthritis; migraine and overweight). Thus Bip-SD is better understood as systemic disorders primarily affecting the central nervous system. The net effect of these different clinical presentations of Bip-SD may be false diagnostic conclusions and thus inadequate treatment, sometimes with tragic outcome (e.g. severe somatic complications, suicide). This state-of-the-art review will use clinical vignettes and examples from arts and literature to illustrate the many faces of Bip-SD.
Keynote address 3
PTSD and Other Trauma Related Disorders: Epidemiology, Intervention, Treatment and Planning
Professor Robert J Ursano
Center for the Study of Traumatic Stress, Uniformed Services University, School of Medicine, Bethesda, Maryland, USA
Traumatic events are both an ordinary and an extra-ordinary part of life. From motor vehicle accidents to natural and human made disasters, substantial numbers of the world population are exposed to trauma every year. In the United States, there were over 10 million motor vehicle accidents (MVAs) and more than 35,000 people died in MVAs in 2009. War is a particular type of human made disaster. At present, there are 24 armed conflicts occurring around the globe. Similarly, natural disasters such as Hurricane Katrina, the recent disaster in Japan, the Tsunami of 2005, and earthquake in New Zealand have all brought our attention to disasters which most of the world is at risk of.
How best to deliver informed care following trauma requires understanding the biological disease processes, illness vs disease, treatment efficacy and factors that determine individual and community resilience. Responses to traumatic events include disorders, distress and altered health risk behaviors including suicide behaviors. Resilience is of course the most often found response. The trajectory of onset, recovery, chronicity and resilience are important for planning individual care and population health needs. Understanding post traumatic stress disorder is an important part of treatment planning and research, from gene to social and community recovery resources.
Keynote address 4
Mood, Energy and the Neurobiology of Bipolar Disorder
Professor L Trevor Young
University of Toronto, Toronto, Canada
A key feature of bipolar disorder (BD) is sustained fluctuations in energy in the different phases of the illness, with marked increases in mania and depletion during depression. Energy is intimately linked to mood, and an important target for treatment and improvement is associated with good outcome. Historically, there was interest in energy metabolism in BD, but this was forgotten with an emerging interest in neurotransmitters and newer intracellular targets. A decade of research has now renewed our interest in these systems with an increasing focus on mitochondria, including measurement of electron transport chain components, activity and mitochondrial DNA damage. Strikingly, there is a clear pattern of oxidative damage in a variety of tissues from patients with BD including postmortem brain and blood cells. Oxidative damage may be improved with treatment with mood stabilizing drugs. Animal studies relevant to BD, such as chronic amphetamine administration, also showed oxidative damage in brain tissue which may be improved with lithium treatment. More recently, oxidative damage appears to be very specifically targeted to synaptic proteins in brain tissue which may help link energy metabolism to etiologic factors based on neurotransmitters and synaptic function. This topic illustrates the potential to integrate a historical perspective, clinical findings and neurobiology, which could manifest in the development of novel therapeutic interventions.
Keynote address 5
Is Psychoanalysis Scientifically Viable? The Example of Dream Theory
Professor Mark Solms
Department of Psychology, University of Cape Town, South Africa
In 1963, Karl Popper famously described psychoanalysis as a ‘pseudoscience’. In the decades that followed, an increasing proportion of psychiatrists came to agree with him. In recent years, however, advances in the neurosciences opened Freud’s most fundamental hypotheses to direct experimental scrutiny for the first time; and a surprising number of them are now receiving strong empirical support. Was Freud on the right track after all? This lecture addresses the scientific validity of psychoanalysis via the example of dream theory. Almost all of Freud’s basic propositions were grounded in his dream theory. If that theory is wrong then all of psychoanalytic theory is radically undermined. Indeed, when the brain mechanisms of REM sleep were first laid bare in the 1970s, the wish fulfilment theory of dreams seemed utterly discredited, with devastating consequences for psychoanalysis. But now, 40 years later, a completely different picture of the dreaming brain is emerging. This lecture will describe the new picture, and consider some of the implications for contemporary psychiatry.
Keynote address 6
Cells, Circuits and Consequences: Keeping the Baby in Mind
Frances Thomson-Salo1,2
1The Royal Women’s Hospital, Melbourne, Australia
2University of Melbourne, Melbourne, Australia
Some effects of stress, particularly maternal anxiety and depression, on the foetus and newborn are outlined, in the light of what is known about how ready infants are to communicate and relate from birth, and prepared to enter a social communicative system. The dysregulating effects on an infant’s development and attachment history as a result of parental depression, anxiety, violence and substance use as well as the effect of negative and positive projections are considered. How circuits processing experience and neural plasticity might be affected is illustrated with a vignette of infant autistic defensiveness. Some long-term outcomes in terms of infant anxiety, attachment, vulnerability and physical health are acknowledged – what may be a cascade of consequences of pathology with circuits becoming more fixed. Lastly some consequences of selected interventions are reviewed. Intervention may be with parents whose infant already at birth shows measurable signs of distress or lack of adaptation. A brief perinatal attachment intervention with teenage mothers (n = 73) in The Royal Women’s Hospital, Melbourne, is described, with significant reduction in maternal intrusiveness, and increased maternal sensitivity, with a possible oxytocin boost. Other effective short- and long-term psychotherapeutic interventions (such as home-visiting) are outlined, to consider how relationally-based are the mechanisms for change. While this talk concentrates on parents and infants in the first two years, a case is made for the relevance not only for those working in the perinatal period but for work with all ages.
Keynote address 7
Oxidative and Immune Biomarkers as Targets for the Development of Novel Therapies
Michael Berk1-4
1School of Medicine, Deakin University, Melbourne, Australia
2Department of Psychiatry, University of Melbourne, Australia
3Orygen Youth Health Research Centre, Centre for Youth Mental Health, Parkville, Australia
4The Mental Health Research Institute of Victoria, Parkville, Australia
There is abundant evidence that inflammatory and oxidative processes play a role in mood disorders. There is evidence of increased inflammatory activity in mood disorders, including elevation of cytokines and administration of pro-inflammatory cytokines are among the best models of depression. The brain is the most metabolically active tissue, and disruptions in mitochondrial energy generation and evidence of oxidative stress are extensively described in mood disorders. The consequences of inflammatory and oxidative stress include lipid peroxidation, DNA fragmentation protein carbonylation and an increased vulnerability to apoptosis. Inflammatory and oxidative stress leads to decreased BDNF and other trophic factors, and reductions in neurogenesis. Established antidepressants and mood stabilisers including lithium and valproate have a role in ameliorating oxidative stress, and additionally alter immune markers. N-acetyl cysteine (NAC) is a precursor of glutathione, has anti-inflammatory properties, enhances neurogenesis and reverses animal models of oxidative stress. In this presentation, we will show data suggesting a significant benefit of NAC on measures of depression, quality of life and functioning in bipolar disorder and schizophrenia. Equally, inflammation provides some novel therapeutic targets, which are clinically accessible, including statins, aspirin and NSAIDS. There is data that use of these agents is associated with reduced risk for mood disorders. Lifestyle factors including diet and exercise modify these biomarkers, and modulate risk for development of depression. Such biomarker data are demonstrating potential to lead to the development of novel therapies for mood disorders outside of traditional monoamine targets.