Erlend Bøen

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.

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.

Temperament and character in patients with bipolar II disorder and recurrent brief depression

OBJECTIVES We compared the temperament and character profiles of 21 patients with bipolar II disorder, 40 patients with recurrent brief depression (RBD; at least monthly depressive episodes meeting the diagnostic criteria for major depressive episode except for duration that is less than 2 weeks, typically 2-3 days, without fixed relation to menstrual cycle) of which 21 had no history of hypomania and 19 had experienced hypomanic episodes, and 21 age- and sex-matched controls. METHODS Assessments included the Montgomery-Åsberg Depression Rating Scale, Hypomania Checklist, and Temperament and Character Inventory-125. Patients with cluster A and B personality disorders were excluded. RESULTS Bipolar II and RBD patients had higher harm avoidance (HA) and lower self-directedness (SD) compared with controls. Excluding panic disorder comorbidity effaced this difference in HA and SD (bipolar II only) and harm avoidance. No other differences were found. CONCLUSIONS In this first study comparing personality profiles of patients with bipolar II vs RBD, when controlling for confounders, neither bipolar II nor RBD patients differed significantly from healthy controls. The lower SD scores among RBD patients may reflect sampling bias (a higher rate of Axis 2 cluster C disorders).

Somatic and cognitive symptoms as indicators of potential endophenotypes in bipolar spectrum disorders: An exploratory and proof-of-concept study comparing bipolar II disorder with recurrent brief depression and healthy controls

BACKGROUND We examined whether somatic symptoms reported by patients with bipolar spectrum disorder (BSD), in this study defined as bipolar II (BD-2) or recurrent brief depression with (RBD-H) or without (RBD-O) a history of hypomanic symptoms might point to the possible underlying disease markers (endophenotypes). We hypothesized that somatic symptoms that are possible indirect indicators of endophenotypes should be more prevalent among patients than among healthy controls; should not correlate with neuroticism; should not correlate with the severity of current mental status (e.g., anxiety, depression); and should not correlate with the use of psychotropic drugs including antiepileptics or be explained by co-morbid medical diseases. METHODS Sixty-one patients (BD-2: n=21; RBD-H: n=19; RBD-O: n=21) were compared with 21 healthy controls. Assessments included a 123-item somatic symptom checklist; assessments for neuroticism, anxiety and depression. Candidate somatic symptoms were selected using a 4-step inclusion/exclusion procedure. RESULTS Seven symptoms survived in all three groups: general (fatigue, feeling exhausted); sensory (leaden sensation in legs, pain in the body, impaired sense of smell); cognitive (loss of memory) and autonomic (excessive perspiration). In addition 15 symptoms survived in one or two groups (examples: impaired hearing, hypersensitivity to sound, inability to find words). LIMITATIONS Possible selection bias and small sample size precludes firm conclusions with regards to specific symptoms. CONCLUSION Our approach identified symptoms for which an association with BSDs has been suggested previously, as well as symptoms not commonly associated with BSDs. The findings support the feasibility and validity of using assessment of somatic symptoms as an approach to identify potential endophenotypes in BSDs.

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

We investigated cerebral cortical thickness and its relation to measurements of difficulties with identifying and describing emotions in patients with borderline personality disorder (BPD).

The surface area of early visual cortex predicts the amplitude of the visual evoked potential

The extensive and increasing use of structural neuroimaging in the neurosciences rests on the assumption of an intimate relationship between structure and function in the human brain. However, few studies have examined the relationship between advanced magnetic resonance imaging (MRI) indices of cerebral structure and conventional measures of cerebral functioning in humans. Here we examined whether MRI-based morphometric measures of early visual cortex—estimated using a probabilistic anatomical mask of primary visual cortex (V1)—can predict the amplitude of the visual evoked potential (VEP), i.e., an electroencephalogram signal that primarily reflects postsynaptic potentials in early visual cortical areas. We found that left, right, and total V1 surface area positively predicted the VEP amplitude. In addition, we showed, using whole brain analysis of local surface areal expansion/contraction, that the association between VEP amplitude and surface area was highly specific for regions within bilateral V1. Together, these findings indicate a strong, selective relationship between MRI-based structural measures and functional properties of the human cerebral cortex.