Abstract
If you only read one article this month, then choose ‘Antibodies attacking the brain: Is it time for a paradigm shift in psychiatric practice and service models’ by Thachil and colleagues (2013). This is a clear, comprehensible summary of a new area in clinical psychiatry, and it really is a paradigm shift. The basic tenet is that a proportion of the people we diagnose with psychiatric disorders, especially first-episode psychosis, actually have an autoimmune brain disorder. Therefore, antipsychotics don’t help at all, and these patients miss out on immunotherapy that might cure them.
Articles on autoimmune brain disorders are full of clunky diagnostic terms and clumsy abbreviations, which can deter all but the keenest reader. But do persist. Thachil et al. (2013) describe four disorders where the patient’s own immune system attacks cerebral neurotransmitters, causing psychiatric symptoms. In Adelaide, Tidswell and colleagues (2013) have reported on four cases of first-episode psychosis in young women, all of whom were later found to have anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. In other words, these patients had antibodies to N-methyl-d-aspartate (NMDA) glutamate receptors in the brain; the antibodies were damaging the receptors and causing psychiatric symptoms. Susannah Cahalan (2012), a New York journalist, has written a powerful account of her experience of anti-NMDAR encephalitis in her book Brain on Fire.
These are not obscure conditions. Dalmau et al. (2011), in Lancet Neurology, reports on more than 400 patients with anti-NMDAR encephalitis. Steiner et al. (2013) found that almost 10% of 121 people with schizophrenia had antibodies to the NMDA receptor. This raises the possibility that a proportion of people that we diagnose with chronic, treatment-resistant disorders (usually schizophrenia) actually have a subacute form of autoimmune encephalitis. The situation is perhaps reminiscent of the discovery that general paralysis of the insane, which often began with psychotic symptoms, was due to cerebral syphilis and could be treated with penicillin.
Thachil et al. (2013) describe the assessment of autoimmune encephalitis in detail. Blood tests for anti-NMDA, anti-voltage-gated potassium channel (VGKC) antibodies and anti-glutamic acid decarboxylase (GAD) antibodies are available in Australia. From a clinical perspective, it might be useful to order these tests along with the usual blood tests in people presenting with a first episode of psychosis, and in chronic patients who do not respond to treatment.
This issue of ANZJP contains other articles on this theme. Rege and Hodgkinson (2013) describe immune dysregulation and autoimmunity in bipolar disorder, concluding that the links between these conditions are closer than previously thought. Many people know from their own experience that a period of mild depression after infections, such as influenza, is common. Gunaratne et al. (2013) examine post-infective mood disturbance. They regard the infection as an immunological stressor, and review the contributions of genetic variations, stress response pathways, neurotransmitter abnormalities, and psychosocial factors to the subsequent development of major depression.
This issue of the Journal also looks at childhood disorders, from several different perspectives. Continuing the biological theme, Lu et al. (2013) investigate the effects of childhood trauma on the brain using diffusion tenor imaging (DTI), a method of imaging white matter integrity. There has been controversy about both the autistic spectrum disorders and attention deficit hyperactivity disorder (ADHD), with suggestions that these conditions may be over-diagnosed. The prevalence of these conditions and the impact of the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria are discussed by Basu and Parry (2013) and by Prosser and Reid (2013), respectively. Kennedy (2013) has written a very thoughtful analysis of the risks of selective serotonin reuptake inhibitors (SSRIs) in pregnancy, delving into the underlying data to find out what the published risk ratios actually mean for the individual patient.
Nielssen (2013) also examines the assessment of risk, this time in adult psychiatry. Risk assessment (for violence or suicide) is highly valued by clinical administrators, who often seem to have a fixed belief that conducting enough risk assessments will prevent bad things from happening. Commenting on the paper by Allnutt et al. (2013) in ANZJP, Nielssen (2013) neatly picks apart the myths and misconceptions underlying various types of risk assessment, and the harms that can result from such assessments.