Is there a big role for the little brain in psychiatry?

The cerebellum is a structure situated in the posterior cranial fossa. It has long been assumed that the cerebellum is concerned primarily with motor-related functions. However recent research has demonstrated that the cerebellum also plays a role in psychiatric disorders, including schizophrenia, autism and depression. Recent developments, described in this article, suggest that malfunctioning of the cerebellum can lead to severe emotion dysregulation and to psychopathological conditions.     

Is there a future for gene therapy?

The requirements for successful gene therapy are stated and brief details are given of the gene therapy trials in humans which have been approved by the NIH during the years 1989-1997. An indication is given of the gene therapy trials that have been carried out in animal models of Duchenne muscular dystrophy with emphasis on the Golden Retriever dog model. Problems facing somatic gene therapy for inherited muscle diseases are predominantly the following: the extent of the spread of expression from the injection site, the duration of expression and the need for systemic delivery. Brief details of the problems are given and possible ways of overcoming the difficulties are outlined. These include the use of multiple intramuscular injections, increasing the permeability of the extracellular matrix of muscle, inducing mitosis in myoblasts, the use of ex vivo gene transfer, using modified viruses as vectors or synthesized transporter molecules, the use of mechanisms which combat the action of killer T cells, upregulation of isoforms or of alternative proteins such as utrophin for dystrophin and the use of genetic correction methods such as the use of antisense oligonucleotides. It is concluded that there is a potential future for somatic gene therapy in the inherited muscle diseases.     

Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression?

Chronic inflammation in physically ill patients is often associated with the development of symptoms of depression. The mechanisms that are responsible for inflammation-associated depression have been elucidated over the last few years. Kynurenine produced from tryptophan in a reaction catabolized by indoleamine 2,3 dioxygenase is transported into the brain where it is metabolized by microglial enzymes into a number of neurotropic compounds including quinolinic acid, an agonist of N-methyl-d-aspartate receptors. Quinolinic acid can synergize with glutamate released by activated microglia. This chain of events opens the possibility to treat inflammation-induced depression using therapies that target the transport of kynurenine through the blood–brain barrier, the production of quinolinic acid and glutamate by activated microglia, or the efflux of glutamate from the brain to the blood.     

Is the EQ-5D fit for purpose in mental health?

The EQ-5D is a widely used questionnaire for calculating quality-adjusted life-years (QALYs) for assessing cost-effectiveness in healthcare. It reflects the impact of common mental health conditions such as mild to moderate depression but seems to be more problematic for use in people with psychotic and severe and complex non-psychotic disorders.     

Is there a role for nitric oxide activity in cervicogenic headache?

Cervicogenic headache (CEH) is a unilateral headache that can be provoked by neck movement, awkward head positions or pressure on tender points in the neck. The mechanisms underlying the stimulation of pain in CEH are not clearly known. In this study, we measured serum nitrate and nitrite levels as an index of nitric oxide (NO) activity in 15 patients with CEH during headache and headache-free periods and in 15 healthy controls. Total nitrate+nitrite levels were found to be higher in CEH patients during headache periods than in healthy controls (20.7+/-3.8 micromol/l vs 14.4+/-3.6 micromol/l, p<0.001), but not in CEH patients during headache-free periods (16.1+/-2.2 micromol/l) compared with the controls (p>0.05). In the patients with CEH, serum total nitrate+nitrite levels were found to be higher during headache periods than during headache-free periods (p=0.001). It can thus be hypothesized that the changes observed are a cause of the attack rather than a consequence of the disease process.     

Is there a role for psychiatry in late termination of pregnancy?

The aim of the present review was to explore the role of the psychiatrist in late terminations of pregnancy. A literature review was conducted using MEDLINE and psycINFO databases, focussing on articles that explored (i) existing decision-making processes in late terminations; (ii) psychological sequelae of both early and late termination of pregnancy; (iii) the role of psychiatry in both early and late termination of pregnancy; and (iv) the involvement of psychiatry in complex medical decisions. The decision to perform a late termination of pregnancy is complex. Contributing to its complexity is an array of political, legal, societal, and ethical factors. The literature regarding psychological sequelae is frequently confusing and weakened by methodological problems. Methods of assisting in this decision-making process include the involvement of committees and psychiatrists. There are precedents for the involvement of psychiatrists in such a setting. Historically, psychiatrists played a role in screening women who requested an early termination. Psychiatrists are often involved in ethically challenging and complex clinical decisions in the general hospital setting. The involvement of psychiatry in this complex decision-making process has potential advantages and disadvantages. It is timely for psychiatrists to consider their position on their discipline's involvement.     

Is there a duty for private employers to provide emergency mental health care services?

This article presents a discussion of whether employers in private companies have a duty to provide an emergency action plan with a mental health component for its employees. It discusses basic negligence concepts and focuses mainly on the "duty of care" component of negligence. It then applies the negligence concepts to private employers and discusses how private companies arguably might have a duty under the laws of negligence to provide employees with an emergency action plan, specifically a plan including mental health provisions.     

On the quest for a biomechanism of transsexualism: Is there a role for BDNF?

Previous studies hypothesized a neurobiological mechanism for gender identity disorder (GID). Recently a possible role for serum brain-derived neurotrophic factor (BDNF) was suggested on the basis of reduced serum BDNF levels in male-to-female individuals. Here we review the question whether there is indeed a role of BDNF in the development of transsexualism.     

Is there a role for uridine and pyrimidine nucleosides in the treatment of vascular dementia?

In the 70s, the discovery of a constant loss of acetylcholine (Ach) in the brains of people suffering from dementia led to the development, in order to improve cognitive functions, of drugs that increased Ach levels. The possibility that loss of a given neurotransmitter might be associated with the onset of a specific neurological syndrome led to suggestions that, as had already been found in Parkinson's disease, replacement therapy might drastically improve the course of the syndrome. We are now aware of the limits of this therapeutic approach. In this review, we analyse potential factors contributing to the partial failure of Ach replacement therapy, contrasting common beliefs regarding the Ach synapse with the difficulties in restoring its activity through replacement drugs. Considering the search for alternative strategies, in the second part of the review, we overview progress of research into pyrimidine compounds, now emerging as a new modulatory system acting through specific pyrimidino-receptors involved in various steps of cell signalling. Pyrimidine nucleosides might be useful in the chronic treatment of cognitive deficits resulting from vascular dementia.     

Is there a role for young hippocampal neurons in adaptation to stress?

The hippocampus has been implicated in many cognitive and emotional behaviors and in the physiology of the stress response. Within the hippocampus, the dentate gyrus has been implicated in the detection of novelty. The dentate is also a major target for stress hormones and modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Whether these functions of the dentate integrate or segregate remains unknown, as most investigations of its role in stress and learning are separate.Since the exciting discovery of adult neurogenesis in the dentate gyrus, adult-born neurons have been implicated in both novelty detection and the stress response. In this perspective we will discuss the literature that implicates the hippocampus, and potentially, adult-born neurons in these two functions. We will attempt to reconcile the seemingly contradictory behavioral results for the function of adult-born neurons. Finally, we will speculate that a key function of adult-born neurons within hippocampal function may be to modulate the stress response and perhaps assign stress salience to the sensory context.     

Is there a future for donepezil therapy in the treatment of multiple sclerosis-related cognitive impairment?

Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 76(17), 1500-1507 (2011). Cognitive impairment is a core feature of multiple sclerosis (MS), is detectable in up to 65% of patients and represents the most important predictor of the subject's work and vocational status. The cognitive domains most frequently involved are attention, information processing speed, episodic memory and executive functions. To date, there is no approved drug or evidence-based strategy for the treatment of this disabling condition. Promising findings were provided in a monocentric randomized trial on donepezil - a reversible inhibitor of acetylcholinesterase - for the treatment of MS-related memory impairment. However, a larger multicentric trial failed to confirm any efficacy of donepezil on memory impairment in MS subjects. Possible implications of these findings are discussed in this article.     

Is health care a right or a commodity? Implementing mental health reform in a recession

The Patient Protection and Affordable Care Act, signed into law by President Obama in March 2010, contains elements of two seemingly contradictory positions: health care as a commodity and as a right. The commodity argument posits that the marketplace should govern demand, supply, and costs of care. The law's establishment of state insurance exchanges reflects this position. The argument that health care is a right posits that it is a need, not a choice, and that government should regulate care standards that may be compromised as insurers attempt to minimize costs. The law's requirement for coverage of mental and substance use disorders reflects this position. This Open Forum examines these arguments in light of current state fiscal crises and impending reforms. Despite the federal government's interest in expanding prevention and treatment of mental illness, states may demonstrate varying levels of commitment, based in part on their perception of health care as a right or a commodity. The federal government should outline clear performance standards, with minimum services specified to maximize state commitments to services.     

Plasma cytokine profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis?

BackgroundFragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement and a strong association with autism. Altered immune responses have been described in autism and there is potential that in children with FXS and autism, an abnormal immune response may play a role.ObjectivesTo delineate specific patterns of cytokine/chemokine profiles in individuals with FXS with and without autism and to compare them with typical developing controls.MethodsAge matched male subjects were recruited through the M.I.N.D. Institute and included: 19 typically developing controls, 64 subjects with FXS without autism and 40 subjects with FXS and autism. Autism diagnosis was confirmed with ADOS, ADI-R and DSM IV criteria. Plasma was isolated and cytokine and chemokine production was assessed by Luminex multiplex analysis.ResultsPreliminary observations indicate significant differences in plasma protein levels of a number of cytokines, including IL-1α, and the chemokines; RANTES and IP-10, between the FXS group and the typical developing controls (p < 0.01). In addition, significant differences were observed between the FXS group with autism and the FXS without autism for IL-6, eotaxin, MCP-1 (p < 0.04).ConclusionsIn this study, the first of its kind, we report a significantly altered cytokine profile in FXS. The characterization of an immunological profile in FXS with and without autism may help to elucidate if an abnormal immune response may play a role and help to identify mechanisms important in the etiology of autism both with and without FXS.