Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I.

BACKGROUND: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. METHODS: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. RESULTS: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (ß = -0.293, p = 0.034) and verbal memory performance (ß = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. CONCLUSIONS: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Latanoprost-Loaded Nanotransfersomes Designed for Scalp Administration Enhance Keratinocytes Proliferation.

Latanoprost (LAT) has been shown to have a hypertrichotic effect, which makes it a promising candidate for alopecia treatments. For the first time, LAT has been encapsulated in nanotransfersomes in order to increase its efficacy. Ex vivo skin biodistribution was studied by confocal laser microscopy both in human scalp and pig skin. Results showed that nanotransfersomes increase the penetration of two different fluorochromes, with similar patterns in both species, compared with fluorochrome solutions containing no nanotransfersomes. Nanotransfersomes were stable under accelerated conditions (40 °C/75% RH) and long-term conditions (25 °C/60% RH) for up to 1 year, with no differences in vesicle size and polydispersity when LAT was loaded. Nanotransfersomes increased the LAT cell proliferation effect in HaCaT cell via MAPK signaling pathway. Collectively, our results demonstrate LAT-nanotransfersomes formulation could be a promising therapy for hair growth disorders.

Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood.

OBJECTIVE: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies. METHODS: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. RESULTS: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. CONCLUSION: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.

The Efficacy and Biopharmaceutical Properties of a Fixed-Dose Combination of Disulfiram and Benzyl Benzoate.

Scabies and hair lice are parasitic diseases that affect human skin and hair, respectively. The incidence and resistances of these infections are increasing. Tenutex® (disulfiram and benzyl benzoate emulsion) is an alternative to standard insecticides to avoid resistances. The aim of the work is to evaluate the transdermal absorption and the in vitro efficacy against scabies and hair lice after different exposition times. Dermatomed human skin was used to assess the dermal absorption using a validated High Performance Liquid Chromatography (HPLC) method. HEK001 keratinocytes were used to evaluate the cytotoxicity of benzyl benzoate. Only benzyl benzoate was able to cross the skin, but it did not show cytotoxicity at any of the tested concentrations. The product efficacy was tested on Psoroptes ovis after direct contact and after administration on sheep skin explants at different contact times. Permethrin/malathion-resistant strains of Pediculus humanis capitis adults and eggs were directly exposed to Tenutex, and the vitality and hatchability, respectively, were evaluated. The anti-scabies study demonstrated that exposure for 6 or 24 h completely eradicated the parasite. The pediculicidal activity of Tenutex exhibited superior efficacy than standard treatment on resistant lice. The positive results obtained suggest that Tenutex® is a good treatment option, especially in drug resistance situations.

Efficacy of an integrative approach for bipolar disorder: preliminary results from a randomized controlled trial.

BACKGROUND: Bipolar disorder (BD) represents one of the most therapeutically complex psychiatric disorders. The development of a feasible comprehensive psychological approach to complement pharmacotherapy to improve its clinical management is required. The main objective of the present randomized controlled trial (RCT) was to test the efficacy of a novel adjunctive treatment entitled integrative approach in patients with BD, including: psychoeducation, mindfulness training, and functional remediation. METHODS: This is a parallel two-armed, rater-blind RCT of an integrative approach plus treatment as usual (TAU), v. TAU alone. Participants were recruited at the Hospital Clinic of Barcelona and randomized to one of the two conditions. They were assessed at baseline and after finishing the intervention. The main outcome variable included changes in psychosocial functioning assessed through the Functioning Assessment Short Test (FAST). RESULTS: After finishing the treatment, the repeated-measures analyses revealed a significant group × time interaction in favor of the patients who received the integrative approach (n = 28) compared to the TAU group (n = 37) (Pillai's trace = 0.10; F(1,57) = 6.9; p = 0.01), improving the functional outcome. Significant effects were also found in two out of the six domains of the FAST, including the cognitive domain (Pillai's trace = 0.25; F(1,57) = 19.1; p < 0.001) and leisure time (Pillai's trace = 0.11; F(1,57) = 7.15; p = 0.01). Regarding the secondary outcomes, a significant group × time interaction in Hamilton Depression Rating Scale changes was detected (Pillai's trace = 0.08; F(1,62) = 5.6; p = 0.02). CONCLUSION: This preliminary study suggests that the integrative approach represents a promising cost-effective therapy to improve psychosocial functioning and residual depressive symptoms in patients suffering from BD.

Improving Functioning, Quality of Life, and Well-being in Patients With Bipolar Disorder.

People with bipolar disorder frequently experience persistent residual symptoms, problems in psychosocial functioning, cognitive impairment, and poor quality of life. In the last decade, the treatment target in clinical and research settings has focused not only on clinical remission, but also on functional recovery and, more lately, in personal recovery, taking into account patients' well-being and quality of life. Hence, the trend in psychiatry and psychology is to treat bipolar disorder in an integrative and holistic manner. This literature review offers an overview regarding psychosocial functioning in bipolar disorder. First, a brief summary is provided regarding the definition of psychosocial functioning and the tools to measure it. Then, the most reported variables influencing the functional outcome in patients with bipolar disorder are listed. Thereafter, we include a section discussing therapies with proven efficacy at enhancing functional outcomes. Other possible therapies that could be useful to prevent functional decline and improve functioning are presented in another section. Finally, in the last part of this review, different interventions directed to improve patients' well-being, quality of life, and personal recovery are briefly described.

Modifiable and non-modifiable factors associated with functional impairment during the inter-episodic periods of bipolar disorder.

The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2 = 53.89, df = 5, p < 0.001). Modifiable factors most strongly associated with functional impairment were manic predominant polarity (OR = 1.79, CI 95% 1.09-2.96, p = 0.022), residual depressive symptoms (OR = 1.30, CI 95% 1.18-1.43, p < 0.001) and illness severity (OR = 1.24, CI 95% 1.01-1.52, p = 0.037), whilst non-modifiable factor was illness duration (OR = 1.03, CI 95% 1.01-1.05, p = 0.017). Despite intrinsic and non-modifiable illness characteristics, a clinical-wise choice of treatment may help to improve control of manic relapses. Potential improvement of residual depressive symptoms may alleviate the functional burden associated with bipolar disorder.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients.

Impact of childhood trauma on cognitive profile in bipolar disorder.

OBJECTIVES: Bipolar Disorder (BD) is associated with cognitive impairment even during remission periods. Nonetheless, this impairment seems to adjust to different profiles of severity. Our aim was to examine the potential impact of childhood trauma (CT) on cognitive performance and, more specifically, on neurocognitive profile membership. METHODS: Using a data-driven strategy, 113 euthymic bipolar patients were grouped according to their cognitive performance using a hierarchical clustering technique. Patients from the three resulting clusters, the so-called "low", "average", and "high performance" groups, were then compared in terms of main sociodemographic, clinical and functioning variables, including CT measures. One-way ANOVA, a chi-square test and partial correlations were used for this purpose, as appropriate. A multinomial logistic regression model was used to determine which variables contributed to neurocognitive clustering membership. RESULTS: Patients from the three neurocognitive clusters differed in terms of sociodemographic, clinical, functioning and CT variables. Scores on the Childhood Trauma Questionnaire (CTQ), especially on the physical negligence subscale, were also associated with a poor cognitive performance. The multinomial regression model indicated that CTQ total scores and the estimated intelligence quotient (IQ) significantly contributed to differentiation among the three neurocognitive groups. CONCLUSIONS: Our results confirmed that CT significantly impacts on cognitive performance during adulthood in BD. The data obtained suggest that a history of CT could act as a liability marker for cognitive impairment. A higher estimated IQ may act as a protective factor against cognitive decline in this group of patients.

Functional Impairment in Older Adults With Bipolar Disorder.

Data describing bipolar disorder in older adults people are scarce, particularly with regard to functional status. This observational, comparative study assessed psychosocial functioning in 33 euthymic older adults with bipolar disorder compared with 30 healthy controls. In addition, we evaluated the association between clinical variables and poor functioning in the patient group. The mean age of the group was 68.70 years. Patients with bipolar disorder experienced poorer psychosocial functioning (19.15 ± 11.36) than healthy controls (5.17 ± 3.72; p = 0.0001), as assessed using the Functioning Assessment Short Test. Significant differences between the groups were found for specific domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, and interpersonal relationships (p = 0.0001, respectively). The largest variation was observed in overall functioning (Cohen's d = 0.63). The number of previous hospitalizations was strongly associated with poor overall functioning (F = 7.217, p = 0.002). Older patients with bipolar disorder had a greater functional impairment than the healthy control group. Implementation of novel rehabilitation models is critical to help patients manage their illness.

Cognitive variability in bipolar II disorder: who is cognitively impaired and who is preserved.

OBJECTIVES: Although it is well established that euthymic patients with bipolar disorder can have cognitive impairment, substantial heterogeneity exists and little is known about the extent and severity of impairment within the bipolar II disorder subtype. Therefore, the main aim of this study was to analyze cognitive variability in a sample of patients with bipolar II disorder. METHODS: The neuropsychological performance of 116 subjects, including 64 euthymic patients with bipolar II disorder and 52 healthy control subjects, was examined and compared by means of a comprehensive neurocognitive battery. Neurocognitive data were analyzed using a cluster analysis to examine whether there were specific groups based on neurocognitive patterns. Subsequently, subjects from each cluster were compared on demographic, clinical, and functional variables. RESULTS: A three-cluster solution was identified with an intact neurocognitive group (n = 29, 48.3%), an intermediate or selectively impaired group (n = 24, 40.0%), and a globally impaired group (n = 7, 11.6%). Among the three clusters, statistically significant differences were observed in premorbid intelligence quotient (p = 0.002), global functional outcome (p = 0.021), and leisure activities (p = 0.001), with patients in the globally impaired cluster showing the lowest attainments. No differences in other clinical characteristics were found among the groups. CONCLUSIONS: These results confirm that neurocognitive variability is also present among patients with bipolar II disorder. Approximately one-half of the patients with bipolar II disorder were cognitively impaired, and among them 12% were severely and globally impaired. The identification of different cognitive profiles may help to develop cognitive remediation programs specifically tailored for each cognitive profile.

Self-monitoring and psychoeducation in bipolar patients with a smart-phone application (SIMPLe) project: design, development and studies protocols.

BACKGROUND: New technologies have recently been used for monitoring signs and symptoms of mental health illnesses and particularly have been tested to improve the outcomes in bipolar disorders. Web-based psychoeducational programs for bipolar disorders have also been implemented, yet to our knowledge, none of them have integrated both approaches in one single intervention. The aim of this project is to develop and validate a smartphone application to monitor symptoms and signs and empower the self-management of bipolar disorder, offering customized embedded psychoeducation contents, in order to identify early symptoms and prevent relapses and hospitalizations. METHODS/DESIGN: The project will be carried out in three complementary phases, which will include a feasibility study (first phase), a qualitative study (second phase) and a randomized controlled trial (third phase) comparing the smartphone application (SIMPLe) on top of treatment as usual with treatment as usual alone. During the first phase, feasibility and satisfaction will be assessed with the application usage log data and with an electronic survey. Focus groups will be conducted and technical improvements will be incorporated at the second phase. Finally, at the third phase, survival analysis with multivariate data analysis will be performed and relationships between socio-demographic, clinical variables and assessments scores with relapses in each group will be explored. DISCUSSION: This project could result in a highly available, user-friendly and not costly monitoring and psychoeducational intervention that could improve the outcome of people suffering from bipolar disorders in a practical and secure way. TRIAL REGISTRATION: Clinical Trials.gov: NCT02258711 (October 2014).

Making sense of DSM-5 mania with depressive features.

OBJECTIVE: The assessment of the depressive component during mania has become critical for the accurate diagnosis of mixed states, which were defined very narrowly in the past classification systems before Diagnostic and Statistical Manual of Mental Disorders (5th ed.). The aim of this study was to compare socio-demographic, clinical and therapeutic characteristics, as well as clinical and functional outcomes, between manic patients with and without mixed features to validate the relevance of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) mixed specifier. METHODS: This is a subanalysis of a multicentre naturalistic study MANía Aguda y COnsumo de Recursos (acute mania and health resource consumption [MANACOR]) on the burden of mania in bipolar patients from four hospitals in Catalonia (Spain). The sample consisted of 169 adult patients presenting a manic episode and systematically assessed during a 6-month period. RESULTS: A total of 27% (n = 46/169) of manic patients showed mixed features. Total number of episodes (p = 0.027), particularly depressive and mixed, was greater in manic patients with mixed features, as well as depressive onset (p = 0.018), suicide ideation (p = 0.036), rapid cycling (p = 0.035) and personality disorders (p = 0.071). In contrast, a higher percentage of pure manic subjects were inpatients (p = 0.035), started the illness with mania (p = 0.018) and showed family history of bipolar disorder (p = 0.037), congruent psychotic symptoms (p = 0.001) and cannabis use (p = 0.006). At baseline, pure manic patients received more risperidone (p = 0.028), while mixed patients received more valproate (p = 0.049) and antidepressants (p = 0.005). No differences were found in syndromic recovery at the end of the study. However, depressive change was higher in the mixed group (p = 0.010), while manic change was higher in the pure manic group (p = 0.029). At the end of follow-up, the group with mixed features showed a significant trend towards higher psychosocial dysfunction. CONCLUSION: A total of 27% of manic patients showed mixed features. Groups differed regarding clinical characteristics, course of illness, psychosocial functioning, prescribed treatment and symptom progress. Depressive symptoms in mania should be routinely assessed and considered to guide treatment.

A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

Polarity index of psychological interventions in maintenance treatment of bipolar disorder.

BACKGROUND: Although several adjunctive psychological interventions are effective in the maintenance of bipolar disorders (BD), no attempt has been made to classify them according to their ability to prevent manic versus depressive episodes. Our study aims to rank the adjunctive psychotherapies for the prophylaxis of BD by means of their polarity index (PI). METHODS: Randomized controlled trials comparing the efficacy of a psychological intervention with a comparator in BD maintenance treatment in patients aged over 18 were systematically reviewed. Exclusion criteria were a small sample size, a study sample not exclusively composed of bipolar patients and the absence of a control group. PI is a novel metric indicating the relative antimanic versus antidepressive preventive efficacy of treatments. PI was retrieved by calculating the ratio of the number needed to treat (NNT) for prevention of depression and the NNT for prevention of mania. PI >1.0 indicates a relatively higher antimanic prophylactic efficacy and PI <1.0 a greater antidepressive efficacy. RESULTS: A total of 9 studies were included. PI was 0.33, 0.63 and 0.89 for cognitive-behavioral therapy, 0.42 for family-focused therapy, 0.73 and 0.78 for psychoeducation, 1 for enhanced relapse prevention, 1.78 for caregiver group psychoeducation and 3.36 for brief technique-driven interventions. With regard to the PI for 1 cognitive-behavioral study, enhanced relapse prevention and brief technique-driven interventions may not be reliable since those trials were negative. CONCLUSIONS: The PI provides a measure of how much depression-preventive or (hypo) mania-preventive an intervention is and may guide the choice of adjunctive psychotherapy in the context of individualized long-term treatment of BD.

Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel.

Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis.

EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

Aging in bipolar disorder: Cognitive performance and clinical factors based on an adulthood-lifespan perspective.

BACKGROUND: The evolution of cognitive performance throughout the lifespan in bipolar disorder (BD) is understudied. This cross-sectional study aims to describe the cognitive performance across age groups. METHODS: A sample of 654 participants was recruited for this study (BD = 432 and healthy controls -HC- =222). Three subgroups, divided according to age range (18 to 35, 36 to 49, and ≥50 years old) were analyzed after administering a comprehensive neuropsychological battery including six cognitive domains. Demographic, clinical, and psychosocial functioning data were also analyzed. Generalized linear models (GLM) with age, diagnostic group, and age × group as main effects were carried out to examine their potential association on cognitive domains. Subsequently, a GLM in the BD sample was conducted to analyze interactions of several clinical variables by age on each cognitive domain. RESULTS: Main effects of diagnostic group and age were found in all cognitive domains. Significant group × age effect interaction was found for attention domain (p = 0.02) demonstrating a worse cognitive evolution across age in BD, driven by older age, but not in HC. Significant interaction effects of higher number of manic episodes and older age were also found in attention and verbal memory. Older age was also associated with a longer duration of illness, higher number of episodes, more somatic comorbidities, and poorer psychosocial functioning. CONCLUSIONS: These results suggest that older age was associated with a selective cognitive decline in BD in the attentional domain. These findings highlight the importance of developing interventions targeting cognitive dysfunction throughout the BD adulthood lifespan.

Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections.

Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections.

Shaped before birth: Obstetric complications identify a more severe clinical phenotype among patients presenting a first affective or non-affective episode of psychosis.

Obstetric complications (OCs) may contribute to the heterogeneity that characterizes psychiatric illness, particularly the phenotypic presentation of first episode psychoses (FEP). Our aim was to examine the relationship between OCs and socio-demographic, clinical, functioning and neuropsychological characteristics in affective and non-affective FEP. We performed a cross-sectional,study where we recruited participants with FEP between 2011 and 2021, and retrospectively assessed OCs using the Lewis-Murray scale. OCs were used as a dichotomous variable and further stratified into three subtypes: complications of pregnancy, abnormal fetal growth and development, and difficulties in delivery. We performed a logistic stepwise forward regression analysis to examine variables associated with the presence of OCs. Of the 104 participants (67 affective FEP and 37 non-affective FEP), 31.7% (n = 33) had experienced OCs. Subjects with OCs showed a more gradual emergence of prodromal symptoms as well as higher negative and total Positive and Negative Syndrome Scale (PANSS) scores. In the multivariate analysis, the presence of OCs was independently associated with a younger age at first episode of any type (OR = 0.904, p = 0.003) and slower emergence of prodromal symptoms (OR = 0.274, p = 0.011). When considering specific types of OCs, those related with fetal growth were associated with worse neuropsychological performance, while OCs at delivery were related to earlier onset of illness and more severe symptoms. In conclusion, OCs signaled a specific FEP phenotype characterized by earlier and more protracted onset of illness as well as more burdensome symptoms, independently of FEP type (i.e., affective vs non-affective). These results indicate a potential target of early intervention in FEP.