Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.

Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis.

BACKGROUND: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD. METHOD: Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions. RESULTS: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52). CONCLUSIONS: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.

Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.

BACKGROUND: Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples. METHODS: The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics. RESULTS: From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings. LIMITATIONS: Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets. CONCLUSION: This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.

The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.

BACKGROUND: Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment. OBJECTIVE: A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement. METHODS: A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device. RESULTS: The overall retention rate was 60%. Higher-intensity treatment (χ21=4.6; P=.03) and higher baseline anxiety (t56.28=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t50.4=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list. CONCLUSIONS: Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.

Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.

INTRODUCTION: Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment. METHODS AND ANALYSIS: This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/PMYTA.

Clinical Targets and Attitudes Toward Implementing Digital Health Tools for Remote Measurement in Treatment for Depression: Focus Groups With Patients and Clinicians.

BACKGROUND: Remote measurement technologies, such as smartphones and wearable devices, can improve treatment outcomes for depression through enhanced illness characterization and monitoring. However, little is known about digital outcomes that are clinically meaningful to patients and clinicians. Moreover, if these technologies are to be successfully implemented within treatment, stakeholders' views on the barriers to and facilitators of their implementation in treatment must be considered. OBJECTIVE: This study aims to identify clinically meaningful targets for digital health research in depression and explore attitudes toward their implementation in psychological services. METHODS: A grounded theory approach was used on qualitative data from 3 focus groups of patients with a current diagnosis of depression and clinicians with >6 months of experience with delivering psychotherapy (N=22). RESULTS: Emerging themes on clinical targets fell into the following two main categories: promoters and markers of change. The former are behaviors that participants engage in to promote mental health, and the latter signal a change in mood. These themes were further subdivided into external changes (changes in behavior) or internal changes (changes in thoughts or feelings) and mapped with potential digital sensors. The following six implementation acceptability themes emerged: technology-related factors, information and data management, emotional support, cognitive support, increased self-awareness, and clinical utility. CONCLUSIONS: The promoters versus markers of change differentiation have implications for a causal model of digital phenotyping in depression, which this paper presents. Internal versus external subdivisions are helpful in determining which factors are more susceptible to being measured by using active versus passive methods. The implications for implementation within psychotherapy are discussed with regard to treatment effectiveness, service provision, and patient and clinician experience.

A systematic review of engagement reporting in remote measurement studies for health symptom tracking.

Remote Measurement Technologies (RMTs) could revolutionise management of chronic health conditions by providing real-time symptom tracking. However, the promise of RMTs relies on user engagement, which at present is variably reported in the field. This review aimed to synthesise the RMT literature to identify how and to what extent engagement is defined, measured, and reported, and to present recommendations for the standardisation of future work. Seven databases (Embase, MEDLINE and PsycINFO (via Ovid), PubMed, IEEE Xplore, Web of Science, and Cochrane Central Register of Controlled Trials) were searched in July 2020 for papers using RMT apps for symptom monitoring in adults with a health condition, prompting users to track at least three times during the study period. Data were synthesised using critical interpretive synthesis. A total of 76 papers met the inclusion criteria. Sixty five percent of papers did not include a definition of engagement. Thirty five percent included both a definition and measurement of engagement. Four synthetic constructs were developed for measuring engagement: (i) engagement with the research protocol, (ii) objective RMT engagement, (iii) subjective RMT engagement, and (iv) interactions between objective and subjective RMT engagement. The field is currently impeded by incoherent measures and a lack of consideration for engagement definitions. A process for implementing the reporting of engagement in study design is presented, alongside a framework for definition and measurement options available. Future work should consider engagement with RMTs as distinct from the wider eHealth literature, and measure objective versus subjective RMT engagement.Registration: This review has been registered on PROSPERO [CRD42020192652].

Digital health tools for the passive monitoring of depression: a systematic review of methods.

The use of digital tools to measure physiological and behavioural variables of potential relevance to mental health is a growing field sitting at the intersection between computer science, engineering, and clinical science. We summarised the literature on remote measuring technologies, mapping methodological challenges and threats to reproducibility, and identified leading digital signals for depression. Medical and computer science databases were searched between January 2007 and November 2019. Published studies linking depression and objective behavioural data obtained from smartphone and wearable device sensors in adults with unipolar depression and healthy subjects were included. A descriptive approach was taken to synthesise study methodologies. We included 51 studies and found threats to reproducibility and transparency arising from failure to provide comprehensive descriptions of recruitment strategies, sample information, feature construction and the determination and handling of missing data. The literature is characterised by small sample sizes, short follow-up duration and great variability in the quality of reporting, limiting the interpretability of pooled results. Bivariate analyses show consistency in statistically significant associations between depression and digital features from sleep, physical activity, location, and phone use data. Machine learning models found the predictive value of aggregated features. Given the pitfalls in the combined literature, these results should be taken purely as a starting point for hypothesis generation. Since this research is ultimately aimed at informing clinical practice, we recommend improvements in reporting standards including consideration of generalisability and reproducibility, such as wider diversity of samples, thorough reporting methodology and the reporting of potential bias in studies with numerous features.

Comparison of short-term (saliva) and long-term (hair) cortisol levels in out-patients with melancholic and non-melancholic major depression.

BACKGROUND: Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration. METHOD: Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva - the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) - were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures. RESULTS: The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs. CONCLUSIONS: The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.

Cortisol levels in chronic fatigue syndrome and atypical depression measured using hair and saliva specimens.

BACKGROUND: Several diagnostic criteria for major depressive disorder (MDE) overlap with those of Chronic Fatigue Syndrome (CFS). Furthermore, atypical MDE (A-MDE), a subtype of MDE characterised by profound fatigue and which has frequently been linked with CFS, exhibits similar low cortisol levels to CFS. However, this result has been only found in specimens designed for measuring acute cortisol levels. In this study, we measure cortisol levels in subjects with CFS and in subjects with A-MDE, without psychiatric comorbidity, using both hair and saliva specimens, to gain a measure of both short and long-term cortisol levels in these two conditions. METHODS: Hair cortisol concentration, representing the cortisol concentration of the previous three months, and salivary cortisol, measured at six time-points across one day and including the cortisol awakening response (CAR), post-awakening delta cortisol and the total daily output, were assessed in an age and gender matched group of 34 controls, 15 subjects with A-MDE and 17 with CFS. RESULTS: CFS (mean 92.2 nmol/l.h, s.d. 33.2 nmol/l.h) and A-MDE (mean 89.1 nmol/l.h, s.d. 22.6 nmol/l.h) subjects both showed lower cortisol total daily output in saliva (AUCg) in comparison to healthy controls (mean 125.5 nmol/l.h, s.d. 40.6 nmol/l.h). However, hair cortisol concentration was not lower than that of controls in either patient group. CFS and A-MDE did not differ from one another on any cortisol measures. CFS subjects reported fewer daily hassles and less severe psychic anxiety symptoms in comparison to A-MDE subjects (all p < 0.05). However, they did not differ in the severity of somatic anxiety symptoms. There was also no difference in the presence of overlapping symptoms such as fatigability and concentration/memory problems between A-MDE and CFS subjects. CONCLUSION: Low levels of cortisol found using short-term measures of daily output may be transient, since cortisol levels were normal when a long-term measure (hair) was studied. This might be explained by a potential cortisol rhythm alteration. Although these disorders have their distinctive depressive and somatic features, they may from part of a wider group of Somatic Symptom Disorders (SSD), given the findings of the same pattern of cortisol secretion in both disorders and increased frequency of overlapping clinical features.

Cortisol levels in unmedicated patients with unipolar and bipolar major depression using hair and saliva specimens.

BACKGROUND: Differentiating between unipolar and bipolar depression can be clinically challenging, especially at first presentation. Patterns of cortisol secretion could aid diagnostic discrimination in affective disorders although there has been little comparative research to date. In this study, we investigated acute (saliva) and chronic (hair) cortisol levels concurrently in unmedicated unipolar and bipolar disorders by using conventional diagnostic criteria and self-report measures. METHODS: Patients with unipolar and bipolar major depression and healthy controls were recruited and assessed. Cortisol levels were extracted from saliva and hair specimens. Depressive features were investigated according to diagnostic groups and with a continuous self-report measure of bipolarity using the Hypomania Checklist (HCL-33). RESULTS: Whilst a trend towards a reduction in the total daily salivary cortisol output-area under the curve with respect to the ground (AUCg)-was detected in depressive disorders across diagnosis, the self-administrated bipolarity index suggested that an increase in bipolarity symptoms predicted lower cortisol levels using AUCg. Chronic cortisol measurement did not discriminate unipolar from bipolar depression. CONCLUSION: Results suggested that whilst a low total daily salivary cortisol output (AUCg) might be associated with depressive symptoms, a self-reported measure of bipolarity predicts lower daily cortisol output.

Early psychosis detection program in Chile: A first step for the South American challenge in psychosis research.

AIM: Early detection and intervention (EDI) is a main challenge in psychosis research. The Chilean schizophrenia (SZ) national program has universal support and treatment by law for all SZ patients, but this does not yet extend to earlier stages of illness. Therefore, we have piloted an ultra-high risk (UHR) program to demonstrate the utility and feasibility of this public health approach in Chile. METHODS: We introduce "The University of Chile High-risk Intervention Program," which is the first national EDI program for UHR youths. Longitudinal follow-up included clinical and cognitive assessments, and monitoring of physiological sensory and cognitive indices, through electroencephalographic techniques. RESULTS: We recruited 27 UHR youths over 2 years. About 92.6% met criteria for attenuated psychosis syndrome (APS). Mean Scale of Psychosis-Risk Symptoms (SOPS) ratings in the cohort were 6.9 (SD 4.6) for positive, 9.1 (SD 8.3) for negative, 5.4 (SD 5.3) for disorganized and 6.3 (SD 4.1) for general symptoms. About 14.8% met criteria for comorbid anxiety disorders and 44.4% for mood disorders. Most participants received cognitive behavioural therapy (62.9%) and were prescribed low dose antipsychotics (85.2%). The transition rate to psychosis was 22% within 2 years. CONCLUSIONS: We describe our experience in establishing the first EDI program for UHR subjects in Chile. Our cohort is similar in profile and risk to those identified in higher-income countries. We will extend our work to further optimize psychosocial and preventive interventions, to promote its inclusion in the Chilean SZ national program and to establish a South American collaboration network for SZ research.

The relative prevalence of schizophrenia among cannabis and cocaine users attending addiction services.

BACKGROUND: Cannabis and cocaine are the most common illicit drugs for which people are treated in addiction services in Latin America. Much research has suggested that the use of cannabis increases the risk of schizophrenia; there is less evidence concerning cocaine. The aim of the present study was to establish the relative prevalence of schizophrenia in people treated for cannabis use and cocaine use disorders in Chile. METHODS: A sample of 22,615 people treated for illicit drug use disorders was obtained from a national registry of addiction service users in Chile. Clinical diagnoses were established at admission to substance use treatment programs or at any point during the period of treatment. Prevalence rates of schizophrenia and related disorders, and affective disorders were calculated for the groups of people with cocaine use disorders, and cannabis use disorders. Odds ratios (OR) for schizophrenia and for affective disorders were calculated for cannabis users using the group of people treated for cocaine use disorders as reference category. RESULTS: The prevalence of schizophrenia and related disorders was 1.1% in those with cocaine use disorders, but 5.2% in those with cannabis use disorders (OR 4.9; p<0.01). The prevalence of affective disorders was 9.3% in cocaine use disorders, and 13.2% in cannabis use disorders (OR 1.5; p<0.01). CONCLUSIONS: The prevalence of schizophrenia and to a lesser extent affective disorders is higher among people with cannabis use disorder than cocaine use disorder among those attending addiction services.

Cortisol levels in fingernails, neurocognitive performance and clinical variables in euthymic bipolar I disorder.

OBJECTIVES: Neurocognitive impairment has been found in bipolar patients. Hypercortisolemia is one possible cause but there has been no agreement on this. Previous sampling methods assessed only acute cortisol levels, whereas the association between cortisol and psychopathology might be better understood by investigating chronic levels. Fingernails are a novel method for measuring chronic cortisol concentration (CCC). Here, we measured CCC in euthymic bipolar disorder I (BD-I) patients and healthy controls using fingernails to investigate whether differences in CCC influenced neurocognitive performance. We also investigated whether differences in clinical illness variables influenced CCC in euthymic BD-I patients. METHODS: A previous study demonstrated neurocognitive impairment in euthymic BD-I patients. The current study included a portion of this sample: 40 BD-I versus 42 matched controls who provided fingernail samples. RESULTS: There was no statistically significant difference in CCC between controls and BD-I (P = .09). Logistic regression analyses revealed that euthymic bipolar I subjects with more than five years of current euthymia had decreased odds of having higher fingernail cortisol concentration (>71.2 pg/mg) compared to those with less than 1.5 years (P = .04). There was no association between CCC and cognitive impairment in all domains before and after adjustment for age and sex. CONCLUSIONS: The current evidence suggests CCC is not a trait biomarker in euthymic BD-I (BD-I). Longer periods of stability in affective disorders are associated with lower CCC. Fingernail cortisol does not seem to be implicated in neurocognitive impairment and BD-I. Future studies may investigate CCC in different illness phases of BD-I.

Elevated fingernail cortisol levels in major depressive episodes.

BACKGROUND: The extent to which cortisol levels are elevated in major depressive episodes (MDE), and hence could act as a biomarker of illness, remains unclear. Although patient characteristics may explain some of this variation - for example elevated cortisol being more often found in patients with severe, psychotic or melancholic depression - problems with the methods used to measure cortisol may also have contributed to the inconsistent findings. Fingernails are a novel sample that can be used to assess aggregate cortisol concentrations over a 15-day period, and may provide a more accurate reflection of longer term cortisol level changes in MDE and help clarify this issue. This methodology has not yet been utilised in MDE. METHODS: Cortisol levels reflecting a period of 15days were measured using fingernails in a group of 26 subjects experiencing a major depressive episode (MDE) and in an age and gender matched group of 45 healthy controls. RESULTS: Depressed subjects showed significantly higher mean cortisol levels measured in fingernails when compared with control subjects. Higher levels of cortisol were associated with higher depression severity scores, a diagnosis of non-reactive depression, and more prominent melancholic symptoms. Conversely, fatigue was negatively correlated with cortisol levels. CONCLUSION: There is elevated cortisol in MDE when assessed using an aggregate measure over two weeks.Alterations in fingernail cortisol correlate with key clinical symptoms and subtypes of depression.

Cognitive impairment in agricultural workers and nearby residents exposed to pesticides in the Coquimbo Region of Chile.

Chronic exposure to organophosphate pesticides is a worldwide public health concern associated with several psychiatric disorders and dementia. Most existing studies on the effects of pesticides only evaluate agricultural workers. Therefore, this study sought to establish if individuals indirectly exposed to pesticides, such as residents in agricultural areas, also suffer cognitive impairments. Neuropsychological evaluations were carried out on three groups (n=102): agricultural workers directly exposed to pesticides (n=32), individuals living in agricultural areas indirectly (i.e. environmentally) exposed to pesticides (n=32), and an unexposed control group (n=38). The assessed cognitive processes included memory, executive functions, attention, language praxis, and visuoconstruction. The direct exposure group performed significantly lower in executive function, verbal fluency, and visual and auditory memory tests than the indirect exposure group, which, in turn, performed worse than the unexposed group. Even after adjusting for age, gender, and educational level, both exposure groups showed higher rates of cognitive deficit than control individuals. In conclusion, both direct and indirect chronic exposure to pesticides affects cognitive functioning in adults and, consequently, actions should be taken to protect the health of not only agricultural workers, but also of residents in agricultural areas.

The feasibility and acceptability of a preventive intervention programme for children with depressed parents: study protocol for a randomised controlled trial.

BACKGROUND: One of the most important risk factors for childhood depression is being the child of a depressed parent. These at-risk children have two to four times the probability of having an affective episode compared with their peers. Preventive interventions such as Beardslee's Preventive Intervention Program (PIP) that are targeted at children of depressed parents have proven effective in many countries. The PIP is a family-based approach that works by promoting resilience in children and increasing positive interactions within the family. In this pilot randomised controlled trial (RCT), we will determine the acceptability and feasibility of an adapted version of this intervention in Chile. METHODS/DESIGN: We are conducting a pilot RCT with a manualized intervention. The intervention will be delivered in seven weekly sessions at the family home. It is targeted mostly at parents but will also measure outcomes among the children. Control subjects will follow their treatment as usual. Feasibility and acceptability will be assessed by recruitment, adherence, dropout and level of missing data, as well as the burden of scales and measurement tools. Families will be followed for 11 months. DISCUSSION: Given the negative lifelong consequences of depression and the burden they represent, preventive programmes are not only feasible but necessary. Despite the successful implementation of this intervention in different countries, an adaptation to the Chilean reality will be prerequisite. The results of this pilot study will inform a definitive trial that will make the case for its national implementation. TRIAL REGISTRATION: Clinicaltrials.gov trial identifier: NCT02593266 . Registration date: 30 Octo 2015.

Association between Unmet Needs and Clinical Status in Patients with First Episode of Schizophrenia in Chile.

BACKGROUND: Schizophrenia is a severe mental disorder involving needs in several matters that are often not covered. A need is defined as a gap between the ideal state and the current state of a patient about a specific topic. AIM: To describe needs in patients with first episode of schizophrenia at the start of treatment and to describe associated clinical factors. METHODS: Observational descriptive cross-sectional design. Patients were over 15 years old, with first episode schizophrenia, and admitted to treatment in the public health system from six districts in two cities of Chile, between 2005 and 2006. Sociodemographic data, clinical evaluations of current psychosis based on the Positive and Negative Syndrome Scale (PANSS), and the time of untreated psychosis were obtained. A clinical interview was carried out followed by the Camberwell Assessment of Need. RESULTS: Twenty-nine patients were evaluated, 79.3% male, mean age 21.9 years old. The areas with more needs reported were; psychotic symptoms with 65.5% of sample, 21.1% of which reported it unmet; and daytime activities, where 44.8% of patients reported a need, 61.54% of them as unmet. The percentage of unmet needs correlated with PANSS score (r = 0.55; p = 0.003), and with time of positive symptoms prior to diagnosis (r = 0.416; p = 0.03). DISCUSSION: Needs assessment in schizophrenia is necessary. It may affect its clinical course, be relevant in its management, and help monitor recovery. Defining the main needs in people with first episode schizophrenia and associated factors allows for a better design of treatment strategies in order to obtain better therapeutic results and recovery.