Exploitation of grape marc as functional substrate for lactic acid bacteria and bifidobacteria growth and enhanced antioxidant activity.

This study aimed at using grape marc for the growth of lactic acid bacteria and bifidobacteria with the perspective of producing a functional ingredient having antioxidant activity. Lactobacillus plantarum 12A and PU1, Lactobacillus paracasei 14A, and Bifidobacterium breve 15A showed the ability to grow on grape marc (GM) based media. The highest bacterial cell density (>9.0 CFU/g) was found in GM added of 1% of glucose (GMG). Compared to un-inoculated and incubated control fermented GMG showed a decrease of carbohydrates and citric acid together with an increase of lactic acid. The content of several free amino acids and phenol compounds differed between samples. Based on the survival under simulated gastro-intestinal conditions, GMG was a suitable carrier of lactic acid bacteria and bifidobacteria strains. Compared to the control, cell-free supernatant (CFS) of fermented GMG exhibited a marked antioxidant activity in vitro. The increased antioxidant activity was confirmed using Caco-2 cell line after inducing oxidative stress, and determining cell viability and radical scavenging activity through MTT and DCFH-DA assays, respectively. Supporting these founding, the SOD-2 gene expression of Caco-2 cells also showed a lowest pro-oxidant effect induced by the four CFS of GMG fermented by lactic acid bacteria and bifidobacteria.

Alexithymia, Suicide Ideation, C-Reactive Protein, and Serum Lipid Levels Among Outpatients with Generalized Anxiety Disorder.

The aim of the present study was to investigate the relationships between alexithymia, suicide ideation, C-Reactive Protein (CRP), and serum lipid levels in adult outpatients with a DSM-IV diagnosis of Generalized Anxiety Disorder (GAD). Seventy consecutive patients with GAD were recruited and evaluated. Measures were the Hamilton Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), and the Montgomery Åsberg Depression Rating Scale (MADRS). All patients were assessed for: CRP, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceridaemia (TG), and very-low-density lipoprotein cholesterol (VLDL-C). TC/HDL-C and LDL-C/HDL-C ratios were also evaluated. Alexithymic patients showed higher scores on almost all rating scales and altered serum CRP and lipid levels vs. non-alexithymics. In the hierarchical regression model, the presence of higher MADRS scores together with higher scores at the Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher rates of suicide ideation. Although alexithymic subjects with GAD may show a CRP and cholesterol dysregulation, this latter seems independent on increased suicide ideation, rather to Difficulty in Identifying Feelings, and subthreshold depressive symptoms. Study limitations and future research implications are discussed.

Kisspeptin system in pejerrey fish (Odontesthes bonariensis). Characterization and gene expression pattern during early developmental stages.

In vertebrates, kisspeptins and their receptors are known to be related to puberty onset and gonadal maturation, however, there are few studies concerning their role in early development. Here, we characterize the kisspeptin system in the pejerrey, Odontesthes bonariensis, a fish with strong temperature-dependent sex determination. We reconstructed the phylogenetic history of the two ligands (kiss1 and kiss 2) and two receptors (kissr2 and kissr3) in pejerrey in the context of recent classifications of bony fishes, determined their tissue distribution and documented the early expression pattern of these ligands and receptors. Phylogenetic analysis of these gene families clearly resolved the percomorph clade and grouped pejerrey with Beloniformes. Paralogous sets of genes putatively arising from the teleost-specific genome duplication event (3R) were not detected. Kisspeptins and their receptors showed a wide tissue distribution in adult pejerrey, including tissues not related to reproduction. In larvae reared at 24°C, the four kisspeptin elements were expressed in the head from week 1 to week 8 of life, with no differences in transcript levels. Larvae kept at a female-producing temperature (17°C) did not show statistically significant differences in the transcript levels of all analyzed genes during the sex determination/differentiation period; however, in those larvae raised at male producing temperature (29°C), kiss2 levels were increased at week 4 after hatching. These results showed that all members of the kisspeptin system are expressed at this early period, and the increase of kiss2 transcripts at week 4 could be interpreted as it would be related to the differentiation of the brain-pituitary axis in male development.

Microbiota and metabolome of un-started and started Greek-type fermentation of Bella di Cerignola table olives.

This study aimed to utilize an "omics" approach to evaluate the ability of selected lactobacilli and yeasts to improve the fermentation process of Bella di Cerignola table olives. Four types of fermentations were performed at the pilot-plant scale: un-started fermented olives used as a control (Ctrl); olives started with a commercial Lactobacillus plantarum strain (S); commercial L. plantarum strain and autochthonous yeast Wickeramomyces anomalus DiSSPA73 (SY); and L. plantarum, W. anomalus DiSSPA73, autochthonous L. plantarum DiSSPA1A7 and Lactobacillus pentosus DiSSPA7 (SYL). Compared to Ctrl, S, SY, SYL showed a higher acidification (P < 0.05) of the brine, which reached a pH value of 4.49 after one day of fermentation. The microbiota of unfermented olives and brine after one day of fermentation was primarily composed of Enterobacteria that belonged to Hafnia alvei and Methylobacterium. However, L. plantarum and L. pentosus dominated the total and metabolically active microbiota of the Ctrl brines and olives at the end of the fermentation. The use of lactobacilli and W. anomalus DiSSPA73 as a starter culture markedly affected the microbiota of the brines after one day of fermentation. The number of species (OTU) and the results of an alpha diversity analysis indicated that the microbial diversity of the brines was markedly simplified by the S, SY and, in particular, SYL fermentations. According to the lowest biodiversity, S, SY and SYL samples showed the lowest abundance of Proteobacteria, including Enterobacteriacea, Lactococcus lactis, Propionibacterium acidipropionici and Clostridium. The lactobacilli and W. anomalus DiSSPA73 used in this study markedly affected the amounts of free amino acids, phenolic and volatile organic compounds. Both a texture profile analysis and a sensory evaluation showed the highest appreciation for all of the started table olives. As shown through microbiological, biochemical, and sensory analyses, an accelerated fermentation of Bella di Cerignola table olives was achieved using the selected lactobacilli and yeast strains.

Cotard's Syndrome after breast surgery successfully treated with aripiprazole augmentation of escitalopram: a case report.

In 1880 the French neurologist Jules Cotard described a condition characterized by delusion of negation (nihilistic delusion) in a melancholia context. Recently, there has been a resurgence of interest in Cotard's syndrome (CS), but the nosographical figure of CS remains unclear. It isn't determined if it pertains to the delusional themes area or if it is related to the sense of immanent ruin in some depressive episodes. For these reasons CS has recently been supposed to be an intermediate form. Furthermore, since even less is known about secondary CS in subjects who had never suffered of psychiatric disorders, in the present case we report the development of a secondary CS in a female patient who underwent a lumpectomy for the removal of a benign fibroadenoma. The patient responded well to aripiprazole augmentation of escitalopram and totally remitted.

Comparative proteomic analysis of biofilm and planktonic cells of Lactobacillus plantarum DB200.

This study investigated the relative abundance of extracellular and cell wall associated proteins (exoproteome), cytoplasmic proteins (proteome), and related phenotypic traits of Lactobacillus plantarum grown under planktonic and biofilm conditions. Lactobacillus plantarum DB200 was preliminarily selected due to its ability to form biofilms and to adhere to Caco2 cells. As shown by fluorescence microscope analysis, biofilm cells became longer and autoaggregated at higher levels than planktonic cells. The molar ratio between glucose consumed and lactate synthesised was markedly decreased under biofilm compared to planktonic conditions. DIGE analysis showed a differential exoproteome (115 protein spots) and proteome (44) between planktonic and biofilm L. plantarum DB200 cells. Proteins up- or downregulated by at least twofold (p < 0.05) were found to belong mainly to the following functional categories: cell wall and catabolic process, cell cycle and adhesion, transport, glycolysis and carbohydrate metabolism, exopolysaccharide metabolism, amino acid and protein metabolisms, fatty acid and lipid biosynthesis, purine and nucleotide metabolism, stress response, oxidation/reduction process, and energy metabolism. Many of the above proteins showed moonlighting behavior. In accordance with the high expression levels of stress proteins (e.g., DnaK, GroEL, ClpP, GroES, and catalase), biofilm cells demonstrated enhanced survival under conditions of environmental stress.

Multi-locus fossil-calibrated phylogeny of Atheriniformes (Teleostei, Ovalentaria).

Phylogenetic relationships among families within the order Atheriniformes have been difficult to resolve on the basis of morphological evidence. Molecular studies so far have been fragmentary and based on a small number taxa and loci. In this study, we provide a new phylogenetic hypothesis based on sequence data collected for eight molecular markers for a representative sample of 103 atheriniform species, covering 2/3 of the genera in this order. The phylogeny is calibrated with six carefully chosen fossil taxa to provide an explicit timeframe for the diversification of this group. Our results support the subdivision of Atheriniformes into two suborders (Atherinopsoidei and Atherinoidei), the nesting of Notocheirinae within Atherinopsidae, and the monophyly of tribe Menidiini, among others. We propose taxonomic changes for Atherinopsoidei, but a few weakly supported nodes in our phylogeny suggests that further study is necessary to support a revised taxonomy of Atherinoidei. The time-calibrated phylogeny was used to infer ancestral habitat reconstructions to explain the current distribution of marine and freshwater taxa. Based on these results, the current distribution of Atheriniformes is likely due to widespread marine dispersal along the margins of continents, infrequent trans-oceanic dispersal, and repeated invasion of freshwater habitats. This conclusion is supported by post-Gondwanan divergence times among families within the order, and a high probability of a marine ancestral habitat.

Neural correlates of negative emotion processing in bipolar disorder.

INTRODUCTION: Bipolar disorder type I (BD-I) is characterized by a severe impairment in emotional processing during both acute and euthymic phases of the illness. The aim of the present study was to investigate negative emotion processing in both euthymic patients and non-affected first-degree relatives, looking for state and trait markers of BD-I. METHODS: 22 healthy relatives of BD-I patients (mean age 31.5±7.3 years; 15 females), 23 euthymic BD-I patients (mean age 35.2±7.9 years; 14 females), and 24 matched controls (mean age 32.5±6.2 years; 16 females) performed an IAPS-based emotional task during 1.5T fMRI. They were required to identify vegetable items (targets) inside neutral or negative pictures. RESULTS: Euthymic BD-I patients showed a significant reduced accuracy in target detection during both neutral and negative images presentation, whereas first-degree relatives performed similarly to normal comparisons. We found a reduced activation of Left precuneus during negative images condition in the patients only. By contrast, both patients and relatives hyperactivated the Left insula and hypoactivated the Right supramarginal gyrus with respect to controls. Moreover, relatives showed an increased activation of Right lingual gyrus and lower activation of pre-supplementary motor area and Right superior frontal gyrus. CONCLUSIONS: During a negative emotion task, euthymic BD-I patients and non-affected first-degree relatives shared an abnormal activation of a limbic area (Left insula) coupled with a reduced activation of a parietal region (Right supramarginal gyrus), thus suggesting a trait-like anomalous processing of affective contents. On the other hand, functional abnormalities found only in unaffected relatives and not in patients and controls may correspond to resilience factors.

Alexithymia, responsibility attitudes and suicide ideation among outpatients with obsessive-compulsive disorder: an exploratory study.

AIMS: Obsessive-compulsive disorder (OCD) is psychiatric disorder with a significant suicide risk, and the presence of alexithymia may increase this risk. As several studies attribute an important role, in OCD, to responsibility, the aims of this study were to evaluate possible clinical differences between patients positive or not for alexithymia concerning disorder severity, responsibility attitudes and suicide ideation and investigate which variables were associated with increased suicide ideation. METHODS: 104 adult outpatients with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale (TAS-20), attitude about responsibility was tested with Responsibility Attitude Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI) and depressive symptoms were evaluated with Montgomery Åsberg Depression Rating Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of insight. RESULTS: Patients positive for alexithymia showed higher responsibility attitudes and more severe suicide ideation. In a blockwise regression model, the presence of lower insight, higher RAS scores and difficulty in identifying feelings dimension of TAS-20 were associated with higher SSI scores. CONCLUSIONS: OCD patients with alexithymia may show higher disorder severity, lower insight and inflated responsibility, all related to suicide ideation, independently from depressive symptoms. Implications were discussed and study limitations considered and reported.

Agomelatine beyond borders: current evidences of its efficacy in disorders other than major depression.

Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression.

Use of sourdough fermentation and mixture of wheat, chickpea, lentil and bean flours for enhancing the nutritional, texture and sensory characteristics of white bread.

This study aimed at investigating the addition of legume (chickpea, lentil and bean) flours to wheat flour bread. Type I sourdough containing legumes or wheat-legume flours were prepared and propagated (back slopped) in laboratory, according to traditional protocols that are routinely used for making typical Italian breads. Based on kinetic of acidification and culture-dependent data, the wheat-legume sourdough was further characterized and selected for bread making. As determined by RAPD-PCR and partial sequencing of 16S rDNA gene analyses, lactic acid bacteria in wheat-legume sourdough included Lactobacillus plantarum, Lactobacillus sanfranciscensis, Leuconostoc mesenteroides, Lactobacillus fermentum, Weissella cibaria, Lactobacillus pentosus, Lactobacillus coryneformis, Lactobacillus rossiae, Lactobacillus brevis, Lactobacillus parabuchneri and Lactobacillus paraplantarum. Two breads containing 15% (w/w) of legume (chickpea, lentil and bean) flours were produced using selected wheat-legume sourdough (WLSB) and traditional wheat sourdough (WSB). Compared to wheat yeasted bread (WYB), the level of total free amino acids (FAA) was higher in WSB and WLSB. Phytase and antioxidant activities were the highest in WLSB. Compared to bread WYB, the addition of legume flours decreased the in vitro protein digestibility (IVPD) (WYB versus WSB). However, the dough fermentation with WSLB favored an increase of IVPD. According to the levels of carbohydrates, dietary fibers and resistant starch, WSB and WLSB showed lower values of hydrolysis index (HI) compared to WYB. As showed by texture and image analyses and sensory evaluation of breads, a good acceptability was found for WSB and, especially, WLSB breads.

Fermentation and proteome profiles of Lactobacillus plantarum strains during growth under food-like conditions.

This study aimed at investigating the proteomic adaptation of Lactobacillus plantarum strains. Cultivation of L. plantarum strains under food-like conditions (wheat flour hydrolyzed, whey milk, tomato juice) affected some metabolic traits (e.g., consumption of carbohydrates and synthesis of organic acids) compared to de Man, Rogosa and Sharpe (MRS) broth. The analysis of the fermentation profile showed that the highest number of carbon sources metabolized by L. plantarum strains was found using cells cultivated in media containing low concentration of glucose or no glucose at all. The proteomic maps of the strains were comparatively determined after growth on MRS broth and under food-like conditions. The amount of proteins depended on strain and, especially, on culture conditions. Proteins showing decreased or increased amounts under food-like conditions were identified using MALDI-TOF-MS/MS or LC-nano-ESI-MS/MS. Changes of the proteome concerned proteins that are involved in carbohydrate transport and metabolism, energy metabolism, Sec-dependent secretion system, stress response, nucleotide metabolism, regulation of nitrogen metabolism, and protein biosynthesis. A catabolic repression by glucose on carbohydrate transport and metabolism was also found. The characterization of the proteomes in response to changing environmental conditions could be useful to get L. plantarum strains adapted for specific applications. BIOLOGICAL SIGNIFICANCE: Microbial cell performance during food biotechnological processes has become one of the greatest concerns all over the world. L. plantarum is a lactic acid bacterium with a large industrial application for fermented foods or functional foods (e.g., probiotics). The present study compared the fermentation and proteomic profiling of L. plantarum strains during growth under food-like conditions and under optimal laboratory conditions (MRS broth). This study provides specific mechanisms of proteomic adaptation involved in the microbial performances (carbohydrates utilization, energy metabolism, stress resistance, etc.) affecting the main biotechnological tracts of L. plantarum strains. The finding of this study provides evidences that may be exploited to get strains adapted for specific applications in food biotechnology.

Osmotic induction marking with Alizarin Red S on juveniles of pejerrey, Odontesthes bonariensis (Atherinopsidae)

Juveniles of pejerrey, Odontesthes bonariensis, were exposed to 0.1% Alizarin Red S (ARS) alone or with a previous immersion in 2.2% saline solution (Osmotic Induction, OI) to enhance the ARS marking method. Fish were marked in the field and immediately released in 1 m3 cages in "La Salada de Monasterio" lagoon, Chascomús, Buenos Aires , Argentina. After 73 days, clear marks were observed in the otoliths, caudal fin rays and scales with both treatments, being the intensity of the signal in the scales of OI+ARS treated fish higher. On the other hand, no marks were observed in the control group on the same structures. Approximately one year post-treatment (385 days), only marks in caudal fin rays were found clearly in OI+ARS treated fish. After this period, no significant differences in total length or weight between marked or control fish were observed and the mortality ranged between 30-40 % in all cages. These results provide strong evidence for the potential applicability of this cost-effective marking technique in differentiation of wild and hatchery-produced pejerrey. The success in the caudal fin rays marking is also important because it is easy to do and does not require the sacrifice of fish.

Juvenis de pejerrey, Odontesthes bonariensis, foram expostos a Vermelho de Alizarina S (ARS) 0,1% de duas formas, sozinho ou com uma imersão anterior em 2,2% de solução salina (Indução osmótica, IO) para melhorar o método de marcação ARS. Os procedimentos foram realizados no campo e os peixes foram liberados em gaiolas (tanques-rede) de 1 m3 na lagoa "La Salada de Monasterio", Chascomús, Buenos Aires, Argentina. Após 73 dias, marcas claras foram observadas nos otólitos, raios da nadadeira caudal e escamas em ambos os tratamentos, sendo que a intensidade do sinal nas escalas de IO + ARS de peixe tratado foi superior. Por outro lado, não foram observados marcas no grupo controle sobre as mesmas estruturas. Aproximadamente um ano pós-tratamento (385 dias), apenas marcas nos raios da nadadeira caudal foram encontrados claramente nos peixes tratados com IO+ARS. Entre os peixes observados, após este período, não houve diferenças significativas no comprimento total ou peso entre o grupo controle e marcados, ademais, a mortalidade variou entre 30-40% em todas as gaiolas. Estes resultados fornecem fortes evidências e um grande potencial para aplicação desta técnica rentável de marcação que diferencia o pejerrey selvagem e o produzido em cativeiro. O sucesso na marcação dos raios da nadadeira caudal também é de grande importância, pois sua verificação é fácil e não requer o sacrifício de peixes.

Effects of the peptide pheromone plantaricin A and cocultivation with Lactobacillus sanfranciscensis DPPMA174 on the exoproteome and the adhesion capacity of Lactobacillus plantarum DC400.

This study aimed at investigating the extracellular and cell wall-associated proteins (exoproteome) of Lactobacillus plantarum DC400 when cultivated on modified chemically defined medium (CDM) supplemented with the chemically synthesized pheromone plantaricin A (PlnA) or cocultured with L. plantarum DPPMA20 or Lactobacillus sanfranciscensis DPPMA174. Compared to monoculture, two-dimensional gel electrophoresis (2-DE) analysis showed that the exoproteome of L. plantarum DC400 was affected by PlnA and cocultivation with strains DPPMA20 and, especially, DPPMA174. The highest similarity of the 2-DE maps was found between DC400 cells cultivated in monoculture and in coculture with strain DPPMA20. Almost all extracellular proteins (22 spots) and cell wall-associated proteins (40 spots) which showed decreased or increased levels of synthesis during growth in CDM supplemented with PlnA and/or in coculture with strain DPPMA20 or DPPMA174 were identified. On the basis of the sequences in the Kyoto Encyclopedia of Genes and Genomes database, changes to the exoproteome concerned proteins involved in quorum sensing (QS), the transport system, stress response, carbohydrate metabolism and glycolysis, oxidation/reduction processes, the proteolytic system, amino acid metabolism, cell wall and catabolic processes, and cell shape, growth, and division. Cultivation with PlnA and cocultivation with strains DPPMA20 and, especially, DPMMA174 markedly increased the capacity of L. plantarum DC400 to form biofilms, to adhere to human Caco-2 cells, and to prevent the adhesion of potential intestinal pathogens. These phenotypic traits were in part related to oversynthesized moonlighting proteins (e.g., DnaK and GroEL, pyruvate kinase, enolase, and glyceraldehyde-3-phosphate dehydrogenase) in response to QS mechanisms and interaction with L. plantarum DPPMA20 and, especially, L. sanfranciscensis DPPMA174.

Alexithymia, suicide risk and serum lipid levels among adult outpatients with panic disorder.

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs.

Safety and efficacy of combined clozapine-azathioprine treatment in a case of resistant schizophrenia associated with Behçet's disease: a 2-year follow-up.

Behçet's disease (BD) is a recurrent inflammatory disorder involving multisystems of the body. Neuropsychiatric symptoms, like psychosis and depression, often occur in BD, but the safety and efficacy of combined clozapine-azathioprine treatment have never been assessed. We here report on a 37-year-old man with BD and treatment-resistant schizophrenia who obtained an improvement following the introduction of clozapine in addition to azathioprine, without developing agranulocytosis or other severe adverse side effects during a 2-year follow-up.

Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study.

OBJECTIVE: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD-I) and also in non-affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD-I patients and non-affected relatives during a sustained attention task. METHODS: Twenty-four euthymic BD-I patients, 22 non-affected first-degree relatives of BD-I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event-related fMRI scanning. RESULTS: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between-group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule - limited to the higher attention load - and an augmented deactivation of the posterior cingulate/retrosplenial cortex. CONCLUSIONS: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD-I patients and non-affected first-degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD-I.

Update on the adverse effects of clozapine: focus on myocarditis.

Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. In accordance to several studies, it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine appears to be particularly beneficial in patients with schizophrenia who are suicidal and in those with comorbid substance use disorder. However, despite its efficacy, the general use of clozapine in clinical practice is somewhat limited because of the risk of several serious adverse effects such as agranulocytosis and thromboembolism. Clozapine may be associated with fatal myocarditis and cardiomyopathy in physically healthy young adults. Consequently, the FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. In the present paper the literature on clozapine-related myocardis will be reviewed and practical advice will be given concerning the diagnosis and management of such potentially fatal adverse effect.