Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial.

RATIONALE: Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality. OBJECTIVE: To examine the acute and post-acute effect of ayahuasca on suicidality among individuals with MDD. METHODS: We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received a single dose of ayahuasca (N = 17). Suicidality was assessed at baseline; during the intervention; and 1, 7, 14, and 21 days after the intervention. RESULTS: Among individuals with suicidality at baseline (n = 15), there were significant acute (i.e., 40, 80, 140, and 180 min after administration) and post-acute (1, 7, 14, and 21 days after administration) decreases in suicidality following administration of ayahuasca. Post-acute effect sizes for decreases in suicidality were large (Hedges' g = 1.31-1.75), with the largest effect size 21 days after the intervention (g = 1.75). CONCLUSIONS: When administered in the appropriate context, ayahuasca may lead to rapid and sustained reductions in suicidality among individuals with MDD. Randomized, double-blind studies with larger sample sizes are needed to confirm this early finding.

Clinical validity and intrarater and test-retest reliability of the Structured Clinical Interview for DSM-5 - Clinician Version (SCID-5-CV).

AIM: The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID-5-CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test-retest, joint interview, face-to-face vs telephone application) of the SCID-5-CV in a large sample of 180 non-prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience. METHODS: The SCID-5-CV was administered face-to-face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM-5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses. RESULTS: The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test-retest interviews. CONCLUSION: The SCID-5-CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). CONCLUSIONS: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Borderline personality disorder and bias in the recognition of facial expressions of emotion: a pathway to understand the psychopathology

Abstract Background The identification of facial emotions is a key skill as it promotes rapid and accurate recognition of emotions and enables better communication and greater social adaptation. More recent studies have suggested that impaired social interactions may be related to deficits in social cognition and therefore in the recognition of facial expressions, contributing to social disturbance among individuals with borderline personality disorder (BPD). Objective To present the results of an empirical study assessing the recognition of facial emotion expressions in women with BPD, having as reference a group of healthy women from the general population. Methods The subjects (40 female with BPD and 40 controls) were assessed with a dynamic task on a computer screen for recognition of facial expressions of emotion. Results The BPD group had a lower accuracy in perceiving emotions of fear and surprise and slowness in recognising happiness. Logistic regression analyses also identified an association between BPD and higher sensitivity in the recognition of anger. Discussion Women with BPD made more mistakes in the recognition of negative emotions, which can bias the behaviour and regulation of affective states, favouring in turn the emergence of some typical symptoms associated with BPD.

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT). Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings.

Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): transcultural adaptation of the Brazilian version

Abstract Background DSM-5 introduced some modifications on Posttraumatic Stress Disorder (PTSD) criteria. The instruments developed for the assessment of aspects related to PTSD needed a reformulation, as was the case of the Posttraumatic Stress Disorder Checklist (PCL). Objectives To present the process of transcultural adaptation of the three forms of the PCL-5 to Brazilian Portuguese, as well as its face validity. Methods The procedure involved independent translations, a synthesis version, back translation by an independent translator, evaluation by the original author, analysis by an expert committee, and a pretesting study (10 subjects with/without experience of a traumatic situation). The last two steps formed the face validity procedure. Results The synthesis version was approved by the original author and the agreement percentage by the expert committee was excellent, with only two items showing < 90%. The pretesting study showed that the Brazilian version was well understood and linguistically and culturally accepted by the participants, which did not make significant suggestions for changes. Discussion Transcultural adaptation of the PCL-5 for Brazilian Portuguese followed a rigid and standardized procedure. Therefore, after having its face validity assessed by an expert committee and by the target population, it is apt to be used.

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and ß-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the ß-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

OBJECTIVES: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. METHODS: Open-label trial conducted in an inpatient psychiatric unit. RESULTS: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. CONCLUSIONS: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder. .

Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans.

Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.

Encefalopatias: etiologia, fisiopatologia e manuseio clínico de algumas das principais formas de apresentação da doença / Encephalopathies: etiology, pathophysiology, and clinical management of some major forms of disease presentation

JUSTIFICATIVA E OBJETIVOS: As encefalopatias compõem um grupo heterogêneo de etiologias, onde a pronta e correta atuação médica direcionada à causa da doença, pode modificar o prognóstico do paciente. O objetivo deste estudo foi rever os aspectos fisiopatológicos das diferentes encefalopatias bem como seus principais fatores desencadeantes e manuseio clínico.CONTEÚDO: Foram selecionadas as mais frequentes encefalopatias observadas na prática clínica e discutir sua fisiopatologia, bem como sua abordagem terapêutica, destacando: encefalopatia hipertensiva, hipóxico-isquêmica, metabólica, Wernicke-Korsakoff, traumática e tóxica.CONCLUSÃO: Trata-se de uma complexa condição clínica que exige rápida identificação e preciso manuseio clínico com o intuito de reduzir sua elevada taxa de morbimortalidade. O atraso no reconhecimento dessa condição clínica poderá ser extremamente prejudicial ao paciente que estará sofrendo lesão cerebral muitas vezes irreversível.

BACKGROUND AND OBJECTIVES: Encephalopathies comprise a heterogeneous group of clinical conditions, in which the prompt and adequate medical intervention can modify patient prognosis. This paper aims to discuss the pathophysiological aspects of different encephalopathies, their etiology, and clinical management.CONTENTS: We selected the main encephalopathies observed in clinical practice, such as hypertensive, hypoxic-ischemic, metabolic, Wernicke-Korsakoff, traumatic, and toxic encephalopathies, and to discuss their therapeutic approaches.CONCLUSION: This is a complex clinical condition that requires rapid identification and accurate clinical management with the aim of reducing its high morbidity and mortality rates. Delay in recognizing this condition can be extremely harmful to the patient who is suffering from often irreversible brain injury.

Genetic analysis of tropical rust resistance in popcorn lines / Análise genética da resistência à ferrugem tropical em linhagens de milho-pipoca

The objectives of this study were to identify promising popcorn lines and hybrids for genetic resistance to tropical rust (Tr, Physopella zeae) in diallel crosses of nine lines derived from a large part of Brazilian popcorn germplasm and to estimate genetic parameters for Tr resistance. Crosses and checks were tested in a random block design, with artificial inoculations under greenhouse conditions. Plots consisted of a single 14-L pot, with four plants. Tr was measured by severity and area under the disease progress curve. Data was analyzed by Griffing's diallel model, and genetic parameters were estimated. Heritability estimates to Tr resistance was medium. Specific combining ability-SCA had significant effects (P<0.10) for resistance, and was eight to nine times larger than general combining ability-GCA (P>0.10). This indicated the major importance of non additive gene effects. In general, breeding possibilities for resistance was restricted. The line 9 (L7.4) had the most outstanding GCA for resistance to Tr, and hybrids 1×7 and 3×6 had outstanding SCA and were recommended for breeding.

Os objetivos deste estudo foram identificar linhagens e híbridos de milho-pipoca promissores quanto à resistência genética à ferrugem tropical (Ftrop, Physopella zeae) em cruzamentos dialélicos, envolvendo nove linhagens derivadas de uma grande parte do germoplasma brasileiro de milho-pipoca, e estimar parâmetros genéticos envolvendo a resistência à Ftrop. Cruzamentos e testemunhas foram testados em delineamento de blocos ao acaso, sob condições de casa-de-vegetação e inoculação artificial. As parcelas consistiram de um vaso de 14 litros, com quatro plantas. A Ftrop foi avaliada pela severidade e pela área abaixo da curva de progresso da doença. Os dados foram analisados pelo modelo dialélico de Griffing e parâmetros genéticos foram estimados. As estimativas de herdabilidade foram médias. A capacidade específica de combinação-CEC teve efeito significativo (P<0,10) para a resistência e foi oito a nove vezes maior que a capacidade geral de combinação-CGC (P>0,10). Isso indicou que os efeitos gênicos não aditivos foram mais importantes. Em geral, as possibilidades de melhoramento foram restritas. A linhagem 9 (L7.4) teve a mais destacada CGC para a resistência e os híbridos 1×7 e 3×6 tiveram destacada CEC e foram recomendados para melhoramento.

Validity of the PHQ-2 for the screening of major depression in Parkinson's disease: two questions and one important answer.

INTRODUCTION: Depression is the most common psychiatric comorbidity in Parkinson's disease (PD), but is often under-diagnosed and under-recognized. OBJECTIVES: To evaluate and compare the psychometric qualities of the Patient Health Questionnaire (PHQ-2) and the depression item of the Unified Parkinson's Disease Rating Scale (UPDRS). METHOD: Cross-sectional study conducted at a movement disorders outpatient clinic. One hundred ten patients with a diagnosis of PD without dementia were evaluated. A neurologist administered the PHQ-2 and the UPDRS, and the diagnosis of major depression was performed using the structured clinical interview for DSM disorders - clinical version. Two self-rating scales (Zung Self-rating Depression Scale and 15-item Geriatric Depression Scale) were also used. RESULTS: The prevalence of current depression in the sample was 25.5% (n = 28). The scores of the PHQ-2 discriminated between subjects with and without depression, with an area under the receiver operating characteristic curve of 0.90. The sensitivity and specificity for a cut-off score of three were 75% and 89%, respectively. The values for the depression item of the UPDRS were slightly lower. CONCLUSION: The PHQ-2 is a valid tool for screening depression in PD.