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Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.

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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.

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Objective: Patients with chronic hepatitis C (CHC) have a poorer quality of life than those with other chronic liver diseases. However, some of the factors that determine health-related quality of life (HRQOL) in these patients, such as the degree of liver fibrosis, are still controversial. Therefore, the aim of the present study was to investigate the impact of CHC on HRQOL by conducting clinical, psychiatric, and sociodemographic evaluations. Methods: One hundred and twenty-four consecutive patients attending a referral center for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview, the Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Multiple linear regression analyses were used to quantify independent associations between HRQOL and the clinical, psychiatric, and sociodemographic variables of interest. Results: Reduced HRQOL was independently associated with major depressive disorder (MDD) and with elevated levels of alanine aminotransferase, but was not associated with hepatic cirrhosis. Conclusions: MDD rather than the grade of liver fibrosis was strongly associated with HRQOL impairment in patients with CHC. These findings highlight that, in patients with CHC, the psychological effects of the disease deserve more attention and the implementation of integrated medical, psychiatric, and psychological care may be helpful.

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Objectives: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. Methods: The sample consisted of 8,646 individuals (24.7% men and 75.3% women) who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Temperament and Character Inventory - Revised (TCI-R), respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Results: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Conclusions: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

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Objective: To evaluate the dichotomy of type I/II and type A/B alcoholism typologies in opiate-dependent patients with a comorbid alcohol dependence problem (ODP-AP). Methods: The validity assessment process comprised the information regarding the history of alcohol use (internal validity), cognitive-behavioral variables regarding substance use (external validity), and indicators of treatment during 6-month follow-up (predictive validity). Results: ODP-AP subjects classified as type II/B presented an early and much more severe drinking problem and a worse clinical prognosis when considering opiate treatment variables as compared with ODP-AP subjects defined as type I/A. Furthermore, type II/B patients endorse more general positive beliefs and expectancies related to the effect of alcohol and tend to drink heavily across several intra- and interpersonal situations as compared with type I/A patients. Conclusions: These findings confirm two different forms of alcohol dependence, recognized as a low-severity/vulnerability subgroup and a high-severity/vulnerability subgroup, in an opiate-dependent population with a lifetime diagnosis of alcohol dependence.

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Objective: Peritraumatic reactions feature prominently among the main predictors for development of posttraumatic stress disorder (PTSD). Peritraumatic tonic immobility (PTI), a less investigated but equally important type of peritraumatic response, has been recently attracting the attention of researchers and clinicians for its close association with traumatic reactions and PTSD. Our objective was to investigate the role of PTI, peritraumatic panic, and dissociation as predictors of PTSD symptoms in a cohort of police recruits (n=132). Methods: Participants were asked to complete the following questionnaires during academy training and after the first year of work: Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C), Physical Reactions Subscale (PRS), Peritraumatic Dissociative Experiences Questionnaire (PDEQ), Tonic Immobility Scale (TIS), and Critical Incident History Questionnaire. Results: Employing a zero-inflated negative binomial regression model, we found that each additional point in the TIS was associated with a 9% increment in PCL-C mean scores (RM = 1.09), whereas for PRS, the increment was 7% (RM = 1.07). As the severity of peritraumatic dissociation increased one point in the PDEQ, the chance of having at least one symptom in the PCL-C increased 22% (OR = 1.22). Conclusions: Our findings highlight the need to expand investigation on the incidence and impact of PTI on the mental health of police officers.

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Objective: War veterans are at high risk of developing posttraumatic stress disorder (PTSD), and the development of brief self-report instruments that enable screening for PTSD in this population is crucial. The PTSD Checklist-Military Version (PCL-M) is widely used for this purpose. This study sought to explore the diagnostic utility of the Portuguese version of the PCL-M. Methods: The participants were 86 Portuguese Colonial War veterans (42 with a PTSD diagnosis and 44 without PTSD). Participants completed a self-report instrument designed to collect sociodemographic data, the PCL-M, and the Clinician-Administered PTSD Scale (CAPS). Results: The area under the receiver operator characteristic (ROC) curve showed excellent discriminant ability between subjects with and without PTSD (AUC = 0.94). To achieve a positive PTSD diagnosis, an optimal cutoff point of 49 for the PCL-M total score and cutoff points for each of its 17 items are recommended. Conclusions: This work is a relevant contribution for research and clinical practice in the vast population of Portuguese Colonial War veterans. Use of the PCL-M as a screening tool for PTSD symptoms will allow easier, resource-aware targeting of subjects with a potential PTSD diagnosis, adding to the improvement of public health in Portugal.

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Objective: To evaluate the impact of a training program on autism spectrum disorder (ASD) identification offered to Brazilian health professionals. Methods: Twenty-two primary care providers participated in five 3-hour weekly training sessions. Results: The trained providers significantly improved their ASD knowledge after training in comparison with pre-training (mean score, 6.73 vs. 9.18, p < 0.01). Clinical practice also changed: 4 months after the training program, the providers had referred six times as many suspected cases of ASD to a specialized mental health service in comparison with the previous 4 months. Conclusion: This pilot training model seems a promising, feasible, and inexpensive way to improve early identification of ASD in the primary care system.

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Objective: To estimate the economic consequences of the current Brazilian government policy for attention-deficit/hyperactivity disorder (ADHD) treatment and how much the country would save if treatment with immediate-release methylphenidate (MPH-IR), as suggested by the World Health Organization (WHO), was offered to patients with ADHD. Method: Based on conservative previous analyses, we assumed that 257,662 patients aged 5 to 19 years are not receiving ADHD treatment in Brazil. We estimated the direct costs and savings of treating and not treating ADHD on the basis of the following data: a) spending on ADHD patients directly attributable to grade retention and emergency department visits; and b) savings due to impact of ADHD treatment on these outcomes. Results: Considering outcomes for which data on the impact of MPH-IR treatment are available, Brazil is probably wasting approximately R$ 1.841 billion/year on the direct consequences of not treating ADHD in this age range alone. On the other hand, treating ADHD in accordance with WHO recommendations would save approximately R$ 1.163 billion/year. Conclusions: By increasing investments on MPH-IR treatment for ADHD to around R$ 377 million/year, the country would save approximately 3.1 times more than is currently spent on the consequences of not treating ADHD in patients aged 5 to 19 years.

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Objective: Schizophrenia is one of the most severe psychiatric disorders, and its current treatment relies on antipsychotic medications with only partial effectiveness. Clozapine is an atypical antipsychotic with a specific profile of action indicated for treatment-resistant schizophrenia. Neuroimaging studies assessing the effects of clozapine could help shed light on the neural underpinnings of the effects of this drug in the brain. The objective of this study was to review the available literature on the structural and functional neuroimaging findings associated with use of clozapine. Method: We conducted a systematic review of the indexed literature using the PubMed, BIREME, and ISI Web of Knowledge search engines and the following keywords: clozapine, neuroimaging, computed tomography, MRI, functional magnetic resonance, PET, SPECT, and DTI. Results: A total of 23 articles were included in the review. In structural studies, the use of clozapine was associated with volume reductions in the basal ganglia, especially the caudate nucleus, where functional neuroimaging studies also found decreased perfusion. In the frontal lobe, clozapine treatment was associated with increased gray matter volume and reduced perfusion. Conclusion: The results of the studies reviewed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics.