Joseph J. Cooper

A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain.

Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common single-nucleotide polymorphism (SNP) most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs, we would predict better response in patients without the risk allele, because they have increased CACNA1C expression.

The Relationship Between Schizophrenia and Frontotemporal Dementia

Schizophrenia is a relatively common disorder diagnosed by the presentation of psychotic symptoms in the absence of identifiable neurologic or other organic cause. Frontotemporal dementia (FTD) is a relatively rare progressive neurodegenerative disorder that can present with a multitude of cognitive and behavioral symptoms including psychosis. At times, this phenotypic overlap can mean that schizophrenia and FTD are 2 possibilities in the differential diagnosis of a psychotic presentation. In this article, we systematically review the literature on the relationship between schizophrenia and FTD including case reports that highlight the potential for diagnostic confusion, clinical studies examining the relationship between the disorders, and the molecular evidence of shared pathophysiologic mechanisms. Although a relationship between the disorders is not definitively supported by the current literature, we identify the characteristics of a psychotic presentation that should alert the clinician to the possibility of FTD and describe the areas where further research is needed to clarify the pathophysiologic relationship.

Catatonia Under-Diagnosis in the General Hospital

Catatonia is under-diagnosed in psychiatric settings. No studies have explored the under-diagnosis of catatonia in general hospitals. The authors conducted a retrospective chart review using DSM-5 criteria to diagnose catatonia in medical inpatients between 2011 and 2013. Of 133 case subjects meeting DSM-5 criteria for catatonia retrospectively, 79 had never been diagnosed and 54 had a documented diagnosis. Multiple logistic regression revealed that psychiatry consultation significantly decreased the odds of under-diagnosis of catatonia, whereas presence of agitation, grimacing, or echolalia increased the likelihood of under-diagnosis. Under-diagnosed case subjects received significantly lower doses of lorazepam, and increased mortality during admission and increased length of hospital stay both fell short of statistical significance in this group. Catatonia appears to be frequently under-diagnosed in the general hospital, and psychiatry consultation services play a crucial role in its detection and treatment. Strategies to improve recognition and treatment of catatonia should be implemented.

Suspected Delirium Predicts the Thoroughness of Catatonia Evaluation

Although commonly linked to psychiatric disorders, catatonia is frequently identified secondary to neurological and general medical conditions (GMCs). The present study aimed to characterize the diagnostic workup of cases of catatonia in a general hospital setting. The authors performed a retrospective chart review of 54 cases of catatonia, over 3 years. Clinical suspicion of comorbid delirium was the strongest predictor of a more thorough general medical workup. Attribution of catatonia to a psychiatric etiology was associated with significantly less diagnostic workup. Prospective studies should help clarify the relationship between catatonia and delirium and standardize the diagnostic approach to patients presenting with catatonia.

Electroconvulsive Therapy in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report and Review of the Literature.

Objectives There is a growing scientific literature describing the neuropsychiatric symptoms of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, including the use of electroconvulsive therapy (ECT) to treat those symptoms. We sought to consolidate this literature into a review that highlights its relevance to ECT practitioners. Methods We performed a PubMed search using the terms electroconvulsive therapy and encephalitis, autoimmune encephalitis, or anti-NMDA receptor encephalitis. We reviewed all relevant studies in detail, cross-referenced all bibliographies, and collected key clinical information related to the practice of ECT. Results We identified 6 studies offering patient-level descriptions of the use of ECT in patients with anti-NMDA receptor encephalitis. In all cases ECT was used to target symptoms of catatonia. Electroconvulsive therapy was delivered safely and effectively irrespective of the timing of diagnosis, tumor removal, or immunotherapy. Conclusions There are no controlled data on the use of ECT in anti-NMDA receptor encephalitis. Further investigation is needed to determine whether ECT has a disease-modifying effect on this form of autoimmune encephalitis.

Catatonia Education: Needs Assessment and Brief Online Intervention.

ObjectivesThere are no studies investigating physicians’ knowledge of catatonia. The authors aimed to assess and increase physicians’ awareness of catatonia.MethodsA survey with clinical questions about catatonia was administered, followed by a brief online teaching module about catatonia and a post-education survey.ResultsTwenty-one psychiatry residents (response rate, 70%) and 36 internal medicine residents (response rate, 34%) participated in the pre-education survey. Psychiatry residents identified 75% of the correct answers about catatonia, compared to 32% correct by internal medicine residents (p < 0.001). Twenty participants (response rate, 35%) completed the online education module and second survey, which resulted in a significant improvement in correct response rates from 60 to 83% in all the participants (p < 0.001).ConclusionsResidents’ baseline knowledge of catatonia is low, particularly among internal medicine residents. A brief online module improved resident physicians’ knowledge of catatonia. Educational strategies to improve recognition of catatonia should be implemented.

Correction to: Recommendations for the use of ECT in pregnancy: literature review and proposed clinical protocol

The name of Heather Burrell Ward was incorrectly captured.

Refractory OCD Due to Thalamic Infarct With Response to Dronabinol

Structural brain lesions can be a rare cause of refractory psychiatric symptoms. The analysis of such cases may lead to insights into psychiatric neurobiology. Here we present a case of a dronabinol-responsive obsessive-compulsive syndrome after thalamic infarct.