A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder.

S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression

Aripiprazole Augmentation in Patients with Resistant Obsessive Compulsive Disorder: a Pilot Study

Background: Antipsychotic augmentation is an effective treatment intervention for Obsessive Compulsive Disorder (OCD) patients resistant to Selective Serotonin Reuptake Inhibitors (SSRI) agents. This pilot study was conducted to evaluate the effectiveness and tolerability of Aripiprazole for the augmentation of standard treatments in patients with resistant OCD. Methods: Twenty patients diagnosed with OCD according to DSM-IV TR criteria and having a history of resistance to standard pharmacological treatment were included in the study. Aripiprazole was added to ongoing SSRI or clomipramine treatment with a starting dose of 5 mg/day and titrated up to a maximum of 20 mg/day (mean dose 12.62 mg ± 4.25). Efficacy was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS) and the Clinical Global Improvement-severity scale (CGI-S) at baseline and at week 12 of Aripiprazole augmentation. Side effects were monitored by the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale. Results: All 20 subjects enrolled in our study completed the full 12-week course of treatment. A significant improvement over the 12-week study period was observed (paired t-test for mean Y-BOCS total score at week 12 as compared with baseline - all patients: t = 13.146, d.f. = 19, p= 0.0001). Aripiprazole was generally well tolerated and no changes were observed in vital signs. The most commonly observed side effects after the introduction of the augmenting agent included: akathysia, nausea/vomiting, hyperkinesia, tension/inner unrest, tremors, asthenia/lassitude/increased fatiguability. Conclusions: Although results of this pilot study are preliminary and require confirmation in randomized controlled trials, our experience suggested that Aripiprazole is effective and well-tolerated as an augmenting agent in patients with treatment resistant OCD. © Delle Chiaie et al

Investigating the link between drug-naive first episode psychoses (FEPs), weight gain abnormalities and brain structural damages: Relevance and implications for therapy

Evidence suggests that obesity and overweight may be associated with severe brain structural abnormalities and poor cognitive and functional outcomes in the general population. Despite these observations and the high prevalence of weight gain abnormalities in patients with psychosis spectrum disorders (PSDs), no studies have investigated the impact that these metabolic disturbances may have on brain structures and development in the earliest stages of PSDs. In the present review we shed light on the association between weight gain and brain structural abnormalities that may affect the course of illness in drug-naïve FEPs. Given the lack of studies directly investigating this issue, we firstly identified and critically evaluated the literature assessing weight gain abnormalities and gray or white matter (GM, WM) volumes (either globally or in specific regions of interest) in otherwise healthy obese/overweight adolescents and young adults. We then compared the results of this systematic review with those of two recent meta-analysis investigating GM and WM abnormalities in drug-naïve FEPs. Weight gain in otherwise healthy subjects was consistently associated with frontal and temporal GM atrophy and with reduced integrity of WM in the corpus callosum. Of relevance, all these brain regions are affected in drug-naïve FEPs, and their integrity is associated with clinical, cognitive and functional outcomes. The underlying mechanisms that may explain the association between weight gain, adiposity, and brain damage in both healthy subjects and drug-naïve FEPs are widely discussed. On the basis of this knowledge, we tried: a) to deduce an integrative model for the development of obesity in psychosis spectrum disorders; b) to identify the key vulnerability factors underlying the association between weight gain and psychosis; c) to provide information on new potential targets of intervention

P300 component in euthymic patients with bipolar disorder type I, bipolar disorder type II and healthy controls: a preliminary event-related potential study

The aim of the present study was to investigate P300 event-related potential components in euthymic bipolar disorder type I (BDI) and bipolar disorder type II (BDII) patients and matched controls. A total of 10 BDI patients, 10 BDII patients and 10 healthy individuals were enrolled in the study. Event-related potential data were collected according to a standard auditory 'oddball' paradigm. A significant groups effect in both the peak amplitude (P<0.001) and the mean amplitude (P<0.001) was observed; post-hoc comparisons showed that the peak and mean amplitudes of BDI and BDII patients were significantly lower than the peak and mean amplitudes of the healthy controls. The neurophysiological patterns found in the present study might at least partially reflect the presence of a mild selective cognitive impairment in euthymic BDI and BDII patients. From a clinical point of view, these evidences support the potential role of cognitive interventions in the treatment of BD

ECT, rTMS, and deepTMS in pharmacoresistant drug-free patients with unipolar depression: a comparative review

Background: Biological treatments are considered as additional options for the treatment of resistant unipolar depression. Controversial data exist about the efficacy and tolerability of three of the most used somatic treatments: electroconvulsive therapy (ECT), transcranial magnetic stimulation (rTMS), and deep transcranial magnetic stimulation (deepTMS). The aim of this review is to investigate and compare the efficacy and tolerability of these three techniques in drug-free patients with pharmacoresistant unipolar depression. Methods: Three independent reviewers extracted data and assessed the quality of methodological reporting of selected studies. The first outcome was the clinical response to the three different techniques defined as a percentage improvement of Hamilton Depression Rating Scale (HDRS). The second outcome was the evaluation of their neuropsychological effects. The third outcome was the evaluation of the number of remitted patients; remission was defined as an absolute HDRS-24 score of &lt;= 11 or as an absolute HDRS-17 score of &lt;= 8. Tolerability was the fourth outcome; it was evaluated by examining the number of dropped-out patients. Results: The comparative evaluation of HDRS percentage variations shows ECT as the most effective method after 4 weeks of therapy; on the other hand, a better efficacy is obtainable by deepTMS after 2 weeks of therapy. DeepTMS is the technique that gives the best improvement of cognitive performances. The percentage of remitted patients obtained with ECT treatment is the same obtained in the deepTMS group. Both techniques have a remitted patients percentage two times larger than the rTMS. DeepTMS shows a tolerability, measured by the number of dropped-out patients, worse than ECT. Conclusion: Our investigation confirms the great therapeutic power of ECT. DeepTMS seems to be the only therapy that provides a substantial improvement of both depressive symptoms and cognitive performances; nevertheless it is characterized by a poor tolerability. rTMS seems to provide a better tolerability for patients, but its therapeutic efficacy is lower. Considering the small therapeutic efficacy of deepTMS in the last 2 weeks of treatment, it could be reasonable to shorten the standard period of deepTMS treatment from 4 to 2 weeks, expecting a reduction of dropped-out patients and thus optimizing the treatment outcome

Stereoselective ROP of rac- and meso-lactides using achiral TBD as catalyst

1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) polymerizes rac-lactide (rac-LA) to form highly isotactic polylactide (PLA) with a Pm = 0.88, while meso-LA yields heterotactic PLA (Pm ~ 0.8) at −75 °C. The stereocontrol of the cryogenic-based ring-opening polymerization comes from a perfect imbrication of both chiral LA and the propagating chiral end-group interacting with the achiral TBD catalyst

Prefronto-cerebellar transcranial direct current stimulation increases amplituded 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

Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system

A critical research goal is to identify modifiable risk factors leading to functional disabilities in young psychiatric patients. The authors developed a multidimensional trans-diagnostic predictive model of functional outcome in patients with the recent-onset of a psychiatric illness. Baseline clinical, psychosis-risk status, cognitive, neurological-soft-signs measures, and dopamine-related-gene polymorphisms (DRD1-rs4532, COMT-rs165599, and DRD4-rs1300955) were collected in 133 young non-psychotic outpatients. 116 individuals underwent follow-up (mean = 22 years, SD = 0.9) examination, A binary logistic model was used to predict low-functioning status at follow-up as defined by a score lower than 65 in the social occupational functioning assessment scale. A total of 54% of patients experiences low functioning at follow-up. Attention, Avolition, and Motor-Coordination subscale were significant predictors of low-functioning with an accuracy of 79.7%. A non-significant trend was found for a dopamine-related-gene polymorphism (DRD1-rs4532). The model was independent of psychotic risk status, DSM-diagnosis, and psychotic conversion. A trans-diagnostic approach taking into account specific neurocognitive, clinical, and neurological information has the potential to identify those individuals with low-functioning independent of DSM diagnosis or the level of psychosis-risk. Specific early interventions targeting modifiable risk factors and emphasize functional recovery in young psychiatric samples, independent of DSM-diagnosis and psychosis-risk, are essential. (C) 2016 Elsevier B.V. All rights reserved

Comparison of cerebellar grey matter alterations in bipolar and cerebellar patients: evidence from voxel-based analysis

The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder

Aberrant cerebello-cerebral connectivity in remitted bipolar patients 1 and 2: new insight into understanding the cerebellar role in mania and hypomania

Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia