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.

The BAT: A videotaped battery to assess theory of mind in schizophrenia.

The ability of attributing mental states to oneself and to the others (theory of mind, ToM) is impaired in schizophrenia. ToM is not a monolithic function, it includes different capacities: some implies the decoding of affective states, others the reasoning about mental states. We have developed the BAT, a Battery to Assess Theory of mind abilities in adult psychotic subjects in an ecological audiovisual format. The performance on the BAT and three other test of social cognition was compared in a sample of schizophrenic patients with a control group. The samples were matched in terms of age and premorbid IQ. The BAT was sensitive to detect the ToM impairments in schizophrenia, showed good internal consistency and concurrent validity. The area under the ROC curves established a cutoff point that would correctly classify controls and patients in a 96.6% of cases. The factorial analysis isolated two factors: empathy and reasoning, with a good adjustment. Our results showed that the BAT could be a valid, ecological and usable tool to assess ToM in psychotic patients, with good psychometric properties, that would allow obtaining a more complete profile of their impairment.

Longitudinal brain functional changes between mania and euthymia in bipolar disorder.

OBJECTIVES: While widespread cortical and subcortical brain functional abnormalities have been found in bipolar disorder, the changes that take place between illness phases and recovery are less clearly documented. Only a small number of longitudinal studies of manic patients, in particular, have been carried out. METHODS: Twenty-six bipolar patients underwent fMRI during performance of the n-back working memory task when manic and again after recovery. Twenty-six matched healthy controls were also scanned on two occasions. Task-related activations and de-activations were examined. RESULTS: When manic, the patients showed clusters of significantly reduced activation in the left dorsolateral prefrontal cortex (DLPFC)/precentral cortex and the parietal cortex/superior precuneus bilaterally. They also showed failure of de-activation in the ventromedial frontal cortex (vmPFC). After recovery, activation in the left DLPFC/precentral cortex and in the bilateral parietal cortex/superior precuneus clusters increased significantly. However, failure of de-activation remained present in the vmPFC. CONCLUSIONS: Recovery from mania is associated with normalization of DLPFC and parietal hypoactivation, but not with vmPFC failure of de-activation, which accordingly appears to represent a trait abnormality in the disorder.

Larger Gray Matter Volume in the Basal Ganglia of Heavy Cannabis Users Detected by Voxel-Based Morphometry and Subcortical Volumetric Analysis.

Background: Structural imaging studies of cannabis users have found evidence of both cortical and subcortical volume reductions, especially in cannabinoid receptor-rich regions such as the hippocampus and amygdala. However, the findings have not been consistent. In the present study, we examined a sample of adult heavy cannabis users without other substance abuse to determine whether long-term use is associated with brain structural changes, especially in the subcortical regions. Method: We compared the gray matter volume of 14 long-term, heavy cannabis users with non-using controls. To provide robust findings, we conducted two separate studies using two different MRI techniques. Each study used the same sample of cannabis users and a different control group, respectively. Both control groups were independent of each other. First, whole-brain voxel-based morphometry (VBM) was used to compare the cannabis users against 28 matched controls (HC1 group). Second, a volumetric analysis of subcortical regions was performed to assess differences between the cannabis users and a sample of 100 matched controls (HC2 group) obtained from a local database of healthy volunteers. Results: The VBM study revealed that, compared to the control group HC1, the cannabis users did not show cortical differences nor smaller volume in any subcortical structure but showed a cluster (p < 0.001) of larger GM volume in the basal ganglia, involving the caudate, putamen, pallidum, and nucleus accumbens, bilaterally. The subcortical volumetric analysis revealed that, compared to the control group HC2, the cannabis users showed significantly larger volumes in the putamen (p = 0.001) and pallidum (p = 0.0015). Subtle trends, only significant at the uncorrected level, were also found in the caudate (p = 0.05) and nucleus accumbens (p = 0.047). Conclusions: This study does not support previous findings of hippocampal and/or amygdala structural changes in long-term, heavy cannabis users. It does, however, provide evidence of basal ganglia volume increases.

Concurrent Use of Cannabis and Alcohol: Neuropsychiatric Effect Consequences.

BACKGROUND: Concurrent use of cannabis and alcohol is frequent. According different studies, the prevalence is among 20-34% depending on different samples studied. OBJECTIVE: In contrast with the wide evidence available about neuropsychiatric effects associated to the use of cannabis or alcohol separately, there are few studies of the neuropsychiatric effects of their combination. Our aim was to review the literature regarding this topic. CONCLUSION: We performed a search in MEDLINE and from 114 potentially eligible studies, 27 were selected. Most of them studied the relation between cannabis and alcohol, and with them combined to other substances of abuse, but only a few considered their concurrent effect among mental disorders (ADHD, bipolar disorder) and neuropsychological performance. More research in the neuropsychiatric effects of the concomitant use of cannabis and alcohol is needed.

Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids with Drugs of Abuse and Medicines.

BACKGROUND & OBJECTIVE: Cannabis is the most widely used illicit drug. The two most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The THC content of cannabis has been increasing during the last years and recently appeared in the market as a series of synthetic cannabinoids with potent agonist activity. Recreational users frequently combine cannabis with other drugs of abuse as alcohol, amphetamines and derivatives, nicotine and cocaine. In addition, these subjects can be taking medicines for acute and chronic medical conditions. The increasing use of medicinal cannabis for chronic pain and neurological and psychiatric disorders can produce potential interactions with medications used for the symptomatic treatment of these or other diseases. CONCLUSION: THC and CBD are metabolized mainly in the liver by cytochrome P-450 isoenzymes (mainly CYP2Cs and CYP3A4). In vitro studies indicate that THC and CBD both inhibit CYP1A1, 1A2 and 1B1 enzymes, and recent studies have indicated that CBD is also a potent inhibitor of CYP2C19 and CYP3A4. Both cannabinoids may interact with other medications metabolized by the same pathway or by inducers/inhibitors of the isoenzymes. Cannabis produces sedation, impairs psychomotor performance, and increases blood pressure and heart rate. Pharmacodynamic interactions with other sedatives can potentiate the central effects but can be decreased by psychostimulants. This review focuses on the interactions between cannabinoids and alcohol, other drugs of abuse, and prescription medicines.

Validation of the Spanish version of the Clinical Assessment for Negative Symptoms (CAINS).

Negative symptoms are a core feature of schizophrenia and their reliable and valid assessment is a prerequisite for developing effective therapeutic interventions. This study examined the psychometric properties and validity of the Spanish version of a new rating instrument, the Clinical Assessment Interview for Negative Symptoms (CAINS). Outpatients and inpatients (N=100) with DSM-IV schizophrenia were administered the translated CAINS, the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS). A subsample (N=46) was rated for Parkinsonism using the Extrapyramidal Symptoms Rating Scale (ESRS). The scale showed good inter-rater and intra-rater reliability. Both the CAINS overall and the subscales for motivation/pleasure (CAINS-Map) and expression (CAINS-Exp) scores correlated significantly with the SANS and PANSS negative symptom scale. Significant correlations with positive symptoms and general psychopathology were also found, but these reduced and mostly became insignificant when overall severity of illness was controlled for. Significant correlations with depression also disappeared when severity was controlled for. There was a trend-level correlation between the CAINS total score and Parkinsonism, which reflected an association with the CAINS-Exp subscale only. Factor analysis revealed a two-dimensional structure that explained the 67.44% of the variance. Overall, the Spanish version of the CAINS appears to be a valid tool for measuring negative symptoms in schizophrenia.

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.

Driving and legal status of Spanish opioid-dependent patients.

BACKGROUND: Opioid dependent patients have legal problems, driving violations and accidents more frequently than the general population. We have hypothesized that those patients currently driving may have better legal outcomes than those who do not possess a valid driving license. With this aim we have analyzed the information gathered in the PROTEUS study regarding the legal and driving statuses and assessed the possible association between them. The PROTEUS study was an observational, cross-sectional, descriptive, multicenter nationwide representative study, conducted in Spanish healthcare centers for opioid dependent patients. FINDINGS: The driving and legal statuses of a population of opioid dependent patients ≥ 18 years and enrolled in Opioid Agonist Therapy treatment centers in Spain, were assessed using a short specific questionnaire and the EuropASI questionnaire to highlight distinct individual clinical needs. 621 patients were evaluable (84% men, 24.5% active workers). 321 patients (52%) drove on a regular basis. Nineteen percent of patients had some problem with the criminal justice system. There was a significant difference (p = 0.0433) in status, according to the criminal justice system, between patients who drove on a regular basis and those who did not, with a higher percentage of patients with non-pending charges among usual drivers. CONCLUSIONS: Regular drivers showed fewer legal problems than non-regular drivers, with the exception of those related to driving (driving violations and drunk driving). Driving is a good prognostic factor for the social integration of the patients and policies should be implemented to enable these patients to drive safely under medical authorization. The legal description will be useful to assess treatment efficacy.