Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis

Background Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs). Method In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500. Results Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men. Conclusions Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosi

The random case of Conley's theorem: III. Random semiflow case and Morse decomposition

In the first part of this paper, we generalize the results of the author \cite{Liu,Liu2} from the random flow case to the random semiflow case, i.e. we obtain Conley decomposition theorem for infinite dimensional random dynamical systems. In the second part, by introducing the backward orbit for random semiflow, we are able to decompose invariant random compact set (e.g. global random attractor) into random Morse sets and connecting orbits between them, which generalizes the Morse decomposition of invariant sets originated from Conley \cite{Con} to the random semiflow setting and gives the positive answer to an open problem put forward by Caraballo and Langa \cite{CL}.Comment: 21 pages, no figur

Burning mouth syndrome: pathogenic and therapeutic

Summary Burning mouth syndrome (BMS) is a chronic pain condition characterized by pain, burning sensations and dryness within an oral mucosa, without any clinical changes of the latter. It occurs approximately seven times more frequently in women, mostly in perimenopausal age. The psychiatric aspect of BMS is significant: the most frequent co-morbidities are depression and anxiety disorders, and a number of psychotropic drugs play an essential role in its treatment. In the present review, the most important pathogenic and treatment concepts of BMS have been discussed. The BMS may be similar to neuropathic pain and has some related pathogenic elements with fibromyalgia and the restless leg syndrome. In primary BMS, the features of presynaptic dysfunction of dopaminergic neurons and deficiency of endogenous dopamine levels have been demonstrated. Other neurotransmitters such as serotonin, noradrenaline, histamine as well as hormonal and inflammatory factors may also play a role in the pathogenesis of BMS. In the pharmacological treatment of BMS a variety of drugs have been used including benzodiazepines, anticonvulsants, antidepressants and atypical antipsychotic drugs. In the final part of the paper, the possibility of using atypical antipsychotic drug, olanzapine, in the treatment of BMS has been discussed. In the context of the recent studies on this topic, a case of female patient with the BMS lasting more than ten years has been mentioned, in whom the treatment with olanzapine brought about a rapid and significant reduction of symptoms. The probable mechanism of the therapeutic effect of olanzapine in BMS can include its effect on dopaminergic receptors and probably also on histaminergic, noradrenergic and serotonergic ones. Key words: burning mouth syndrome, dopaminergic system, olanzapine Burning mouth syndrome (BMS) is a chronic pain syndrome which affects oral mucous membrane. It is characterized by burning sensations, pain, pinching or numbness within oral mucosa, accompanied by dryness, paresthesia, dysgeusia or hypersensitivity to some food

Eating disorders: from twin studies to candidate genes and beyond

Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Brain Derived Neurotrophic Factor (BDNF) Expression Is Regulated by MicroRNAs miR-26a and miR-26b Allele-Specific Binding

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an essential role in neuronal development and plasticity. MicroRNA (miRNAs) are small non-coding RNAs of about 22-nucleotides in length regulating gene expression at post-transcriptional level. In this study we explore the role of miRNAs as post-transcriptional inhibitors of BDNF and the effect of 3′UTR sequence variations on miRNAs binding capacity. Using an in silico approach we identified a group of miRNAs putatively regulating BDNF expression and binding to BDNF 3′UTR polymorphic sequences. Luciferase assays demonstrated that these miRNAs (miR-26a1/2 and miR-26b) downregulates BDNF expression and that the presence of the variant alleles of two single nucleotide polymorphisms (rs11030100 and rs11030099) mapping in BDNF 3′UTR specifically abrogates miRNAs targeting. Furthermore we found a high linkage disequilibrium rate between rs11030100, rs11030099 and the non-synonymous coding variant rs6265 (Val66Met), which modulates BDNF mRNA localization and protein intracellular trafficking. Such observation led to hypothesize that miR-26s mediated regulation could extend to rs6265 leading to an allelic imbalance with potentially functional effects, such as peptide's localization and activity-dependent secretion. Since rs6265 has been previously implicated in various neuropsychiatric disorders, we evaluated the distribution of rs11030100, rs11030099 and rs6265 both in a control and schizophrenic group, but no significant difference in allele frequencies emerged. In conclusion, in the present study we identified two novel miRNAs regulating BDNF expression and the first BDNF 3′UTR functional variants altering miRNAs-BDNF binding

Impaired Flush Response to Niacin Skin Patch Among Schizophrenia Patients and Their Nonpsychotic Relatives: The Effect of Genetic Loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia

Season of birth, clinical manifestations and Dexamethasone Suppression Test in unipolar major depression

<p>Abstract</p> <p>Background</p> <p>Reports in the literature suggest that the season of birth might constitute a risk factor for the development of a major psychiatric disorder, possibly because of the effect environmental factors have during the second trimester of gestation. The aim of the current paper was to study the possible relationship of the season of birth and current clinical symptoms in unipolar major depression.</p> <p>Methods</p> <p>The study sample included 45 DSM-IV major depressive patients and 90 matched controls. The SCAN v. 2.0, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) were used to assess symptomatology, and the 1 mg Dexamethasone Suppression Test (DST) was used to subcategorize patients.</p> <p>Results</p> <p>Depressed patients as a whole did not show differences in birth season from controls. However, those patients born during the spring manifested higher HDRS while those born during the summer manifested the lowest HAS scores. DST non-suppressors were almost exclusively (90%) likely to be born during autumn and winter. No effect from the season of birth was found concerning the current severity of suicidal ideation or attempts.</p> <p>Discussion</p> <p>The current study is the first in this area of research using modern and rigid diagnostic methodology and a biological marker (DST) to categorize patients. Its disadvantages are the lack of data concerning DST in controls and a relatively small size of patient sample. The results confirm the effect of seasonality of birth on patients suffering from specific types of depression.</p