Self-reported psychosis-like experiences in patients with mood disorders.

BACKGROUND: Self-reported psychosis-like experiences (PEs) may be common in patients with mood disorders, but their clinical correlates are not well known. We investigated their prevalence and relationships with self-reported symptoms of depression, mania, anxiety, borderline (BPD) and schizotypal (SPD) personality disorders among psychiatric patients with mood disorders. METHODS: The Community Assessment of Psychic Experiences (CAPE-42), Mood Disorder Questionnaire (MDQ), McLean Screening Instrument (MSI), The Beck Depressive Inventory (BDI), Overall Anxiety Severity and Impairment Scale (OASIS) and Schizotypal Personality Questionnaire-Brief form (SPQ-B) were filled in by patients with mood disorders (n=282) from specialized care. Correlation coefficients between total scores and individual items of CAPE-42 and BDI, SPQ-B, MSI and MDQ were estimated. Hierarchical multivariate regression analysis was conducted to examine factors influencing the frequency of self-reported PE. RESULTS: PEs are common in patients with mood disorders. The "frequency of positive symptoms" score of CAPE-42 correlated strongly with total score of SPQ-B (rho=0.63; P<0.001) and moderately with total scores of BDI, MDQ, OASIS and MSI (rho varied from 0.37 to 0.56; P<0.001). Individual items of CAPE-42 correlated moderately with specific items of BDI, MDQ, SPQ-B and MSI (rφ varied from 0.2 to 0.5; P<0.001). Symptoms of anxiety, mania or hypomania and BPD were significant predictors of the "frequency of positive symptoms" score of CAPE-42. CONCLUSIONS: Several, state- and trait-related factors may underlie self-reported PEs among mood disorder patients. These include cognitive-perceptual distortions of SPD; distrustfulness, identity disturbance, dissociative and affective symptoms of BPD; and cognitive biases related to depressive or manic symptoms.

Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

BACKGROUND: Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. METHODS: Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. RESULTS: The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. CONCLUSIONS: The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.

Level of functioning, perceived work ability, and work status among psychiatric patients with major mental disorders.

BACKGROUND: Major mental disorders are highly disabling conditions that result in substantial socioeconomic burden. Subjective and objective measures of functioning or ability to work, their concordance, or risk factors for them may differ between disorders. METHODS: Self-reported level of functioning, perceived work ability, and current work status were evaluated among psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) within the Helsinki University Psychiatric Consortium Study. Correlates of functional impairment, subjective work disability, and occupational status were investigated using regression analysis. RESULTS: DD patients reported the highest and SSA patients the lowest perceived functional impairment. Depressive symptoms in all diagnostic groups and anxiety in SSA and BD groups were significantly associated with disability. Only 5.3% of SSA patients versus 29.3% or 33.0% of BD or DD patients, respectively, were currently working. About half of all patients reported subjective work disability. Objective work status and perceived disability correlated strongly among BD and DD patients, but not among SSA patients. Work status was associated with number of hospitalizations, and perceived work disability with current depressive symptoms. CONCLUSIONS: Psychiatric care patients commonly end up outside the labour force. However, while among patients with mood disorders objective and subjective indicators of ability to work are largely concordant, among those with schizophrenia or schizoaffective disorder they are commonly contradictory. Among all groups, perceived functional impairment and work disability are coloured by current depressive symptoms, but objective work status reflects illness course, particularly preceding psychiatric hospitalizations.

Anxiety symptoms in a major mood and schizophrenia spectrum disorders.

BACKGROUND: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear. METHODS: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups. RESULTS: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P=0.010) and less often avoided anxiety-provoking situations (P=0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders. CONCLUSIONS: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis.

Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders.

BACKGROUND: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. METHODS: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n=282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. RESULTS: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho=0.616, P<0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (rφ varied between 0.2 and 0.4, P<0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. CONCLUSIONS: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping.

Bose-Einstein condensation of magnons in atomic hydrogen gas.

We report on experimental observation of Bose-Einstein condensation (BEC)-like behavior of quantized electron spin waves (magnons) in a dense gas of spin-polarized atomic hydrogen. The magnons are trapped and controlled with inhomogeneous magnetic fields and described by a Schrödinger-like wave equation, in analogy to the BEC experiments with neutral atoms. We have observed the appearance of a sharp feature in the ESR spectrum displaced from the normal spin wave spectrum. We believe that this observation corresponds to a sudden growth of the ground-state population of the magnons and emergence of their spontaneous coherence for hydrogen gas densities exceeding a critical value, dependent on the trapping potential. We interpret the results as a BEC of nonequilibrium magnons which were formed by applying the rf power.

Hazardous organic compounds in biogas plant end products--soil burden and risk to food safety.

The end products (digestate, solid fraction of the digestate, liquid fraction of the digestate) of ten biogas production lines in Finland were analyzed for ten hazardous organic compounds or compound groups: polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCB(7)), polyaromatic hydrocarbons (PAH(16)), bis-(2-ethylhexyl) phthalate (DEHP), perfluorinated alkyl compounds (PFCs), linear alkylbenzene sulfonates (LASs), nonylphenols and nonylphenol ethoxylates (NP+NPEOs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA). Biogas plant feedstocks were divided into six groups: municipal sewage sludge, municipal biowaste, fat, food industry by-products, animal manure and others (consisting of milling by-products (husk) and raw former foodstuffs of animal origin from the retail trade). There was no clear connection between the origin of the feedstocks of a plant and the concentrations of hazardous organic compounds in the digestate. For PCDD/Fs and for DEHP, the median soil burden of the compound after a single addition of digestate was similar to the annual atmospheric deposition of the compound or compound group in Finland or other Nordic countries. For PFCs, the median soil burden was somewhat lower than the atmospheric deposition in Finland or Sweden. For NP+NPEOs, the soil burden was somewhat higher than the atmospheric deposition in Denmark. The median soil burden of PBDEs was 400 to 1000 times higher than the PBDE air deposition in Finland or in Sweden. With PBDEs, PFCs and HBCD, the impact of the use of end products should be a focus of further research. Highly persistent compounds, such as PBDE- and PFC-compounds may accumulate in agricultural soil after repeated use of organic fertilizers containing these compounds. For other compounds included in this study, agricultural use of biogas plant end products is unlikely to cause risk to food safety in Finland.

Method of assessment determines prevalence of suicidal ideation among patients with depression.

BACKGROUND: How different ways of assessing suicidal ideation influence its prevalence, correlates and predictive validity among patients with major depressive disorder (MDD) remains unclear. METHODS: Within the Vantaa Primary Care Depression Study (PC-VDS, 91 patients) and the Vantaa Depression Study (VDS, 153 psychiatric out-and 41 inpatients), suicidal ideation was assessed with the Scale for Suicidal Ideation (SSI), Hamilton Depression Scale (HAM-D) item 3 and Beck Depression Inventory (BDI) item 9, and by asking whether patients had seriously considered suicide during the episode. The positive and negative predictive values (PPV, NPV) for suicide attempts during a six-month follow-up were investigated. RESULTS: Depending on the setting, 56-88% of patients had suicidal ideation in some of the assessments, but only 8-44% in all of them. Agreement ranged from negligible to moderate (kappa 0.06-0.64), being lowest among primary care patients. The correlates of suicidal ideation overlapped. No assessment had optimal sensitivity, specificity, PPV and NPV. Nevertheless, PPVs ranged up to 43%. CONCLUSIONS: Which MDD patient is classified as having suicidal ideation depends strongly on the method of assessment, with the greatest variation likely in primary care. Differences in assessments may cause inconsistency in risk factors. Predicting suicide attempts is difficult, but not futile.

White matter hyperintensities and cognitive performance in adult patients with bipolar I, bipolar II, and major depressive disorders.

PURPOSE: We evaluate for the first time the associations of brain white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) with neuropsychological variables among middle-aged bipolar I (BPI), II (BPII) and major depressive disorder (MDD) patients and controls using a path model. METHODS: Thirteen BPI, 15 BPII, 16 MDD patients, and 21 controls underwent brain MRI and a neuropsychological examination. Two experienced neuroradiologists evaluated WMHs on the MRI scans. We constructed structural equation models to test the strength of the associations between deep WMH (DWMH) grade, neuropsychological performance and diagnostic group. RESULTS: Belonging in the BPI group as opposed to the control group predicted higher DWMH grade (coefficient estimate 1.13, P=0.012). The DWMH grade independently predicted worse performance on the Visual Span Forward test (coefficient estimate -0.48, P=0.002). Group effects of BPI and MDD were significant in predicting poorer performance on the Digit Symbol test (coefficient estimate -5.57, P=0.016 and coefficient estimate -5.66, P=0.034, respectively). LIMITATIONS: Because of the small number of study subjects in groups, the negative results must be considered with caution. CONCLUSIONS: Only BPI patients had an increased risk for DWMHs. DWMHs were independently associated with deficits in visual attention.

Temperament, character and personality disorders.

OBJECTIVE: To study, whether temperament and character remain stable over time and whether they differ between patients with and without personality disorder (PD) and between patients with specific PDs. METHODS: Patients with (n=225) or without (n=285) PD from Jorvi Bipolar Study, Vantaa Depression Study (VDS) and Vantaa Primary Care Depression Study were interviewed at baseline and at 18 months, and in the VDS also at 5 years. A general population comparison group (n=264) was surveyed by mail. RESULTS: Compared with non-PD patients, PD patients scored lower on self-directedness and cooperativeness. Cluster B and C PDs associated with high Novelty Seeking and Harm Avoidance, respectively. In logistic regression models, sensitivity and specificity of Temperament and Character Inventory (TCI) dimensions for presence of any PD were 53% and 75%, and for specific PDs from 11% to 41% and from 92% to 100%, respectively. The 18-month test-retest correlations of TCI-R dimensions ranged from 0.58 to 0.82. CONCLUSIONS: Medium-term temporal stability of TCI in a clinical population appears good. Character scores differ markedly between PD and non-PD patients, whereas temperament scores differ only somewhat between the specific PDs. However, the TCI dimensions capture only a portion of the differences between PD and non-PD patients.

The Autonomic Nervous System Questionnaire and the Brief Patient Health Questionnaire as screening instruments for panic disorder in Finnish primary care.

PURPOSE: As panic disorder often remains unrecognized in the health care system, some screening methods have been developed to enhance its recognition. The aim of this study was to test and compare the Autonomic Nervous System Questionnaire (ANS) and the Brief Patient Health Questionnaire (BPHQ) in primary care. SUBJECTS AND METHODS: A total sample of 211 primary care outpatients was studied. The Structured Clinical Interview for DSM-IV was the criterion standard for the presence of panic disorder. Indices of diagnostic utility for both screening methods were calculated and compared. RESULTS: The AUC (area under the ROC curve) was 0.885 for the ANS and 0.877 for the BPHQ. At the optimal cut-off level, the ANS had the sensitivity of 0.88 and specificity of 0.77; the BPHQ had the sensitivity of 0.79 and the specificity of 0.87. There was not any statistically significant difference between the screens. CONCLUSIONS: Both screening methods can be recommended both for clinical practice and research use. In busy primary care practice, the BPHQ may be more useful, as it can be used together with the depression module of the BPHQ.

Typology of clinical course in bipolar disorder based on 18-month naturalistic follow-up.

BACKGROUND: Individual variation in the clinical course of bipolar disorder may have prognostic and therapeutic implications but is poorly reflected in current classifications. We aimed to establish a typology of the individual clinical trajectories based on detailed prospective medium-term follow-up. Method Latent class analysis (LCA) of nine characteristics of clinical course (time depressed, severity of depression, stability of depression, time manic, severity of mania, stability of mania, mixed symptoms, mania-to-depression and depression-to-mania phase switching) derived from life charts prospectively tracking the onsets and offsets of (hypo)manic, depressive, mixed and subsyndromal episodes in a representative sample of 176 patients with bipolar disorder. RESULTS: The best-fitting model separated patients with bipolar disorder into large classes of episodic bipolar (47%) and depressive type (32%), moderately sized classes characterized by prolonged hypomanias (10%) and mixed episodes (5%) and five small classes with unusual course characteristics including mania-to-depression and depression-to-mania transitions and chronic mixed affective symptoms. This empirical typology is relatively independent of the distinction between bipolar disorder type I and type II. Lifetime co-morbidity of alcohol use disorders is characteristic of the episodic bipolar course type. CONCLUSIONS: There is potential for a new typology of clinical course based on medium-term naturalistic follow-up of a representative clinical sample of patients with bipolar disorder. Predictive validity and stability over longer follow-up periods remain to be established.

Guiding and trapping of electron spin waves in atomic hydrogen gas.

We present a high magnetic field study of electron spin waves in atomic hydrogen gas compressed to high densities of ∼10(18) cm(-3) at temperatures ranging from 0.26 to 0.6 K. We observed a variety of spin wave modes caused by the identical spin rotation effect with strong dependence on the spatial profile of the polarizing magnetic field. We demonstrate confinement of these modes in regions of strong magnetic field and manipulate their spatial distribution by changing the position of the field maximum.

Occurrence of PCDD/F, PCB, PBDE, PFAS, and organotin compounds in fish meal, fish oil and fish feed.

We analysed polychlorinated dibenzo-p-dioxins and furans (PCDD/F, dioxins), and polychlorinated biphenyls (PCB) in 13 fish meal, five fish oil, and seven fish feed samples. Polybrominated diphenyl ethers (PBDE), organotin compounds (OTC), and perfluoroalkylated substances (PFAS) were analysed in ten fish meal, two fish oil, and two fish feed samples. All measured TEQ concentrations of PCDD/F and PCB were below the maximum levels set by Directive 2002/32/EC. There was no correlation between concentrations of WHOPCDD/F-TEQ and indicator PCB in our samples. The most common congeners among PBDEs were BDE-47 and BDE-100. BDE-209 was present in five fish meals of the ten analysed. Tributyltin (TBT) was the predominant congener in all samples except in three fish meals, where monobutyltin (MBT) was the major congener. Perfluorooctane sulphonate (PFOS) was the predominant congener in six fish meals of the ten analysed. There was large variation in concentrations and congener distributions of the studied compounds between our samples. Our results underline a need to pay special attention to the origin and purity of feed raw material of marine origin.

Perceived burden of illness in patients entering for treatment in a university hospital--is the threshold to secondary care higher for patients with depression than for those with somatic disorders?

BACKGROUND: The threshold to secondary health care should be similar for all patients independent of the underlying disease. This study compared, using a validated health-related quality of life (HRQoL)-instrument, whether the perceived burden of illness is similar in patients admitted for secondary care treatment into a university hospital because of one of six common conditions. METHODS: HRQoL, assessed by the generic 15D instrument before elective treatment, was compared in six groups: operative treatment of cataract (n=219), operative treatment of cervical or lumbar radicular pain (n=270), hysterectomy due to benign uterine conditions (n=337), hip or knee replacement surgery (n=223), coronary angiography due to suspected coronary artery disease (n=261), and secondary care treatment of depression (n=89). RESULTS: Mean (±SD) HRQoL score was clearly highest in patients with benign uterine conditions (0.908±0.071) and lowest in patients with depression (0.729±0.120) (P<0.001 between the groups). Also all the other groups had a significantly (P<0.001) higher baseline HRQoL score (ranging from 0.802 to 0.824) than patients with depression. Outcome of treatment, in terms of HRQoL improvement, was in depressive patients at least equal, and in some cases even better, than that in the other groups. DISCUSSION: Our results imply that, at least concerning perceived burden of illness, patients with depression are worse off when admitted to secondary care treatment than patients with many somatic conditions. That may be a consequence of poor motivation of depressive patients to seek treatment or that, contradictory to guidelines, the health care system does nor give priority to those worst off and sets a higher threshold for specialized care of patients with depression than of those with common somatic disorders.

Differences in temperament and character dimensions in patients with bipolar I or II or major depressive disorder and general population subjects.

BACKGROUND: Whether temperament and character differ between bipolar disorder (BD) and major depressive disorder (MDD) patients and general population subjects, or between BD I and BD II patients, remains unclear. METHOD: BD patients (n=191) from the Jorvi Bipolar Study and MDD patients (n=266) from the Vantaa Depression Study (VDS) and the Vantaa Primary Care Depression Study were interviewed at baseline, at 6 and 18 months, and in the VDS at 5 years. A general population comparison group (n=264) was surveyed by mail. BD patients' scores on the Temperament and Character Inventory-Revised were compared at an index interview, when levels of depression and mania were lowest, with scores of MDD patients and controls. BD I (n=99) and BD II (n=92) patients were compared. RESULTS: Compared with controls, both BD and MDD patients had higher harm avoidance [odds ratio (OR) 1.027, p<0.001 and OR 1.047, p<0.001, respectively] and lower persistence (OR 0.983, p=0.006 and OR 0.968, p<0.001, respectively) scores. Moreover, BD patients had lower self-directedness (OR 0.979, p=0.003), MDD patients lower reward dependence (OR 0.976, p=0.002) and self-transcendence (OR 0.966, p<0.001) scores. BD patients scored lower in harm avoidance (OR 0.980, p=0.002) and higher in novelty seeking (OR 1.027, p<0.001) and self-transcendence (OR 1.028, p<0.001) than MDD patients. No differences existed between BD I and II patients. CONCLUSIONS: The patterns of temperament and character dimensions differed less between BD and MDD patients, than patients from their controls. The most pronounced difference was higher novelty seeking in BD than MDD patients. The dimensions investigated are unlikely to differ between BD I and BD II patients.

Sweating impairment in patients with multiple sclerosis.

OBJECTIVES: To measure sweating in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sweating was measured by an evaporimeter after a heating stimulus in 29 MS patients and in 15 healthy control subjects. RESULTS: The MS patients sweated markedly less than the controls. After 10 min of heating the sweating was significantly lower in the forehead (P = 0.034), feet (right, P = 0.033; left, P = 0.037) and legs (right, P = 0.043; left, P = 0.029) of the MS patients than in those of the controls. After 15 min of heating the difference was statistically significant only in the feet (right, P = 0.043; left, P = 0.029). The Expanded Disability Status Scale score correlated inversely with sweating at 15 min of heating in the left hand (r = 0.42, P < 0.05), and in the left (r = 0.36, P < 0.05) and right foot (r = 0.37, P < 0.05). CONCLUSIONS: MS is associated with an impairment in thermoregulatory sweating which seems to be related to the disease severity.

Gender differences in bipolar disorder type I and II.

OBJECTIVE: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in- and out-patients. METHOD: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in- and out-patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. RESULTS: After adjusting for confounders, no marked differences in illness-related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12-16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16-0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22-3.27). CONCLUSION: Men and women with type I and II BD have fairly similar illness-related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium-term follow-up, females appear to have a higher hazard of recurrence than males.

DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.

Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.

Topographic electroencephalogram in children during mask induction of anaesthesia with sevoflurane.

BACKGROUND: Epileptiform patterns, spikes, polyspikes and periodic epileptiform discharges (PED) have been reported in electroencephalograms (EEGs) during anaesthesia induction with sevoflurane in healthy adults and children. Published recordings have been performed with a limited number of channels, and therefore the topographic distributions of these patterns are not known. METHODS: Twenty ASA I children aged 4-10 years undergoing routine operations were anaesthetized with 8% sevoflurane in 50%/50% oxygen and nitrous oxide using mask induction with controlled normoventilation. An EEG was recorded with a full 10-20 electrode system including orbitofrontal and ear electrodes, and a recording band of 0.016-70 Hz. Beat-to-beat heart rate (HR) was calculated off-line. RESULTS: Nineteen out of 20 children developed multifocal spikes and polyspikes with a maximum over the frontal lobes. Four patients developed suppression, which was almost continuous and lasted several minutes, and thereafter a continuous EEG resumed, a few spikes were seen and then a nonepileptiform pattern. In three children a couple of PED waves were seen at the onset of a continuous EEG. HR increased maximally before the onset of spikes. No motor phenomena were seen. CONCLUSION: These recordings confirm the epileptogenic property of sevoflurane in mask induction. The spikes and polyspikes had frontal multifocal maxima and may be missed in recordings from frontopolar electrodes used by depth-of-anaesthesia monitors. PED and burst suppression were synchronous over the whole cortex. Epileptiform activity was indiscernible from epileptiform waveforms without anaesthesia, such as the patterns seen in status epilepticus.