Performance of euthymic patients with bipolar disorder I (BD I), bipolar disorder II (BD II), and healthy controls (C) on a neuropsychological test battery.

<p>The neuropsychological measures are arranged according to the size of the OPLS-DA loadings. Results are expressed as means, 95% confidence intervals (CIs) and effect sizes (<i>η</i>²). Percentage was calculated of patients scoring ≤ the 1.25 s.d. of the control group.</p><p><i>Note.</i></p><p>^a Pålsson et al, 2012,</p><p>^b loading on predictive component,</p><p>^c Games Howell otherwise Scheffé.</p><p>Performance of euthymic patients with bipolar disorder I (BD I), bipolar disorder II (BD II), and healthy controls (C) on a neuropsychological test battery.</p

Summary of demographic and clinical characteristics in patients with bipolar disorder I (n = 64) and bipolar disorder II (n = 44).

<p>The controls (n = 86) were matched for age and sex (X% female). No differences were found regarding education level between the bipolar disorder groups and the control group.</p><p>^a data from 47–64 patients</p><p>^b data from 36–44 patients</p><p>Summary of demographic and clinical characteristics in patients with bipolar disorder I (n = 64) and bipolar disorder II (n = 44).</p

OPLS-DA score plot showing a partial separation between patients with bipolar disorder I (top panel), bipolar disorder II (middle panel) and healthy controls (lower panel).

<p>Each participant’s score is represented by a circle. The scores were t[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115562#pone.0115562.ref001" target="_blank">1</a>] values on the component predictive of diagnostic group. The vast majority (97%) of the participants were within a ±2 standard deviation limit according to Hotelling’s T². Positive values represent better overall performance.</p

Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls

<div><h3>Background</h3><p>Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder.</p> <h3>Methodology/Principal Findings</h3><p>We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 µm in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR = 48, 95% CL: 8.2–550, p<0.0001) and the co-twin-group (OR = 16, 95% CL: 2.0–218, p = 0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication.</p> <h3>Conclusion</h3><p>Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder.</p> </div

Subgroups for analysis of CSF data and the distribution of the diagnostic categories.

*<p>Indicates the disease status of the proband, 11 complete discordant twin pairs in total.</p>**<p>In total 65 singletons and 4 complete twin pairs.</p

Albumin ratio CSF/serum versus blood leukocytes in 37 twin subjects.

<p>A nonparametric bivariate density graphic plot of the albumin ratio expressed as cerebrospinal fluid (CSF) albumin (mg/L)/serum albumin (g/L) on the ordinate vs. the leukocyte number ×10^9/L on the abscissa in 37 twins. To the right are two outliers with a high albumin ratio, indicating that they have a defect in their blood-CSF barrier function (for individual albumin ratio see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045994#pone.0045994.s001" target="_blank">Table S1</a> in Supporting Information).</p

Sample demographics and laboratory data of 102 subjects included in the study.

a<p>) Defined as living with partner/family.</p>b<p>) Defined as studies on University level.</p>c<p>) Defined as employment in the open labor.</p>d<p>) Defined as prescribed medication taken daily.</p>*<p>A twin pair unaffected by schizophrenia or bipolar disorder were on antidepressants at the time of lumbar puncture.</p

First fraction of cerebrospinal fluid (0.2 mL of 0.6 mL) examined with scanning electron microscope in twins and singleton controls.

<p>First fraction of cerebrospinal fluid (0.2 mL of 0.6 mL) examined with scanning electron microscope in twins and singleton controls.</p

Second fraction of cerebrospinal fluid (0.2 mL of 12 mL) examined with scanning electron microscope in twins and singleton controls.

<p>Second fraction of cerebrospinal fluid (0.2 mL of 12 mL) examined with scanning electron microscope in twins and singleton controls.</p

Scanning electron microscopy (SEM) pictures from investigation of fresh cerebrospinal fluid (CSF).

<p>Microscopic pictures of representative structures categorized as containing ‘no particles’, ‘few particles’, ‘several particles’ and ’many particles’. A) No particles ×2000, B) few particles ×4000, C) several particles ×2000, and D) many particles ×2000. The CSF is applied on gold plated polycarbonate filters with 0.6 µm pores that may be used for size reference. A) Demonstrates a filter from a healthy singleton control free of spherical particles and with a small peel of skin in the middle. B) The size of the spherical particles from an unaffected co-twin in is about 0.1 µm in diameter similar to the size of microvesicles. C) A filter from a twin with schizoaffective disorder showing spherical particles with the appearance of small lipid bodies, sizes between 0.1 to 8.0 µm, mainly located in the margin of compact aggregates adhering together in a viscous state. D) CSF from a patient with more than 30 years history of schizophrenia, displaying spherical particles ranging from 0.2 to 5 µm in diameter dispersed over a larger part of the filter.</p