Peripheral arterial disease progression and ankle brachial index: a cohort study with newly diagnosed patients with type 2 diabetes.

BACKGROUND: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis. METHODS: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms. RESULTS: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05). CONCLUSION: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients.

Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naïve first-episode psychosis.

AIM: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up. METHODS: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions. RESULTS: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment. CONCLUSION: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP.

Oxidative stress in drug naïve first episode psychosis and antioxidant effects of risperidone.

BACKGROUND: Schizophrenia is accompanied by increased lipid peroxidation and nitric oxide (NO) levels and by lowered antioxidant levels. However, the effect of antipsychotic agents on these processes remains unclear. The objective of this study is to determine the oxidative stress (OS) status in drug naïve first-episode psychotic patients (FEP) compared to healthy controls and to delineate the effects of risperidone on these biomarkers. METHODS: 51 drug naive FEP patients and 61 healthy controls were enrolled; FEP patients were reassessed 11 weeks after risperidone treatment. Three OS biomarkers, i.e. lipid hydroperoxides - LOOH, NO metabolites - NOx, and advanced oxidation protein products - AOPP, and two antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter - TRAP, and paraoxonase 1 - PON1, were measured. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. RESULTS: Significantly lower PON1 activity and increased TRAP values were found in FEP patients. There were no significant associations between any of the OS/antioxidant biomarkers and clinical data. Risperidone treatment significantly increased PON1 activity and decreased LOOH levels. These effects of risperidone were not significantly associated with the clinical response and risperidone dosage. DISCUSSION: Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive FEP. Risperidone may have antioxidant effects by lowering lipid peroxidation and increasing the antioxidant defenses against lipid peroxidation related to PON1. None of the biomarkers predicted treatment outcome.

Lowered paraoxonase 1 (PON1) activity is associated with increased cytokine levels in drug naïve first episode psychosis.

BACKGROUND: Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naïve first episode psychosis (FEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels. METHODS: A total of 51 drug-naïve FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-α and activity of PON1 were quantified. RESULTS: Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-α. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-α. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile). CONCLUSION: The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10. It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies FEP and that increased cytokine levels may further modulate PON1 activity.

Effects of depression on the cytokine profile in drug naïve first-episode psychosis.

Schizophrenia is accompanied by alterations in immuno-inflammatory pathways, including abnormalities in cytokine profile. The immune assessment of patients in a first episode of psychosis (FEP) and particularly in drug naïve patients is very important to further elucidate this association. The objectives of this study are to delineate the cytokine profile (IL-2, IL-10, IL-4, IL-6, IFNγ, TNFα and IL-17) in FEP patients (n=55) versus healthy controls (n=57) and to examine whether the presence of depressive symptoms in FEP is accompanied by a specific cytokine profile. We found increased levels of IL-6, IL-10 and TNFα in FEP patients when compared to healthy controls. FEP patients with depression showed higher IL-4 and TNFα levels versus those without depression. Cytokine levels were not correlated to the total PANSS and the positive or negative subscale scores. Our results suggest that FEP is accompanied by a cytokine profile indicative of monocytic and T regulatory cell (Treg) activation. Depression in FEP is accompanied by monocytic and Th-2 activation, whereas FEP without depression is characterized by Treg activation only. In conclusion, depression emerged as a key component explaining the cytokines imbalance in FEP that is responsible for a large part of the immune-inflammatory abnormalities described.

Alexithymia, suicidal ideation, and serum lipid levels among drug-naïve outpatients with obsessive-compulsive disorder

Objective: As obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder with a significant suicide risk, the individuation of potential biomarkers of suicidality, such as cholesterol levels, may enable recognition of at-risk subjects. Therefore, the aims of this study were to: 1) evaluate potential differences in clinical and laboratory parameters between patients with and without alexithymia and compare them with healthy controls; and 2) investigate which clinical and laboratory variables were associated with suicidal ideation. Methods: 79 drug-naïve adult outpatients with a DSM-IV diagnosis of OCD were recruited. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), suicidal ideation was assessed with the Scale for Suicide Ideation, and depressive symptoms were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS). Serum lipid levels of 40 healthy controls were also evaluated. Results: Alexithymic patients had altered serum lipid levels in comparison with non-alexithymics and healthy controls. Using a linear regression model, the presence of symmetry/ordering obsessions and compulsions, lower HDL-C levels, and difficulty in identifying feelings dimension of the TAS-20 were associated with higher suicidal ideation. Conclusions: Alexithymic individuals with OCD may exhibit dysregulation of the cholesterol balance, which in turn may be linked to suicidal ideation. Further prospective studies are required to elucidate this potential association. .