Immunological perturbations, psychiatric disorders and associated therapeutics: a new era for psychiatry?

The three main theories explaining major mental illness, namely mood disorders, psychoses and dementias, have been partially discredited. Alongside this, there are emerging links between perturbations of the immune system and the onset and phenotypic features of these disorders. This article outlines the alternative pathophysiology and suggests potential treatments which could improve disease burden and avoid the need for psychotropic medication, with their associated side effects and relapse following withdrawal.

Are sweetened drinks a gateway to alcohol, opiate and stimulant addiction? Summary of evidence and therapeutic strategies.

1. Drinks sweetened with both sugar and artificial additives lead to dopamine release at the nucleus accumbens (NAc) in rat models; the basis of experiences of pleasure in humans, resulting in impulsive binging behaviour at times. 2. Evidence from rat models show cross sensitisation between sweetened drinks, alcohol, opiates and stimulants. Therefore, it could be hypothesised that sweetened drinks could be a gateway to multiple substance abuse among humans via 'alcopops'. 3. Identification of an allelic variant of the cyclic adenosine monophosphate responsive element modulator gene (CREM), linking impulsivity and multiple substance abuse, opens up prospects of mass screening to advice on harm reduction. 4. Furthermore, therapies involving cannabinoid receptor antagonists and transcranial brain stimulation are being currently investigated; of benefit to limit binge use of sweetened drinks.

Is the General Medical Council in need of revalidation?

The General Medical Council was originally set up to 'protect, promote and maintain the health and safety of the public'. In 2012, the Privy Council instructed the General Medical Council to set up and run a licensing and revalidation system for all practicing doctors in the UK, to protect patients from actions of medical staff. Despite this mandate, the General Medical Council has been a bystander in a series of regulatory failures. Without these episodes having been highlighted by family members, public investigations would not have been carried out. The maintenance of medical performance is delegated to NHS employers, which could cause conflicts of interests when employers have to investigate doctors as part of a team. The other responsibility of the General Medical Council is to monitor teaching standards and curricula of medical schools in the UK, which it does by eliciting feedback from students and trainees. The General Medical Council has not responded to 'new ways of working' (especially in England) involving non-medical staff undertaking tasks previously carried out by doctors. Furthermore, the General Medical Council has not updated its description of the role of the future doctor in light of increasing use of technology, use or non-use of which could both be considered to be evidence of poor practice.

Use of appropriate technology to improve mental health service delivery.

This article reviews currently available appropriate technologies which have been used in mental health, in order to reduce confusion and delay. Confusion (for example when and where to refer) can lead to error and waste. Similarly delay impacts quality and accessibility of the whole range of mental health services. As most secondary care mental health services use electronic patient records, it is arguably easier to apply technology in this speciality. However, consideration needs to be given to confidentiality and data security. Doctors of all specialities will be exposed to 'new' technologies over the next decade, and need to be aware of the direction of travel and its implications.

Closing the medical mortality gap in patients with major psychiatric conditions.

This article discusses options for closing the mortality gap between the general population and people with major psychiatric conditions such as psychosis, autism, learning disability and dementia. Most of the mortality (85%) involves physical disease, with most deaths occurring in general hospitals or care homes, so is relevant to all doctors. The main focus of psychiatric treatments has been to reduce suicide, although there is no evidence that they achieve this. This article calls for psychiatrists to collaborate with medical colleagues to help reduce excess deaths from physical causes. The practicalities of combined physical and mental health monitoring and prescribing clinics are discussed, based on experience in Whitby. Potential national solutions are summarized including options for smoking cessation, sugar restriction, nutritional supplementation and flu vaccination.

How to improve psychiatric services: a perspective from critical psychiatry.

Concern has been expressed from both within and outwith psychiatry about the relative lack of improvement of mental health services. Critical psychiatry is an emerging school of thought, mainly the product of practicing clinicians, which could be useful in remedying this situation. This article outlines, for psychiatrists and doctors of other specialities, practices which could be improved, and the competencies required to achieve this, in terms of knowledge, skills and attitudes.

Does the association with diabetes say more about schizophrenia and its treatment?--the GLUT hypothesis.

All effective anti psychotic drugs block glucose transporter proteins (GLUTs), peripherally and in the brain. These drugs are implicated in hyperglycaemia as demonstrated in mouse and human studies. Clozapine is the strongest blocker, with Haloperidol the weakest. The GLUT hypothesis suggests that schizophrenia is partly due to poor functioning of brain glucose transporters (GLUT 1 and 3). Neuronal glucose malnutrition could result in excessive neuronal pruning (so called Crow's Type 2 with a predominance of negative symptoms) or result in recurrent/ineffective pruning (Type 1 with positive symptoms). GLUT blockade by anti psychotic agents could assist Type 1 patients to complete the pruning process by deactivating already damaged neurones and circuits, but will make Type 2 patients more cognitively impaired. Future treatment options are discussed in line with the above formulation.

Impaired neuronal glucose uptake in pathogenesis of schizophrenia - can GLUT 1 and GLUT 3 deficits explain imaging, post-mortem and pharmacological findings?

The largely empirical dopamine theory has limited value in clarifying the pathogenesis of schizophrenia, due to its inability to explain consistent imaging findings, such as cortical grey matter loss, reduced frontal and thalamic activity, and, reduced D1 receptor load. Furthermore, the most effective drug for treating positive and negative symptoms - clozapine - has minimal dopaminergic activity. We present an alternative hypothesis centring on presumed deficits in membrane bound glucose transporter proteins GLUT 1 and GLUT 3, either in absolute numbers or functional capacity. In situations of high demand, intracellular hypoglycaemia in neurones and astrocytes will produce acute symptoms of misperceptions, misinterpretations, anxiety and irritability - the usual features of prodromal and first onset schizophrenia. Furthermore, reduced glucose uptake will disrupt production of glutamate--functionally similar to the schizophrenia-like syndrome produced by PCP, a glutamate antagonist. In the longer term, reduced neuronal growth and poor synaptic contacts will produce chronic cognitive difficulties and perpetuate acute symptoms. A backlog effect due to reduced brain uptake of glucose would produce systemic hyperglycaemia observed in drug nai ve subjects. Rat studies have shown that clozapine and similar compounds block GLUT proteins in the brain and peripherally, more so than selective dopamine blockers. By blocking GLUT proteins, clozapine would break malfunctioning circuits, resulting in the disappearance of cognitive and perceptual symptoms. Unfortunately, these drugs would also raise systemic glucose levels, increasing the risk of diabetes, as observed in longer term studies of clozapine in particular. We summarise potentially useful research strategies, including studying the genotype of GLUT proteins with respect to schizophrenia phenotypes, activation studies involving fMRI using deoxyglucose as a substrate, and investigating clinical features of schizophrenic patients prior to and following treatment for co-existing diabetes.