Search

Identifying individual patient characteristics that contribute to long-term mental health deterioration following diagnosis of breast cancer (BC) is critical in clinical practice. The present study employed a supervised machine learning pipeline to address this issue in a subset of data from a prospective, multinational cohort of women diagnosed with stage I–III BC with a curative treatment intention. Patients were classified as displaying stable HADS scores (Stable Group; n = 328) or reporting a significant increase in symptomatology between BC diagnosis and 12 months later (Deteriorated Group; n = 50). Sociodemographic, life-style, psychosocial, and medical variables collected on the first visit to their oncologist and three months later served as potential predictors of patient risk stratification. The flexible and comprehensive machine learning (ML) pipeline used entailed feature selection, model training, validation and testing. Model-agnostic analyses aided interpretation of model results at the variable- and patient-level. The two groups were discriminated with a high degree of accuracy (Area Under the Curve = 0.864) and a fair balance of sensitivity (0.85) and specificity (0.87). Both psychological (negative affect, certain coping with cancer reactions, lack of sense of control/positive expectations, and difficulties in regulating negative emotions) and biological variables (baseline percentage of neutrophils, thrombocyte count) emerged as important predictors of mental health deterioration in the long run. Personalized break-down profiles revealed the relative impact of specific variables toward successful model predictions for each patient. Identifying key risk factors for mental health deterioration is an essential first step toward prevention. Supervised ML models may guide clinical recommendations toward successful illness adaptation.

Funding Information: The authors would like to acknowledge clinicians from the Breast and Neuropsychiatry Units of the Champalimaud Clinical Centre (Champalimaud Foundation), for assistance in patient recruitment and assessment, and the BOUNCE and FAITH Consortium members for their contributions to this study. Funding Information: RL is supported by the 2018 Scientific Employment Stimulus from Fundação para a Ciência e Tecnologia, Portugal (CEECIND/04157/2018). DF, BC, BS, and AO-M were supported by the BOUNCE project (grant agreement number 777167), and DS and AO-M are supported by the FAITH project (grant agreement number 875358), both funded by the European Union’s Horizon 2020 research and innovation programme. AO-M is supported by grants FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, and FCT-PTDC/MED-NEU/31331/2017, both funded by FCT/MCTES and the former co-funded by FEDER, under the Partnership Agreement Lisboa 2020 – Programa Operacional Regional de Lisboa. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: Copyright © 2023 Almeida, Rodrigues da Silva, Frasquilho, Costa, Sousa, Mourinho Baptista, Grácio, Lemos and Oliveira-Maia. Background: A diagnosis of cancer, and the resulting treatment process, can be perceived as a life-threatening event, affecting not only patients but also their social network and, more specifically, their relatives. While the ability to cope and adjust to difficult health situations may be challenging, family resilience may optimize a positive adaptation to adversity and contribute to enhance the patient’s quality of life. The Family Resilience Questionnaire (FaRE) is a self-report measure of family resilience that assesses this construct systematically. We aimed to validate the Portuguese version of a short form of the FaRE (FaRE-SF-P) in a sample of women with breast cancer. Methods: 147 women recently diagnosed with early breast cancer were recruited at the Champalimaud Clinical Centre in Lisbon. Participants completed psychometric assessment including the Portuguese version of the FaRE-SF-P, composed by two subscales of the original version – the FaRE Perceived Family Coping (FaRE-PFC) and the FaRE Communication and Cohesion (FaRE-CC). Confirmatory factor analysis (CFA) was performed to assess the factor structure of the FaRE-SF-P. Construct validity was assessed using the Hospital Anxiety and Depression Scale (HADS) for divergent validity, and the Modified Medical Outcomes Study Social Support Survey (mMOS-SS) as well as the social functioning subscale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) for convergent validity. Results: The CFA results confirmed a correlated two-factor structure model consistent with the Perceived Family Coping and the Communication and Cohesion subscales. Internal consistency reliability indicated good values both for Perceived Family Coping and Communication and Cohesion subscales. The results for construct validity showed acceptable convergent and divergent validity. Discussion: The FaRE-SF-P showed good psychometric properties demonstrating to be a valid and reliable family resilience measure to use in Portuguese women diagnosed with breast cancer. Since FaRE-SF-P is a short instrument it may be a useful screening tool in an oncological clinical practice routine. publishersversion published

IntroductionObsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures.MethodsWe conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment.ResultsFrom 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported.DiscussionOur work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].

BackgroundTreatment resistant depression is common in older adults and treatment is often complicated by medical comorbidities and polypharmacy. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for this group due to its favorable profile. However, early influential studies suggested that rTMS is less effective in older adults. This evidence remains controversial.MethodsHere, we evaluated the rTMS treatment outcomes in a large international multicenter naturalistic cohort of >500 patients comparing older vs. younger adults.ResultsWe show that older adults, while having similar antidepressant response to younger adults, respond more slowly, which may help to explain differences from earlier studies when the duration of a treatment course was shorter.ConclusionsSuch evidence helps to resolve a long-standing controversy in treating older depressed patients with rTMS. Moreover, these findings provide an important data point in the call to revise policy decisions from major insurance providers that have unfairly excluded older adults.

OBJECTIVE The main objective of this prospective multicenter study was to examine whether illness representations of control, affect, and coping behaviors mediate the effects of self-efficacy to cope with cancer on psychological symptoms and overall quality of life, in breast cancer patients. METHOD Data from 413 women (Mean age = 54.87; SD = 8.01), coming from four countries (i.e., Finland, Israel, Italy, Portugal), who received medical therapy for their early breast cancer, were analyzed. Coping self-efficacy was assessed at baseline. Potential mediators were assessed three months later, and outcomes after six months. RESULTS Coping self-efficacy was related to all mediators and outcomes. Illness representations of treatment control, positive and negative affect, and certain coping behaviors (mostly, anxiety preoccupation) mediated the effects of coping self-efficacy. Coping self-efficacy was related to each outcome through a different combination of mediators. CONCLUSIONS Coping self-efficacy is a major self-regulation factor which is linked to well-being through multiple cognitive, emotional, and behavioral pathways. Enhancement of coping self-efficacy should be a central intervention goal for patients with breast cancer, towards promotion of their well-being.

The current study aimed to track the trajectory of quality of life (QoL) among subgroups of women with breast cancer in the first 12 months post-diagnosis. We also aimed to assess the number and portion of women classified into each distinct trajectory and the sociodemographic, clinical, and psychosocial factors associated with these trajectories. The international sample included 699 participants who were recruited soon after being diagnosed with breast cancer as part of the BOUNCE Project. QoL was assessed at baseline and after 3, 6, 9, and 12 months, and we used Latent Class Growth Analysis to identify trajectory subgroups. Sociodemographic, clinical, and psychosocial factors at baseline were used to predict latent class membership. Four distinct QoL trajectories were identified in the first 12 months after a breast cancer diagnosis: medium and stable (26% of participants); medium and improving (47%); high and improving (18%); and low and stable (9%). Thus, most women experienced improvements in QoL during the first year post-diagnosis. However, approximately one-third of women experienced consistently low-to-medium QoL. Cancer stage was the only variable which was related to the QoL trajectory in the multivariate analysis. Early interventions which specifically target women who are at risk of ongoing low QoL are needed.

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique that was cleared by the Food and Drug Administration (FDA) for the treatment of Obsessive-Compulsive Disorder (OCD) in 2018. The approved protocol includes individualized symptom provocation before each stimulation session, to elicit a moderate level of obsessional distress. Although symptom provocation can be a delicate, demanding, and uncomfortable procedure, structured training methods for those who are going to apply it are not available. Here, we describe a model for training in symptom provocation for TMS technicians, developed at the Champalimaud Clinical Centre in Lisbon, Portugal. Our programme includes two-sessions dedicated to clinical communication and symptom provocation techniques from a theoretical and practical perspective. Additionally, supervision meetings are conducted during treatment of patients, allowing regular case discussion and redefinition of symptom provocation hierarchy, as needed. In addition to having a strong practical component, our training program is short and pragmatic, allowing for easy implementation and fluid transition to clinical practice. By sharing our experience, we hope to contribute to systematize training procedures required for symptom provocation in the context of TMS, and to qualitatively describe a methodology that can be used for implementation of TMS programmes for the treatment of OCD.

Guidance about treatment-resistant depression (TRD) in Portugal is very limited, even though depression prevalence is among the highest in European countries. A questionnaire was conducted, followed by two advisory boards with seven Portuguese psychiatry experts, to characterize and discuss MDD and TRD epidemiology, diagnosis, patient journey, treatment options, and unmet clinical needs. Consensus was reached on the main issues. In daily practice, TRD can be defined as moderate to severe MDD episodes with insufficient clinical improvement after two antidepressant treatments, taken in adequate doses and duration. TRD diagnosis and treatment are mostly decided by psychiatrists at public hospitals. Treatment type and duration must be adjusted to characteristics of the patient and the depressive episode, including symptoms, number of previous episodes, comorbidities, and previous treatment response and side effects. The most relevant objectives of TRD treatment are reaching response and remission, prevention of suicide, and improvement of quality of life, functionality, and wellbeing. Regarding pharmacotherapy, antidepressant switch occurs more frequently with non-response, while optimization, combination, and augmentation are considered for patients with partial response. Psychotherapy should be considered in parallel to pharmacological treatment. Brain stimulation techniques are underused. Lifelong treatment is required for recurrent or more chronic TRD episodes, but patient adherence is also poorer in these cases. In Portugal, TRD management is limited by lack of access to specialist care and to many treatment options. These aspects highlight that conventional pharmacotherapy does not lead to remission in many patients and that optimization strategies are frequently necessary to achieve satisfactory treatment outcomes.

Funding GC is supported by a Doctoral Fellowship (SFRH/ BD/130210/2017) from Fundação para a Ciência e Tecnologia (FCT). AJO-M is supported by grant PTDC/MEC-PSQ/30302/2017- IC&DT-LISBOA-01-0145-FEDER, funded by Portuguese national funds from FCT and co-funded by FEDER, under the Partnership Agreement Lisboa 2020—Programa Operacional Regional de Lisboa, and by a Starting Grant from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 950357). GC and AJO-M are supported by Portuguese national funds from FCT through grant PTDC/ MED-NEU/31331/2017. MDF is supported by the Sidney R. Baer, Jr. Foundation, the Nancy Lurie Marks Foundation, the Mather’s Foundation, and the National Institutes of Health (R01 MH113929, R01 MH115949, R01 AG060987). None of the funding agencies had a role in the design and conduct of the study, in the collection, management, analysis and interpretation of the data, in the preparation, review or approval of the manuscript, nor in the decision to submit the manuscript for publication. Lesion network mapping is a neuroimaging technique that explores the network of regions functionally connected to lesions causing a common syndrome. The technique uses resting state functional connectivity from large databases of healthy individuals, i.e., connectomes, and has allowed for important insight into the potential network mechanisms underlying several neuropsychiatric disorders. However, concerns regarding reproducibility have arisen, that may be due to the use of different connectomes, with variable MRI acquisition parameters and preprocessing methods. Here, we tested the impact of using different connectomes on the results of lesion network mapping for mania. We found results were reliable and consistent independent of the connectome used. publishersversion published

BACKGROUND Despite the continued progress of medicine, dealing with breast cancer is becoming a major socio-economic challenge, particularly due to its increasing incidence. The ability to better manage and adapt to the entire care process depends not only on the type of cancer, but also on the patient's socio-demographic and psychological characteristics and on the social environment in which a person lives and interacts. Therefore, it is important to understand which factors may contribute to a successful adaptation to breast cancer. To our knowledge, no studies have been already performed on the combination effect of multiple psychological, biological and functional variables in predicting the patient’s ability to bounce back from the stressful life event, such as a breast cancer diagnosis. OBJECTIVE The aim of the study will be to build a quantitative mathematical model of factors associated with optimal adjustment capacity to cancer and study resilience through the cancer continuum in a population of breast cancer patients. METHODS 660 women with breast cancer will be recruited in five European cancer centers in Italy, Finland, Israel and Portugal. Biomedical and psychosocial variables will be collected using the Noona Healthcare platform. Psychosocial, socio-demographic, lifestyle and clinical variables will be measured every 3 months, starting from pre-surgery assessment (baseline) to 18 months after surgery. RESULTS Temporal data mining, time-series prediction, sequence classification methods, clustering time-series data, and temporal association rules will be used to develop the predictive model. Results will be disseminated during 2022. CONCLUSIONS The present study will provide a predictive model able to describe individual resilience and identify different resilience’s trajectories along the care process. The results will allow the implementation of tailored interventions according to the patient’s need, supported by e-health technologies. CLINICALTRIAL ClinicalTrials.gov Identifier: NCT05095675

Objective Obsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways involved in oxidative and nitrosative stress (O&NS) have been implicated. The present study aims to systematically review the literature for quantitative evidence that patients with OCD have altered measures of blood O&NS markers. Methods Independent random-effects meta-analyses using standardized mean differences were conducted to assess each marker separately. Additionally, data from multiple markers were pooled together in a meta-analysis for measures of oxidant activity and another for measures of antioxidant activity. Results Thirteen studies met inclusion criteria, involving 433 OCD patients and 459 controls. Eleven blood O&NS markers were eligible for independent quantitative analyses. We found that, in OCD patients, the oxidant markers 8-hydroxydeoxyguanosine and malondialdehyde, and the antioxidants glutathione peroxidase and superoxide dismutase, were significantly increased while total antioxidant status, vitamin C, and vitamin E were significantly decreased, when comparing with controls. Regarding pooled meta-analyses, we found a statistically significant increase in oxidant markers, but non-significant results regarding antioxidant markers. Conclusions Our meta-analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system. Additional studies are needed in order to support this association.

Background Treatment resistant depression (TRD) characterizes a subgroup of 10–30% of patients with major depressive disorder, and is associated with considerable morbidity and mortality. A consensus treatment for TRD does not exist, which often leads to wide variations in treatment strategies. Real-world studies on treatment patterns and outcomes in TRD patients in Europe are lacking and could help elucidate current treatment strategies and their efficacy. Methods This non-interventional cohort study of patients with TRD (defined as treatment failure on ≥2 oral antidepressants given at adequate dose and duration) with moderate to severe depression collected real-world data on treatment patterns and outcomes in several European countries. Patients were started on a new treatment for depression according to routine clinical practice. Results Among 411 patients enrolled, after 6 months, only 16.7% achieved remission and 73.5% showed no response. At Month 12, while 19.2% achieved remission and 69.2% showed no response, 33.3% of those in remission at Month 6 were no longer in remission. Pharmacological treatments employed were heterogenous; 54 different drugs were recorded at baseline, and the top 5 treatment types according to drug classes accounted for 40.0% of patients. Even though remission rates were very low, at Month 12, 60.0% of patients had not changed treatment since enrolment. Conclusions The heterogeneity of treatments highlights a lack of consensus. Moreover, despite low response rates, patients often remained on treatments for substantial periods of time. These data further support existence of an unmet treatment need for TRD patients in Europe.

Explicit information obtained through instruction profoundly shapes human choice behaviour. However, this has been studied in computationally simple tasks, and it is unknown how model-based and model-free systems, respectively generating goal-directed and habitual actions, are affected by the absence or presence of instructions. We assessed behaviour in a novel variant of a computationally more complex decision-making task, before and after providing information about task structure, both in healthy volunteers and individuals suffering from obsessive-compulsive (OCD) or other disorders. Initial behaviour was model-free, with rewards directly reinforcing preceding actions. Model-based control, employing predictions of states resulting from each action, emerged with experience in a minority of subjects, and less in OCD. Providing task structure information strongly increased model-based control, similarly across all groups. Thus, explicit task structural knowledge determines human use of model-based reinforcement learning, and is most readily acquired from instruction rather than experience.

When referring to the study of Rutherford et al. (2015) on short- and long-term effects of rTMS in Alzheimer's disease, we erroneously stated in our article (Lefaucheur et al., 2020) that a clinical benefit on cognitive performance (tested by the Montreal Cognitive Assessment) was observed at weeks 2–3, only in the real stimulation condition during an initial sham-controlled 4-week period of treatment, and that then this benefit was prolonged by “2 additional weeks” of open-label real rTMS. In fact, this extended open-label treatment was administered for up to 19 months in multiple 2-week blocks with 2–7 months intervals between blocks and was not limited to a single additional 2-week block of treatment immediately following the original 4 weeks of treatment. Therefore, the results of that open-label extended follow-up study support the value of long-term maintenance treatment using multiple rTMS sessions rather than be interpreted as short-term 2-week extension.

IntroductionObsessive compulsive disorder (OCD) affects 2-3% of the general population. The neurobiology of OCD has been linked to dysfunction of cortico-striatal circuits connecting the orbitofrontal (OFC) to the striatum. Recently, this loop has become an approved target for non-invasive neuromodulatory treatment of OCD.ObjectivesTo explore structural and functional connectivity of the OFC in OCD subjects and healthy controls.Methods14 OCD patients and 12 age/sex-matched controls underwent magnetic resonance imaging (MRI) (3T-Philips scanner) for diffusion tensor imaging (DTI) and resting state functional connectivity (rsFC). DTI images were brain extracted and corrected for movement and eddy currents. A diffusion tensor model was fitted to each voxel and used to generate Fractional Anisotropy (FA) maps. Voxel-wise statistical analysis of FA was performed using Tract-Based Spatial Statistics. RsFC images were preprocessed and seed-based correlation (SBC) analysis was performed using Data Processing Assistant for Resting-State fMRI.ResultsWe found decreased values of FA in the body of the Corpus Callosum bilaterally (MNI_coordinates: x= 16, y= -16, z= 33 and x= -19, y= -16, z= 42) and left superior longitudinal fasciculus in OCD patients (fig 1, left), as well as decreased rsFC of the right superior orbitofrontal seed with the left inferior frontal gyrus and left middle occipital gyrus (fig 2, right).ConclusionsUsing an exploratory multimodal approach we found evidence of abnormal structural and functional long-range connectivity of the OFC in OCD. If confirmed in a larger sample these connectivity abnormalities could be explored as potential predictors of response to OFC-targeted non-invasive neuromodulatory interventions.DisclosureNo significant relationships.

This study provides support for the hypothesis that treatment response to an initial course of repetitive transcranial magnetic stimulation (rTMS) for depression predicts the magnitude of response to a subsequent course of rTMS in the setting of symptom relapse.

Introduction Focal drug-resistant epilepsy (DRE) has been associated with a significant burden of psychiatric comorbidity and low health-related quality of life (HRQoL). There is ample disagreement in previous studies as to which factors decisively influence HRQoL in this population. Here, we sought to assess the relationship between sociodemographic factors, epilepsy-related variables, and psychiatric comorbidity with HRQoL in a well-defined group of patients with focal DRE. Methods We consecutively recruited a sample of adult patients with confirmed focal DRE being considered for epilepsy surgery in a reference center in Lisbon, Portugal. Psychiatric diagnoses were defined according to the Mini-International Neuropsychiatric Interview (M.I.N.I.), and HRQoL was measured using the Quality-of-Life in Epilepsy Inventory (QOLIE-31). Associations with QOLIE-31 total score were tested using regression models. Results Among the forty patients included in the study, being diagnosed with a mood disorder was significantly associated with a lower total QOLIE-31 score (β = − 21.18, p = 0.001) in univariate analysis. Multivariate analysis additionally identified female gender as a second determinant of lower HRQoL (β = − 21.22, p = 0.001 for being diagnosed with a mood disorder; β = − 8.98, p = 0.048 for female gender; adjusted R2 = 0.290). Sociodemographic and epilepsy-related variables were not associated with HRQoL. Conclusions In our sample of adult patients with focal DRE, female gender and being diagnosed with a mood disorder were the only factors significantly associated with a poorer HRQoL. While clinical care often focuses on seizure control, epilepsy-related factors such as seizure frequency were not shown to have a significant influence on HRQoL. We suggest that an early comprehensive psychiatric evaluation and intervention can help improve HRQoL in these patients.

The COVID-19 pandemic has important consequences for the mental health of populations. Patients with cancer, already at risk for poor mental health outcomes, are not expected to be spared from these consequences, prompting the need for health services to improve responsiveness. This article presents the research protocol for an implementation study designed to describe the uptake of a well-studied and recognized system for the treatment of depression and anxiety (Stepped-care) during the specific context of a Pandemic in an oncological site. The system set-up will be assisted by a digital platform (MoodUP), where patients undergoing cancer treatment will be screened for anxiety and depressive symptoms, triaged by severity level and algorithm-matched to recommended interventions. Patients undergoing cancer treatment at a cancer clinic in Portugal will be invited to subscribe to the MoodUP platform where they will complete a self-reported questionnaire (Hospital Anxiety and Depression Scale) to screen their anxiety and depressive symptoms. Data will be instantly collected, and an algorithm will activate severity-matched intervention suggestions, through a case manager that will coordinate care. The specific objectives of this study will be to describe the implementation and acceptability of the care system by patients and staff, the barriers to and facilitators of implementation, the proportion of patients accessing the system and their pathways through the various stepped-care interventions, and patient perceptions regarding the feasibility and appropriateness of the eHealth platform. Moreover, exploratory analyses will be conducted to describe patterns of anxiety and depression symptoms variation across all patients, as well as within sociodemographically, clinically and contextually characterized subgroups, to characterize their care needs and access, as well as to explore for whom the MoodUP care system may be more appropriate. This study is expected to improve processes for collaborative mental healthcare in oncology and accelerate the digitalization of services, towards the improvement of mental healthcare access, and management of high-risk patients, during the COVID-19 pandemic.

IntroductionObsessive-Compulsive Disorder (OCD) is an incapacitating Neuropsychiatric condition characterized by the presence of obsessions and/or compulsions. Although the disorder’s phenotype is well described, its pathophysiology remains elusive (Aouizerate et al, 2004). Over the last decade, techniques to noninvasively study the brain’s neurophysiology, such as Transcranial Magnetic Stimulation (TMS), have found widespread use in psychiatric research. For OCD, single- and paired-pule TMS protocols have been used to explore abnormalities in motor cortex excitability and cortical neuroplasticity. Here we propose to systematically review and, where possible, metanalyse existing case-control studies that compared such measures in patients and healthy subjects.ObjectivesTo systematically review and meta-analyse published case-control studies comparing cortical excitability measures, as measured by single- or paired-pulse TMS, in subjects with OCD and healthy controls.MethodsWe have conducted a systematic review of published literature (PROSPERO registration CRD42020201764) reporting measures of cortical excitability as measured by single or paired-pulse TMS, in patients with OCD and healthy controls. We searched 4 different electronic libraries (PubMed, Web of Science, EMBASE, PsycINFO). The resulting list of articles was reviewed, separately, by two researchers. Disagreements were discussed and resolved by consensus, until a final list of eligible articles was obtained.Results13 studies reporting motor cortex excitability measures were included in our final list. The total number of participants included in our analyses is 615 (349 OCD; 180 healthy subjects; 86 other conditions)ConclusionsA sufficient number of studies was found to allow for metanalyses, currently ongoing.

Displaying resilience following a diagnosis of breast cancer is crucial for successful adaptation to illness, well-being, and health outcomes. Several theoretical and computational models have been proposed toward understanding the complex process of illness adaptation, involving a large variety of patient sociodemographic, lifestyle, medical, and psychological characteristics. To date, conventional multivariate statistical methods have been used extensively to model resilience. In the present work we describe a computational pipeline designed to identify the most prominent predictors of mental health outcomes following breast cancer diagnosis. A machine learning framework was developed and tested on the baseline data (recorded immediately post diagnosis) from an ongoing prospective, multinational study. This fully annotated dataset includes socio-demographic, lifestyle, medical and self-reported psychological characteristics of women recently diagnosed with breast cancer (N = 609). Nine different feature selection and cross-validated classification schemes were compared on their performance in classifying patients into low vs high depression symptom severity. Best-performing approaches involved a meta-estimator combined with a Support Vector Machines (SVMs) classification algorithm, exhibiting balanced accuracy of 0.825, and a fair balance between sensitivity (90%) and specificity (74%). These models consistently identified a set of psychological traits (optimism, perceived ability to cope with trauma, resilience as trait, ability to comprehend the illness), and subjective perceptions of personal functionality (physical, social, cognitive) as key factors accounting for concurrent depression symptoms. A comprehensive supervised learning pipeline is proposed for the identification of predictors of depression symptoms which could severely impede adaptation to illness.

Introduction: Hypomania symptoms are best described as a continuum, ranging beyond Bipolar Spectrum Disorders (BSD). Other nosological entities, such as major depressive disorder, schizoaffective disorder, or borderline personality disorder, may also share symptoms with BSD, raising challenges for differential diagnosis. While the Hypomania Checklist-32 is one of the most widely used tools for screening hypomania, there is limited evidence describing its use in a real-world outpatient psychiatric clinical setting. Methods: Here we tested the psychometric properties of a European Portuguese adaptation of the HCL-32, establishing its factor structure, reliability and construct validity. Furthermore, we analyzed differences in hypomanic symptoms among several clinical groups and in a non-clinical sample. Data was obtained retrospectively in an ecological setting from a clinical sample of an outpatient psychiatry and psychology clinic, comprising 463 Portuguese individuals, 326 of whom had a psychiatric diagnosis, namely BSD (n = 66), major depressive disorder (n = 116), or other psychiatric disorders (n = 144). A separate non-clinical sample was also collected among healthy volunteers (n = 62). A battery of self-report measures of affective symptoms was applied, and in a subset of patients, diagnosis was established using a structured diagnostic interview. Results: Psychometric properties of the HCL-32 were adequate, with good internal consistency (Cronbach's α = 0.86) and test-retest stability (ICC = 0.86), and two subscores (“active/elated” and “risk-taking/irritable”) defined by Principal Component Analysis. Receiver Operating Characteristic curve analysis demonstrated that the test score discriminated moderately between patients with BSD and other clinical samples as well as healthy volunteers, with a cut-off score of 17 for the total score of the HCL-32 rendering the best combination of sensitivity and specificity. When compared to the HCL-32 total score, the risk-taking/irritable subscore seems to provide additional benefit in discriminating between different clinical groups, namely regarding specificity in the discrimination from patients with a diagnosis of major depressive disorder that was low for the full scale and the alternate subscale. Conclusions: HCL-32 can be used as a screening tool for BSD among adult patients presenting in an outpatient psychiatric clinical setting.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD. Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed. Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time. Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.

Background: While the Yale-Brown Obsessive-Compulsive Scale Second Edition (Y-BOCS-II) is the gold-standard for measurement of obsessive-compulsive (OC) symptom severity, its factor structure is still a matter of debate and, most importantly, criterion validity for diagnosis of OC disorder (OCD) has not been tested. This study aimed to clarify factor structure and criterion validity of the Y-BOCS-II. Methods: We first validated and quantified the psychometric properties of a culturally adapted Portuguese translation of the Y-BOCS-II (PY-BOCS-II). The PY-BOCS-II and other psychometric instruments, including the OCD subscale of the Structured Clinical Interview for the DSM-IV, used to define OCD diagnosis, were administered to 187 participants (52 patients with OCD, 18 with other mood and anxiety disorders and 117 healthy subjects). In a subsample of 20 OCD patients and the 18 patients with other diagnoses, PY-BOCS-II was applied by clinicians blinded to diagnosis. Results: PY-BOCS-II had excellent internal consistency (Cronbach's α = 0.96) and very good test-retest reliability (Pearson's r = 0.94). Exploratory factor analysis revealed a two-factor structure with loadings consistent with the Obsessions and Compulsions subscales, and there was good to acceptable convergent and divergent validity. Importantly, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve suggested elevated accuracy in discriminating between patients with OCD and control subjects (AUC = 0.96; 95% confidence interval [CI]: 0.92-0.99), that was retained in comparisons with age, gender and education matched controls (AUC = 0.95; 95% CI: 0.91-0.99), as well as with patients with other mood and anxiety disorders (AUC = 0.93; 95% CI: 0.84-1). Additionally, a cut-off score of 13 had optimal discriminatory ability for the diagnosis of OCD, with sensitivity ranging between 85 and 90%, and specificity between 94 and 97%, respectively when all samples or only the clinical samples were considered. Conclusion: The PY-BOCS-II has excellent psychometric properties to assess the severity of obsessive-compulsive symptoms, reflecting obsessive, and compulsive dimensions, compatible with currently defined subscales. Furthermore, we found that a cut-off of 13 for the Y-BOCS-II total score has good to excellent sensitivity and specificity for the diagnosis of OCD. publishersversion published

© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., Obesity-associated differences in hedonic hunger, while consistently reported, have not been adequately quantified, with most studies failing to demonstrate strong correlations between Body Mass Index (BMI) and hedonic hunger indicators. Here, we quantified and assessed the nature of the relationship between hedonic hunger and BMI, in a cross-sectional study using the Portuguese version of the PFS (P-PFS) to measure hedonic hunger. Data were collected from 1266 participants belonging to non-clinical, clinical (candidates for weight-loss surgery) and population samples. Across samples, significant but weak positive associations were found between P-PFS scores and BMI, in adjusted linear regression models. However, in logistic regression models of data from the clinical and non-clinical samples, the P-PFS Food Available domain score was significantly and robustly associated with belonging to the clinical sample (OR = 1.8, 95%CI: 1.2-2.8; p = 0.008), while in the population sample it was associated to being obese (OR = 2.1, 95%CI: 1.6-2.7; p, This work was supported by grants to AJO-M from BIAL Foundation (176/10), Fundação para a Ciência e Tecnologia (Junior Research and Career Development Award from the Harvard Medical Portugal Program; HMSP/ICJ/0020/2011) and the European Union’s Horizon 2020 research and innovation programme (H2020 SC1-2017-CNECT-2, project 777167), and to ST from Fundação para a Ciência e Tecnologia through the Center for Psychology at University of Porto (UID/PSI/00050/2013). DECO PROTESTE funded the sampling, data collection and database development for the population sample.

Background Pharmacological and conventional nonpharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) have only modest efficacy. Furthermore, pharmacotherapy carries the risk of important side effects. Noninvasive brain stimulation (repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS)) are valuable and safe for cognitive function in Alzheimer disease (AD). However, there have been few studies, and there is no consensus, regarding the use of these techniques to treat BPSD. Methods We performed a systematic review of the literature and meta-analysis of studies reporting the effect of rTMS or tDCS on BPSD. Results Seven articles were included: five randomized, controlled clinical trials and two open-label clinical trials. Five studies investigated the effects of rTMS and two the effects of tDCS. Both studies using tDCS reported no evidence of efficacy on BPSD, while two of the three RCTs using rTMS found statistically significant benefits. In an exploratory meta-analysis with four of the RCT studies, we did not find evidence of efficacy of noninvasive brain stimulation techniques, with an overall effect of -0.02 (95% CI = -0.90, 0.94; I2 = 85%). However, when we used only the data from the studies that applied rTMS, we found a positive effect on BPSD, with an overall effect of -0.58 (95% CI = -1.02, -0.14; I2 = 0%). With regards to the adverse effects reported, these were mild and not clinically relevant. Conclusions Our results establish a tendency for efficacy of rTMS protocols on BPSD, while corroborating their safety and tolerability, suggesting the need for further research.

Copyright © Ordem dos Médicos 2015, INTRODUCTION: The Power of Food Scale measures appetite for, rather than consumption of, palatable foods - a construct frequently designated as hedonic hunger. The purpose of this study was to examine the psychometric properties of a Portuguese version of the Power of Food Scale, namely reliability and construct validity. MATERIAL AND METHODS: Data was obtained from 1266 adult participants sampled from three different populations in Portugal: two nonclinical samples and one multi-center sample of severely obese candidates for weight-loss surgery. RESULTS: We found that the factor structure of the Portuguese version of the Power of Food Scale is similar to that of the original scale and that the Portuguese version of the Power of Food Scale has good internal structure, test-retest reliability and construct validity. In addition, we provide the first contribution towards defining population norms for Power of Food Scale scores. DISCUSSION: The Portuguese version of the Power of Food Scale proved to have good psychometric properties: it is a valid and reliable tool for measuring hedonic hunger, supporting its use both in clinical and non-clinical samples, as well as in prospective studies. CONCLUSION: Our results show that the Portuguese version of the Power of Food Scale is a useful measure for researchers and clinicians who are interested in exploring the construct of hedonic hunger in Portuguese-speaking populations, including those suffering from obesity., Introdução: A Power of Food Scale é uma escala que avalia um constructo designado por fome hedónica, frequentemente definido como o apetite por alimentos de elevada palatibilidade, mais do que a sua ingestão propriamente dita. Este estudo teve como objetivo a caracterização das propriedades psicométricas de uma versão portuguesa da Power of Food Scale, nomeadamente da sua fiabili¬dade e validade de constructo. Material e Métodos: Os dados foram obtidos de 1266 participantes adultos, provenientes de três amostras distintas: duas amostras não clínicas e uma amostra clínica de indivíduos com obesidade severa, candidatos a cirurgia da obesidade. Resultados: Verificamos que a estrutura factorial da versão portuguesa da Power of Food Scale é semelhante à do questionário original e que apresenta fiabilidade teste-reteste e validade de constructo adequadas. Adicionalmente, apresentamos neste estudo o primeiro contributo para a definição de normas populacionais para os scores da Power of Food Scale. Discussão: A versão portuguesa da Power of Food Scale apresentou boas propriedades psicométricas: é um instrumento válido e fiável para a avaliação do constructo fome hedónica, suportando a sua utilização tanto em amostras clínicas como não clínicas, bem como em estudos longitudinais. Conclusão: Estes resultados demostram que a versão portuguesa da Power of Food Scale é um instrumento útil, tanto em contexto clínico, como de investigação, nomeadamente para o estudo do constructo fome hedónica em populações de língua portuguesa, in¬cluindo populações clínicas de indivíduos com obesidade., This work was supported by Fundação para a Ciência e Tecnologia through a Junior Research and Career Development Award from the Harvard Medical SchoolPortugal Program to AJO-M (HMSP/ICJ/0020/2011). EUROCONSUMERS supported costs related to recruitment of the population sample.

Objective Despite the evidence supporting the association between infection and bipolar disorder (BD), the genetic vulnerability that mediates its effects has yet to be clarified. A genetic origin for the immune imbalance observed in BD, possibly involved in the mechanisms of pathogen escape, has, however, been suggested in recent studies. Method Here, we present a critical review based on a systematic literature search of articles published until December 2016 on the association between BD and infectious/immunogenetic factors. Results We provide evidence suggesting that infectious insults could act as triggers of maladaptive immune responses in BD and that immunogenetic vulnerability may amplify the effects of such environmental risk factors, increasing susceptibility to subsequent environmental encounters. Quality of evidence was generally impaired by scarce attempt of replication, small sample sizes and lack of high-quality environmental measures. Conclusion Infection has emerged as a potential preventable cause of morbidity in BD, urging the need to better investigate components of the host–pathogen interaction in patients and at-risk subjects, and thus opening the way to novel therapeutic opportunities.

We describe a case of coeliac disease that was diagnosed in the psychiatry inpatient unit of a general hospital. The patient was admitted due to suicidal behaviours and developed an agitated catatonic state while in the inpatient psychiatry unit. An extensive diagnostic study allowed for the diagnosis of coeliac disease and while her state was unresponsive to antidepressants, anxiolytics, antipsychotics and electroconvulsive therapy, the patient improved significantly when a gluten-free diet was started. While it is well known that, occasionally, gluten sensitivity and coeliac disease can present as brain gluten sensitivity, such cases are typically characterised by motor and/or cognitive symptoms and by white matter abnormalities. Psychiatric presentations of these conditions have only rarely been reported.

While neuroleptic malignant syndrome (NMS) is typically characterised by delirium, motor rigidity, fever and dysautonomia, the syndrome is not pathognomonic, and NMS remains a diagnosis of exclusion. Here, we describe the case of a 44-year-old woman, with no relevant psychiatric history, admitted to a nephrology unit due to acute renal failure. After administration of antipsychotics, she presented with mental status alteration, generalised tremor, rigidity and autonomic nervous system dysfunction. Fever and rhabdomyolysis, however, were not prominent, and NMS was not considered initially in the differential diagnosis. The resulting delay in diagnosis, with continued administration of antipsychotics, led to progressive clinical deterioration. Once NMS was considered, however, antipsychotics were withdrawn and the patient was treated with electroconvulsive therapy (ECT), followed by administration of a dopamine receptor agonist, with close to full remission of all symptoms. Importantly, during outpatient follow-up, sustained mild and asymmetric tremor and rigidity was noted, leading to a diagnosis of Parkinson’s disease. While this raises questions regarding differential diagnosis between NMS in Parkinson’s disease, versus worsening of Parkinson’s disease due to antipsychotic treatment, the former is supported by the acute and rapidly progressive onset of exuberant autonomic dysfunction and clouded conscience, after administration of a neuroleptic. Ultimately, a definitive distinction between these two alternatives for diagnosis of the inaugural neurological presentation in this patient is not possible. Nevertheless, we believe this case illustrates that NMS can be easily missed, particularly in atypical cases, delaying appropriate treatment, and that a flexible multimodal treatment approach, involving ECT, should be considered for complex clinical cases. Furthermore, it also underlines the importance of post-NMS follow-up, to investigate underlying neurological or medical disorders, particularly in those patients who do not have a full recovery.

Non-motor symptoms contribute significantly to Parkinson’s disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5 −/− mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products.

The understanding of obsessive compulsive disorder (OCD) has evolved with the knowledge of behavior, the brain, and their relationship. Modern views of OCD as a neuropsychiatric disorder originated from early lesion studies, with more recent models incorporating detailed neuropsychological findings, such as perseveration in set-shifting tasks, and findings of altered brain structure and function, namely of orbitofrontal corticostriatal circuits and their limbic connections. Interestingly, as neurobiological models of OCD evolved from cortical and cognitive to sub-cortical and behavioral, the focus of OCD phenomenology also moved from thought control and contents to new concepts rooted in animal models of action control. Most recently, the proposed analogy between habitual action control and compulsive behavior has led to the hypothesis that individuals suffering from OCD may be predisposed to rely excessively on habitual rather than on goal directed behavioral strategies. Alternatively, compulsions have been proposed to result either from hyper-valuation of certain actions and/or their outcomes, or from excessive uncertainty in the monitoring of action performance, both leading to perseveration in prepotent actions such as washing or checking. In short, the last decades have witnessed a formidable renovation in the pathophysiology, phenomenology, and even semantics, of OCD. Nevertheless, such progress is challenged by several caveats, not least psychopathological oversimplification and overgeneralization of animal to human extrapolations. Here we present an historical overview of the understanding of OCD, highlighting converging studies and trends in neuroscience, psychiatry and neuropsychology, and how they influenced current perspectives on the nosology and phenomenology of this disorder. publishersversion published

To the Editor: Brain tumors can produce psychiatric symptoms, particularly if malignant1 and fast growing.2 Among gliomas, growth rate seems to be particularly relevant for the occurrence of mental disturbance, with symptoms in up to 80% of glioblastomas and only 25%–35% of lower-grade astrocytomas.1 We report a case of glioblastoma multiforme, a very fast-growing brain tumor, initially presenting as acute mania. Case report. Mr A, a 76-year-old white man, was admitted to our psychiatric inpatient ward with euphoric mood, increased sexual activity, excessive money spending, and overvalued ideas of grandiose capacity starting 2 months prior. Results of physical and neurologic examination and cognitive evaluation (Mini-Mental State Examination3,4 [MMSE] score: 30/30) were normal, as were brain computed tomography (CT) scan (Figure 1A), electrocardiogram, and chest radiograph results. Blood and urine analyses, including toxicology screening, revealed only mild leucocytosis. Mr A had a 12-year history of treatment-resistant depression (DSM-IV-TR criteria). During the last depressive episode, a neurologist considered the possibility of Parkinson’s disease and dementia and started Mr A on selegiline (5 mg/d), donepezil (10 mg/d), amitriptyline (25 mg/d), and perphenazine (2 mg/d). Depression symptoms remitted 1 year prior to the current episode, leading to discontinuation of amitriptyline and perphenazine. In addition, Mr A had a history of hypertension, benign prostatic hypertrophy, glaucoma, gastric ulcer, and degenerative lumbar disc disease, and, at the onset of the current episode, was also taking telmisartan (40 mg/d) and tamsulosin (0.4 mg/d). Figure 1. Mr A’s Initial and Follow-Up Computed Tomography (CT) Scans On the basis of a working diagnosis of acute mania (DSM-IV-TR criteria), Mr A was started on valproic acid (1,000 mg/d), risperidone (2 mg/d), and flurazepam (15 mg if needed). Selegiline and donepezil were discontinued, with no adverse consequences. There was a gradual improvement, leading to full symptomatic remission, with no significant side effects, and he was discharged after 1 month with a diagnosis of bipolar disorder (DSM-IV-TR criteria). At his first follow-up consultation 1 month later, Mr A showed marked sedation and significant cognitive deficits (Montreal Cognitive Assessment5,6 score: 18/30; MMSE score: 23/30), prompting reduction of risperidone to 1 mg/d and replacement of flurazepam with lorazepam. At subsequent evaluations, Mr A remained sedated, and his cognitive function further deteriorated, leading to requests for an electroencephalogram, which was normal, and brain magnetic resonance imaging (MRI). Four months after being discharged, Mr A developed left-side hemiparesis and was referred to our emergency department, where a repeat brain CT scan (Figure 1B) revealed a large right frontal lobe tumor, confirmed by the MRI scan and later diagnosed “postoperatively” as glioblastoma. In late-onset bipolar disorder, there is a higher likelihood of underlying organic causes meriting, as exemplified here, extensive diagnostic testing.7,8 In this patient, while an iatrogenic cause could be considered on initial presentation,9,10 the subsequent follow-up highlights the need for careful longitudinal investigation. We note that a brain CT, concomitant with an inaugural presentation of mania, was normal, and the same examination performed 5 months later revealed a large tumor in the right frontal lobe. Frontal brain tumors can present symptomatically as mood disorders,11–13 with right hemisphere tumors more frequently associated with mania-like syndromes and left hemisphere tumors with depression-like syndromes.11,14 Similar laterality trends have been described for cerebrovascular lesions.15 In Mr A, the use of brain MRI at presentation could possibly have allowed for an earlier diagnosis of the lesion.7 Nevertheless, it is tempting to speculate that the inaugural manic episode was the first expression of a tumor developing in the right frontal lobe, even prior to structural evidence of the lesion, raising interesting possibilities regarding the mechanisms mediating this association.14

Objective Bipolar Disorder (BPD) is a severe mood disorder, affecting 1.5%–4.4% of the population, and manifesting as an episodic, recurrent disturbance of mood, sleep, and behaviour. Secondary BPD (SBPD) develops following a brain insult, and is traditionally associated with right frontal lobe lesions. Yet, evidence supporting this association is mostly anecdotal. Here, we use two methodologies to study the neuroanatomy of SBPD: a systematic review of SBPD cases published in the literature, and reconstitution of brain lesions from a cohort of patients with SBPD in a single 3D template brain. Method Systematic search of pubmed and WebOfScience for SBPD. For the lesion-map, data were collected from 16 consecutive patients (6 women, 10 men, mean age 60,75±14,27 years) with SBPD developing after an MRI-documented right-sided brain-lesion. For each scan we selected the sequence (T1, T2, or FLAIR) providing the best lesion discrimination. Lesions were manually segmented using MITK software.1 After segmentation, each scan was co-registered onto a template reference brain2 using 3DSlicer software.3 Co-registration applies a transformation vector along the three axes of the source image, such that its voxels match the reference brain voxels to the highest possible degree. The resulting transformation vector was then applied to the image of each segmented lesion, and all the co-registered lesions were overlapped on the template brain scan (Automated anatomical labelling atlas or John Hopkins University white matter tractography Atlas for gray- and white-matter analysis, respectively). Results 1476 articles were found in literature review, with 207 eligible cases, including 193 with focal brain lesions, mostly right-sided (84.5%) and more rarely left-sided (34.7%). Lesions were overrepresented in the frontal and temporal lobes bilaterally. In the 3D lesion-map, lesions were spread over the right hemisphere, with highest overlap in a medial area of the superior frontal gyrus (6 patients). Grey-matter quantitative mapping showed that the right superior frontal gyrus right anterior cingulate and supramarginal gyrus and right insula were lesioned in the highest number of patients (respectively 8, 7 and 6 patients). White-matter analysis highlighted the right superior longitudinal fasciculus and superior corona radiata (6 patients each), anterior corona radiata and body of corpus callosum (5 patients each). Conclusion Our systematic review confirmed that right-sided frontotemporal lesions predominate in SBPD. In our cohort lesions converged on areas of the right executive control and anterior salience networks. Both have been implicated in the neurophysiology of primary BPD.4,5