Electroconvulsive Therapy for Neuropsychiatric Symptoms due to Major Neurocognitive Disorder: A Prospective, Observational Study.

OBJECTIVES: Neuropsychiatric symptoms (NPSs) in those with major neurocognitive disorder (MNCD) include the responsive behaviors of agitation and aggression. Electroconvulsive therapy (ECT) has shown some effectiveness based on retrospective studies and one open label prospective study. We hypothesized that ECT will reduce NPSs between baseline and after treatment in those with medication-refractory behaviors. METHOD/DESIGN: This Canadian prospective multicenter study included MNCD patients admitted to geriatric psychiatry units for the management of refractory NPSs. All treatment-refractory participants suffered from advanced MNCD. We conducted the Neuropsychiatric Inventory-Clinician version and the Pittsburgh Agitation Scale at baseline, and during and after the ECT course. A bitemporal or bifrontal ECT series based on dose titration to 1.5 to 2.5 times seizure threshold was administered. RESULTS: Data were collected for 33 patients with a mean age of 73 and categorized with severe MNCD using the Functional Assessment Staging of Alzheimer's Disease scale (stages 6 and 7). The data showed a drop in mean Neuropsychiatric Inventory-Clinician version from 58.36 to 24.58 (P < 0.0001). Mean Neuropsychiatric Inventory agitation subscale dropped from 7.12 to 3.09 (P = 0.007). Mean Neuropsychiatric Inventory aggression subscale dropped from 6.94 to 0.97 (P < 0.0001). There was a concomitant significant decline in Pittsburgh Agitation Scale scores. No participants dropped out because of intolerance of ECT. One participant died from pneumonia, which did not appear related to ECT. CONCLUSIONS: In this naturalistic study, ECT was found to be a safe and effective treatment for certain NPSs in people with MNCD. This can translate into improving quality of life.

Efficacy and safety of maintenance electroconvulsive therapy for sustaining resolution of severe aggression in a major neurocognitive disorder.

We report a novel electroconvulsive therapy (ECT) regimen for sustaining the resolution of behavioural and psychological symptoms of dementia (BPSD) using alternating acute and maintenance ECT (M-ECT) trials. A 64-year-old man presenting with major neurocognitive disorder was admitted for acute behavioural disturbances and physical aggression. With few treatment options, the impact on patients' quality of life often supersedes cognitive symptoms and is a predictor of long-term institutionalisation. Recent studies indicate that ECT may be an effective and safe way to address BPSD. Clinicians have little information about when and how to stop a successful course of acute ECT or the long-term advantages of M-ECT with subsequent intermittent acute ECT. This case emphasises the benefit of M-ECT and describes potential challenges associated with abrupt discontinuation. This case is the first to detail tapering ECT for treatment of aggression in dementia by interchanging acute and M-ECT courses in response to symptom burden.

Functional neuroimaging of conversion disorder: the role of ancillary activation.

BACKGROUND: Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder. METHODS: Ten subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions. RESULTS: All subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p < .05) when stimulation was applied to the anesthetic body part compared to the contralateral sensate mirror region. They included right paralimbic cortices (anterior cingulate cortex and insula), right temporoparietal junction (angular gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus), right caudate, right ventral-anterior thalamus and left angular gyrus. There was a trend for activation of the somatosensory cortex contralateral to the anesthetic region to be decreased relative to the sensate side. CONCLUSIONS: Sensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder.

Occupational attainment as a marker of cognitive reserve in multiple sclerosis.

Cognitive dysfunction affects half of MS patients. Although brain atrophy generally yields the most robust MRI correlations with cognition, significant variance in cognition between individual MS patients remains unexplained. Recently, markers of cognitive reserve such as premorbid intelligence have emerged as important predictors of neuropsychological performance in MS. In the present study, we aimed to extend the cognitive reserve construct by examining the potential contribution of occupational attainment to cognitive decline in MS patients. Brain atrophy, estimated premorbid IQ, and occupational attainment were assessed in 72 MS patients. The Minimal Assessment of Cognitive Functioning in MS was used to evaluate indices of information processing speed, memory, and executive function. Results showed that occupational attainment was a significant predictor of information processing speed, memory, and executive function in hierarchical linear regressions after accounting for brain atrophy and premorbid IQ. These data suggest that MS patients with low occupational attainment fare worse cognitively than those with high occupational attainment after controlling for brain atrophy and premorbid IQ. Occupation, like premorbid IQ, therefore may make an independent contribution to cognitive outcome in MS. Information regarding an individual's occupation is easily acquired and may serve as a useful proxy for cognitive reserve in clinical settings.

Imaging genetics in multiple sclerosis: a volumetric and diffusion tensor MRI study of APOE ε4.

Evidence linking the ε4 allele of APOE to more severe brain MRI abnormalities in multiple sclerosis (MS) has been conflicting and limited to studies of lesion load and whole brain atrophy. The purpose of the present study was to determine whether the ε4 allele of APOE is associated with more extensive brain pathology in MS using structural and diffusion tensor MRI. Using a case-control design, 43 MS patients with the ε4 allele and 47 ε4 negative MS patients underwent structural and diffusion tensor imaging (DTI) at 3T. Hypo- and hyperintense lesion volumes, whole brain and medial temporal volumes, and DTI parameters (fractional anisotropy (FA) and mean diffusivity (MD)) in normal-appearing brain tissue and lesions were compared between the groups. ε4+ and ε4- MS patients were well-matched on demographic characteristics, disease variables, and proportions receiving disease-modifying therapy. ε4+ and ε4- patients did not differ on any MRI or DTI measure. This study refutes a role for the ε4 allele in MRI abnormalities in MS, particularly those linking ε4 to greater T1 hypointense lesion volume and brain atrophy. Previous work on this putative gene-MRI relationship is extended by comparing DTI measures within lesions and normal-appearing brain tissue. A lack of differences in medial temporal regions, areas that have been linked to ε4-associated changes in health and disease, further supports the conclusion that that ε4 is not associated with more subtle MRI markers of brain pathology in MS.

APOE epsilon4 and cognitive dysfunction in multiple sclerosis: a review.

The authors present a literature review exploring the possible association between APOE epsilon4 and cognitive dysfunction in multiple sclerosis. Differences in magnetic resonance (MR)-elicited brain pathology between epsilon4+ and epsilon4- multiple sclerosis patients were also considered. Overall, the cognitive literature suggests the likelihood of a gene-cognition relationship. A less certain picture pertains to the gene-MR data. Methodological considerations, however, leave many questions unanswered and the conclusions should be viewed in this light. No study has yet combined neuropsychological inquiry, brain imaging, and genetic determination, an approach that has the potential to pull together various pieces of the puzzle.

Neuroimaging week: a novel, engaging, and effective curriculum for teaching neuroimaging to junior psychiatric residents.

OBJECTIVE: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice. METHODS: The authors present the format and curriculum of a highly interactive, 5-day intensive neuroimaging course, taught by psychiatry, neurology, radiology, nuclear medicine, and sleep medicine staff, covering psychiatrically oriented neuroanatomy; neuroimaging techniques and principles; clinical skills, including interpretation of computed tomography and MRI in neuropsychiatric cases; and formal approaches to critiquing neuroimaging research and applying its findings to clinical practice. Detailed questionnaires assessed the subjective and objective impact of the course on residents' knowledge of, and attitudes toward, neuroimaging in psychiatry before and after the course. RESULTS: Twenty-five first-year residents completed the questionnaires. Participants were enthusiastic about the content and interested in improving their skills in interpreting clinical neuroimaging studies. By the end of the course, residents also reported large gains in subjective comfort level with neuroimaging literature appraisal and functional neuroanatomy and believed that the course was effective in meeting their own specific learning objectives. Objective measures showed significant gains in most areas of the curriculum. CONCLUSION: This short, intensive course effectively teaches clinically oriented neuroimaging principles to psychiatric residents and can be readily adapted to other postgraduate programs or continuing medical education.

Multiple sclerosis and cannabis: a cognitive and psychiatric study.

BACKGROUND: A significant minority of patients with multiple sclerosis (MS) use cannabis, yet no study has examined the possible effects on mentation. Here, we report the emotional and cognitive correlates of street cannabis use in patients with MS. METHODS: A sample of 140 consecutive patients with MS were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I disorders (SCID-IV) from which details of cannabis use were recorded. Cognition was assessed using the Neuropsychological Battery for MS supplemented with the Symbol Digit Modalities Test (SDMT), an index of information processing speed, working memory, and sustained attention. RESULTS: Ten subjects (7.7%) were defined as current cannabis users based on use within the last month. Compared to non-cannabis users (n = 130), they were younger (p = 0.001). Each of the 10 current cannabis users was matched on demographic and disease variables to four subjects with MS who did not use cannabis (total control sample n = 40). Group comparisons revealed that the proportion of patients meeting DSM-IV criteria for a psychiatric diagnosis was higher in cannabis users (p = 0.04). In addition, on the SDMT, cannabis users had a slower mean performance time (p = 0.006) and a different pattern of response compared to matched controls (group x time interaction; p = 0.001). CONCLUSIONS: Inhaled cannabis is associated with impaired mentation in patients with multiple sclerosis, particularly with respect to cognition. Future studies are required to clarify the direction of this relationship.

Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior.

DNA methylation differences between identical twins could account for phenotypic twin discordance of behavioral traits and diseases. High throughput epigenomic microarray profiling can be a strategy of choice for identification of epigenetic differences in phenotypically different monozygotic (MZ) twins. Epigenomic profiling of a pair of MZ twins with quantified measures of psychometric discordance identified several DNA methylation differences, some of which may have developmental and behavioral implications and are consistent with the contrasting psychometric profiles of the twins. In particular, differential methylation of CpG islands proximal to the homeobox DLX1 gene could modulate stress responses and risk taking behavior, and deserve further attention as a potential marker of aversion to danger. The epigenetic difference detected at DLX1 of approximately 1.2 fold change was used to evaluate experimental design issues such as the required numbers of technical replicates. It also enabled us to estimate the power this technique would have to detect a functionally relevant epigenetic difference given a range of 1 to 50 twin pairs. We found that use of epigenomic microarray profiling in a relatively small number (15-25) of phenotypically discordant twin pairs has sufficient power to detect 1.2 fold epigenetic changes.

Neuroanatomy of pseudobulbar affect : a quantitative MRI study in multiple sclerosis.

Pseudobulbar affect (PBA) is defined as episodes of involuntary crying, laughing, or both in the absence of a matching subjective mood state. This neuropsychiatric syndrome can be found in a number of neurological disorders including multiple sclerosis (MS). The aim of this study was to identify neuroanatomical correlates of PBA in multiple sclerosis (MS) using a case-control 1.5T MRI study. MS patients with (n = 14) and without (n = 14) PBA were matched on demographic, disease course, and disability variables. Comorbid psychiatric disorders including depressive and anxiety disorders were absent. Hypo- and hyperintense lesion volumes plus measurements of atrophy were obtained and localized anatomically according to parcellated brain regions. Between-group statistical comparisons were undertaken with alpha set at 0.01 for the primary analysis. Discrete differences in lesion volume were noted in six regions: Brainstem hypointense lesions, bilateral inferior parietal and medial inferior frontal hyperintense lesions, and right medial superior frontal hyperintense lesions were all significantly higher in the PBA group. A logistic regression model identified four of these variables (brainstem hypointense, left inferior parietal hyperintense, and left and right medial inferior frontal hyperintense lesion volumes) that accounted for 70% of the variance when it came to explaining the presence of PBA. In conclusion, MS patients with PBA have a distinct distribution of brain lesions when compared to a matched MS sample without PBA. The lesion data support a widely-dispersed neural network involving frontal, parietal, and brainstem regions in the pathophysiology of PBA.

The neuropsychiatry of multiple sclerosis: a review of recent developments.

PURPOSE OF REVIEW: The aim of this review is to summarize the current literature on the neuropsychiatry of multiple sclerosis (MS). RECENT FINDINGS: Data from community samples have supported earlier findings from tertiary referral centres of high rates of depression in MS patients. Neuroimaging offers important clues as to the pathogenesis of depression, but psychosocial factors cannot be ignored and emerge as equally important predictors. Cognitive-behavioural therapy is an effective treatment, rivalling standard dosing of sertraline in patients with depression. An allied disorder--pseudobulbar affect--occurs in up to 10% of MS patients and responds well to a combination of dextromethorphan and quinidine. Cognitive dysfunction affects approximately 40% of MS patients. Markers of cerebral atrophy have emerged as more important correlates of impaired cognition than lesion volume. Moreover, functional MRI studies have demonstrated the brain's ability to compensate, in part, for damage. Should the disease burden be too severe, however, compensatory mechanisms fail and cognitive deficits increase accordingly. SUMMARY: Neuropsychiatric abnormalities are common in MS patients. No aspect of mentation is spared. Advances in neuroimaging are increasing our understanding of the pathogenesis of these disorders. Translating these findings into improved methods of treatment for patients presents researchers with pressing challenges.

Unexplained neurologic symptoms: an fMRI study of sensory conversion disorder.

We investigated three subjects with unexplained sensory loss meeting criteria for conversion disorder using brain fMRI during unilateral and bilateral vibrotactile stimulation. In each subject, stimulation of the affected limb did not produce activation of the contralateral primary somatosensory (S1) region, whereas bilateral limb stimulation did. These findings implicate selective alterations in primary sensorimotor cortex activity in conversion disorder, and may also reconcile the discordant results of previous studies.

Randomized treatment trial in mild traumatic brain injury.

OBJECTIVE: To determine whether multidisciplinary treatment of mild traumatic brain injury (MTBI) improves neurobehavioral outcome at 6 months postinjury. METHODS: Subjects with MTBI were randomly assigned to treatment (n=97) or nontreatment (control, n=94) groups. Treated patients were assessed within 1 week of injury and thereafter managed by a multidisciplinary team according to clinical need for a further 6 months. Control subjects were not offered treatment. Six-month outcome measures included: severity of postconcussive symptoms (Rivermead Post-Concussion Disorder Questionnaire), psychosocial functioning (Rivermead Follow-up Questionnaire), psychological distress (General Health Questionnaire), and cognition (neurocognitive battery). RESULTS: Treatment and control subjects were well-matched for demographic and MTBI severity data. In addition, the two groups did not differ on any outcome measure. However, in individuals with preinjury psychiatric difficulties (22.9% of the entire sample), subjects in the treatment group had significantly fewer depressive symptoms 6 months postinjury compared with untreated controls (P=.01). CONCLUSIONS: These findings suggest that routine treatment of all MTBI patients offers little benefit; rather, targeting individuals with preinjury psychiatric problems may prove a more rational and cost-effective approach.