Esquizofrenia: se a morte acontece sem aviso prévio, o que devemos propor para o futuro próximo?

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaNational Institutes of Health National Institute of Mental HealthUNIFESP, EPMSciEL

A wake-up call : Sleep physiology and related translational discrepancies in studies of rapid-acting antidepressants

Depression is frequently associated with sleep problems, and clinical improvement often coincides with the normalization of sleep architecture and realignment of circadian rhythm. The effectiveness of treatments targeting sleep in depressed patients, such as sleep deprivation, further demonstrates the confluence of sleep and mood. Moreover, recent studies showing that the rapid-acting antidepressant ketamine influences processes related to sleep-wake neurobiology have led to novel hypotheses explaining rapid and sustained antidepressant effects. Despite the available evidence, studies addressing ketamine's antidepressant effects have focused on pharmacology and often overlooked the role of physiology. To explore this discrepancy in research on rapid acting antidepressants, we examined articles published between 2009-2019. A keyword search algorithm indicated that vast majority of the articles completely ignored sleep. Out of the 100 most frequently cited pre clinical and clinical research papers, 89 % and 71 %, respectively, did not mention sleep at all. Furthermore, only a handful of these articles disclosed key experimental variables, such as the times of treatment administration or behavioral testing, let alone considered the potential association between these variables and experimental observations. Notably, in preclinical studies, treatments were preferentially administered during the inactive period, which is the polar opposite of clinical practice and research. We discuss the potential impact of this practice on the results in the field. Our hope is that this perspective will serve as a wake-up call to (re)-examine rapid-acting antidepressant effects with more appreciation for the role of sleep and chronobiology.Peer reviewe

SHAPS-C: the Snaith-Hamilton pleasure scale modified for clinician administration

Anhedonia, a diminished or lack of ability to experience and anticipate pleasure represents a core psychiatric symptom in depression. Current clinician assessment of anhedonia is generally limited to one or two all-purpose questions and most well-known psychometric scales of anhedonia are relatively long, self-administered, typically not state sensitive, and are unsuitable for use in clinical settings. A user-friendly tool for a more in-depth clinician assessment of hedonic capacity is needed. The present study assessed the validity and reliability of a clinician administered version of the Snaith-Hamilton Pleasure Scale, the SHAPS-C, in 34 depressed subjects. We compared total and specific item scores on the SHAPS-C, SHAPS (self-report version), Montgomery-Åsberg Depression Rating Scale (MADRS), and the Inventory of Depressive Symptomatology-Self Rating version (IDS-SR). We also examined construct, content, concurrent, convergent, and discriminant validity, internal consistency, and split-half reliability of the SHAPS-C. The SHAPS-C was found to be valid and reliable. The SHAPS and the SHAPS-C were positively correlated with one another, with levels of depression severity, as measured by the MADRS, and the IDS-SR total scores, and with specific items of the MADRS and IDS-SR sensitive to measuring hedonic capacity. Our investigation indicates that the SHAPS-C is a user friendly, reliable, and valid tool for clinician assessment of hedonic capacity in depressed bipolar and unipolar patients

Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia

Anhedonia—defined as loss of interest or pleasure—is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcers—activities with the potential to be positive experiences—is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individual’s unique set of ‘liked’ and ‘disliked’ activity words. A negative correlation was observed between anhedonia and the number of ‘liked’ activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward ‘disliked’ activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD

A Double-Blind, Randomized, Placebo-Controlled 4-Week Study on the Efficacy and Safety of the Purinergic Agents Allopurinol and Dipyridamole Adjunctive to Lithium in Acute Bipolar Mania

The therapeutics for Bipolar Disorders (BD) is still far from adequate and new options with improved effectiveness, safety and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting at the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania

Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania

Although lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint. (C) 2012 Elsevier Ltd. All rights reserved.Stanley Medical Research Institute [03T-356