The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients. METHODS: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations. RESULTS: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype. CONCLUSION: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients.

Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients.

AIMS: To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines. METHODS: A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models. RESULTS: The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082*A, IL10-819*T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms. CONCLUSIONS: This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.

Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

OBJECTIVE: Circadian rhythms have been linked to psychiatric disorders such as Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian disturbances as well as the genetic susceptibility for BD, we decided to investigate the possible link between the PERIOD3 (Per3) circadian gene and BD. METHODS: This is a genetic association case (BD) vs. control study of the Per3 gene. We further subdivided our BD sample into "good sleepers" (PSQI ≤5) and "poor sleepers" (PSQI>5) according to the Pittsburgh Sleep Quality Index (PSQI) global score, and then we assessed genetic association of the Per3 gene with sleep quality in the BD group. RESULTS: There were 209 cases and 213 controls in our sample. The GT genotype of the SNP rs707467 significantly associated with BD (χ2=8.80; p-value=0.01; adjusted residual=±2.6). We also found significant association of the SNP rs10462020 allele T with BD (χ2=5.81; p-value=0.01) as well as the genotype TT (χ2= 6.01; p-value=0.04; adjusted residual=±2.4). CONCLUSION: In this study we demonstrated evidences of genetic association between the Per3 gene and BD. The results of association between the Per3 gene and BD in our sample may bring additional evidence to the former findings of association between the Per3 gene and BD.

Analysis of telomere attrition in bipolar disorder.

BACKGROUND: Telomeres can be considered a marker of biological aging. Studies have suggested that telomere shortening may be associated with aging related diseases and also psychiatric disorders. OBJECTIVES: Investigate whether bipolar disorder (BD) and its clinical specificities are associated with telomere shortening. METHODS: Eighty-five BD patients and 95 healthy controls were paired for age, sex and educational level. Volunteers were submitted to a psychiatric interview and clinical evaluation. Patients and controls were compared as a whole sample and within specific telomere range (short and long telomeres). Intrapatients group comparison involved type of BD and comorbidities. A Real Time Quantitative PCR was performed in order to verify leukocytes telomere length. RESULTS: Bipolar disorder patients presented shorter telomeres when compared to controls (p<0.001). However, there was no significant difference in telomere length between different BD subtypes. When two groups of patients (long and short telomeres) were compared, only panic disorder showed an association with telomere categories (χ(2)=6.91; p=0.009; OR=4.27). LIMITATIONS: It was not possible to collect information about time since diagnosis, which limited conclusions regarding BD chronicity and telomere length. Furthermore, medication interference upon telomere length was not controlled. CONCLUSIONS: Results suggest that BD is associated with reduced telomere length. Also, panic comorbidity may represent an additive risk factor. Understanding aspects that contribute to determination of telomere size in bipolar patients allows us to understand what the impact on telomeres size is, which is a health vulnerability marker.

Affective temperaments and antidepressant response in the clinical management of mood disorders.

BACKGROUND: The aim of this study was to investigate the presence of a relationship between affective temperament and antidepressant treatment response in mood disorder patients. METHODS: The lifetime history of antidepressant response of 90 bipolar disorder patients and 88 major depressive disorder patients were retrospectively evaluated and then assigned to one of four subgroups: complete response (CR), partial response (PR), no response (NR), and antidepressant associated mania response (AAMR). Using TEMPS-Rio de Janeiro - the brief Brazilian version of TEMPS-A - we compared affective temperament subscale scores across these groups. RESULTS: We observed a statistically significant relationship between depressive and anxious affective temperaments and no antidepressant response. In bipolar disorder patients, cyclothymic temperament (p<0.01) and hyperthymic temperament (p<0.05) were associated with antidepressant-associated mania. Hyperthymic temperament was associated with complete antidepressant responses in major depressive disorder patients. LIMITATIONS: The evaluation of antidepressant response was retrospective. CONCLUSIONS: Our data are consistent with the theory that affective temperament traits are factors that can influence the antidepressant response and the recovery from depressive episodes, but more longitudinal studies are needed to confirm this theory and our findings.

Transtorno afetivo bipolar e doença periodontal / Bipolar affective disorder and disease periodontal – literature review

Estudos epidemiológicos sugerem que o transtorno afetivo bipolar pode alterar a instalação e a progressão da doença periodontal. O processo inflamatório, induzido por esta alteração psiquiátrica, e o biofilme dentário podem atuar sinergicamente estimulando uma intensa resposta do sistema imunológico, influenciando a progressão das doenças periodontais. O objetivo do presente trabalho foi revisar a literatura em relação aos principais estudos que investigaram a possível correlação entre o transtorno afetivo bipolar e a doença periodontal. Concluiu-se que a maioria dos estudos publicados, até o momento, não apresenta estratégias metodológicas que avaliem corretamente a possível associação entre a doença periodontal e o transtorno bipolar especificamente. São necessários maiores estudos com metodologias que envolvam as características epidemiológicas, microbiológicas e imunológicas desta possível associação, propiciando um melhor entendimento da mesma.

Epidemiological studies suggest that bipolar disorder can alter the onset and progression of periodontal disease. The inflammatory process induced by this amendment psychiatric, and dental biofilm can act synergistically stimulate an intense immune response influencing the progression of periodontal diseases. The objective of this paper is to review the literature in relation to the main studies that investigated the possible correlation between bipolar affective disorder and periodontal disease. It was concluded that most studies published so far do not present search strategies that evaluate the association between periodontal disease and bipolar disorder specifically. Larger studies with methodologies involving epidemiological, microbiological and immunological features of this possible association, providing better understanding of it are needed.

Significant sleep disturbances in euthymic bipolar patients.

OBJECTIVE: A growing amount of data suggests that sleep dysfunction is frequently observed in bipolar disorder (BD) patients even when they do not fulfill the criteria for major mood episodes. Thus, we performed a case-control study assessing sleep status in a group of euthymic BD patients and a group of health controls. METHODS: A total of 209 subjects (104 health controls and 105 BD patients) were enrolled in the study. The Pittsburgh Sleep Quality Index (PSQI) was used for sleep assessment. Inclusion criteria for the BD group were a diagnosis of BD, following DSM-IV-TR criteria, according to the MINI-plus structured clinical interview. Euthymia was established as a score lower than 7 both in the Hamilton Depression Rating Scale (HDRS) and in the Young Mania Rating Scale (YMRS). Health controls were also interviewed using the MINI-plus and included in this study if they were free of any current or past DSM-IV-TR axis I psychiatric disorder as well the actual use of psychopharmacological medications. RESULTS: While 21.2 % of the control group displayed poor sleep quality according to the global PSQI-BR score, 82.9 % of the euthymic BD patients had poor sleep quality (p=0.000). PSQI sleep duration subcomponent showed comparable results in the two groups (p=0.535), even though BD patients had significant disruptions in sleep latency (p=0.000) and sleep efficiency (p=0.000) subcomponents. CONCLUSION: We were able to show that BD patients, even in euthymic phase, exhibit a significantly worse sleep quality as compared with health controls as assessed by PSQI total score and five of its seven subcomponents.

Affective temperaments: familiality and clinical use in mood disorders.

BACKGROUND: The affective temperament profiles among patients with mood disorders may be an important parameter in the clinical evaluation of these patients. It has been proposed that temperament traits have familiality and may represent vulnerability markers to identify the risk to developing specific clinical type of mood disorders. To test these theories, measures of temperament were examined in bipolar patients (BP), unipolar major depressive patients (UP), healthy relatives of these patients (HRP) and normal controls (NC). METHODS: We compared affective temperament scores, using the brief Brazilian version of TEMPS-A--TEMPS-Rio de Janeiro, between 90 BP, 88 UP, 132 HRP and 136 NC. A MANCOVA model was constructed. Dependent variables were the six subscales of the TEMPS-RJ (depressive, cyclothymic, irritable, hyperthymic, anxious and worrying temperaments). The effects of age and gender were adjusted as covariates. Furthermore, we performed a comparison between a subgroup of 68 HRP, relatives of bipolar patients (HRBP), and the remainders 64 HRP, relatives of unipolar patients (HRUP) and controls. RESULTS: The clinical group (BP, UP) showed higher temperament scores than NC, except for hyperthymic scores. BP showed higher cyclothymic (p<0.001), hyperthymic (p<0.001) and lower anxious (p<0.01) temperament scores than UP. HRP showed lower scores than clinical groups. HRBP scored higher cyclothymic subscale than HRUP and NC groups. LIMITATIONS: Bipolar I and II subjects were placed in the same group. CONCLUSIONS: The cyclothymic and hyperthymic traits were associated with bipolarity in patients and cyclothymic temperament could be a characteristic trait of the healthy relatives of bipolar patients. Our data support that affective temperament might become a useful tool for clinical evaluation and research purposes in mood disorders.

Aspectos psicossociais associados à doença periodontal / Psychosocial aspects associated with periodontal disease

Estudos epidemiológicos sugerem que alterações psicossociais, como a ansiedade, o estresse e a depressão, podem alterar a instalação e a progressão da doença periodontal. O processo inflamatório, induzido por estas alterações psicossociais, pode atuar sinergicamente, estimulando uma intensa resposta do sistema imunológico e influenciando a progressão das doenças periodontais. O objetivo do presente trabalho foi revisar a literatura em relação aos principais trabalhos que investigaram a possível correlação entre as principais alterações psicossociais e a doença periodontal. Concluiu-se que a maioria dos estudos publicados até o momento sugere que estas alterações podem alterar significativamente a resposta do hospedeiro, tanto no nível comportamental quanto imunológico.

Relationship between neuropsychological and clinical aspects and suicide attempts in euthymic bipolar patients / Relação entre aspectos clínicos e neuropsicológicos e as tentativas de suicídio em pacientes eutímicos com transtorno afetivo bipolar

Some studies have investigated the possible relationship between suicide attempts and impulsivity in patients with bipolar disorder. The objective of this study was to assess the relationship between neuro-psychological and clinical aspects and suicide behavior in euthymic bipolar patients. The Iowa Gambling Task and the Conner's Continuous Performance Test evaluated impulsivity in 95 euthymic bipolar patients - 42 suicide attempters and 115 normal control participants. A factorial analysis evaluated the adequacy of the instruments. Furthermore, a multiple regression analysis was done in order to develop a model to predict suicide attempts. Our results point to a specific type of impulsivity related to making decisions, lack of planning and borderline personality disorder comorbidity. This type of impulsivity is a risk factor for suicide attempts in patients with bipolar disorder.

Alguns estudos investigaram a possível relação entre tentativas de suicídio e impulsividade em pacientes com transtorno bipolar. O objetivo do estudo foi avaliar a relação entre características neuropsicológicas e clínicas e o comportamento suicida em pacientes bipolares eutímicos. Utilizamos o Iowa Gambling Task e o Conner's Continuous Performance Test para avaliar a impulsividade em 95 pacientes eutímicos com transtorno bipolar (42 com tentativas de suicídio) e 155 controles normais. Uma análise fatorial avaliou a adequação dos instrumentos e foi criado um modelo para previsão do número de tentativas de suicídio usando regressão linear múltipla. Nossos resultados apontam para um tipo específico de impulsividade relacionada à tomada de decisões, falta de planejamento e para a comorbidade Transtorno de Personalidade Borderline. A impulsividade por não planejamento é um fator de risco para tentativas de suicídio em pacientes com Transtorno Bipolar.

A depressão como fator de risco para periodontite – revisão de literatura / Depression as a risk factor for periodontitis – literature review

Estudos epidemiológicos sugerem que a depressão pode alterar a instalação e progressão da doença periodontal. O processo inflamatório, induzido pela depressão e o biofilme dentário, podem atuar sinergicamente estimulando uma intensa resposta do sistema imunológico influenciando a progressão das doenças periodontais. O objetivo do presente trabalho é revisar a literatura em relação aos principais trabalhos que investigaram a possível correlação entre a depressão e a doença periodontal. Concluiu-se que a maioria dos estudos publicados até o momento sugere que a depressão pode alterar significativamente a resposta do hospedeiro tanto no nível comportamental quanto imunológico

Epidemiological studies suggest that depression can after the onset and progression of periodontal disease. The inflammatory process induced depression and biofilm can act synergistically stimulate an intense immune response influencing the progression of periodontal diseases. The aim of this paper is to review the literature on the main studies that investigated the possible correlation between depression and periodontal disease. It was concluded that most studies published to date suggests that depression can significantly alter the host response at both the behavioral and immune

A kinematic analysis of the association between impulsivity and manual aiming control.

Two characteristics usually found in impulsive behavior are deficits in response inhibition and the inability to delay gratification. The former behavior is called motor impulsivity, and the second is called cognitive impulsivity. This study investigates the association of motor and cognitive impulsivity with manual aiming control. We administered two neuropsychological tests to 81 healthy participants to measure their levels of motor and cognitive impulsivity. A manual aiming motor task was also applied. Subsequently, from the initial group of 81 participants, two subgroups of 27 individuals were selected by their scores on (1) motor impulsivity and (2) cognitive impulsivity, and their motor performances were compared. While a group was comprised by the top 33.3% high-impulsive participants, the other was comprised by the bottom 33.3% low-impulsives participants. The results indicate that motor impulsivity is more related to motor control than cognitive impulsivity. Differences between motor impulsivity groups were found in the duration of the primary submovement, peak velocity, score of response inhibition errors and incorrect hits score. It was found that in situations in which the temporal and spatial demands to the motor system were high, the impulsivity had a functional, adaptive effect on motor control.

The 5-HTTLPR polymorphism, impulsivity and suicide behavior in euthymic bipolar patients.

BACKGROUND: Suicide behavior is very frequent in Bipolar Disorder (BD) and they are both closely associated with impulsivity. Furthermore they are, impulsivity, BD and suicide behavior, associated with serotonergic function, at least partially, under genetic determinism and somewhat associated with the serotonin transporter gene polymorphism, the 5-HTTLPR. We aimed to assess different impulsivity components in BD sub-grouped by suicidal attempt and healthy controls. We hypothesized that the non-planning/cognitive impulsivity, could be more closely associated with suicidal behavior. We further associated 5-HTTLPR genotypes with neuropsychological results to test the hypothesis that this polymorphism is associated with cognitive impulsivity. METHOD: We assessed 95 euthymic bipolar patients sub-grouped by suicidal attempt history in comparison with 94 healthy controls. All subjects underwent a laboratory assessment of impulsivity (Continuous Performance Test and Iowa Gambling Test). Furthermore the genotyping of 5-HTTLPR was performed in all subjects. RESULTS: We found that bipolar patients are more impulsive than healthy controls in all impulsivity dimensions we studied. Furthermore bipolar patients with a suicide attempt history have a greater cognitive impulsivity when compared to both bipolar patients without such a history as well when compared to healthy controls. No association was found between 5-HTTLPR genotypes and neuropsychological measures of impulsive behavior. LIMITATIONS: The sample studied can be considered small and a potentially confounding variable - medication status - was not controlled. CONCLUSION: A lifetime suicide attempt seems associated with cognitive impulsivity independently of the socio-demographic and clinical variables studied as well with 5-HTTLPR genotype. Further studies in larger samples are necessary.

Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder.

Bipolar disorder (BD) has been associated with a proinflammatory state in which TNF-α seems to play a relevant role. The aim of the present study was to evaluate the plasma levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in BD patients in mania and euthymia in comparison with control subjects. We evaluated 53 BD patients (34 in mania and 19 in euthymia) and 38 healthy subjects. All subjects were assessed by the Mini-International Neuropsychiatry Interview (MINI-Plus). Patients were also evaluated by the Young Mania Rating Scale (YMRS) and by Hamilton Depression Rating Scale (HDRS). Plasma TNF-α and its soluble receptors were measured by ELISA. The plasma TNF-α and sTNFR2 levels did not differ between groups, but higher sTNFR1 levels were found in BD patients. Of note, BD patients in mania had higher sTNFR1 levels than BD patients in euthymia and controls. The sTNFR1 and sTNFR2 levels correlated with BD duration, and sTNFR2 levels correlated with age of patients. Our data indicate a proinflammatory status in BD patients during mania and further suggest that inflammatory mechanisms may be involved with the physiopathology of BD.

Impaired nerve growth factor homeostasis in patients with bipolar disorder.

OBJECTIVE: Neuro-trophins are critically involved in neuro-plasticity, the impairment of which is a major role-player in bipolar disorder (BD), and their altered levels have been recently advocated in the patho-physiology of this affective malady. The aim of this study, therefore, was to evaluate the plasma levels of nerve growth factor (NGF) in BD patients in comparison with control subjects. METHODS: Forty-nine BD type-I individuals (30 in mania and 19 in euthymia) and 36 healthy controls were assessed by Mini-plus, Young mania and Hamilton depression rating scales. NGF levels were detected by ELISA. RESULTS: Plasma NGF concentrations were decreased in BD patients when compared to that seen with controls. BD individuals in mania had lower NGF levels than euthymic patients or controls. NGF levels were negatively correlated with the severity of mania. CONCLUSIONS: This is the first study to evaluate NGF levels in BD patients, providing further support to the hypothesis of impaired neuro-plasticity in BD. These data also suggest that NGF measurement could be used for the biological marker for manic state.