Oxidative stress (OS) has been demonstrated to be involved in the pathogenesis of the two major types of dementia: Alzheimer's disease (AD) and vascular dementia (VaD). Evidence of OS and OS-related damage in AD is largely reported in the literature. Moreover, OS is not only linked to VaD, but also to all its risk factors. Several researches have been conducted in order to investigate whether antioxidant therapy exerts a role in the prevention and treatment of AD and VaD. Another research field is that pertaining to the heat shock proteins (Hsps), that has provided promising findings. However, the role of OS antioxidant defence system and more generally stress responses is very complex. Hence, research on this topic should be improved in order to reach further knowledge and discover new therapeutic strategies to face a disorder with such a high burden which is dementia.

BackgroundAs lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.MethodsWe carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.ResultsOf 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.ConclusionsThe present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.Trial registrationClinicalTrials.gov identifier: NCT00927550

Alexithymia more than depression influences glycaemic control. When evaluating a diabetic patient, a rapid screening for psychopathological alterations would guarantee a more accurate management. The treatment of any associated psychiatric disorders would improve the patients' quality of life.

Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative disorders, and major depression (MD). The latter is a very frequent psychiatric illness characterized by accelerated aging, neurodegeneration, high comorbidity with age-related disorders, and premature mortality; all of these conditions find an explanation in an altered redox homeostasis. If aging, neurodegeneration, and major depression share a common biological base in their pathophysiology, common therapeutic tools could be investigated for the prevention and treatment of these disorders. As an example, antidepressants have been demonstrated to present neuroprotective and anti-inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants that stimulate the antioxidant defense systems and interact with the monoaminergic system show an antidepressant-like activity. Further research on this topic could lead, in the near future, to the expansion of the therapeutic possibilities for the treatment of NOS-related disorders.

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Neuroglia is an umbrella term indicating different cellular types that play a pivotal role in the brain, being involved in its development and functional homeostasis. Glial cells are becoming the focus of recent researches pertaining the pathogenesis of neurodegenerative disorders, Alzheimer’s Disease (AD) in particular. In fact, activated microglia is the main determinant of neuroinflammation, contributing to neurodegeneration. In addition, the oxidative insult occurring during pathological brain aging can activate glial cells that, in turn, can favor the production of free radicals. Moreover, the recent Glycogen Synthase Kinase 3 (GSK-3) hypothesis of AD suggests that GSK3, involved in the regulation of glial cells functioning, could exert a role in amyloid deposition and tau hyper-phosphorylation. In this review, we briefly describe the main physiological functions of the glial cells and discuss the link between neuroglia and the most studied molecular bases of AD. In addition, we dedicate a section to the glial changes occurring in AD, with particular attention to their role in terms of neurodegeneration. In the light of the literature data, neuroglia could play a fundamental role in AD pathogenesis and progression. Further studies are needed to shed light on this topic.

To review the literature related to recent temperamental and biological findings on borderline personality disorder (BPD) and major depression, the close link between the two disorders, and the latest therapeutical findings on BPD, focusing on the conditions of co-morbidity between depression and BPD. The National Institutes of Health's PubMed database was used to identify indexed studies on BPD, depression and the co-morbidity between the two. Only studies published between 2000 and 2011 were assessed. Similar temperamental features have been demonstrated in BPD and depression. The strong link between the two disorders seems to be widely recognized by scientific community. Psychotherapy and new antipsychotics are the topics of current major interest of research. The therapeutic targets in the case of co-morbidity are BPD features associated with depressive symptoms, thus influencing prognosis. A global assessment is, in fact, fundamental for a successful therapy for the treatment of the several aspects of a complex psychopathological phenomenon.

Psoriasis is an inflammatory disease frequently associated with psychiatric disturbances and sleep disorders. The aim of the study was to assess the prevalence of depression, interaction anxiety, audience anxiety, and sleep quality in psoriatic patients. One hundred and two psoriatic patients were enrolled and underwent the following questionnaires: Zung Self-Rating Depression Scale (SDS), Interaction Anxiousness Scale (IAS), Audience Anxiousness Scale (AAS), Pittsburgh Sleep Quality Index (PSQI). The severity of skin lesions was assessed by Psoriasis Area Severity Index (PASI). The presence of a link between clinical variables and with demographic data has been investigated. Psoriasis was linked to depression, interaction and audience anxiety, as well as to poor sleep quality; 37.5% of patients were depressed, 46.1% scored above 37 at the IAS, 47.1% scored above 33 at the AAS. Thirty-nine subjects (38.2%) presented a PSQI ≥ 5. An association between interaction anxiety and lower limbs psoriasis-related erythema as well as between PSQI and head psoriasis-related erythema was found, particularly among male patients. Hence, psoriatic patients should be assessed from a holistic point of view, in order to identify associated disorders that could benefit from targeted treatments.