[Analysis of the interruptions generated by the use of smartphones among Primary Care Health professionals]. / Análisis de las interrupciones generadas por el uso de los smartphones entre los profesionales sanitarios de Atención Primaria.

OBJECTIVE: To analyze the particular use of smartphones among Primary Care Health professionals during the care act and its consequences. DESIGN: Multicenter, cross-sectional study in a primary care setting, carried out in 3phases: survey of professionals, checklist of professionals and survey of patients. PARTICIPANTS: Primary Care Health professionals from the Territorial Primary Care Management of Barcelona (online survey) and health professionals (checklist) and patients (patient survey) from 2primary care teams in Barcelona city. MAIN MEASUREMENTS: Bivariate descriptive analysis of the variables from the different surveys. Use of the mobile phone in the consultation, time, reason, type of use and perception of appropriateness. Characteristics of interruptions. RESULTS: In relation to patients, 31% consider that the health professional should only consult the mobile phone if it is to resolve some aspect of their reason for consultation and 10% consider it a lack of respect. Eighteen percent of patients describe interruptions, the majority lasting between 10 and 30s and considering them mostly avoidable. In relation to professionals, the majority (96%) claim to have their mobile phone in the consultation and on mute (77%), with only 2% recognizing its use in the presence of the patient, which is in line with what the patients describe. Furthermore, 80% of professionals say they ask permission to use it, contrasting with what patients report (50%). Eighty-five percent of professionals consider its use appropriate. CONCLUSIONS: The use of mobile phones is perceived by patients as an interruption that can affect the care act, generating dissatisfaction, which must be taken into account by health professionals. Healthcare organizations should establish recommendations regarding the use of mobile phones in consultations.

Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome.

Extracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disorders remain mostly unknown. Here, by using next-generation discovery-driven proteomics, we investigate the potential role(s) of brain EVs (bEVs) in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: the prefrontal cortex (PFC), hippocampus (HC), and caudate (CAU). The results obtained indicate that bEVs from SZ-affected brains contain region-specific proteins that are associated with abnormal GABAergic and glutamatergic transmission. Similarly, these vesicles from the analyzed regions were implicated in synaptic decay, abnormal brain immunity, neuron structural imbalances, and impaired cell homeostasis. Our findings also provide evidence, for the first time, that networks of molecular exchange (involving the PFC, HC, and CAU) are potentially active and mediated by EVs in non-diseased brains. Additionally, these bEV-mediated networks seem to have become partially reversed and largely disrupted in the brains of subjects affected by SZ. Taken as a whole, these results open the door to the uncovering of new biological markers and therapeutic targets, based on the compositions of bEVs, for the benefit of patients affected by SZ and related psychotic disorders.

Correlation between C-reactive protein and the inflammatory ratios in acute schizophrenia inpatients: are they associated?

C-reactive protein (CRP) and inflammatory ratios have been proposed to study immune dysregulation in schizophrenia. Nevertheless, links between CRP and inflammatory ratios in acute SCZ inpatients have been understudied. This study investigated the relationship between CRP and inflammatory ratios (Neutrophil-Lymphocyte Ratio [NRL], Platelet-Lymphocyte Ratio [PLR], Monocyte-Lymphocyte ratio [MLR] and Basophil-Lymphocyte Ratio [BLR]) in a total of 698 acute SCZ inpatients; and analysed how this relationship is affected by sex and type of episode. CRP correlated with NLR (rs = 0.338, p < 0.001), PLR (rs = 0.271, p < 0.001) and MLR (rs = 0.148, p < 0.001) but not with BLR (rs = 0.059, p = 0.121). Multiple lineal regression analysis showed that high levels of NLR, MLR and PLR but not BLR were independently associated with high CRP levels. No sex-related variations were found. Significant associations were maintained for NLR and MLR in first-episode and multiepisode SCZ, although the strength of the association was stronger in multiepisode SCZ. Again, no sex-related differences were found in these associations. In conclusion, inflammatory ratios were low to moderately associated with CRP in acute SCZ inpatients. NLR and multiepisode SCZ showed the highest associations with CRP. Future studies should consider inflammatory ratios not as a substitute for CRP but as a complementary biomarker.

High neutrophil-lymphocyte ratio upon admission is associated with better response in psychotic depression.

Recent evidence relates the inflammatory system to the aetiology and evolution of mood disorders. The Neutrophil-Lymphocyte Ratio (NLR) is an affordable and reproducible biomarker of inflammation. The aim of the study is to retrospectively evaluate the association between NLR and response to treatment in 50 patients aged over 50 with a diagnosis of Psychotic Depression (PD) who were admitted to an acute psychiatric unit between 2010 and 2018. They were stratified according to sex and treatment received: antidepressants, antipsychotics and electroconvulsive therapy (ECT). The NLR was collected on admission and the clinical response was quantified by the Global Assessment of Functioning (GAF) scale. In the simple linear regression, high NLR upon admission was associated with better clinical response during hospitalization as measured by GAF. When stratifying the patients, this association was maintained in women, in patients who received antidepressant treatment with tricyclics and SNRIs, antipsychotic treatment with olanzapine/quetiapine and those who did not receive ECT. NLR is an accessible biomarker in clinical practice, and in PD patients it could guide the therapeutic strategy and be a predictor of response.

High BDNF serum levels are associated to good cognitive functioning in bipolar disorder.

BACKGROUND: Neurotrophins such as brain-derived neurotrophic factor (BDNF), inflammation and oxidative damage may contribute to the pathophysiology of bipolar disorder (BD) in terms of illness activity. To date, there is a lack of studies linking the cognitive impairment observed in BD with these neurobiological mechanisms. This study aimed to investigate the role of these neurobiological factors in clinical and cognitive outcomes in a sample of bipolar individuals. METHODS: We measured serum BDNF, cytokines and oxidative stress markers in a sample of 133 individuals: 52 euthymic bipolar patients, 32 manic patients and 49 healthy controls. They were all assessed with a comprehensive cognitive battery. Sociodemographic and clinical data were collected. Multiple linear regression models were built to study associations of neurotrophins and inflammatory and oxidative measures with cognitive functioning. RESULTS: BDNF levels were decreased in euthymic (p = 0.039) and manic (p < 0.001) individuals. Conversely, inflammatory (interleukin 6 (IL-6)) (p = 0.019) and oxidative stress (p = 0.003) measures were increased in bipolar individuals compared to controls. BDNF levels were associated with executive functioning (ß = 0.01, p = 0.02) and verbal memory (ß = 0.013, p = 0.005), together with other demographic variables. In particular, verbal memory was also associated with obesity (ß=-0.04, p = 0.005). Neither inflammatory markers, oxidative stress markers nor other relevant clinical variables showed any association with cognitive outcome. CONCLUSIONS: Of all the peripheral neurobiological factors analysed, BDNF was the only one significantly associated with cognitive dysfunction in bipolar disorder individuals. This study emphasizes the role of BDNF not only across mood phases but also in cognitive functioning.

The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study.

OBJECTIVE: To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. METHOD: A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m²) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m²; and obese, BMI ≥ 30 kg/m²). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. RESULTS: Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F7,111 = 2.54, P = .018 and F19,23 = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (ß = -0.44, SE = 0.14, P = .002), current age (ß = -0.44, P < .0001), and premorbid IQ (ß = 0.28, P = .0002), which explained 56% of variance (F5,115 = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (ß = -0.8, SE = 0.33, P = .022) and cognition at baseline (ß = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F6,40 = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ²1 = 5.37, P = .02), age (Wald χ²1 = 22.08, P < .0001), and premorbid IQ (Wald χ²1 = 25.65, P < .0001) were the significant predictors. CONCLUSIONS: Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term.

Are patients with bipolar disorder and comorbid attention-deficit hyperactivity disorder more neurocognitively impaired?

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

Farmacocinética plasmática y urinaria de marbofloxacina intramuscular en caninos / Plasma and urine pharmacokinetics of intramuscular marbofloxacin in canines / Farmacocinética plasmática e urinária de marbofloxacina intramuscular em caninos

Resumen: Se estudió la disposición plasmática y urinaria de marbofloxacina en caninos (n = 6) tras la aplicación intramuscular de 2 mg/kg. En distintos tiempos posadministración se tomaron muestras de sangre hasta las 24 h, y de orina solo en los caninos machos (n = 4) a las 4, 8, 12 y 24 h. Se realizó una extracción líquido-líquido del analito con agua, metanol y centrifugado a 13.500 r. p. m. a 4 °C. La separación y cuantificación se realizó por HPLC mediante la elusión isocrática en fase reversa, utilizando columna C-18, detector de fluorescencia a 295 nm de excitación y 490 nm de emisión y fase móvil compuesta por agua, acetonitrilo y trietilamina. Las concentraciones plasmáticas temporales se analizaron con el software no compartimental PK Solution 2.0. Los resultados conseguidos indican pronta absorción, rápida y amplia distribución. El Cl y los valores conseguidos de t1/2β y TMR indican lenta depuración y prolongada permanencia. El ensayo determinó concentraciones plasmáticas perdurables hasta 24 h, y que exceden la CMI de patógenos relevantes. El cociente ABC/CMI indica eficacia frente a microorganismos con CMI ≤ 0,15 μg/ml. Las concentraciones urinarias de marbofloxacina son más significativas que las plasmáticas. No obstante, se requieren nuevos estudios que avalen su empleo con la dosis y vía de aplicación ensayada.

Abstract: Plasma and urinary disposition of marbofloxacin was studied in canines (n = 6) after intramuscular administration of 2 mg/kg. At different times post-administration, blood samples were collected until 24 h, and urine samples, only from male dogs (n = 4) at 4; 8; 12, and 24 h. Liquid-liquid extraction of analyte with water, methanol, and centrifugation at 13500 rpm at 4 °C were performed. Separation and quantification were made using HPLC by reverse phase isocratic elution with a C18 column, fluorescence detector at 295 nm excitation and 490 nm emission, and a mobile phase consisting of water, acetonitrile, and triethylamine. Temporary plasma concentrations were analyzed with non-compartmental PK Solution 2.0 software. The results obtained indicate rapid absorption, as well as rapid and wide distribution. Cl and values of t1/2β and MRT indicate slow clearance and prolonged stay. The study evidenced plasma concentrations up to 24 h, which exceed the MIC of relevant pathogens. The AUC/MIC ratio indicates efficacy against microorganisms with MIC ≤ 0.15 μg/ml. Urinary levels of marbofloxacin are more significant than plasmatic levels. However, new studies are required to assess their use with the tested dose and route of application.

Resumo: Se estudou a disposição plasmática e urinária de marbofloxacina em caninos (n = 6) após a aplicação intramuscular de 2 mg/kg. Em diferentes tempos pós-administração se tomaram amostras de sangue hasta as 24 h, e de urina somente nos caninos machos (n = 4) a as 4; 8; 12 e 24 h. Se realizou uma extração líquido-líquido do analito com água, metanol e centrifugado a 13500 r. p. m. a 4 °C. A separação e quantificação se realizou por HPLC mediante a eluição isocrática em fase reversa, utilizando coluna C-18, detector de fluorescencia a 295 nm de excitação e 490 nm de emissão e fase móvel composta por água, acetonitrilo e trietilamina. As concentrações plasmáticas temporárias se analisaram com o software não compartimental PK Solution 2.0. Os resultados conseguidos indicam pronta absorção, rápida e ampla distribuição. O Cl e os valores conseguidos de t1/2β e TMR indicam lenta depuração e prolongada permanência. O ensaio determinou concentrações plasmáticas perduráveis hasta 24 h, e que excedem a CMI de patógenos relevantes. O cociente ABC/CMI indica eficácia frente a micro-organismos com CMI ≤ 0,15 μg/ml. Os níveis urinários de marbofloxacina são mais significativos que os plasmáticos. Não obstante, se requerem novos estudos que avalizem seu uso com a dose e via de aplicação ensaiada.

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.

Predictors of functional outcome after a manic episode.

BACKGROUND: The identification of functional outcome predictors after acute episodes of bipolar disorders (BD) may allow designing appropriate treatment aiming at restoring psychosocial functioning. Our objective was to identify the best functional outcome predictors at a 6-month follow-up after an index manic episode. METHODS: We conducted a naturalistic trial (MANACOR) focusing on the global burden of BD, with special emphasis on manic episode-associated costs. We observed patients with BD seen in services of four hospitals in Catalonia (Spain).The total sample included 169 patients with chronic DSM-IV-TR BD I suffering from an acute manic episode who were followed-up for 6 months. In this subanalysis we report the results of a stepwise multiple regression conducted by entering in the model those clinical and sociodemographic variables that were identified through preliminary bivariate Pearson correlations and using total scores on the Functioning Assessment Short Test (FAST) at the 6-month follow-up as the dependent variable. RESULTS: Number of previous depressive episodes (Beta=3.25; t=3.23; p=0.002), presence of psychotic symptoms during the manic index episode (Beta=7.007; t=2.2; p=0.031) and the Body Mass Index (BMI) at baseline (Beta=0.62; t=2.09; p=0.041) were best predictors of functional outcome after a manic episode. LIMITATIONS: The main limitations of this study include the retrospective assessment of the episodes, which can be a source of bias, and the 6-month follow-up might have been too short for assessing the course of a chronic illness. CONCLUSIONS: Psychotic symptoms at index episode, number of past depressive episodes, and BMI predict worse outcome after 6 months follow-up after a manic episode, and may constitute the target of specific treatment strategies.

The real world cost and health resource utilization associated to manic episodes: The MANACOR study.

INTRODUCTION: Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. METHODS: Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. RESULTS: One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. CONCLUSIONS: Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.

Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (ß = -0.47, p < 0.0001), Executive Index (ß = 0.62, p < 0.0001) and Visual Memory Index (ß = 0.44, p = 0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.

Functioning Assessment Short Test (FAST): validity and reliability in adults with attention-deficit/hyperactivity disorder.

Studies highlight that the functional deficits in different areas of a subject's life are an important characteristic that define adult attention-deficit/hyperactivity disorder (ADHD). On the other hand, in the scientific literature, there are no evaluation instruments with psychometric studies concerning their reliability and validity for this variable in adults with ADHD. The aim of the present study is to evaluate the psychometric properties of the Functioning Assessment Short Test (FAST), regarding its reliability and validity, as a measure of adult ADHD functioning. A case-control study was carried out in a sample of 152 adult subjects (88 with ADHD diagnosis and 64 healthy controls). The psychometric properties of the instrument were analyzed regarding feasibility, internal consistency, concurrent validity, discriminant validity (ADHD vs. controls) and factor analysis. For the total scale, Cronbach's alpha was of 0.83, and strong values in the measures of its discriminant capacity were obtained, AUC ROC = 0.98, IC (0.96-0.99). The test is reliable as the internal consistency was high. Significant differences are observed in the correlation between domains, between healthy subjects and subjects with ADHD. ADHD subjects showed impairments in all areas of their life, especially in the cognitive functioning domain, followed by the autonomy, occupational functioning and interpersonal relationships domains. The FAST is an easily administered short interview and has good psychometric properties, in terms of reliability and validity, as a measure of the functional level in adults with ADHD. The study also showed that subjects with adult ADHD may be functionally impaired.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with Bipolar Disorder and their relatives.

BACKGROUND: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. METHODS: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. LIMITATIONS: Cross-sectional design. RESULTS: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. CONCLUSIONS: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions.

Influence of clinical and neuropsychological variables on the psychosocial and occupational outcome of remitted bipolar patients.

OBJECTIVE: To measure the impact of the clinical course, the residual mood symptoms and the cognitive variables on the psychosocial and occupational functioning in bipolar disorder patients in remission. METHOD: Forty-four euthymic DSM-IV-TR bipolar lithium-treated outpatients were assessed with a clinical interview and neuropsychological testing. To assess psychosocial function, some psychometric scales were administered (Global Assessment of Functioning Scale and World Health Organization Disability Assessment Schedule), and to evaluate occupational function, the sample was divided according to the current work status (active vs. inactive). Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). RESULTS: Measures of psychosocial functioning were significantly correlated with cognition (processing speed, p = 0.004), clinical severity (p = 0.03) and residual depressive symptoms (p = 0.05). Occupational functioning showed a significant effect with a cognitive domain (visual memory, p = 0.006) and a clinical variable (chronicity, p = 0.04) but not with residual mood symptoms (p > 0.2). CONCLUSIONS: Remission in bipolar disorder is not synonymous with recovering in psychosocial and occupational functioning. Cognitive deficits, clinical course and persistent subsyndromal symptoms may compromise psychosocial functioning, and neurocognitive symptoms and chronicity may particularly affect occupational functioning.

Long-term stability of cognitive impairment in bipolar disorder: a 2-year follow-up study of lithium-treated euthymic bipolar patients.

OBJECTIVE: To determine the course of cognitive impairment of bipolar disorder with a 2-year longitudinal study and to investigate whether the neuropsychological profile is related to clinical and psychosocial variables in a sample of lithium-treated euthymic bipolar outpatients. METHOD: Thirty-three bipolar disorder patients (all of whom were diagnosed according to DSM-IV-TR criteria and were treated during 2003 at the Lithium Clinic Program at Santa Maria Hospital, Lleida, Spain) and 33 healthy, matched controls were cognitively assessed twice over a 2-year follow-up period. All patients were receiving the same mood-stabilizer pharmacotherapy (lithium) at the first evaluation, and they were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young Mania Rating Scale score lower than 6) for at least 3 months before both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory, and visual memory). RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain (p < .04) and in processing speed (p < .04). Multiple linear regression analysis showed that none of the variables predicted psychosocial functioning (as measured with the Global Assessment of Functioning scale) (R(2) = 0.12, F = 2.08, p = .1). Multilevel logistic regression analysis showed that processing speed appeared to be significant as an indicator of low work activity (Exp[B] = 1.25, 95% CI = 1.005 to 1.547, p = .04). CONCLUSIONS: Executive function and processing speed are the cognitive domains affected in euthymic bipolar outpatients, and such deficits are maintained over time. Our results show that executive dysfunction is the main long-term neuropsychological deficit of bipolar disorder. Slower processing seems to be related to worse work adaptation.

Persistent neuropsychological deficit in euthymic bipolar patients: executive function as a core deficit.

OBJECTIVE: To characterize neuropsychological deficits during the euthymic phase in a sample of bipolar outpatients treated with lithium as the principal mood-stabilizer medication. We sought to determine cognitive functioning of typical bipolar outpatients treated in clinical settings. METHOD: Forty-four stable outpatients, fulfilling criteria of bipolar disorder (DSM-IV), were consecutively recruited from a defined catchment area and compared with 46 healthy matched controls in 2003. Patients were remitted for at least 3 months and euthymic (Hamilton Rating Scale for Depression score < 8 and Young Mania Rating Scale score < 6 for at least 3 months). They were receiving lithium as monotherapy (45.5%) or combined with other psychotropic medication (54.5%). Neuropsychological assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory, and visual memory). RESULTS: Multivariate analysis of variance showed that euthymic bipolar patients performed significantly worse than controls in measures of executive function (F = 2.57, df = 4,82; p = .04) and inhibition (F = 3.83, df = 2,84; p = .03), after controlling for subclinical symptomatology, years of education, and premorbid intelligence quotient. Processing speed also differed significantly between groups (F = 3.73, df = 2,84; p = .03). The subgroup of patients on lithium monotherapy (45.5%) differed significantly from healthy matched controls on tasks of lack of inhibition (F = 5.8, df = 2,36; p = .007). Executive tasks showed between-subject effects. CONCLUSIONS: These results suggest that impaired executive function and loss of inhibition might be an important feature of bipolar disorder regardless of the severity of the disease or the effects of medication. Also, these executive-type cognitive traits may constitute an endophenotype for further studies on the etiology of bipolar disorder.

Pericias medicas em investigacao de paternidade pelos principais sistemas geneticos / Paternity testing by main genetic systems

O desenvolvimento da biologia molecular proporcionou recentemente novos metodos de investigacao de paternidade que foram incorporados a rotina de nosso laboratorio. Entre eles citaremos as "impressoes digitais do DNA" observadas pelo metodo do RFLP ou polimorfismo de tamanho de fragmentos de restricao ("restriction fragment lenght polymorphism") e a tipagem dos antigenos leucocitarios humanos (HLA) pela amplificacao alelo-especifica do DNA, pelo metodo da reacao em cadeia da polimerase (PCR). Tendo em vista o controle de qualidade obrigatorio no atendimento dos clientes, introduzimos em nosso trabalho a analise matematica computadorizada por intermedio de digitalizacao direta das bandas de DNA por programa desenvolvido para estes estudos, proporcionando resultados estatisticos perfeitos na analise de casos simples ou complexos, onde o possivel pai e falecido. A pesquisa estatistica com a formacao de um banco de dados de frequencias de alelos dos sistemas geneticos por nos utilizados em estudos de investigacao de paternidade na populacao brasileira sera resumidamente analisada junto com os resultados de 1000 pericias efetuadas