The Lancet Student

Latest blog post:"Academic Psychiatry? What's that?"

This blog was submitted by RoxanneKeynejad on 25th July 2014.
Tagged with Psychiatry, research, Genetics and Genomics, career, Mental health

I’ve heard my fair share of prejudicial comments about my chosen specialty, from those who should know better. “You do realise that you will become mentally ill? I’ve seen it happen” (a registrar while I was a medical student). “But you care so much about your patients! You don’t seem the type” (my CT1 while I was an F1). “You’re too good to go into psychiatry! Become a medic” (an SpR during an F2 on-call). You’d think I was used to this by now, but what I heard last month still took my breath away.

A neurology registrar, whom I had just met, feigned confusion: “Academic Psychiatry? What’s that? There haven’t been any research findings in psychiatry in the last twenty years!” I regret to confess that in my astonishment, a satisfactory riposte did not trip readily off the tongue.

What a heartening antidote, then, to spend four days in July at the Cardiff MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) fifth annual summer school in brain disorder research [1]. My experience is that even doing one’s best to skim the weekly BMJ on the train into work, it is genuinely difficult to keep up to date with the latest research evidence. During the foundation programme, we learn to practise medicine by applying guidelines to clinical cases. Although they are evidence-based and regularly updated, medical flowcharts create the illusion for the junior doctor that we know the truth about the human body, and there’s an app for that on our smartphones. It can be tempting to rest on knowledge gleaned from medical school, plus what you derive from professional examinations, which aren’t always especially up to date.

Perhaps that is why, despite colleagues’ best efforts, a career in academic psychiatry continues to appeal. During a Psychology and Philosophy degree, I learned first that much of what we know about the brain is a best-guess hypothesis. And while we’re at it, just what do you mean by ‘knowledge’ anyway? Writing essays debating the potential functions of the amygdala in 2007 inspired me to apply for graduate-entry medicine. So to this day I remain bemused that we practise medicine as though working with irrefutable facts. In psychiatry, at least, we admit that there is a lot still to ‘know’ [2, 3].

If only the aforementioned registrar could have attended the Cardiff CNGG summer school, she might have retracted her contempt. Luckily, she didn’t have to. She didn’t need to go out of her way to read a psychiatry journal [4], or Nature [5]; last week, even The Daily Mail was talking about it [6].

At the summer school, I learned things which didn’t come up at medical school. How dramatic falls in technology costs revolutionised our ability to scrutinise the genetic codes of people suffering from a range of neuropsychiatric disorders. How unprecedented international academic collaboration between formerly rival groups facilitated studies with the sample sizes (say, 34,241 cases and 45,604 controls) necessary to power genome wide association studies. How understanding copy number variants has focused psychiatric research attention on “a coherent biological pathway at the synapse, with a specific role in plasticity,” with corresponding implications for developing animal models and drug targets [7, 8]. How the discovery of pluripotent stem cells could transform not only psychiatric research [9], but personalise treatments [10]. How the latest findings “challenge the current nosological dichotomy between schizophrenia and bipolar disorder” [11, 12] and “suggest that more attention should be given to the relationship between the functional psychoses and neurodevelopmental disorders such as autism” [13].

There were other insights, too. Using carbon dating to demonstrate hippocampal neurogenesis in adults [14], supporting our understanding of how antidepressants work [15]. How rat studies of epigenetic changes in glucocorticoid receptor expression according to maternal care [16] help us to understand the long-term effects of child abuse [17], to name only two.

It wasn’t all optimism. At the same time as genetic and genomic studies are beginning to yield results, drug companies have reduced their focus on neuropsychiatric disorders [18]. Attempts to ‘re-purpose’ existing drugs with known synaptic effects are beginning to translate laboratory findings into potential benefits for patients, but new drug development must be an increasing priority.

These research findings and Daily Mail headlines will not make a tangible difference to the lives of people living with mental illness overnight. But they do offer a glimmer of hope that by the time I retire, our knowledge of neuropsychiatric disorders may be transformed. Our diagnostic tests and treatment approaches might be considerably enhanced. Our treatment modalities could be better and our preventative interventions targeted and specific.

For so many reasons to hope, I thank the eminent and clearly rather busy researchers at Cardiff for sharing their enthusiasm with those of us fortunate enough to attend the summer school. I look forward, with excitement, to starting academic psychiatry training in August.

References

[1] Cardiff University (2014). Annual Summer School in Brain Disorder Research [online]. Available from: http://medicine.cf.ac.uk/event/cngg-summer-school/

[2] Bullmore E, Fletcher P, Jones PB (2009). Why psychiatry can’t afford to be neurophobic. British Journal of Psychiatry 194: 293-5. DOI:10.1192/bjp.bp.108.058479.

[3] Editorial (2010). A decade for psychiatric disorders. Nature 463: 9. DOI:10.1038/463009a.

[4] Owen MJ, O’Donovan MC, Thapar A & Craddock N (2011). Neurodevelopmental hypothesis of schizophrenia. British Journal of Psychiatry 198: 173-5. DOI:10.1192/bjp.bp.110.084384.

[5] Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature. DOI:10.1038/nature13595.

[6] Macrae F (2014). New DNA hope on schizophrenia: Discovery of 100 genes could help transform the condition [online]. Available from: http://www.dailymail.co.uk/health/article-2700793/New-DNA-hope-schizophr...

[7] Hall J, Trent S, Thomas KL et al. (2014). Genetic risk for schizophrenia: A convergence on synaptic pathways involved in plasticity. Biological Psychiatry [online]. DOI: 10.1016/j.biopsych.2014.07.011.

[8] Fromer M, Pocklington AJ, Kavanagh DH et al. (2014). De novo mutations in schizophrenia implicate synaptic networks. Nature 506: 179-84. DOI:10.1038/nature12929.

[9] Marchetto MCN, Carromeu C, Acab A et al. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143: 527-39. DOI: 10.1016/j.cell.2010.10.016.

[10] Hamburg MA & Collins FS (2010). The path to personalized medicine. New England Journal of Medicine 363: 301-04. DOI: 10.1056/NEJMp1006304.

[11] Lichtenstein P, Yip BH, Björk C et al. (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. The Lancet 373: 17-23. DOI: 10.1016/S0140-6736(09)60072-6.

[12] Craddock N & Sklar P (2013). Genetics of bipolar disorder. The Lancet 381: 1654-62. DOI: 10.1016/S0140-6736(13)60855-7.

[13] Craddock N & Owen M (2010). The Kraepelinian dichotomy – going, going… but still not gone. British Journal of Psychiatry 196: 92-5. DOI:10.1192/bjp.bp.109.073429.

[14] Spalding KL, Bergmann O, Alkass K et al. (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell 153: 1219-27. DOI: 10.1016/j.cell.2013.05.002.

[15] Santarelli L, Saxe M, Gross C et al. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301: 805-09. DOI: 10.1126/science.1083328.

[16] Weaver ICG, Dioro J, Seckl JR et al. (2004). Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Annals of the New York Academy of Sciences 1024: 182-212. DOI: 10.1196/annals.1321.099.

[17] McGowan PO, Sasaki A, D’Alessio AC et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with child abuse. Nature Neuroscience 12: 342-8. DOI:10.1038/nn.2270.

[18] Karayiorgou M, Flint J, Gogos JA et al. (2012). The best of times, the worst of times for psychiatric disease. Nature Neuroscience 15: 811-12. DOI:10.1038/nn.3115.