Improved estimation of the risk of manic relapse by combining clinical and brain scan data.

INTRODUCTION: Estimating the risk of manic relapse could help the psychiatrist individually adjust the treatment to the risk. Some authors have attempted to estimate this risk from baseline clinical data. Still, no studies have assessed whether the estimation could improve by adding structural magnetic resonance imaging (MRI) data. We aimed to evaluate it. MATERIAL AND METHODS: We followed a cohort of 78 patients with a manic episode without mixed symptoms (bipolar type I or schizoaffective disorder) at 2-4-6-9-12-15-18 months and up to 10 years. Within a cross-validation scheme, we created and evaluated a Cox lasso model to estimate the risk of manic relapse using both clinical and MRI data. RESULTS: The model successfully estimated the risk of manic relapse (Cox regression of the time to relapse as a function of the estimated risk: hazard ratio (HR)=2.35, p=0.027; area under the curve (AUC)=0.65, expected calibration error (ECE)<0.2). The most relevant variables included in the model were the diagnosis of schizoaffective disorder, poor impulse control, unusual thought content, and cerebellum volume decrease. The estimations were poorer when we used clinical or MRI data separately. CONCLUSION: Combining clinical and MRI data may improve the risk of manic relapse estimation after a manic episode. We provide a website that estimates the risk according to the model to facilitate replication by independent groups before translation to clinical settings.

Evolución longitudinal y cambios de función cerebral entre fases del trastorno bipolar / Longitudinal evolution and changes in brain function between phases of bipolar disorder

Mediante resonancia magnética funcional (fMRI) se han señalado alteraciones en el sistema límbico y en el lóbulo prefrontal del cerebro de los pacientes bipolares sobre todo durante episodios de manía y depresivos, aunque también en la eutimia. La relación entre cambios funcionales cerebrales y las distintas fases del trastorno bipolar (TB) es menos clara y la manera ideal de investigarlos es examinar a los mismos pacientes en fases distintas de la enfermedad. Se presentan los resultados de dos estudios longitudinales que examinaron mediante fMRI las activaciones y desactivaciones cerebrales durante una tarea de memoria de trabajo (n-back) en pacientes durante un episodio afectivo agudo que luego alcanzaron la eutimia. Entre otros hallazgos, la corteza dorsal prefrontal (dlPFC) se mostró hipoactivada durante el episodio de manía y se normalizaba durante la eutimia, mientras que el área ventromedial de la corteza prefrontal (vmPFC) mostró un fracaso en la desactivación durante la tarea n-back, tanto durante la manía y la depresión, como en la eutimia. Teniendo en cuenta que el área vmPFC es uno de los nodos principales de la red neuronal por defecto, los resultados sugieren una disfunción de esta red neuronal más como rasgo que como marcador de estado en el TB (AU)

Functional magnetic resonance imaging (fMRI) has revealed alterations in the limbic system and the prefrontal lobe of the brain in bipolar patients, especially during episodes of mania and depression, but also in euthymia. The relationship between functional brain changes and the different phases of bipolar disorder (BD) is less clear and the ideal way to investigate them is to examine the same patients in different phases of the illness. We present the results of two longitudinal studies that examined by fMRI the brain activations and deactivations during a working memory task (n-back) in patients during an affective acute episode who later reached euthymia. Among other findings, during the manic episode the dorsal prefrontal cortex (dlPFC) showed hypoactivation during the task, but it normalised during the euthymia, while the ventromedial prefrontal cortex (vmPFC) showed a failure to deactivate both during mania and depression, as well as in euthymia. Considering that the vmPFC area is one of the main nodes of the default neural network (DMN), the results suggest dysfunction of this neural network more as a trait than as a state marker in TB (AU)

Emerging cycloid psychosis episodes during COVID-19 pandemic: a case series.

AIMS: Cycloid psychosis (CP) is a clinical entity characterized by sudden onset of psychotic polymorphic symptomatology and fluctuant course. It has a reported rate of psychosocial precipitating factors ranging 30-65%. The aim of the study was to describe all cases of CP, admitted in our Psychiatry ward, during the first two months of the COVID-19 pandemic. METHOD: In this retrospective and observational study, we reported a sample of eight patients who were treated as inpatients in the psychiatric ward of our hospital during the first two months of COVID-19 pandemic (mid-March to mid-May 2020) and compared it with previous years. All our patients fulfilled all four Perris & Brockington criteria for CP. We reported the sociodemographic, clinical and biological parameters. RESULTS: In our sample, all of the patients had maladaptive personality traits; the major external stressing factor was COVID-19; all our patients had short prodromal symptomatology, short Duration of Untreated Psychosis (DUP) and high score at the Positive Scale at Positive and Negative Syndrome Scale (PANSS-P) at hospital admission with the majority showing psychotic symptoms related to the actual COVID-19 pandemic. The predominant treatment during admission was olanzapine and a short time to full remission of psychotic symptoms was observed in all patients. CONCLUSION: We found an increase in the admission of patients with CP during the first two months of the actual pandemic. Stress caused by the COVID-19 situation has possibly incremented the frequency of stress-related disorders and it has also influenced its clinical presentation.

Differential failure to deactivate the default mode network in unipolar and bipolar depression.

OBJECTIVES: Neuroimaging studies have revealed evidence of brain functional abnormalities in bipolar depressive disorder (BDD) and major depressive disorder (MDD). However, few studies to date have compared these two mood disorders directly. METHODS: Matched groups of 26 BDD type I patients, 26 MDD patients and 26 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the n-back working memory task. A whole-brain ANOVA was used to compare the three groups and clusters of significant difference were examined further using region-of-interest (ROI) analysis. RESULTS: The whole-brain ANOVA revealed a single cluster of significant difference in the medial frontal cortex. The BDD and MDD patients both showed failure to deactivate in this area compared to the controls. The BDD patients showed significantly greater failure of deactivation than the MDD patients, which was not accounted for by differences in severity or chronicity of illness between them. CONCLUSIONS: Failure of deactivation, considered to reflect default mode network dysfunction, is present to a greater extent in bipolar than unipolar depression. The study of this network may be useful in the search for brain markers that distinguish the two disorders.

Evaluation of machine learning algorithms and structural features for optimal MRI-based diagnostic prediction in psychosis.

A relatively large number of studies have investigated the power of structural magnetic resonance imaging (sMRI) data to discriminate patients with schizophrenia from healthy controls. However, very few of them have also included patients with bipolar disorder, allowing the clinically relevant discrimination between both psychotic diagnostics. To assess the efficacy of sMRI data for diagnostic prediction in psychosis we objectively evaluated the discriminative power of a wide range of commonly used machine learning algorithms (ridge, lasso, elastic net and L0 norm regularized logistic regressions, a support vector classifier, regularized discriminant analysis, random forests and a Gaussian process classifier) on main sMRI features including grey and white matter voxel-based morphometry (VBM), vertex-based cortical thickness and volume, region of interest volumetric measures and wavelet-based morphometry (WBM) maps. All possible combinations of algorithms and data features were considered in pairwise classifications of matched samples of healthy controls (N = 127), patients with schizophrenia (N = 128) and patients with bipolar disorder (N = 128). Results show that the selection of feature type is important, with grey matter VBM (without data reduction) delivering the best diagnostic prediction rates (averaging over classifiers: schizophrenia vs. healthy 75%, bipolar disorder vs. healthy 63% and schizophrenia vs. bipolar disorder 62%) whereas algorithms usually yielded very similar results. Indeed, those grey matter VBM accuracy rates were not even improved by combining all feature types in a single prediction model. Further multi-class classifications considering the three groups simultaneously made evident a lack of predictive power for the bipolar group, probably due to its intermediate anatomical features, located between those observed in healthy controls and those found in patients with schizophrenia. Finally, we provide MRIPredict (https://www.nitrc.org/projects/mripredict/), a free tool for SPM, FSL and R, to easily carry out voxelwise predictions based on VBM images.

Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder.

INTRODUCTION: Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. METHODS: Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. RESULTS: No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. CONCLUSIONS: Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.

Prevalence of cavum vergae in psychosis and mood spectrum disorders.

BACKGROUND: Midline brain abnormalities might increase susceptibility to both first-episode and chronic mental disorder. Evidence of cavum vergae (CV) abnormality in mental disorders is scarce. METHODS: The presence of CV was assessed by a researcher blind to clinical information in a cross-disorder sample of 639 patients with mood and psychotic disorders and in 223 healthy controls. Homogeneous magnetic resonance imaging methods of acquisition and assessment were applied. RESULTS: Seven out of 639 patients with mood or psychotic disorders were detected with CV which corresponds to a prevalence of 1.1%. There were no concurrent cases of CV in the healthy control group. Identified cases which are briefly described were diagnosed from bipolar I disorder (n=2), delusional disorder (n=1), brief psychotic disorder (n=1) and schizoaffective disorder (n=3). Patients with CV had descriptively lower current IQ, executive functioning and memory scores in relation to patients without CV but this was not statistically significant. LIMITATIONS: Effects of medication and lack of statistical power of the CV patient group. CONCLUSIONS: Midline brain abnormalities, such as CV, might represent an unspecific risk factor for the development of severe mental disorders.

Transcultural adaption and validation of the Spanish version of the Bipolar Depression Rating Scale (BDRS-S).

BACKGROUND: The Bipolar Depression Rating Scale (BDRS) arguably better captures symptoms in bipolar depression especially depressive mixed states than traditional unipolar depression rating scales. The psychometric properties of the Spanish adapted version, BDRS-S, are reported. METHODS: The BDRS was translated into Spanish by two independent psychiatrists fluent in English and Spanish. After its back-translation into English, the BDRS-S was administered to 69 DSMI-IV bipolar I and II patients who were recruited from two Spanish psychiatric hospitals. The Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS) were concurrently administered. 42 patients were reviewed via video by four psychiatrists blind to the psychopathological status of those patients. In order to assess the BDRS-S intra-rater or test-retest validity, 22 subjects were assessed by the same investigator performing two evaluations within five days. RESULTS: The BDRS-S had a good internal consistency (Cronbach׳s α=0.870). We observed strong correlations between the BDRS-S and the HDRS (r=0.874) and MADRS (r=0.854) and also between the mixed symptom cluster score of the BDRS-S and the YMRS (r=0.803). Exploratory factor analysis revealed a three factor solution: psychological depressive symptoms cluster, somatic depressive symptoms cluster and mixed symptoms cluster. LIMITATIONS: A relatively small sample size for a 20-item scale. CONCLUSIONS: The BDRS-S provides solid psychometric performance and in particular captures depressive or mixed symptoms in Spanish bipolar patients.

Successful treatment of hydroxyzine and dexclorfeniramine maleate in combination with electroconvulsive therapy in a neuroleptic malignant catatonia: a case report.

Malign neuroleptic syndrome is a potentially life-threatening condition that is normally treated with electroconvulsive therapy (ECT). In this case report, we discuss a severely agitated and catatonic bipolar I patient who developed a neuroleptic malignant syndrome and did not improve with benzodiazepines and ECT. On the basis of anecdotal reports of the positive effects of antihistamines in psychosis and ECT, we treated our case with a combination of two antihistamines, hydroxyzine and dexclorfeniramine maleate, and ECT, which improved the clinical picture to the point of clinical remission.

Brain functional changes across the different phases of bipolar disorder.

BACKGROUND: Little is known about how functional imaging changes in bipolar disorder relate to different phases of the illness. AIMS: To compare cognitive task activation in participants with bipolar disorder examined in different phases of illness. METHOD: Participants with bipolar disorder in mania (n = 38), depression (n = 38) and euthymia (n = 38), as well as healthy controls (n = 38), underwent functional magnetic resonance imaging during performance of the n-back working memory task. Activations and de-activations were compared between the bipolar subgroups and the controls, and among the bipolar subgroups. All participants were also entered into a linear mixed-effects model. RESULTS: Compared with the controls, the mania and depression subgroups, but not the euthymia subgroup, showed reduced activation in the dorsolateral prefrontal cortex, the parietal cortex and other areas. Compared with the euthymia subgroup, the mania and depression subgroups showed hypoactivation in the parietal cortex. All three bipolar subgroups showed failure of de-activation in the ventromedial frontal cortex. Linear mixed-effects modelling revealed a further cluster of reduced activation in the left dorsolateral prefrontal cortex in the patients; this was significantly more marked in the mania than in the euthymia subgroup. CONCLUSIONS: Bipolar disorder is characterised by mood state-dependent hypoactivation in the parietal cortex. Reduced dorsolateral prefrontal activation is a further feature of mania and depression, which may improve partially in euthymia. Failure of de-activation in the medial frontal cortex shows trait-like characteristics.

Bipolar depressed patients show both failure to activate and failure to de-activate during performance of a working memory task.

BACKGROUND: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated. METHOD: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network. LIMITATIONS: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls. CONCLUSIONS: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity.

Failure of de-activation in the medial frontal cortex in mania: evidence for default mode network dysfunction in the disorder.

OBJECTIVES: Manic patients have been found to show reduced activation in the prefrontal cortex and other regions during performance of cognitive tasks. However, little is known about de-activations associated with the disorder. This study aimed to examine, at the whole-brain level, abnormal patterns of task-related activation and de-activation during performance of a working memory task. METHODS: Twenty-nine DSM-IV bipolar patients and 46 healthy controls underwent fMRI during performance of the n-back task. The patients were scanned while they were in a manic episode. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The manic patients showed reduced activation compared to the controls in the bilateral dorsolateral prefrontal cortex and the right parietal cortex. They also showed failure of de-activation in the medial frontal cortex, extending to the temporal poles and parts of the limbic system bilaterally. The failure of activation in the dorsolateral prefrontal cortex disappeared when differences in task performance were controlled for in the analysis. However, the medial frontal failure of de-activation survived controlling for this. CONCLUSIONS: This study suggests that, in addition to reduced prefrontal activation, failure of de-activation is an important functional imaging abnormality in mania. This, together with its location in the medial prefrontal cortex, implies default mode network dysfunction in the disorder.

ECT in a patient with Parkinson's disease and schizophrenia, with dopamine transporter visualisation using 123I-ioflupane SPET.

A 58-year old woman with chronic schizophrenia developed worsening parkinsonian symptoms over the previous 6 years, and was eventually diagnosed as having Parkinson's disease. Antipsychotics were stopped because they worsened these symptoms. Antiparkinsonian treatment led to a significant increase in delusions and behavioural disorganisation. The patient underwent electroconvulsive-therapy which improved both her psychiatric and motor symptoms. After treatment, 123I-Ioflupane uptake was mildly increased in the left caudate nucleus, but uptake in right caudate nucleus was lower than in a pretreatment scan.