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 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 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 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 role for music therapy in the recovery approach in mental health?

The recovery approach in mental health care emphasises the importance of the service user leading a fulfilling, meaningful life beyond the limitations of illness or symptomatology. This approach to care is increasingly included as a central part of mental health policy and service provision in a number of countries including the UK and Ireland, to address the needs of people who have severe and enduring mental disorders. It is an autonomous, holistic and empowering way of working with individuals as they journey towards healing. Fundamental to this model is the relationship fostered between service users and health professionals. The recovery philosophy of care mirrors some of the core principles of music therapy, including the importance of the therapeutic relationship and the possibilities for change and growth within this. This paper explores the congruence between music therapy and the recovery approach by providing: (1) An overview of current published evidence for music therapy in mental health care. (2) A discussion of this psycho-social creative arts therapy intervention within the specialized area of recovery in psychiatry, and (3) case vignettes to illustrate the application of this philosophy in music therapy work within a recovery service.     

Anticonvulsant hypersensitivity syndrome: Is there a role for immunomodulation?

The anticonvulsant hypersensitivity syndrome (AHS) is an idiosyncratic immunologic reaction to certain anticonvulsant medications, in which internal organ involvement may lead to fatal multisystemic failure. This syndrome has been associated with the use of aromatic ring-containing agents such as phenytoin, carbamazepine, or phenobarbitone. Clinically, this condition presents with the classic triad of fever, rash, and lymphadenopathy. We review the existing literature on AHS pathogenesis and illustrate a case complicated by liver dysfunction where the use of N-acetylcysteine (N-AC) and intravenous immunoglobulin (IVIG) may have altered the course of the disease. The rationale of suggesting N-AC and IVIG for the treatment of this syndrome relies on the theoretical synergistic effects of the two agents. Although treatment for this syndrome remains controversial and relies heavily on anecdotal evidence, the progression of hepatic injury may be prevented by the addition of N-AC. The scavenging properties of N-AC may palliate and possibly prevent free radical-mediated liver damage. In addition, IVIG may effectively modulate the overreactive immune system in AHS. We discuss the possible role of using immunomodulating agents for the treatment of this syndrome and suggest that alternative regimens should be given special consideration especially in those critical clinical situations where supportive measures appear to be unsuccessful.     

Osmotic regulation of neuronal nitric oxide synthase expression in the rat amygdala: Functional role for nitric oxide in adaptive responses?

Water-deprivation-induced osmotic stress leads to activation of a number of adaptive responses. Nitric oxide (NO) has been implicated in the modulation of these responses, as the amygdala has been implicated in ingestive behavior and modulation of autonomic homeostatic functions. Here we investigated the effects of water deprivation on neuronal nitric oxide synthase (nNOS) expression within the rat amygdala; a brain area involved in modulating ingestive behavior and autonomic function. Water deprivation resulted in significant increases in nNOS immunoreactivity (-ir) within different regions of the amygdala compared with euhydrated rats. Maximal increases were observed in the anteroventral (118 +/- 9 vs. 47 +/- 3 neurons), anteriodorsal (133 +/- 9 vs. 77 +/- 3), and posterioventral (175 +/- 5 vs. 71 +/- 5) parts of the medial amygdala. The basomedial nucleus (65 +/- 4 vs. 39 +/- 3) and posterior basolateral nucleus (19 +/- 2 vs. 5 +/- 1) of the amygdala and the capsular (21 +/- 2 vs. 6 +/- 1) and medial (44 +/- 6 vs. 22 +/- 3) parts of the central nucleus of the amygdala also showed increased nNOS-ir in dehydrated rats. Water deprivation had no effect on nNOS-ir in areas such as the cortical, anterior basolateral, and intercalated nuclei of the amygdala. Microinjection of an NO donor, DEA-NONOate, into the central amygdala resulted in a pressor and tachycardic response that was attenuated by a soluble guanylate cyclase inhibitor. These observations suggest that activation of the nitrergic system is prevalent throughout the amygdala following water deprivation and suggest that the up-reguation of nNOS could play a significant role in the integrative response to osmotic stress.     

Is there a role of visual cortex in spatial hearing?

The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head-centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye-in-head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory-visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.     

Is there a place for cellular therapy in depression?

Although efforts have been made to improve the pharmacological treatment of depression, approximately one-third of patients with depression do not respond to conventional therapy using antidepressants. Other potential non-pharmacological therapies have been studied in the last years, including the use of mesenchymal stem cell therapies to treat depression. These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients. Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its anti-inflammatory and neurotrophic properties. However, some clinical trials involving treatment of depression with stem cells are in progress, but with no published results. These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.     

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 cellular prion protein in intrathymic T cell differentiation and migration?

The cellular prion protein (PrP(C)) is expressed in the nervous and immune systems. Functionally, PrP(C) has been suggested to participate in neuron survival, neuritogenesis and T lymphocyte activation. Moreover, PrP(C) interaction with laminin influences neuronal adhesion and neurite extension. Nevertheless, so far the physiological role of PrP(C) has not been completely elucidated, particularly in the immune system. The aim of the study was to evaluate the possible participation of PrP(C) in intrathymic T cell development. We evaluated T cell differentiation markers in thymocytes and peripheral lymphocytes, as well as thymocyte death in PrP(C)-null or PrP(C)-overexpressing (Tga20) mice, compared to wild-type controls. In these same animals, we ascertained laminin-driven thymocyte migration. Compared to controls, only marginal differences were found in PrP(C)-null animals. However, Tga20 mice exhibited a severe thymic hypoplasia, with 10-20% lymphocytes compared to wild-type counterparts. In particular, the frequency of CD4+CD8+ cells was largely reduced, and this was accompanied by a dramatic increase in the frequency of CD4-CD8- thymocytes, which could be as high as 60-65% of the whole-cell suspensions. Moreover, Tga20 mice exhibited an increase in thymocyte death, comprising the CD4+CD8+, as well as CD4+ and CD8+ single-positive cells. Additionally, laminin-driven migration was largely impaired in Tga20 mice, in which we also found a significant decrease in total T lymphocytes in the spleen and lymph nodes. Our results show that PrP(C) overexpression alters intrathymic T cell development, a defect that likely has a negative impact in the formation of the T cell peripheral pool.