Development of a bipolar disorder biobank: differential phenotyping for subsequent biomarker analyses.

BACKGROUND: We aimed to establish a bipolar disorder biobank to serve as a resource for clinical and biomarker studies of disease risk and treatment response. Here, we describe the aims, design, infrastructure, and research uses of the biobank, along with demographics and clinical features of the first participants enrolled. METHODS: Patients were recruited for the Mayo Clinic Bipolar Biobank beginning in July 2009. The Structured Clinical Interview for DSM-IV was used to confirm bipolar diagnosis. The Bipolar Biobank Clinical Questionnaire and Participant Questionnaire were designed to collect detailed demographic and clinical data, including clinical course of illness measures that would delineate differential phenotypes for subsequent analyses. Blood specimens were obtained from participants, and various aliquots were stored for future research. RESULTS: As of September 2014, 1363 participants have been enrolled in the bipolar biobank. Among these first participants, 69.0 % had a diagnosis of bipolar disorder type I. The group was 60.2 % women and predominantly white (90.6 %), with a mean (SD) age of 42.6 (14.9) years. Clinical phenotypes of the group included history of psychosis (42.3 %), suicide attempt (32.5 %), addiction to alcohol (39.1 %), addiction to nicotine (39.8 %), obesity (42.9 %), antidepressant-induced mania (31.7 %), tardive dyskinesia (3.2 %), and history of drug-related serious rash (5.7 %). CONCLUSIONS: Quantifying phenotypic patterns of illness beyond bipolar subtype can provide more detailed clinical disease characteristics for biomarker research, including genomic-risk studies. Future research can harness clinically useful biomarkers using state-of-the-art research technology to help stage disease burden and better individualize treatment selection for patients with bipolar disorder.

Management of psychiatric symptoms in anti-NMDAR encephalitis: a case series, literature review and future directions.

Anti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007, has been increasingly identified as a significant cause of autoimmune and paraneoplastic encephalitis. Approximately 80% of the patients are females. The characteristic syndrome evolves in several stages, with approximately 70% of the patients presenting with a prodromal phase of fever, malaise, headache, upper respiratory tract symptoms, nausea, vomiting and diarrhoea. Next, typically within two weeks, patients develop psychiatric symptoms including insomnia, delusions, hyperreligiosity, paranoia, hallucinations, apathy and depression. Catatonic symptoms, seizures, abnormal movements, autonomic instability, memory deficits may also develop during the course of the disease. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis, which also should prompt a thorough search for an underlying tumor. Age, gender, and ethnicity may all play a role, as black females older than 18 years of age have an increased likelihood of an underlying tumor. Treatment is focused on tumor resection and first-line immunotherapy [corticosteroids, plasma exchange, and intravenous immunoglobulin]. In non-responders, second- line immunotherapy [rituximab or cyclophosphamide or combined] is required. More than 75% of the patients recover completely or have mild sequelae, while the remaining patients end up demonstrating persistent severe disability or death. There is a paucity of literature on the management of psychiatric symptoms in this population. Given the neuropsychiatric symptoms in the relatively early phase of the illness, approximately 77 % of the patients are first evaluated by a psychiatrist. Earlier recognition of this illness is of paramount importance as prompt diagnosis and treatment can potentially improve prognosis. We describe two patients diagnosed with NMDAR encephalitis presenting with two different psychiatric manifestations. The first patient presented with psychotic mania and catatonic symptoms, while the second suffered from depression with psychotic and catatonic features refractory to psychotropic medications. We review of the use of psychotropic medications and ECT to address insomnia, agitation, psychosis, mood dysregulation and catatonia in NMDAR encephalitis.

Serial infusions of low-dose ketamine for major depression.

BACKGROUND: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. METHODS: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. RESULTS: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. CONCLUSIONS: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

An updated review of implantable cardioverter/defibrillators, induced anxiety, and quality of life.

Despite overall favorable acceptance of implantable cardioverter-defibrillators (ICDs), patients may experience discharges as frightening and painful. The authors reviewed ICD-induced psychopathology in 2005. During the past 2 years the number of studies examining psychopathology and quality of life after ICD implantation has increased dramatically, warranting this update of that review. Variables assessed have included recipient age, gender, social support network, perception of control and predictability of shocks, and personality style. Now the picture of what is known is, if anything, cloudier than it was 2 years ago, with little definitive and much contradictory data emerging in most of these categories.

Electroconvulsive therapy-responsive catatonia in a medically complicated patient.

BACKGROUND: Profoundly depressed states of awareness classified as either catatonia or akinetic mutism have been reported in patients with various general medical conditions including encephalitis, frontal lobe tumors, or paraneoplastic limbic encephalitis. Catatonic features are often difficult to apprise in this context. This can result in electroconvulsive therapy (ECT) discontinuation, although it remains the most effective treatment of catatonia. CASE REPORT: We describe the case of a patient with a history of unresectable right retroorbital squamous cell carcinoma, status poststereotactic radiation and cisplatin, and subsequent pneumococcal meningitis of the temporal lobe with abscess formation who became catatonic after receiving 3 bitemporal treatments with ECT for severe depression and whose catatonia improved with continued ECT. Furthermore, she demonstrated progressive improvement in mood, interactivity, and overall neurologic function after ECT treatment was completed. CONCLUSIONS: The search for an etiology of a profound catatonic state should include the probability of underlying medical disorder. Although lorazepam may be helpful in some cases, ECT deserves early consideration in catatonia, especially in cases where the underlying cause seems to be uncertain, even if the catatonia begins in the midst of treatment.

An updated review of implantable cardioverter/defibrillators, induced anxiety, and quality of life.

During the past 2 years the number of studies examining psychopathology and quality of life after ICD implantation has increased dramatically. Variables assessed have included recipient age, gender, and social support network. How recipients respond to having the device, particularly after experiencing firing, has been evaluated in light of new depression and anxiety disorder diagnoses as well as premorbid personality structure. Now the picture of what is known is, if anything, cloudier than it was 2 years ago, with little definitive and much contradictory data emerging in most of these categories. It still seems clear that in a significant minority of ICD recipients the device negatively affects quality of life, probably more so if it fires. Education about life with the device before receiving it remains paramount. Reports continue to appear of patients developing new-onset diagnosable anxiety disorders such as panic and posttraumatic stress disorder. Until recently the strongest predictors of induced psychopathology were considered to be the frequency and recency of device firing. It now seems that preimplantation psychologic variables such as degree of optimism or pessimism and an anxious personality style may confer an even greater risk than previously thought. Certainly many variables factor into the induction of psychopathology in these patients. Among these factors are age, gender, and perception of control of shocks, as well as the predictability of shocks and psychologic attributions made by the patient regarding the device. Another source of variability is this population's medical heterogeneity. Some patients receive ICDs after near-death experiences; others get them as anticipatory prophylaxis. Some have longstanding and entrenched heart disease; others were apparently healthy before sudden dangerous arrhythmias. Diagnoses as diverse as myocardial infarction in the context of advanced coronary artery disease and dilated cardiomyopathy after acute viral infection may warrant ICD placement. Moreover the course of cardiac disease after ICD placement may vary from relative stability to continuing disease progression and severe functional compromise. Unless these and other pre- and postimplantation differences are taken into account, it is almost impossible to make meaningful comparisons between studies. Ideally, future research would consist either of large-scale, randomized, prospective studies using validated structured-interview tools to supplement a literature dominated by self-report measures, unstructured assessments, and anecdotal reports, or of smaller studies designed to focus on particular diagnostic subsets. As ICDs become the standard of care for potentially life-threatening arrhythmias, the rate of implantations continues to increase. Because negative emotions have been linked to an increased incidence of arrhythmias, and untreated or unrecognized psychiatric illness can interfere with adaptation to an ICD, assessing and managing both pre-existing and induced psychiatric disorders becomes even more critical. Greater research attention should be paid to determining which patients meet criteria for anxiety disorders before and after implantation and what premorbid traits predispose to postimplantation psychopathology. The authors predict that psychiatrists will be involved increasingly in caring for this population, offering insights into treatment options that increase the likelihood of successful ICD acceptance and decrease the psychosocial costs of these devices.

Benefits of an electronic consultation-liaison note system: better notes faster.

OBJECTIVE: The authors determined the efficiency of electronic documentation in consultation-liaison psychiatry. METHOD: An electronic note system was customized for a psychiatric consultation note. Specific attention given to common diagnoses permitted rapid documentation. RESULTS: Residents learned the system quickly. The standardized nature of the system ensured thorough documentation. Notes were immediately available and more legible. A survey indicated that this system was well received and saved time. Among the eight residents who used both handwriting and typing, an estimated average of 17.5 minutes per note was saved by typing. CONCLUSIONS: This program had clear benefits in reinforcing more complete documentation.

Anticipating potential linezolid-SSRI interactions in the general hospital setting: an MAOI in disguise.

Linezolid, a novel antimicrobial with activity against gram-positive bacteria including pathogens resistant to traditional antimicrobials, also inhibits monoamine oxidase. This latter property can cause potentially lethal adverse interactions with antidepressant medications. Long known to psychiatrists, monoamine oxidase inhibitors (MAOIs) and complications of their use may be unfamiliar to medical and surgical practitioners who may thus unwittingly precipitate a hypertensive crisis or serotonin syndrome. We review the pharmacology of MAOis and describe 3 clinical situations In which linezolid-selective serotonin inhibitor (SSRI) interactions, actual or potential, figured prominently.

Implantable cardioverter-defibrillators, induced anxiety, and quality of life.

Since its approval in 1985, the implantable cardioverter-defibrillator (ICD) has supplanted antiarrhythmic drugs as the standard of care for patients with potentially lethal ventricular arrhythmias. The increased popularity of ICDs stems primarily from their safety and tolerability compared with commonly used medications notorious for adverse drug reactions. As ICD indications have broadened, the number of implantations has increased substantially, and more attention has been directed to sequelae of implantation, particularly after ICD firing. Although scant, studies of quality of life and psychiatric symptoms in patients with ICDs consistently report assorted psychiatric disturbances affecting up to 87% of recipients. Depression and anxiety predominate: up to 38% of patients experience symptoms that meet diagnostic criteria for an anxiety disorder. Psychological theories such as the classic conditioning model, learned helplessness model, and cognitive appraisal model have been invoked to conceptualize these new-onset ICD-induced anxiety disorders. Small trials of psychosocial interventions, including support groups and cognitive behavioral therapy, have had mixed results. Little is known about preexisting anxiety disorders in ICD recipients, particularly which premorbid features predict a worse prognosis, other than suggestions that younger patients and those receiving multiple shocks are at greater risk. Prospective studies of the psychopathology of patients with ICDs, both before and after implantation, are warranted.

Familial hemiplegic migraine, neuropsychiatric symptoms, and Erdheim-Chester disease.

We report the occurrence of unilateral cerebral hemisphere edema with subsequent cortical laminar necrosis in the setting of familial hemiplegic migraine (FHM) and permanent neurologic sequelae after resolution of an attack in 1 patient. Contemporaneous with this severe attack of FHM, the patient was found to exhibit multiple systemic and neurological symptoms referable to Erdheim-Chester disease (a rare non-Langerhans cell histiocytosis) that was confirmed by bone biopsy. This case demonstrates the severity possible with a migrainous infarction associated with FHM. The co-occurrence of two such rare entities in 1 patient suggests a possible relationship.