Journal of molecular psychiatry最新文献

The goal of this review is to integrate - in its two parts - the considerable amount of information that has accumulated during these recent years over the morphology, biology and functions of astrocytes - first part - and to illustrate the active role of these cells in pathophysiological processes implicated in various psychiatric and neurologic disorders - second part.

Objective: This review aimed to investigate the therapeutic potential of Deep Brain Stimulation (DBS) for treating resistant Major Depressive Disorder (MDD). We explored the role of Nucleus accumbens (Nac) as a target for treatment.

Method: We made a systematic review of all studies examining the mechanisms of action of high frequency brain stimulation and the pathophysiology of MDD. We also reported all the studies exploring the therapeutic potential of DBS in MDD.

Results: As a central relay-structure, the Nac seems to play a central role in MDD symptomatology. We investigated its role as a primary target for DBS in depressed patients. Anatomically the Nac is at the centre of the interactions between dopaminergic, serotoninergic and glutamatergic systems. Functionally, the Nac is involved in both normal and abnormal reward processes and in anhedonia and loss of motivation. Due to its central location between the emotional system, the cognitive system and motor control system, the Nac seems to have a central role in mood and feeling regulation.

Conclusion: According to encouraging recent studies, DBS seems to be a promising technique in resistant MDD treatment.

Autism Spectrum Disorders (ASD) are group of developmental disabilities with a complex neurobiological basis including putative changes in the immune system. They are characterized by pervasive qualitative abnormalities in social interactions, communication, and stereotyped behaviour. Matrix metalloproteinases (MMPs) represent a group of proteases which play an important role in neuroinflammation and neurodevelopment. Therefore, they possibly have a crucial function in the etiopathology of ASD. In this review, we summarize the plausibility of the hypothesis that MMPs are involved in the neuropathology of ASD. Possible pathways through which MMPs can contribute to the pathogenesis of ASD are discussed including neuroinflammatory mechanisms inclusive of mediating neuropathological effects of infections, the associations between MMPs and other biomarkers such as cytokines, chemokines and neurotrophic factors. Despite sufficient evidence for such an involvement of MMPs in the neuropathology of ASD, they have not yet been extensively studied in this context. Thus, further research in this field is not only urgently needed but also very promising and may also lead to new therapeutic approaches.

Background: Depression is a prevalent neuropsychiatric disorder that affects an estimated 350 million people worldwide. Currently available treatments for depression are lacking in both speed of onset and efficacy. Recent pharmacological efforts have targeted the glutamatergic neurotransmitter system using the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine to produce rapid and robust antidepressant effects, however the widespread clinical use of ketamine is limited due to side effects and abuse liability. More recently, work evaluating metabotropic mGluR2/3 receptor antagonists has demonstrated many similarities with ketamine.

Methods: Male, Sprague-Dawley rats were exposed to a chronic unpredictable stress paradigm, which produces decreased sucrose preference, a measure of anhedonia. Rats were then treated with vehicle or a single injection of the mGluR2/3 antagonist LY341495 (3 mg/kg, i.p.) and tested at 24 hrs, 48 hrs or 10 days after a single treatment.

Results: We demonstrate that a single treatment with LY341495 produces a rapid (within 1-2 days) and long-lasting (10 days) reversal of anhedonia caused by chronic unpredictable stress in rats. This model provides a rigorous test of rapid-acting agents as typical antidepressants require several weeks of treatment to produce a response.

Conclusions: These data suggest that LY341495 has the ability to produce rapid and robust antidepressant effects similar to ketamine. Together, the results highlight the potential for similar compounds to produce rapid and lasting efficacy for the treatment of depression.

Background: Alcohol-induced damages such as brain atrophy and fatty liver are closely related to a disturbed lipid metabolism. In animal models, a linkage between chronic alcohol consumption and changes in fatty acid (FA) composition in various organs and cells is well known and there is some indication that this phenomenon could be linked to behavioural alterations associated with alcohol addiction such as craving. However, the influence of ethanol on secretory FA has not been investigated so far. In this study, we therefore aimed at investigating whether there is a significant change of serum FA composition in patients suffering from alcohol dependence. We compared patients before and after treatment (detoxication) with control individuals who did not suffer from addiction. The roles of age, the duration and intensity of alcohol use and lifestyles were considered.

Methods: Serum FA was measured in 73 male ethanol dependent patients before and after alcohol withdrawal in an in-patient setting. Additionally, of this group, 45 patients were matched with 45 healthy male volunteers as controls.

Results: We found significant differences in the FA composition before and after detoxication as well as between patients and controls. After detoxication, the values changed towards the ones in healthy controls. The main finding during acute alcohol use was an increased oleic acid concentration above the level of the linoleic acid concentration.

Conclusions: An elevated oleic/linoleic acid ratio seems to be a state marker for acute alcohol use and may be a relevant trait marker during detoxification and possibly the subsequent therapeutic measures. The results of this pilot study need to be replicated in a larger study also including female patients. Further, the specificity of this potential biomarker needs to be determined.

Ageing is associated with changes in the function of various organ systems. Changes in the cardiovascular system affect both directly and indirectly the function in a variety of organs, including the brain, with consequent neurological (motor and sensory performance) and cognitive impairments, as well as leading to the development of various psychiatric diseases. Post-stroke depression (PSD) is among the most frequent neuropsychiatric consequences of cerebral ischemia. This review discusses several animal models used for the study of PSD and summarizes recent findings in the genomic profile of the ageing brain, which are associated with age-related disorders in the elderly. Since stroke and depression are diseases with increased incidence in the elderly, great clinical benefit may especially accrue from deciphering and targeting basic mechanisms underlying PSD. Finally, we discuss the relationship between ageing, circadian rhythmicity and PSD.

In the last years, physiological aging became a general concept that includes all the changes that occur in organism with old age. It is obvious now, that in developing and developed countries, new health problems concerning older population appear. One of these major concerns is probably dementia. Sooner or later, all forms of dementia lead to learning deficit, memory loss, low attention span, impairment of speech and poor problem solving skills. Normal ageing is a physiological process that also involves a lot of neurological disorders with the same type of symptoms and effects that many researchers are trying to minimize in demented patients. In this review we try to highlight some of the newest aspects of therapeutic strategies that can improve natural neuroregeneration.

Alcohol dependence is a severe and common disorder associated with high morbidity and mortality rates. Genetic as well as environmental factors are known to modulate susceptibility to alcohol dependence. There is a growing body of evidence suggesting that this interaction between the genome and the environment is mediated by epigenetic mechanisms, e.g. DNA methylation at CpG sites. Following an introduction of epigenetic regulation of gene transcription, this review will provide an overview over recent genetic and epigenetic findings in the context of alcohol dependence focusing on human studies. Finally, we will discuss the current limitations of epigenetic studies as well as the implications of genetic and epigenetic findings for the development of better treatment and prevention strategies.

The amygdala is a structure of the temporal lobe thought to be involved in assigning emotional significance to environmental information and triggering adapted physiological, behavioral and affective responses. A large body of literature in animals and human implicates the amygdala in fear. Pain having a strong affective and emotional dimension, the amygdala, especially its central nucleus (CeA), has also emerged in the last twenty years as key element of the pain matrix. The CeA receives multiple nociceptive information from the brainstem, as well as highly processed polymodal information from the thalamus and the cerebral cortex. It also possesses the connections that allow influencing most of the descending pain control systems as well as higher centers involved in emotional, affective and cognitive functions. Preclinical studies indicate that the integration of nociceptive inputs in the CeA only marginally contributes to sensory-discriminative components of pain, but rather contributes to associated behavior and affective responses. The CeA doesn't have a major influence on responses to acute nociception in basal condition, but it induces hypoalgesia during aversive situation, such as stress or fear. On the contrary, during persistent pain states (inflammatory, visceral, neuropathic), a long-lasting functional plasticity of CeA activity contributes to an enhancement of the pain experience, including hyperalgesia, aversive behavioral reactions and affective anxiety-like states.