New Antidepressant class: New mechanism of action Many unfortunate individuals suffer year after year of depression. Depressive illness becomes the defining feature of their lives, as one tablet after another fails, and the psychotherapies reveal themselves as blunt instruments.  For decades, psychopharmacologists have sought a new class of antidepressant, based on new mechanisms, rather those which target the brainstem-derived neuromodulators, serotonin, noradrenaline and dopamine. Finally, there has been a breakthrough. Ketamine, a molecule familiar to the anaesthetists, has repea ..read more

The previous post in this series described the symptoms of schizophrenia. Here we turn to the causes of schizophrenia. There has been major progress in this area over the last twenty years. A number of factors have been identified which carry a risk for schizophrenia. Some of these factors are genetic, others impact during the course of life. Usually schizophrenia emerges in late adolescence or early adulthood, as the intellect, personality and neural networks are being sculpted. The population risk is slightly less than 1%, with a slight excess of male sufferers (1.4:1). Males also tend to sh ..read more

Schizophrenia has long been the heartland of psychiatry, but can be as confusing now as it was 100 years ago. Lay opinion is that schizophrenia is commensurate with hearing voices and paranoia, but this is not true. Hearing voices and paranoia are non-specific phenomena which can occur in normal psychic life. So what exactly is schizophrenia? Well it is also not commensurate with psychosis. In fact, there is a long list of conditions in which psychosis can occur (Figure 1). Psychosis we can define as a fundamental shift in a person’s experience of lived reality, affecting the highest faculties ..read more

Long stretches of DNA, from 1000 to several million base pairs, can be deleted or duplicated within a chromosome. These changes are known as copy number variants (CNVs). It is now recognised that eight CNVs are associated with schizophrenia. For a person carrying a CNV, their risk of developing schizophrenia is increased by 3-58 times compared to the general population. It is also known that approximately 2.5-5% of people suffering from schizophrenia will carry at least one of these CNVs. A new paper by Danish researchers serves as an excellent introduction to this rapidly developing and funda ..read more

Psychiatric genetics can be daunting for the non-expert. But it is so important for all mental health researchers and clinicians to have some understanding of where this field is at. Unlike much of the rest of psychiatric research and theory, modern genetics represents a firm foundation of valid and reliable knowledge. That knowledge is slowly unfurling how we think about psychiatric disorders such as ADHD, autism, depression, OCD, substance abuse, schizophrenia and bipolar. A 2018 paper by Kendler and colleagues is an ideal overview, a straightforward, highly readable account of where things ..read more

One goal in modern medicine is to use genetics to determine the best treatment strategy for an individual patient. A simple, cheap genetic test which predicts response to a particular treatment has clear utility for patients. To date, psychiatry has lagged behind general medicine, no doubt due to the complexity of CNS tissue and the sheer number of components involved in CNS processing, but the picture is changing. One particular area of interest is the treatment of alcohol dependence. The pharmacogenomics of topiramate The drug topiramate started off as an anticonvulsant, but was also been fo ..read more

Many patients go through years and years of depression which stubbornly resists treatment. Therapy, SSRIs, even ECT, can all fail to provide any shift. But a recent paper by Oxford psychiatrist Phil Cowen brings some light. In a readable and straightforward account, Cowen weighs-up the various options that are available, when first and second line antidepressant treatments are ineffective. Depressed patients, GPs and psychiatrists will find the text very useful in selecting options – and in keeping hope alive. Topics covered include various combination and augmentation strategies and their sta ..read more

The power of the nervous system: The astonishing power of the nervous system does not reside in a single neuron. (That said, an advanced supercomputer is required for the task of modelling the processing power of even a single neuron). Nervous tissue is immensely powerful because of the rich connectivity between neurons. A 1mm voxel of cerebral cortex (a standard fMRI unit), contains ~300 million synaptic connections and ~50 thousand neurons [ref].  Scaled up to the whole human brain, there are estimated to be several hundred trillion synaptic connections within a total pool of ~100 ..read more

Healthcare delivery is at last beginning to adopt mathematical and engineering principles [link]. There is an awareness, especially in the USA, that the leadership of an inherently chaotic system requires a professional mathematical sensibility, infinitely more sophisticated than the tired mix of power-point, polished-comportment, faux-bonhomie, affected-positivity and sloganeering. Complex systems are made up of many components. A decision which impacts upon one component in a healthcare system may affect other components, and indeed the whole system, in a way which was not predicted at ..read more

Congratulations to Dave Nutt, Val Curran and their colleagues at Imperial and UCL. Following on from their groundbreaking studies of MDMA on channel 4, they have now repeated the same format with cannabis. Running live psychopharmacology studies on television is not for the faint hearted, but it offers a unique way to impart public health knowledge in a way which is lively and captures the imagination. And the visual element works well. The personal testimony of Jon Snow and the other participants was particularly revealing. The channel 4 experiments on cannabis demonstrated that CBD can inhib ..read more