Postprandial Glucose Control With Different Hybrid Closed-Loop Systems According to Type of Meal in Adults With Type 1 Diabetes.

BACKGROUND: Hybrid Closed-Loop Systems (HCLs) may not perform optimally on postprandial glucose control. We evaluated how first-generation and advanced HCLs manage meals varying in carbohydrates, fat, and protein. METHOD: According to a cross-sectional design, seven-day food records and HCLs reports from 120 adults with type 1 diabetes (MiniMed670G: n = 40, MiniMed780G: n = 49, Control-IQ [C-IQ]: n = 31) were analyzed. Breakfasts (n = 570), lunches (n = 658), and dinners (n = 619) were divided according to the median of their carbohydrate (g)/fat (g) plus protein (g) ratio (C/FP). After breakfast (4-hour), lunch (6-hour), and dinner (6-hour), continuous glucose monitoring (CGM) metrics and early and late glucose incremental area under the curves (iAUCs) and delivered insulin doses were evaluated. The association of C/FP and HCLs with postprandial glucose and insulin patterns was analyzed by univariate analysis of variance (ANOVA) with a two-factor design. RESULTS: Postprandial glucose time-in-range 70 to 180 mg/dL was optimal after breakfast (78.3 ± 26.9%), lunch (72.7 ± 26.1%), and dinner (70.8 ± 27.3%), with no significant differences between HCLs. Independent of C/FP, late glucose-iAUC after lunch was significantly lower in C-IQ users than 670G and 780G (P < .05), with no significant differences at breakfast and dinner. Postprandial insulin pattern (Ins3-6h minus Ins0-3h) differed by type of HCLs at lunch (P = .026) and dinner (P < .001), being the early insulin dose (Ins0-3h) higher than the late dose (Ins3-6h) in 670G and 780G users with an opposite pattern in C-IQ users. CONCLUSIONS: Independent of different proportions of dietary carbohydrates, fat, and protein, postprandial glucose response was similar in users of different HCLs, although obtained through different automatic insulin delivery patterns.

Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump.

BACKGROUND AND AIMS: Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). METHODS AND RESULTS: In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19-79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. CONCLUSION: Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control.

Delayed prandial insulin boluses are an important determinant of blood glucose control and relate to fear of hypoglycemia in people with type 1 diabetes on advanced technologies.

AIMS: Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH). METHODS: In the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH. RESULTS: Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1-23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045). CONCLUSIONS: In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.

Gut microbiome and blood glucose control in type 1 diabetes: a systematic review.

Objective: The risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D. Methods: Google Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: "gut microbiota," "gut microbiome," "bacteria," "T1D," "type 1 diabetes," "autoimmune diabetes," "glycemic control," "glucose control," "HbA1c," "inflammation," "inflammatory," and "cytokine." The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients. Results: This review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients. Conclusion: We draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies.

Dietary treatment of type 1 diabetes: Beyond carbohydrate counting to fight cardiovascular risk.

AIMS: Type 1 diabetes (T1D) is tied to an increased risk of cardiovascular morbidity and mortality. Dietary treatment would be an elective therapeutic strategy to fight this risk. However, it is not known what the best dietary approach is. We revisited the currently available literature on the nutritional treatment of T1D in the light of their potential comprehensive effects on the management of cardio-metabolic risk factors (body weight, fasting and postprandial glucose and lipid metabolism). DATA SYNTHESIS: Nutritional research in T1D is mainly focused on blood glucose control, with most of the trials aiming at evaluating the acute effects of nutrients on postprandial glycemic response. The effects of the quantity and quality of nutrients and some specific foods on other metabolic risk factors have been explored mainly in cross-sectional analysis. Very few well-designed nutritional trials evaluated the best dietary approach to comprehensively manage cardiovascular risk by targeting along with blood glucose control, overweight, fasting and postprandial dyslipidemia. Therefore, the current best practice guidance for the dietary management of cardiovascular risk in T1D is generally based on evidence from patients with type 2 diabetes. CONCLUSIONS: Well-conducted nutritional trials specifically designed for T1D are needed to identify the best dietary treatment to fight cardiovascular risk in these patients.

Circulating short-chain fatty acids in type 2 diabetic patients and overweight/obese individuals.

AIM: aim of the study was to evaluate serum short chain fatty acids (SCFA) concentrations in patients with Type 2 diabetes (T2D) and overweight/obese individuals. METHODS: In forty-three patients with T2D and twenty-eight overweight/obese patients SCFA were determined by Gas-Chromatography/Flame Ionization Detector (GC/FID). RESULTS: Acetic acid, propionic acid, butyric acid, and total SCFA were significantly reduced in T2D patients compared to overweight/obese in the unadjusted model. Adjusting for all variables only propionic acid remained significantly lower in T2D. CONCLUSION: Only reduction of propionic acid was closely related to diabetes itself, regardless of all other factors.

An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. RESULTS: After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023). CONCLUSIONS: In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial.

BACKGROUND: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or ß-oxidation. METHODS: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma ß-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. RESULTS: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma ß-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). CONCLUSIONS: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.

Chronic Migraine Preventive Treatment by Prefrontal-Occipital Transcranial Direct Current Stimulation (tDCS): A Proof-of-Concept Study on the Effect of Psychiatric Comorbidities.

Chronic migraine (CM) is often complicated by medication overuse headache (MOH) and psychiatric comorbidities that may influence the clinical outcome. This study aimed to investigate the relationship between psychiatric comorbidities and the effect of transcranial direct current stimulation (tDCS) in patients with CM with or without MOH. We recruited 16 consecutive CM patients who had an unsatisfactory response to at least three pharmacological preventive therapies. They were treated with anodal right-prefrontal and cathodal occipital tDCS (intensity: 2 mA, time: 20 min) three times per week for 4 weeks. All patients underwent a psychopathological assessment before and after treatment, and five of them were diagnosed with bipolar disorder (BD). After treatment, all the patients showed a significant decrease of severe and overall headache days per month. Despite having a higher migraine burden at baseline, patients with CM and BD showed a significantly greater reduction of severe headaches and psychiatric symptoms. Overall, tDCS seems to be effective in the treatment of CM patients with a poor response to different classes of pharmacological therapies, whereas BD status positively influences the response of migraineurs to tDCS.

Cognitive remediation for the treatment of neuropsychological disturbances in subjects with euthymic bipolar disorder: findings from a controlled study.

INTRODUCTION: Individuals with euthymic Bipolar Disorder (BD) can experience deteriorated cognitive functioning, with such deterioration being associated with functional impairment. Cognitive remediation (CR) is considered an effective add-on intervention for neuropsychological impairments, but relatively few CR controlled studies have been performed on BD. In the present study the efficacy of a CR intervention designed for the improvement of cognition and functioning in patients with euthymic BD was tested. METHODS: Patients (n = 54) with euthymic BD were assigned to receive active (n = 27) or control (n = 27) intervention. The active intervention (i.e. the Cognitive Remediation in Integrated Treatment - CRIIT - protocol) was made of 20 individual sessions focused on the treatment of attention, memory and executive functioning through the COGPACK software; each session was integrated with psychoeducation and rehabilitation interventions implemented through a metacognitive approach aimed at ameliorating personal agency. RESULTS: A significant (p ≤ 0.015) time x group interaction at repeated measures MANOVA was observed on Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Wisconsin Card Sorting Test, Trail Making Test, Visual Search, Life Skills Profile, and Barratt Impulsiveness Scale. LIMITATIONS: A single-blind approach was used. DISCUSSION: The results showed that patients undergoing active intervention improved in domains related to executive functions, attention, memory, functioning and impulsivity more significantly than patients undergoing control interventions. This study adds to the evidence that CR improves neurocognition in BD, and suggests that CRIIT protocol represents an add-on intervention of potential relevance to increase cognition and functioning in BD euthymic patients.

[Effects of Group Psychoeducation on stress reactivity neuroendocrine profile in stabilized bipolar patients. A controlled study]. / Effetti della psicoeducazione di gruppo sul profilo neuroendocrino di reattività allo stress in pazienti bipolari stabilizzati. Uno studio controllato.

INTRODUCTION: Patients with bipolar disorder show a high relapse rate generally related to their poor adherence to the prescribed medications and to their high stress vulnerability, linked to genetic, neuroendocrine and cognitive factors. AIMS: The first aim of this study was to verify if for a group of pharmacologically stabilized bipolar patients, the attendance to a Group Psychoeducation program according to the Barcelona model would result in an improvement of their stress resilience, as measurable by evaluating their morning cortisol secretory profile. The second aim of the study has been to verify if these effects would maintain stable over time, organizing follow-up evaluations, after one year and after two years form the end of the group psychoeducation program. MATERIALS AND METHODS: 96 patients who had been euthymic for at least 6 months and were under stabilized pharmacologic maintenance treatment, were randomized in two groups: pharmacological treatment as usual (TAU) or pharmacological treatment plus group Psychoeducation (PE). Patients in both groups underwent a psychological assessment (HAMD, YMRS e ARMS), and to a functional assessment of the HPA axis activity, obtained evaluating cortisol levels from salivary samples collected in 5 different moments of the day: at baseline, at the end of the group psychoeducation program, and after 1 year and 2 years from the end of the last PE session. RESULTS: At the end of the study, both groups (PE and TAU) did not show any significant intergroup difference with regard to all the clinical variables and the patients' adherence to the prescribed medications. On the contrary, significative intergroup differences were observed with regard to morning cortisol secretory profile, that was found normalized at the endpoint only among patients of the PE group, but not among those of the TAU group. This normalization of the morning cortisol secretory profile observed among patients of the PE group, proved to maintain stably overtime, since it was observed also in the two follow-up assessments, organized after 1 year and after 2 year from the end the treatment. DISCUSSION: Data collected in this study may indicate that the efficacy of the psychoeducation programs for bipolar patients may activate an improvement of the functional activation of the HPA axis, and so obtaining a reduction of their stress vulnerability.

The Cerebellum Modulates Attention Network Functioning: Evidence from a Cerebellar Transcranial Direct Current Stimulation and Attention Network Test Study.

The functional domain of the cerebellum extends beyond its traditional role in motor control. In recent years, this structure has increasingly been considered to play a crucial role even in cognitive performance and attentional processes. Attention is defined as the ability to appropriately allocate processing resources to relevant stimuli. According to the Posnerian model, three interacting networks modulate attentive processes: the alerting, orienting, and executive networks. The aim of this study was to investigate the role played by the cerebellum in the functioning of the attentive networks using the Attention Network Test (ANT). We studied the effects of transcranial direct current stimulation (tDCS), delivered over the cerebellum in cathodal, anodal, and sham sessions, on ANT parameters in healthy subjects. After anodal and sham tDCS, the efficiency of the three attention networks remained stable, and a significant reduction in reaction time (RT) following the task repetition was observed for both congruent and incongruent targets, indicating a learning effect. After cathodal stimulation, instead, while the efficiency of the alerting and orienting networks remained stable, the efficiency of the executive network was significantly reduced. Moreover, a significant reduction in RT was observed for the congruent target alone, with no difference being detected for the incongruent target, indicating that cerebellar inhibition caused an attentive executive dysfunction specifically related to the ability to process complex stimuli in which conflict signals or errors are present. These results point to a role of the cerebellum, a subcortical structure that is thought to affect error processing both directly, by making predictions of errors or behaviors related to errors, and indirectly, by managing the functioning of brain cortical areas involved in the perception of conflicting signals, in the functioning of the attentional networks, particularly the executive network.

A preliminary study on hot and cool executive functions in bipolar disorder and on their association with emotion regulation strategies.

OBJECTIVE: Individuals with bipolar disorder (BD) experience difficulties in cognitive and emotional regulation in different phases of illness. In the present study, we aimed at exploring differences on hot and cool executive functioning (EF) between BD patients in euthymia (BDe) and mania (BDm), and associations of hot and cool EF with emotion regulation strategies. METHODS: Thirty-seven BD patients (among which 18 with a current manic episode and 19 in euthymia) and 15 healthy controls completed a battery of tests assessing hot and cool EF and emotion regulation strategies. RESULTS: Between group comparisons showed that in all the explored hot dimensions BDm subjects had significantly worse performances than BDe subjects, while in all the explored cool dimensions BDm subjects had significantly worse performances than HC subjects, with BDe patients having an intermediate profile. Results from bivariate correlations among BDe subjects (but not among BDm subjects) showed significant positive correlations (i) between elements of hot EF and elements of cool EF, and (ii) between cognitive reappraisal emotional regulation strategy and planning (i.e., a measure of cool EF), as well as a significant negative correlation between expressive suppression emotional regulation strategy and emotional intelligence. CONCLUSIONS: The results confirm previous findings on a role of impaired EF in BD, and suggest (i) that hot EF is more closely related to mood (i.e., state-dependant) than cool EF, and (ii) that BD patients can more effectively use emotion regulation strategies in association with EF during euthymia than during mania.

Prefronto-cerebellar tDCS enhances neurocognition in euthymic bipolar patients. Findings from a placebo-controlled neuropsychological and psychophysiological investigation.

OBJECTIVES: The present double blind placebo-controlled study aimed at investigating the efficacy of 3-weeks prefronto-cerebellar transcranial direct current stimulation (tDCS) on neurocognitive functioning in euthymic BD patients. METHODS: Forty-two outpatients with BD were randomly assigned to receive either active (n=21) or sham (n=21) prefronto-cerebellar tDCS for 3 consecutive weeks. Neurocognitive abilities were assessed with both neuropsychological testing and psychophysiological evaluation with a P300 novelty task. RESULTS: Our results showed that (i) Trail Making Test-B, a measure of executive functioning, decreased significantly in the active but not in the sham group, (ii) Rey Complex Figure Test Delay Recall, a measure of visuospatial memory, increased significantly in both groups with a greater increase in the active compared to the sham group, and (iii) P3b latency, a measure of brain information processing stream, decreased significantly in the active but not in the sham group. No significant changes were observed in the other explored neuropsychological and psychophysiological measures. CONCLUSIONS: The study suggests that concomitant prefrontal-excitatory and cerebellar-inhibitory tDCS in euthymic BD patients may lead to better neurocognitive performance, quantified through neuropsychological and psychophysiological measures.

Prefrontocerebellar transcranial direct current stimulation increases amplitude and decreases latency of P3b component in patients with euthymic bipolar disorder.

INTRODUCTION: Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD. METHODS: Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation. RESULTS: Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35). CONCLUSION: In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity.

Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder.

OBJECTIVE: The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD) using transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices. METHODS: Twenty-five BD outpatients underwent prefrontal (anodal) and cerebellar (cathodal) tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS. RESULTS: After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved. CONCLUSION: Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto-thalamic-cerebellar circuit activity pattern, which can be disrupted in BD.

Prefronto-cerebellar transcranial direct current stimulation improves sleep quality in euthymic bipolar patients: a brief report.

INTRODUCTION: Sleep problems are common in bipolar disorder (BD) and may persist during the euthymic phase of the disease. The aim of the study was to improve sleep quality of euthymic BD patients through the administration of prefronto-cerebellar transcranial direct current stimulation (tDCS). METHODS: 25 euthymic outpatients with a diagnosis of BD Type I or II have been enrolled in the study. tDCS montage was as follows: cathode on the right cerebellar cortex and anode over the left dorsolateral prefrontal cortex (DLPFC); the intensity of stimulation was set at 2 mA and delivered for 20 min/die for 3 consecutive weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality at baseline and after the tDCS treatment. RESULTS: PSQI total score and all PSQI subdomains, with the exception of "sleep medication," significantly improved after treatment. DISCUSSION: This is the first study where a positive effect of tDCS on the quality of sleep in euthymic BD patients has been reported. As both prefrontal cortex and cerebellum may play a role in regulating sleep processes, concomitant cathodal (inhibitory) stimulation of cerebellum and anodal (excitatory) stimulation of DLPFC may have the potential to modulate prefrontal-thalamic-cerebellar circuits leading to improvements of sleep quality.

Persistence of subsyndromal residual symptoms after remission of major depression in patients without cardiovascular disease may condition maintenance of elevated platelet factor 4 and ß-thromboglobulin plasma levels.

BACKGROUND: Depressive patients show a state dependent platelet activation that may heighten their cardiovascular risk, specially when comorbid with Coronary Artery Disease (CAD). We still have little information however on the possibility that residual symptoms that often persist after recovery from a major depressive episode may contribute to drive forward platelet activation, thus extending the exposure to the associated cardiovascular risk. METHODS: Nineteen major depressed inpatients treated with electroconvulsive therapy (ECT) were enrolled and tested for platelet aggregation by measuring platelet factor-4 (PF4) and ß-thromboglobulin (ß-TG) plasma levels, and for psychometric evaluation by using the 20-item Hamilton Depression Rating Scale (HDRS) and the Symptom Checklist 90 Revised (SCL-90R). Subjects were tested at the beginning of treatment (baseline) and after clinical remission (endpoint). RESULTS: At baseline the patients showed high HDRS (31±6) and total SCL-90R (200±38) scores, followed by a significant decrease at endpoint. However, even if all patients showed full syndromal recovery, SCL-90R "Hostility" and "Psychoticism" subscores showed no significant reduction from baseline, indicating the persistence of subtle residual symptoms. Baseline PF4 and ß-TG plasma levels were found remarkably higher and no significant reduction was observed at the endpoint. LIMITATIONS: Small study population. No follow-up evaluation. CONCLUSIONS: Despite of clinical remission obtained with ECT in patients with major depression, persistence of subsyndromal residual symptoms may contribute to maintain a condition of platelet hyperactivation at the endpoint, increasing their cardiovascular risk and making them more vulnerable to develop cardiovascular disease.

Anti-purkinje cell and natural autoantibodies in a group of psychiatric patients. Evidences for a correlation with the psychopathological status.

Phenomena of autoimmunity are frequent among psychiatric patients, but we don't know yet if they should be considered primary and linked to the pathophisiology of the disorder, or aspecific and associated to a general immune system activation. Paraneoplastic Cerebellar Degeneration (PCD) represents a well known model of specific autoimmunity. In order to better understand the abovementioned issues, we used this condition to compare a set of immune dysfunctions found in a group of psychiatric patients. For this reason we tested sera from 48 psychiatric patients (24 schizophrenics, 17 bipolars and 7 obsessive-compulsive), 22 PCD patients and 52 healthy controls for the presence of anti-Purkinje autoantibodies and of some natural autoantibodies (ANAs, AMAs, APCAs, ASMAs). Psychopatological status of the psychiatric patients was assessed with BPRS, SANS, SAPS, HAM-D, CGI-S. In the psychiatric group anti-Purkinje autoantibodies were identified in 11/48 (22,9%) patients, while they were present in 22/22 (100%) PCD patients and in 0/52 (0%) healthy controls. Among all anti-Purkinje autoantibody positive patients (in the PCD and psychiatric samples), only those belonging to the psychiatric sample, but not those with PCD, were frequently found positive also for natural autoantibodies, that are considered good markers of aspecific immune activation. In these patients, both anti-Purkinje and natural autoantibodies were found associated with acute/positive psychopathological symptoms. These results seem to point out that some phenomena of auto-immunity described in psychiatric patients could be aspecific, unrelated to the pathophysiology of the concomitant mental disorders and could be more frequent during phases of acute/positive symptoms.