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Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ−1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ−1a.

Cannabis is among the most widely used illicit substances. Epidemiological and neuroscientific evidence, though poorly integrated, have established a strong association between cannabis use and increased risk of psychosis. Chronic cannabis use, especially of new synthetic varieties, may trigger psychosis and precipitate schizophrenia in vulnerable individuals. However, the specific pathways by which cannabis affects brain function are unclear. It seems likely that a complex genetic-environmental interaction may underlie the link between cannabis exposure and psychosis onset, with multiple genetic variations and several environmental factors (i.e., trauma or maltreatment during childhood) involved. Also, the possible role of basic symptoms in cannabis users is still not fully acknowledged. Basic symptoms may possibly be a marker for the development of full schizophrenia in cannabis users and their recognition may play a role in prevention strategies. Moreover, the differential impact of different types of cannabis has been generally overlooked and little is known about possible pharmacological treatment approaches (with antipsychotics, cannabis agonists, cannabis antagonists) for cannabis users at risk of psychosis. The aim of the present review is to open this issue with a broad introduction on the clinical and pathophysiological link between cannabis abuse and psychosis onset.

The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy.

Introduction: Depression is a common disorder associated with significant disability and is a substantial burden on the individual, their relatives and friends, and on society as a whole. Sleep disturbances are key features of depressive symptomatology, with more than 80 of depressed patients complaining of poor quality sleep Methods: The range of available antidepressants is here reviewed in relation to mechanisms of action and the evidence of sleep alteration in patients with depression. Results: The available treatments are largely effective but their use is compromised by poor tolerability and low adherence to treatment. It is also clear that currently used antidepressant agents tend to disrupt sleep architecture. Agomelatine, a novel antidepressant, has been found successful in treating depressed patients. Because of its dual mechanism of action on MT1 and MT2 melatonin receptors in the SCN and its 5-HT2c antagonist properties, agomelatine has been effective in improving both quality of sleep and mood in depressed patients. Conclusions: There is clinical and epidemiological evidence that sleep disturbances in depression constitute a risk factor for poor clinical outcomes. Specifically, insomnia complaints precede the onset and recurrence of depression. For this reason antidepressants with a faster onset of action, with less interferences on sleep architecture would be expected to bring larger numbers of depressed patients to full remission.

Objective.The goal of this cross-sectional study was to evaluate the relationships between alexithymia and suicide ideation in 80 adult outpatients with a DSM-IV diagnosis of binge eating disorder (BED). Methods.Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20); suicide ideation was assessed with the Scale of Suicide Ideation (SSI); severity of BED was assessed with the Binge Eating Scale (BES); and depressive and anxiety symptoms were evaluated, respectively, with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (Ham-A). Results.Prevalence of current suicide ideation was 27.5 (n=22) in this sample and 10 subjects (12.5) had attempted suicide at some time in their lives. Subjects with alexithymia had more significant suicide ideation, a higher prevalence of current suicide ideation, and more previous suicide attempts than those without alexithymia. In a linear regression model, higher MADRS scores and higher scores on the Difficulty in Identifying FeelingsDifficulty in Describing Feelings dimensions of the TAS-20 were associated with increased suicide ideation. Discussion.Suicidal behavior is no less common in BED than in other eating disorders. Individuals with BED may show increased suicide ideation, especially in the presence of alexithymia and depressive symptoms, even if these symptoms are subclinical. The authors also discuss limitations of this study and future research needs. (Journal of Psychiatric Practice2012;18:5–11)

Dopamine is the predominant physiological inhibitory factor of prolactin release. Hyperprolactinemia is associated with potentially serious short and long-term clinical consequences. Several physiological and pathological conditions can cause elevated serum prolactin levels. Of these, in the psychiatric population, antipsychotic drugs are the most common. Because treatment of psychiatric illness often begins during adolescence and involves the long-term administration of these medications, the antipsychotic-induced hyperprolactinemia appears to be a major health concern for these patients. There are many possible management strategies of antipsychotic-induced hyperprolactinemia: estrogen/testosterone replacement, adding a dopamine agonist and introducing an alternative antipsychotic. Aripiprazole, a drug with partial agonist activity at dopamine D2 receptors, may be effective for antipsychotic-induced hyperprolactinemia. This paper reviews recent patents, mechanisms and evidences regarding the clinical action of aripiprazole on antipsychotic-induced hyperprolactinemia.

Complex I activity is reduced in cytoplasmic hybrid (cybrid) cell lines that contain mitochondrial DNA (mtDNA) from sporadic Parkinson's disease (PD) patients. This implies that mtDNA aberration occurs in sporadic PD. To assess the integrity of mtDNA in autosomal dominant PD arising from mutation of the α-synuclein gene, we transferred mitochondrial genes from PD-affected members of the Italian-American Contursi kindred to cells previously depleted of their endogenous mtDNA. Unlike cybrid cell lines expressing mtDNA from persons with sporadic or maternally inherited PD, the resultant Contursi cybrid lines did not manifest complex I deficiency, indicating that in Contursi PD mtDNA integrity is relatively preserved. Compared to control cybrids, however, Contursi cybrid lines did show some evidence of oxidative stress. For reasons that are unclear, at least a limited amount of mtDNA damage may nevertheless develop in PD patients with α-synuclein mutation.

A new member of the dystrobrevin gene family was identified using a bioinformatics approach. Sequence analysis indicates that this gene, named DTN‐B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo87 kDa and to the C‐terminus of dystrophin. The coiled‐coil domain, shown to be the site of interaction between dystrobrevins and dystrophin, is highly conserved. Immunostaining studies indicate that DTN‐B and DTN expression is absent in affected muscle fibers from DMD patients and carriers.

A new member of the dystrobrevin gene family was identified using a bioinformatics approach. Sequence analysis indicates that this gene, named DTN-B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo87 kDa and to the C-terminus of dystrophin. The coiled-coil domain, shown to be the site of interaction between dystrobrevins and dystrophin, is highly conserved. Immunostaining studies indicate that DTN-B and DTN expression is absent in affected muscle fibers from DMD patients and carriers.

To assess the presence of viral ribonucleic acid (RNA) in nerve tissues of 15 patients with hepatitis C virus (HCV) infection and peripheral neuropathy with (11) or without (4) mixed cryoglobulinemia, nested reverse transcription–polymerase chain reaction (RT‐PCR) was performed. Amplification of HCV‐RNA was successful in 7 patients with and 3 without mixed cryoglobulinemia. This study demonstrates that the nested RT‐PCR technique is a sensitive method to detect viral RNA in nerve tissue, and offers further evidence that in patients with HCV infection peripheral neuropathy can occur in the absence of mixed cryoglobulinemia. Muscle Nerve 27:102–104, 2003

Chorea-Acanthocytosis (CHAC) is an autosomal recessive disease characterized by neurodegeneration and acanthocytosis. Enhanced creatine kinase concentration is a constant feature of the condition. The mechanism underlying CHAC is unknown. However, acanthocytosis and enhanced creatine kinase suggest a protein defect that deranges the membrane-cytoskeleton interface in erythrocytes and muscle, thereby resulting in neurodegeneration. Acanthocytes have been correlated with structural and functional changes in membrane protein band 3—a ubiquitous anion transporter. Residue Gln-30 of band 3 serves as a membrane substrate for tissue transglutaminase (tTGase), which belongs to a class of intra- and extra-cellular Ca2+-dependent cross-linking enzymes found in most vertebrate tissues. In an attempt to cast light on the pathophysiology of CHAC, we used reverse-phase HPLC and immunohistochemistry to evaluate the role of tTGase in this disorder. We found increased amounts of tTGase-derived Nɛ-(-γ-glutamyl)lysine isopeptide cross-links in erythrocytes and muscle from CHAC patients. Furthermore, immunohistochemistry demonstrated abnormal accumulation of tTGase products as well as proteinaceous bodies in CHAC muscles. These findings could explain the mechanisms underlying the increased blood levels of creatine kinase and acanthocytosis, which are the most consistent features of this neurodegenerative disease.