EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

Effects of Mediterranean diet or mindfulness-based stress reduction on fetal and neonatal brain development: a secondary analysis of a randomized clinical trial.

BACKGROUND: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment. OBJECTIVE: This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development. STUDY DESIGN: This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes. RESULTS: When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm3; standard deviation, 23.92 cm3 vs 294.01 cm3; standard deviation, 26.29 cm3; P=.04), corpus callosum (mean, 1.16 cm3; standard deviation, 0.19 cm3 vs 1.26 cm3; standard deviation, 0.22 cm3; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm3 vs 46.60; standard deviation, 4.69 cm3; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m3 vs 1.79; standard deviation, 0.30 cm3; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01). CONCLUSION: Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development.

Manic episode in a patient with pancreatic adenocarcinoma: a case report.

Psychiatric comorbidity is common in cancer patients, emphasizing the need for comprehensive care. While depressive symptoms in pancreatic cancer have been studied, there is limited attention given to manic symptoms. This case report aims to contribute to the knowledge of pancreatic cancer psychiatric comorbidities by describing a case of a patient with stage IV pancreatic cancer who presented a sudden onset manic episode. The patient, a 61-year-old male with stage IV pancreatic cancer, presented at the Emergency Room with abrupt behavioural changes suggestive of a manic episode of 2 weeks of evolution. The patient had been undergoing chemotherapy and short 3-day cycles of corticosteroids for the past 9 months but had been off this treatment for 20 days when the episode began. Acute organic causes were ruled out. The patient was admitted to the psychiatric unit, where organic screening was expanded and treatment with antipsychotics and a mood stabiliser was initiated with subsequent remission of symptoms after 2 weeks. This case shows a manic episode as a rare psychiatric complication in pancreatic cancer. In the literature reviewed, four other similar cases have been observed. Further research is needed to elucidate the underlying pathophysiology and explore possible treatment strategies.

Effect of a Mediterranean Diet or Mindfulness-Based Stress Reduction During Pregnancy on Child Neurodevelopment: A Prespecified Analysis of the IMPACT BCN Randomized Clinical Trial.

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, Setting, and Participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks' gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main Outcomes and Measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (ß, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (ß, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (ß, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and Relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

Cognitive Behavioral Therapy Program for Cannabis Use Cessation in First-Episode Psychosis Patients: A 1-Year Randomized Controlled Trial.

Despite the negative influence of cannabis use on the development and prognosis of first-episode psychosis (FEP), there is little evidence on effective specific interventions for cannabis use cessation in FEP. The aim of this study was to compare the efficacy of a specific cognitive behavioral therapy (CBT) for cannabis cessation (CBT-CC) with treatment as usual (TAU) in FEP cannabis users. In this single-blind, 1-year randomized controlled trial, 65 participants were randomly assigned to CBT-CC or TAU. The primary outcome was the reduction in cannabis use severity. The CBT-CC group had a greater decrease in cannabis use severity and positive psychotic symptoms over time, and a greater improvement in functioning at post-treatment than TAU. The treatment response was also faster in the CBT-CC group, reducing cannabis use, anxiety, positive and general psychotic symptoms, and improving functioning earlier than TAU in the follow-up. Moreover, patients who stopped and/or reduced cannabis use during the follow-up, decreased psychotic symptoms and increased awareness of disease compared to those who continued using cannabis. Early intervention based on a specific CBT for cannabis cessation, may be effective in reducing cannabis use severity, in addition to improving clinical and functional outcomes of FEP cannabis users.

Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights in Newborns Born to At-Risk Pregnant Individuals: The IMPACT BCN Randomized Clinical Trial.

Importance: Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. Objective: To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes. Design, Setting, and Participants: Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks' gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020). Interventions: Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols. Main Outcomes and Measures: The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity). Results: Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], -7.9 [95% CI, -13.6 to -2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, -6.3 [95% CI, -11.8 to -0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, -7.6 [95% CI, -13.4 to -1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, -6.8 [95% CI, -12.6 to -0.3]; P = .02). Conclusions and Relevance: In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

Mediterranean diet, Mindfulness-Based Stress Reduction and usual care during pregnancy for reducing fetal growth restriction and adverse perinatal outcomes: IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa): a study protocol for a randomized controlled trial.

BACKGROUND: Fetal growth restriction (FGR) affects 7-10% of all pregnancies resulting in a higher risk of perinatal morbidity and mortality, long-term disabilities, and cognitive impairment. Due to its multifactorial etiology, changes in maternal lifestyle, including suboptimal maternal diet and stress, have increasingly been associated with its prevalence. We present a protocol for the Improving Mothers for a better PrenAtal Care Trial Barcelona (IMPACT BCN), which evaluates two different maternal lifestyle strategies (improved nutrition by promoting Mediterranean diet and stress reduction program based on mindfulness techniques) on perinatal outcomes. The primary objective is to reduce the prevalence of FGR. Secondary aims are to reduce adverse perinatal outcomes and to improve neurodevelopment and cardiovascular profile in children at 2 years of age. METHODS: A randomized parallel, open-blind, single-center trial following a 1:1:1 ratio will select and randomize high-risk singleton pregnancies for FGR (N=1218), according to the criteria of the Royal College of Obstetricians and Gynaecologists (19.0-23.6 weeks' gestation), into three arms: Mediterranean diet, mindfulness-based stress reduction program, and usual care without any intervention. Compliance to the interventions will be randomly tested in 30% of participants with specific biomarkers. Maternal socio-demographic, clinical data, biological samples, and lifestyle questionnaires will be collected at enrollment and at the end of the interventions (34.0-36.6 weeks' gestation), together with a fetoplacental ultrasound and magnetic resonance. Fetoplacental biological samples and perinatal outcomes will be recorded at delivery. Postnatal follow-up is planned up to 2 years of corrected age including neurodevelopmental tests and cardiovascular assessment. Intention-to-treat and population per-protocol analysis will be performed. DISCUSSION: This is the first randomized study evaluating the impact of maternal lifestyle interventions during pregnancy on perinatal outcomes. The maternal lifestyle interventions (Mediterranean diet and mindfulness-based stress reduction program) are supported by scientific evidence, and their compliance will be evaluated with several biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166332 . Registered on April 19, 2017.

Effects of an integrative approach to bipolar disorders combining psychoeducation, mindfulness-based cognitive therapy and functional remediation: Study protocol for a randomized controlled trial.

INTRODUCTION: Bipolar disorder is related to a high level of personal, familial, social and economic burden. There is a need for feasible adjunctive psychological interventions easy to implement in clinical practice in order to enhance aspects that medication alone cannot achieve. This study aims to evaluate the impact of a 12-session adjunctive integrative program designed for patients with bipolar disorder. METHODS: This is a single-blind prospective, randomized controlled trial involving a total of 132 outpatients with bipolar disorder who will be recruited from the Hospital Clinic of Barcelona. All participants will be randomly assigned to two arms. All the patients will receive treatment as usual (TAU) but in addition the experimental group will receive an integrative approach consisting of 12-sessions of 90min each in which contents of psychoeducation for patients have been combined with a session for family members, and complemented with aspects related to health promotion, mindfulness training, and strategies for cognitive and functional enhancement. The whole sample will be assessed at baseline, after completion (3-months) and at 12 months from baseline regarding demographic and clinical variables, psychosocial and cognitive functioning, wellbeing and quality of life. The primary outcome measure will be improvement in psychosocial functioning. CONCLUSIONS: If the integrative approach is effective, it would allow clinicians to cover different areas that may be affected by bipolar disorder, by means of a brief intervention that can therefore be easily generalized to clinical practice. TRIAL REGISTRATION: NCT04031560. Date registered July 24, 2019.

Lighting as an aid for recovery in hospitalized psychiatric patients: a randomized controlled effectiveness trial.

Purpose: Artificial indoor lighting can disturb sleep and increase depressive symptoms; both common complaints in psychiatric inpatients. In this trial we aimed to improve sleep in psychiatric inpatients using a circadian lighting environment.Patients and methods: Investigator-blinded parallel-group randomised controlled effectiveness trial in an inpatient psychiatric ward with adjustable lighting. Admitted patients received a pre-set circadian lighting environment (intervention group) or lighting as usual (control group). The primary outcome was the Pittsburg Sleep Quality Index (PSQI) and secondary outcomes included the Major Depression Inventory and WHO-5 Well-Being Index.Results: We assessed 74 patients and included 54 (27 treated and 27 controls). Treated patients reported a non-significant change in mean sleep quality by -1.02 points on the PSQI (95% CI: -3.17; 1.12) and controls by -0.59 points (95% CI: -2.52; 1.33), difference -0.43 (95% CI: -3.05; 2.2, p-value .74). Similarly, treated patients reported a non-significant change in depressive symptoms and well-being compared to controls. Qualitative data indicated no serious side-effects and no patients in the intervention group were submitted to involuntary measures. Collection of data was non-complete and missing data from self-reported questionnaires amounted to 52.5%.Conclusions: The intervention showed no effect on sleep quality, mood or well-being. The circadian lighting environment was safe in our small and diverse patient sample. The trial integrated well with routine clinical care and our sample reflected the heterogeneity of the target population.

Improving Functioning, Quality of Life, and Well-being in Patients With Bipolar Disorder.

People with bipolar disorder frequently experience persistent residual symptoms, problems in psychosocial functioning, cognitive impairment, and poor quality of life. In the last decade, the treatment target in clinical and research settings has focused not only on clinical remission, but also on functional recovery and, more lately, in personal recovery, taking into account patients' well-being and quality of life. Hence, the trend in psychiatry and psychology is to treat bipolar disorder in an integrative and holistic manner. This literature review offers an overview regarding psychosocial functioning in bipolar disorder. First, a brief summary is provided regarding the definition of psychosocial functioning and the tools to measure it. Then, the most reported variables influencing the functional outcome in patients with bipolar disorder are listed. Thereafter, we include a section discussing therapies with proven efficacy at enhancing functional outcomes. Other possible therapies that could be useful to prevent functional decline and improve functioning are presented in another section. Finally, in the last part of this review, different interventions directed to improve patients' well-being, quality of life, and personal recovery are briefly described.

Depressive mood and circadian rhythms disturbances as outcomes of seasonal affective disorder treatment: A systematic review.

BACKGROUND: The present systematic review was aimed at critically summarizing the evidence about interventions focused on circadian rhythms and mood symptoms in seasonal affective disorder (SAD). METHODS: A systematic search of the electronic databases PUBMED, PsycINFO and Web of Science was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original papers reporting data about the effects of treatments on both mood and circadian rhythms disturbances in SAD patients were considered for inclusion. The quality of the evidence provided by the eligible studies was assessed using the Revised Cochrane Risk of Bias Tool (RoB 2.0) and the Cochrane Risk of Bias in Non-Randomized Studies of Interventions Tool (ROBINS-I). RESULTS: Forty papers were deemed eligible for the systematic review. The evidence of treatment outcomes referring to circadian disturbances was not robust. Despite this, bright light therapy (BLT) demonstrates to phase-advance delayed rhythms and to improve sleep-wake disorders. As for mood symptoms, both BLT and selective serotonin reuptake inhibitors (SSRIs) show evidence of efficacy. The possible connection between improvements of mood symptoms and changes in circadian outcomes seems controversial. LIMITATIONS: The included studies presented considerable methodological heterogeneity, small sample sizes and non-optimal sample selection. CONCLUSIONS: The effectiveness of BLT in depressive symptoms and circadian disturbances of SAD was outlined by the present systematic review. The evidence about other biological and pharmacological treatments, although promising, should be replicated. A multifactorial etiopathogenesis could explain the heterogeneous clinical presentations of SAD and the complex link between mood and circadian symptoms.

Behavioural biomarkers and mobile mental health: a new paradigm.

Over recent decades, the field of psychiatry has allocated a vast amount of resources and efforts to make available more accurate and objective methods to diagnose, assess and monitor treatment outcomes in psychiatric disorders. Despite the optimism and some significant progress in biological markers, it has become increasingly evident that they are failing to meet initial expectations due to their lack of specificity, inconsistent reliability and limited availability. On the other hand, there is an increasingly emerging evidence of mobile technologies' feasibility to measure mental illness activity. Moreover, taking into account its widespread use, availability and potential to capture behavioural markers, mobile-connected technologies could be strong candidates to fill and complement-at least at some degree-the gaps that biological markers couldn't. This represents an especially interesting opportunity to reform our current diagnostic system using a bottom-up research methodology based on digital and biological markers data instead of the classical traditional top-down approach. Therefore, the field might benefit of further exploring this promising -and increasingly evidence-based- pathway as well as other auspicious alternatives in order to attain a more holistic and integrative approach in research, which could ultimately impact real-world clinical practice.

The effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Mindfulness-based interventions (MBIs) have been increasingly used as an adjunctive treatment to pharmacotherapy for a few psychiatric disorders. However, few studies have investigated the efficacy of MBIs in bipolar disorder (BD). METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy of MBIs as an adjunctive treatment in BD. Major electronic databases were independently searched by two authors for controlled and uncontrolled studies which examined the effects of MBIs on psychiatric symptoms in subjects with BD. Data from original studies were synthesized by using a random effects model. RESULTS: Twelve trials were eligible for inclusion into current meta-analysis, including three controlled studies (n=132) and nine uncontrolled studies (n=142). In within-group analysis, MBIs significantly reduced depressive (7 studies, n=100, Hedges' g=0.58, p<0.001) and anxiety (4 studies, n=68, Hedges' g=0.34, p=0.043) symptoms, but not manic symptoms (6 studies, n=89, Hedges' g=0.09, p=0.488) and cognition (3 studies, n=43, Hedges' g=0.35, p=0.171), compared to baseline. In between-group analysis (intervention group versus waiting list group, all patients with BD), MBIs did not reduce depressive (3 studies, n=132, Hedges' g=0.46, p=0.315) or anxiety (3 studies, n=132, Hedges' g=0.33, p=0.578) symptoms. LIMITATIONS: Only three controlled trials compared MBIs to control conditions. CONCLUSIONS: Our meta-analysis showed significantly beneficial effects on depressive and anxiety symptoms of BD patients in within-group analysis. However, this significance was not observed in comparison with the control groups. Further clinical trials are warranted to investigate the differences in the benefits of MBIs between treatment and control subjects.

Eye movement desensitization and reprocessing therapy versus supportive therapy in affective relapse prevention in bipolar patients with a history of trauma: study protocol for a randomized controlled trial.

BACKGROUND: Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. METHODS/DESIGN: This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. DISCUSSION: The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.

Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. METHODS: This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain. RESULTS: Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long-term lithium-treated BD-I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas. CONCLUSIONS: The structural differences found among the three groups, and specifically those between long-term lithium-treated and unmedicated BD-I patients, indicate increased limbic structure volumes in lithium-treated patients.

Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.

BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint. RESULTS: Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression. LIMITATIONS: A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence. CONCLUSIONS: This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.

Midline Brain Abnormalities Across Psychotic and Mood Disorders.

Patients with schizophrenia are known to have increased prevalence of abnormalities in midline brain structures, such as a failure of the septum pellucidum to fuse (cavum septum pellucidum) and the absence of the adhesio interthalamica. This is the first study to investigate the prevalence of these abnormalities across a large multidiagnostic sample. Presence of cavum septum pellucidum and absence of the adhesio interthalamica was assessed in 639 patients with chronic schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder, major depressive disorder, or a first episode of psychosis, mania or unipolar depression. This was compared with 223 healthy controls using logistic-regression-derived odds ratios (OR). Patients with psychotic or mood disorders showed an increased prevalence of both abnormalities (OR of cavum septum pellucidum = 2.1, OR of absence of the adhesio interthalamica = 2.6, OR of both cavum septum pellucidum and absence of the adhesio interthalamica = 3.8, all P < .001). This increased prevalence was separately observed in nearly all disorders as well as after controlling for potential confounding factors. This study supports a general increased prevalence of midline brain abnormalities across mood and psychotic disorders. This nonspecificity may suggest that these disorders share a common neurodevelopmental etiology.

Ziprasidone with adjunctive mood stabilizer in the maintenance treatment of bipolar I disorder: long-term changes in weight and metabolic profiles.

This analysis was conducted to compare the effects of adjunctive ziprasidone or placebo on metabolic parameters among patients receiving maintenance treatment with lithium or valproate. We also tested whether metabolic syndrome (MetS) and other risk factors were associated with baseline characteristics and treatment response. In the stabilization phase (Phase 1), 584 bipolar I disorder (DSM-IV) patients received 2.5-4 months of open label ziprasidone (80-160 mg/d) plus lithium or valproic acid (ZIP+MS). Patients who achieved at least 8 weeks of clinical stability were subsequently randomized into Phase 2 to 6-months of double-blind treatment with ZIP+MS (n=127) vs. placebo+MS (n=113). At baseline of Phase 1, MetS was found in 111 participants (23%). Participants with MetS (vs. non-MetS participants) were more likely to be aged 40 years or older, had significantly more severe manic symptoms, higher abdominal obesity, and higher BMI. Increase in abdominal obesity was associated with lower manic symptom improvement (p<0.05, as assessed by MRS change score) during Phase 1, while symptom improvement differed across racial groups. In the Phase 2 double-blind phase, the ZIP+MS group had similar weight and metabolic profiles compared to the placebo+MS group across visits. These results corroborate existing findings on ziprasidone which exhibits a neutral weight and metabolic profile in the treatment of schizophrenia and bipolar patients. Our findings suggest that MetS is highly prevalent in patients with bipolar disorder, may be associated with greater manic symptom severity, and may predict treatment outcomes.

Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use.

OBJECTIVE: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. METHODS: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). RESULTS: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI]=0.65 to 1.86) for functional outcome and -0.72 (95% CI=-1.27 to -0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. CONCLUSION: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

Baseline characteristics and outcomes in patients with first episode or multiple episodes of acute mania.

OBJECTIVE: Previous studies have reported differential responses to therapeutic interventions depending on the patient's history with bipolar disorder, which highlights the importance of understanding the longitudinal nature of the disorder. The goal of the present analyses was to describe and compare the baseline characteristics, response to treatment, and medication patterns in adult patients experiencing a first episode versus multiple episodes of mania. METHOD: The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study was a 2-year prospective, observational study to evaluate outcomes in patients experiencing a DSM-IV- or ICD-10-diagnosed manic or mixed episode. The study was conducted from December 2002 to June 2004. RESULTS: Among 3,115 patients, 256 (8.2%) enrolled with a first manic or mixed episode. Relative to multiple-episode patients, first-episode patients were younger and had a lower body mass index (BMI), a higher incidence of past or current cannabis abuse, significantly higher baseline Young Mania Rating Scale total and Clinical Global Impressions-Bipolar Disorder (CGI-BP) mania scores, and lower CGI-BP depression and Hamilton Depression Rating Scale (5-item version) total scores. At the 12-week endpoint, rates of recovery and remission were greater for first-episode patients, and times to recovery and remission were shorter. CONCLUSIONS: Limitations of the study were that entry of patients into this study with an acute manic or mixed episode was determined by clinical interview but not confirmed with a structured diagnostic interview. That information on the course of illness prior to entry into the study was obtained retrospectively. First-episode patients presented with different baseline illness characteristics and achieved recovery and remission more rapidly than multiple-episode patients.