Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients' Clinical Features.

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.

Asenapine for the treatment of bipolar disorder.

Introduction: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly used in this condition is second-generation antipsychotics (SGAs) including asenapine, one of the latest to be introduced into the clinical practice worldwide to treat manic episodes in BDI. Areas covered: The aim of this paper is to critically review the literature on the pharmacological characteristics, tolerability, and safety data of asenapine, as well as on its short- and long-term clinical trials in manic episodes as both a monotherapy and as an add-on treatment. Expert opinion: The available data indicate that asenapine is an effective antimanic agent in both adult and pediatric patients and that it might also improve depressive symptoms and recurrences in BDI patients. Its tolerability profile is good, and its most common side effects are somnolence, light extrapyramidal symptoms, dizziness, weight gain, and oral (but reversible) hypoesthesia. Taken together, the published studies indicate that asenapine might be an effective therapeutic agent in BDI with a broad spectrum of clinical activities. Further double-blind, short- and long-term studies are, however, necessary to clarify its precise role in the treatment of BD.

Is there a relationship between depression with anxious distress DSM-5 specifier and bipolarity? A multicenter cohort study on patients with unipolar, bipolar I and II disorders.

BACKGROUND: To estimate the prevalence of DSM-5 anxious distress specifier (ADS) in depressed patients with major depressive disorder (MDD) or bipolar I or II disorder (BD), and to compare socio-demographic and clinical characteristics, and response to naturalistic short-term treatment between ADS and non-ADS group. METHODS: 241 outpatients with a major depressive episode (MDE) were consecutively recruited. Outcome were remission (HDRS21 total score < 7), response (≥50% reduction of baseline HDRS21) and improvement (CGI-i score ≤ 2) after 12 weeks of treatment sustained for 4 weeks. RESULTS: ADS was more frequent in BD than in MDD (respectively, 66.9% and 51.2%, χ2 = 6.1, p = 0.013). Compared with those non-ADS, patients with ADS had more severe depressive (respectively, HDRS21 total score 20.0 ±â€¯4.4 and 18.6 ±â€¯3.9, t-test = 2.67, p = 0.008) and mania symptoms (respectively, Y-MRS total score 2.2 ±â€¯2.9 and 1.3 ±â€¯2.3, M-W-test = 2.86; p = 0.004) at intake, a higher rate of BD family history (respectively, 35.2% and 22.2%, Χ2-test 10.4, p = 0.004) and more previous hypomanic episodes (respectively, (median (range) 0 (0-20) and 0 (0-15), MW-test = 2.39 p = 0.017). In the MDD group, patients with ADS had higher scores on hyperthymic temperament and mania symptoms (Y-MRS total score (median (range) 2.2 (0-26) and 0 (0-11), respectively, M-W test 2.071, p = 0.038). ADS and no-ADS patients did not significantly differ on outcome measures. LIMITATIONS: The observational nature of the study and the absence of blinding in outcome assessment. CONCLUSIONS: ADS is the most common DSM-5 specifier for MDE, is more frequent in BD and need a personalized treatment with moderate use of antidepressants, mostly tricyclic.

Emotional Blunting, Cognitive Impairment, Bone Fractures, and Bleeding as Possible Side Effects of Long-Term Use of SSRIs.

OBJECTIVE: Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are amongst the most prescribed drugs worldwide not only for psychiatric conditions, but also for medical purposes. Converging data gathered throughout the decades following their development would indicate that SSRIs have a broader side effect profile than previously assumed. Therefore, the aim of the present paper was to to review available literature highlighting less common side effects emerging with their long-term use. METHOD: This systematic review, carried out according to PRISMA guidelines, was performed through searching electronic databases of PubMed, Google Scholar, Cochrane Library, Embase, MEDLINE, PsycINFO and Scopus. The keyword used was "SSRIs" combined with the following: "Side effects", or "Emotional blunting or flattening", or "Cognition", or "Neuroimaging", or "Bone", "or "Platelet aggregation", or "Bleeding". RESULTS: The most common side effects, besides the classical ones described in the literature are represented by decreased emotional response to both adversive and pleasurable events, some cognitive impairments, bone fractures and prolonged overall bleeding time. CONCLUSIONS: After analyzing critically the available findings, it should be noted that only the so-called "emotional blunting" is supported by converging data, while results on cognitive impairment are extremely controversial, given some evidence showing that SSRIs may improve cognition. Similarly, no agreement exists on the detrimental effects of SSRIs on bone metabolism and coagulation.Large, prospective and long-term studies are needed to clarify the possible impact of SSRIs on emotions, cognitive functions, bone fractures and coagulation, as well to detect other possible still neglected side effects.

Stalking: a neurobiological perspective.

Nowadays stalking is becoming a real social emergency, as it may often fuel severe aggressive behaviours. No exhaustive aetiological hypothesis is still available regarding this complex phenomenon. However, the detailed descriptions of some of its peculiar features allow to draw with cautions some general suggestions. Probably stalking may arise from the derangement of those neural networks subserving the so-called social brain and the pair bonding formation, in particular the processes of attachment/separation, attraction/romantic love/reward. In addition, it seems to be modulated by excessive functioning of the dopamine system coupled with decreased serotonin tone. It is believed that the investigation and deepening of its possible neurobiological substrates may be helpful in the prevention of the severe consequences of stalking.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

OBJECTIVES: The present paper aimed at reviewing literature data on the inflammatory hypothesis of mood spectrum, as well as the overlapping features with some chronic rheumatologic disorders, in particular fibromyalgia and chronic fatigue syndrome. METHODS: A literature search was carried out for English papers published in the years 2000-2014, while using the following words: mood spectrum, depression, bipolar disorders, fibromyalgia, chronic fatigue syndrome, neurotransmitters, inflammation, neuroinflammation, cytokines. RESULTS: Overlapping features were highlighted between mood spectrum, fibromyalgia and chronic fatigue syndrome suggesting common underlying mechanisms at pathophysiological level involving both central nervous and the immune systems. CONCLUSIONS: Taken together, the literature would suggest that the borders between different medical domains should be reconsidered in the light of common processes linking them.

Pharmacokinetics and pharmacodynamics of psychotropic drugs: effect of sex.

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990-2012. Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described. Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Serotonin receptors of type 6 (5-HT6): from neuroscience to clinical pharmacology.

The serotonin (5-HT) receptors of type 6 (5-HT6) are quite different from all other 5-HT receptors, as they include a short third cytoplasmatic loop and a long C-terminal tail, and one intron located in the middle of the third cytoplasmatic loop. A lot of controversies still exist regarding their binding affinity, effects of 5-HT6 ligands on brain catecholamines, behavioral syndromes regulated by them, and brain distribution. In spite of the lack of information on metabolic pattern of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic, antidepressant and anti-obese drugs. The present paper is a comprehensive review on the state of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.