Differences in course of illness between patients with bipolar II disorder with and without epileptiform discharges or other sharp activity on electroencephalograms: a cross-sectional study.

BACKGROUND: A diagnosis of bipolar II disorder requires that the symptoms cannot be better explained by a medical condition. Epilepsy is in some cases associated with an affective syndrome mimicking an unstable bipolar II disorder. Epileptiform discharges on electroencephalograms (EEGs) are typical, but not pathognomonic, for epilepsy. A previous study has found a high frequency of epileptiform discharges and other sharp activity among patients with bipolar disorder. The aim of the study was to identify if epileptic discharges or other sharp activity per se are associated with an altered course of illness among patients with bipolar II disorder. METHODS: Eighty six patients diagnosed with bipolar II disorder at two psychiatric departments were interviewed about prior course of illness and assessed with EEGs. The patients were split into two groups based on the presence (n = 12) or absence (n = 74) of epileptiform discharges or other sharp activity. Wilcoxon rank sum test, Fisher's exact test, and Pearson's chi squared test were used to assess differences between the groups on six variables of course of illness. RESULTS: Patients with epileptiform discharges or other sharp activity had a history of more hypomanic episodes per year (median (interquartile range (IQR)) 1.5 (3.2) vs. 0.61 (1.1), p = 0.0090) and a higher hypomania:depression ratio (median (IQR) 3.2 (16) vs. 1.0 (1.0), p = 0.00091) as compared to patients without. None of the patients with epileptiform discharges or other sharp activity had self-reported epileptic seizures in their history. CONCLUSIONS: Epileptiform discharges or other sharp activity on EEGs are associated with more hypomanic episodes and an increased hypomania:depression ratio. Our results warrant replication in prospective studies, but suggest that EEG findings could be of prognostic importance for patients diagnosed with bipolar II disorder in psychiatric care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00201526 ).

A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders.

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age - and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab-) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab- patients. There were no differences in CSF analysis (n = 6 ab+/12 ab-), EEG (n = 7 ab+/19 ab-) or brain MRI (n = 7 ab+/17 ab-) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.

Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care.

BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in 7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic acid decarboxylase-65 (GAD65) antibodies in 1.9%, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich glioma-inactivated protein-1 (LGI1) and γ-aminobutyric acid B (GABAB) receptor antibodies were not detected. NMDAR antibodies of class IgG were present in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally prevalent in patients with and without psychosis. There were no significant differences in antibody prevalence in the different diagnostic categories, except for a higher odds ratio of being NMDAR antibody positive for patients without a specific psychiatric diagnosis. CONCLUSIONS: NMDAR IgG autoantibodies, which are known to be strongly associated with anti-NMDAR encephalitis, were rarely found. CASPR2 and GAD65 antibodies were more frequently encountered in the present study than previously reported. Further research on the clinical significance of anti-neuronal autoantibodies in patients with acute psychiatric symptoms is needed.