Vítor Santos

NR4A2 and schizophrenia: Lack of association in a Portuguese/Brazilian study

The present study investigates the association of mutations in the nuclear receptor NR4A2 in schizophrenic patients. The human Nur‐related receptor 1, NR4A2, is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Alone or with retinoid X receptor, RXR, NR4A2 influences the expression of several genes important for human brain development and regulation. In the absence of Nurr1 (the mouse homologue to human NR4A2), ventral mesencephalic dopaminergic mouse neurons evidence severe developmental failure, a condition that is lethal soon after birth. Nurr1 involvement in the dopaminergic system makes it a good candidate for study in neuropsychiatric disorders such as schizophrenia and Parkinson disease. Evidence by others support this hypothesis (1) mapping of the NR4A2 gene to chromosome 2q22‐23, a region with suggestive linkage to schizophrenia and (2) identification of mutations in patients with schizophrenia (c.366‐369delTAC, c.308A > G, c.‐469delG), manic depression (c.289A > G), and familial Parkinsons disease (c.‐291delT, c.‐245T > G). To further extend these observations, we searched for all these mutations in 176 Caucasian Portuguese and 82 Caucasian Brazilian subjects with lifetime diagnosis of schizophrenia. The study failed to identify any of the described mutations in patients or controls. Nevertheless, these negative results do not exclude altered expression of nuclear receptors in schizophrenia or the presence of other mutations.

Contextual Cognitive-Behavioral Therapies Across the Psychosis Continuum

Considering several etiologic, therapeutic, and comorbidity-related factors, a psychosis continuum model has been proposed for the understanding and treatment of psychotic disorders. Within the new emerging treatment approaches, Contextual Cognitive-Behavioral Therapies (CCBT) seem to hold promise for the psychosis continuum. However, considering their novelty for this specific population, the quality of efficacy evidence remains unclear. Objective: To examine, critically analyze, and summarize the results from studies based on therapeutic models within the CCBT approach (Mindfulness and Acceptance-based interventions, Compassion-Focused Therapy, Dialectical Behavior Therapy, and Metacognitive Therapy) for patients with a diagnosis within the psychosis continuum (schizophrenia, schizoaffective disorder, bipolar disorder). Methods: Three leading electronic databases (MEDLINE/PUBMED; PsycINFO; Cochrane Library), a grey literature database (OpenGrey), and registered clinical trials (ClinicalTrials.Gov) were searched using combinations of key terms regarding the CCBT models and the diagnosis considered. Reference lists of the relevant studies and reviews were searched. Only Randomized Controlled Trials (RCTs) were included. The “Cochrane Risk of Bias Assessment Tool” was used for quality assessment. Results: A total of 17 articles were included. This review was based on a majority of unclear or low risk of bias studies. Benefits regarding clinical variables such as psychotic symptoms, anxiety and depression, functioning or quality of life were found. Conclusion: Overall the studies supported some benefits of CCBT approaches for the psychosis continuum. The conceptual perspective on treatment has changed, nevertheless the outcomes assessed are still symptom-focused and there is still need for improvement. Methodological considerations and future directions are presented.

Schizophrenia: An Exploration of an Acceptance, Mindfulness, and Compassion-based Group Intervention

Objective This study aimed to develop and apply a brief (five‐session) group‐based intervention called Compassionate, Mindful and Accepting approach to Psychosis (CMAP) for patients diagnosed with paranoid schizophrenia. Methods The intervention was based on three major approaches: the mindfulness framework adapted for psychosis with the proposed modifications for meditation work, the rationales from Acceptance and Commitment Therapy, and Compassion‐Focused Therapy adapted to psychosis. The intervention was in group format, with one therapist (five 1‐hr sessions). Five patients (male, single, between 22 and 35 years old, Caucasian) completed the intervention. Participants completed self‐report measures at baseline (1-week prior to intervention) and post‐treatment (1-week—additionally the Satisfaction with Intervention Questionnaire). Results The intervention seemed acceptable for all participants. For illustration of potential benefits of this approach, pre‐post results are presented and discussed for two patients. Overall, there was improvement in both patients, although in different measures. Both patients’ conviction in paranoid delusions decreased, while an increase in acting with awareness was observed. Conclusions Although preliminary, the results are in line with previous research in psychosis. Future directions and clinical implications are discussed.

Pathways from paranoid conviction to distress: exploring the mediator role of Fears of Compassion in a sample of people with psychosis

Abstract Fears of Compassion (FOC) relate to experiencing defensive emotions and avoidance reactions when receiving and giving compassion. Three different flows have been identified: giving compassion to others, receiving compassion, and self-compassion. This study sought to explore: FOC within a sample of patients with psychosis; the associations between FOC and paranoia; and the mediator role of FOC in the relationship between paranoid conviction and distress. Seventy-two patients with psychosis (74% diagnosed with schizophrenia), mostly male (85%), with a mean age of 33.46 (SD = 9.43), were recruited and assessed with measures of paranoia (conviction and distress) and FOC. Participants presented significantly higher levels of FOC than non-clinical samples and lower levels than depressed patients. Different flows of FOC were associated with each other and with paranoia-related measures. A mediation effect of FOC from others and fears of self-compassion was found. Results support the relevance of including FOC in formulation and treatment protocols for psychosis.

Neural connectivity in youth at-risk for bipolar disorder: a review of functional magnetic resonance imaging studies

Background: Delayed diagnosis of bipolar disorder (BD) is common in adolescents and young adults and the search for biomarkers to help in early diagnosis in BD at-risk populations is an important goal of neuroimaging research. Functional connectivity studies in BD patients suggests that anomalous connectivity between prefrontal and limbic regions could be risk biomarkers for BD. The aim of this review is to provide an overview of the neuroimaging literature that employed functional connectivity techniques in adolescents and young adults at-risk for BD.