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 ).

Borderline patients have difficulties describing feelings; bipolar II patients describe difficult feelings. An alexithymia study.

OBJECTIVE: Apparent similarities between borderline personality disorder (BPD) and bipolar II disorder (BIP-II) contribute to clinical difficulties in distinguishing between the disorders. Here, we aimed to explore how subjective Difficulties with the Identification and Description of Feelings (DIDF), a major constituent of the alexithymia construct and assessed as a part of the Toronto Alexithymia Scale (TAS), are related to relationship problems and health complaints in these groups. METHODS: Twenty-two patients with BPD; 22 patients with BIP-II; and 23 healthy controls (HC) completed TAS. Health complaints, including symptoms associated with mood swings, were assessed with the Giessener Subjective Complaints List (Giessener Beschwerdebogen-GBB), and relationship problems with the Health of the Nation Outcome scale, Relationship item (HoNOSR). Bivariate correlations were run. RESULTS: Both patient groups had high DIDF and GBB scores. In BPD only, there was a significant positive correlation between DIDF and HoNOSR. In BIP-II only, there was a significant positive correlation between DIDF and GBB total score. In BIP-II, DIDF correlated highly with those GBB subscales assessing symptoms typically occurring during bipolar mood swings (cardiovascular and gastrointestinal symptoms, exhaustion). CONCLUSION: Our results suggest that in BPD, high DIDF scores represent genuine problems with identifying and describing emotions which are expected to correlate with relationship problems. In BIP-II, high DIDF scores could potentially represent difficulties with understanding the unpredictable symptoms of bipolar mood swings. The findings suggest that difficulties with identifying and describing feelings in patients should be carefully explored to increase the validity of the diagnostic evaluation.

Cardiovascular risk remains high in schizophrenia with modest improvements in bipolar disorder during past decade.

OBJECTIVE: While CVD risk has decreased in the general population during the last decade, the situation in patients with schizophrenia (SCZ) and bipolar disorder (BD) is unknown. METHODS: We compared CVD risk factors in patients with SCZ and BD recruited from 2002-2005 (2005 sample, N = 270) with patients recruited from 2006-2017 (2017 sample, N = 1011) from the same catchment area in Norway. The 2017 sample was also compared with healthy controls (N = 922) and the general population (N range = 1285-4587, Statistics Norway) from the same area and period. RESULTS: Patients with SCZ and BD in the 2017 sample had significantly higher level of most CVD risk factors compared to healthy controls and the general population. There was no significant difference in the prevalence of CVD risk factors in SCZ between the 2005 and 2017 samples except a small increase in glucose in the 2017 sample. There were small-to-moderate reductions in hypertension, obesity, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure in the BD 2017 sample compared to the 2005 sample. CONCLUSION: Despite major advances in health promotion during the past decade, there has been no reduction in the level of CVD risk factors in patients with SCZ and modest improvement in BD.

Patterns of altered regional brain glucose metabolism in borderline personality disorder and bipolar II disorder.

OBJECTIVE: The relationship between borderline personality disorder (BPD) and bipolar II disorder (BIP-II) is disputed but understudied. Here, we investigated brain glucose metabolism in these patient groups and healthy control subjects (HCs). METHODS: Sixty-five subjects, 22 BPD (19 females), 22 BIP-II (17 females), and 21 HC (14 females), were examined using 2-deoxy-2[18F]-fluoro-d-glucose positron-emission tomography (PET) scanning. Only patients without reciprocal comorbidity were recruited; BPD participants without bipolar spectrum pathology; BIP-II participants without cluster A/B personality pathology. Groups were compared pairwise. Associations with mood state and childhood trauma were analyzed. RESULTS: Both patient groups exhibited hypometabolism compared with HCs in insula, brainstem, and frontal white matter. Additionally, BPD patients showed hypometabolism in hypothalamus, midbrain, and striatum; BIP-II patients in cerebellum. Uncorrected analyses showed cortical areas of higher metabolism in BIP-II than BPD, and associations with clinical variables differed between the groups. CONCLUSION: Reduced metabolism in the insula regions was shown in both disorders, suggesting shared pathophysiological mechanisms. The observed patterns of altered metabolism specific to each patient group, as well as the uncorrected results, may also suggest differential pathophysiology. However, these latter findings must be interpreted cautiously given the non-significant corrected results in the direct comparison between the disorders.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Regional cortical thinning may be a biological marker for borderline personality disorder.

OBJECTIVE: We investigated cerebral cortical thickness and its relation to measurements of difficulties with identifying and describing emotions in patients with borderline personality disorder (BPD). METHOD: Eighteen SCID-II-diagnosed female patients with BPD and 21 healthy female controls underwent magnetic resonance imaging and completed the Toronto Alexithymia Scale (TAS). First, regional cortical thickness across the cerebral surface was compared between patients and healthy controls. Then, analyses of the association between cortical thickness and TAS subscales were performed in patients. RESULTS: Compared with controls, patients exhibited clusters of significantly reduced cortical thickness in the left medial and lateral prefrontal cortex, left temporoparietal junction, bilateral temporal poles, and bilateral paracentral lobules. Significant negative associations were observed between cortical thickness and the 'Difficulties Describing Feelings' TAS subscale (DDF) scores in patients. The anatomical distribution of these associations was highly overlapping with the group differences in cortical thickness. CONCLUSION: The pattern of regions exhibiting cortical thinning in patients resembles a network of cortical structures repeatedly shown to be involved in social cognition. The results of the DDF analyses suggest that the thinning may partly be related to interpersonal dysfunction in patients with BPD. The pattern of thinning may represent a potential biological marker for BPD.