Torbjørn Elvsåshagen

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.

The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder

BACKGROUND It has recently been hypothesized that bipolar disorders are associated with accelerated aging. Telomere dysfunction, a biomarker of aging, is determined by the load of short telomeres, rather than by the mean telomere length. To our knowledge, the load of short telomeres has not been reported in any psychiatric disorder. The aims of the study were to examine the load of short telomeres and the mean telomere length and their relationships with illness duration and lifetime number of depressive episodes in bipolar II disorder (BD-II). METHODS Twenty-eight patients (mean age=34.8 ± 7.7) with a DSM-IV diagnosis of BD-II and 28 healthy control subjects (mean age=34.8 ± 9.2) matched for age, sex, and education participated. The load of short telomeres (percentage of telomeres <3 kilobases) and mean telomere length in peripheral blood mononuclear cells were measured using high-throughput quantitative fluorescence in situ hybridization. RESULTS The load of short telomeres was significantly increased in patients with BD-II relative to healthy controls and may represent 13 years of accelerated aging. The load of short telomeres and the mean telomere length were associated with lifetime number of depressive episodes, but not with illness duration. LIMITATIONS Modest sample size and cross-sectional design. CONCLUSIONS Our results suggest that BD-II is associated with an increased load of short telomeres. Depressive episode-related stress may accelerate telomere shortening and aging. However, longitudinal studies are needed to fully clarify telomere shortening and its relationship with clinical variables in BD-II.

The brain functional connectome is robustly altered by lack of sleep.

Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome.

Bipolar II disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation.

The neurobiological substrate of bipolar II disorder (BD‐II) remains largely unknown. A few previous studies have found evidence for cerebral cortical thinning in mixed samples of BD‐II and bipolar I disorder patients; however, no study of cortical thickness or surface area has been limited to BD‐II. In the present study, we compared magnetic resonance imaging (MRI)‐based indices of cortical thickness and surface area between individuals with BD‐II and healthy controls.

Evidence for Impaired Neocortical Synaptic Plasticity in Bipolar II Disorder

BACKGROUND Synaptic plasticity might play an important role in the pathophysiology and treatment of bipolar disorders. There is, however, a paucity of human evidence supporting this hypothesis, mainly due to a lack of methods for noninvasive assessment of synaptic plasticity. It has recently been demonstrated that plasticity of the visual evoked potential (VEP) induced by repeated visual stimulation might reflect synaptic plasticity. In this study, we examined VEP plasticity in healthy control subjects and patients with bipolar II disorder (BD-II). METHODS Forty healthy control subjects and 26 individuals with a DSM-IV diagnosis of BD-II matched for age and gender participated. The VEPs were evoked by checkerboard reversal stimulation before and after a modulation block of prolonged (10 min) visual stimulation. RESULTS The modulation block resulted in significant VEP plasticity in healthy control subjects. The VEP plasticity was significantly impaired in patients with BD-II. Explorative analyses indicated a trend toward a less severe impairment in medicated than in unmedicated patients. CONCLUSIONS Visual evoked potential plasticity might represent a reliable and robust assay for studies of synaptic plasticity in vivo in humans. In addition, our findings support the hypothesis of impaired synaptic plasticity in BD-II. Longitudinal studies are needed to fully clarify the effects of medication and mood state on VEP plasticity.

Different impulsivity profiles in borderline personality disorder and bipolar II disorder

INTRODUCTION Borderline personality disorder (BPD) and bipolar II disorder (BP II) share clinical characteristics including impulsivity. Their relationship is disputed. In this study, we investigated self-reported impulsivity in these patient groups and in a healthy control group. Effects of current mood state and of traumatic childhood experiences were explored. METHODS Twenty-five patients with BPD without comorbid bipolar disorder; 20 patients with BP II without comorbid BPD; and 44 healthy control subjects completed the UPPS questionnaire which yields assessments of four components of impulsivity: Urgency, Lack of Premeditation, Lack of Perseverance, and Sensation Seeking. Current mood state was rated using the Montgomery Asberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). Traumatic childhood experiences were assessed using the Childhood Trauma Questionnaire (CTQ). Group differences in UPPS levels; and effects of mood state and CTQ score on UPPS scores in patients were investigated. RESULTS BPD patients showed significantly higher levels of Urgency and Lack of Perseverance than BP II patients and controls, and a significantly higher level of Lack of Premeditation than controls. BP II patients showed higher levels of Urgency and Lack of Perseverance than controls. In BP II, higher MADRS scores were associated with higher impulsivity scores. Also, higher CTQ scores were associated with higher Urgency scores in BP II. LIMITATIONS Relatively small sample size; cross-sectional assessment of influence of mood state. CONCLUSIONS BPD patients exhibited markedly elevated UPPS impulsivity scores compared with healthy controls and BP II patients, and the elevations were not related to current mood state. BP II patients showed moderately elevated impulsivity scores which were associated with a depressed mood state and to some extent with a history of childhood trauma. The findings suggest that BPD and BP II have different impulsivity profiles.

Evidence for reduced dentate gyrus and fimbria volume in bipolar II disorder.

Objectives:  Dentate gyrus (DG)‐dependent inhibition of the stress response might play an important role in mood disorders. During stress, hippocampal projections traversing the fimbria, a white matter bundle on the hippocampal surface, inhibit the hypothalamic–pituitary–adrenal (HPA) axis. The aim of the present study was to measure the volumes of the DG–cornu ammonis 4 (DG–CA4) and fimbria in patients with bipolar II disorder (BD‐II) and healthy controls using a recently developed magnetic resonance imaging (MRI)‐based technique.

Widespread changes in white matter microstructure after a day of waking and sleep deprivation.

Background Elucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations. Methods Twenty-one healthy adult males underwent DTI in the morning [7:30AM; time point (TP)1], after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics. Results A day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures. Conclusions This is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness.

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.

Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders

There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.