Tobacco smoking and other substance use disorders associated with recurrent suicide attempts in bipolar disorder.

BACKGROUND: Suicide attempts (SA) are more frequent in bipolar disorder (BD) than in most other mental disorders. Prevention strategies would benefit from identifying the risk factors of SA recurrence in BD. Substance use disorders (SUD) (including tobacco-related) are strongly associated with both BD and SA, however, their specific role for the recurrence of SA in BD remains inadequately investigated. Thus, we tested if tobacco smoking - with or without other SUDs - was independently associated with recurrent SA in BD. METHODS: 916 patients from France and Norway with ascertained diagnoses of BD and reliable data about SA and SUD were classified as having no, single, or recurrent (≥2) SA. Five SUD groups were built according to the presence/absence/combination of tobacco, alcohol (AUD) and cannabis use disorders. Multinomial logistic regression was used to identify the correlates of SA recurrence. RESULTS: 338 (37%) individuals reported at least one SA, half of whom (173, 51%) reported recurrence. SUD comorbidity was: tobacco smoking only, 397 (43%), tobacco smoking with at least another SUD, 179 (20%). Regression analysis showed that tobacco smoking, both alone and comorbid with AUD, depressive polarity of BD onset and female gender were independently associated with recurrent SA. LIMITATIONS: Lack of data regarding the relative courses of SA and SUD and cross-national differences in main variables. CONCLUSION: Tobacco smoking with- or without additional SUD can be important risk factors of SA recurrence in BD, which is likely to inform both research and prevention strategies.

An association between YKL-40 and type 2 diabetes in psychotic disorders.

OBJECTIVE: This study examines if YKL-40 is increased in individuals with psychotic disorders and if elevated YKL-40 levels at baseline is associated with subsequent development of type 2 diabetes. METHOD: A total of 1383 patients with a diagnosis of schizophrenia or affective psychosis and 799 healthy controls were recruited in the period 2002-2015. Plasma YKL-40 and metabolic risk factors were measured and medication was recorded. Using national registry data, association between baseline risk factors and later development of type 2 diabetes was assessed using Cox proportional hazards models. RESULTS: Plasma YKL-40 was higher in patients vs. healthy controls also after adjusting for metabolic risk factors, with no difference between the schizophrenia and affective psychosis groups. Patients were diagnosed with type 2 diabetes at a significantly younger age. Multivariate Cox regression analyses showed that elevated YKL-40 (hazard ratio (HR) = 5.6, P = 0.001), elevated glucose (HR = 3.6, P = 0.001), and schizophrenia diagnosis (HR = 3.0, P = 0.014) at baseline were associated with subsequent development of type 2 diabetes. CONCLUSIONS: Patients with psychotic disorders have at baseline increased levels of YKL-40 beyond the effect of comorbid type 2 diabetes and metabolic risk factors. Elevated YKL-40 level at baseline is associated with later development of type 2 diabetes.

Scattering media characterization with phase-only wavefront modulation.

A new experimental approach is demonstrated to probe the scattering properties of complex media. Using phase-only modulation of the light illuminating a random scattering sample, we induce and record fluctuations in the reflected speckle patterns. Using predictions from diffusion theory, we obtain the scattering and absorption coefficients of the sample from the average change in the speckle amplitude. Our approach, which is based on interference, is in principle able to give better signal to noise ratio as compared to an intensity modulation approach. We compare our results with those obtained from a knife-edge illumination method and enhanced back-scattering cone. Our work can find application in the non-invasive study of biological specimens as well as the study of light propagation in random scattering devices like solar cells or LEDs.

Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use. METHODS: We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case-control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis. RESULTS: Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42). CONCLUSIONS: Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.

Persistent increase in TNF and IL-1 markers in severe mental disorders suggests trait-related inflammation: a one year follow-up study.

OBJECTIVE: We evaluated if plasma levels of inflammatory markers are persistently altered in severe mental disorders with psychotic symptoms or associated with state characteristics in a longitudinal study. METHODS: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF), and osteoprotegerin (OPG) were measured in schizophrenia (n = 69) and affective (n = 55) spectrum patients at baseline and at one-year follow-up, and compared to healthy controls (HC) (n = 92) with analysis of covariance. Association between change in symptoms and inflammatory markers was analyzed with mixed-effects models. RESULTS: sTNF-R1 was higher in the schizophrenia (P < 0.0001) and affective disorders (P = 0.02) compared to HC, while IL-1Ra was higher in schizophrenia (P = 0.01) compared to HC at one year follow-up. There were no significant differences between schizophrenia and affective groups; however, levels in the affective group were in between schizophrenia and HC for sTNF-R1 and IL-1Ra. There were no significant associations between change in symptoms and inflammatory markers. CONCLUSION: Persistently increased sTNF-R1 and IL-1Ra after one year in patients with severe mental disorders primarily reflecting data from the schizophrenia group may suggest that inflammation is a trait phenomenon, and not only the result of stress-related mechanisms associated with acute episodes.

Childhood trauma is associated with increased brain responses to emotionally negative as compared with positive faces in patients with psychotic disorders.

BACKGROUND: Childhood trauma increases risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested the association between childhood trauma and brain activation during emotional face processing in patients diagnosed with psychosis continuum disorders. In particular, we tested if childhood trauma was associated with the differentiation in brain responses between negative and positive face stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces. METHOD: We included 101 patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM) schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Brain activation was measured with functional magnetic resonance imaging during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces. RESULTS: Higher levels of total childhood trauma were associated with stronger differentiation in brain responses to negative compared with positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus and the lateral occipital cortex (Cohen's d = 0.72-0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8). CONCLUSIONS: Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces with higher levels of trauma.

Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.

BACKGROUND: Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. METHOD: A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro. RESULTS: Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset. CONCLUSIONS: Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.

Cannabis use disorder is associated with greater illness severity in tobacco smoking patients with bipolar disorder.

OBJECTIVE: Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients. METHODS: A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses. RESULTS: In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant. LIMITATIONS: Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for. CONCLUSION: Studies have found associations between tobacco smoking and poorer outcomes in BD. In this study on tobacco smoking BD patients we report an association between CUD and illness severity, suggesting that CUD exacerbates the disease evolution independently of tobacco smoking. Specific treatment and prevention programs addressing CUD in BD patients are warranted.

Childhood trauma mediates the association between ethnic minority status and more severe hallucinations in psychotic disorder.

BACKGROUND: Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations. METHOD: In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version. RESULTS: Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations. CONCLUSIONS: More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis.

Polygenic risk score and the psychosis continuum model.

OBJECTIVE: Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical characteristics and genetic risk indicating a psychosis continuum. This is the first study using polygenic risk score (PGRS) to investigate the localization of diagnostic subcategories along the entire psychosis spectrum. METHOD: Based on results from the Psychiatric Genomics Consortium (PGC), we assigned a SZ and BD PGRS to each individual in our independent sample [N=570 BD spectrum cases, 452 SZ spectrum cases and 415 healthy controls (CTR)]. Potential differences in mean SZ and BD PGRS across diagnostic spectrums and subcategories were explored. RESULTS: SZ and BD PGRSs were significantly associated with both SZ and BD spectrums compared with CTR. For the subcategories, SZ PGRS was significantly associated with SZ, schizoaffective disorder, psychosis not otherwise specified, and BD1, while BD PGRS was significantly associated with BD1 and BD2. There were no significant differences between any of the diagnostic spectrums or subgroups for neither the SZ nor BD PGRS. Lifetime psychosis was significantly associated with SZ PGRS but not with BD PGRS. CONCLUSION: These findings further support the psychosis continuum model and provide molecular polygenetic validation of the localization of diagnostic subcategories within this continuum.

Additive effects of childhood abuse and cannabis abuse on clinical expressions of bipolar disorders.

BACKGROUND: Previous studies of bipolar disorders indicate that childhood abuse and substance abuse are associated with the disorder. Whether both influence the clinical picture, or if one is mediating the association of the other, has not previously been investigated. METHOD: A total of 587 patients with bipolar disorders were recruited from Norway and France. A history of childhood abuse was obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical variables, including substance abuse, were based on structured clinical interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French version of the Diagnostic Interview for Genetic Studies). RESULTS: Cannabis abuse was significantly associated with childhood abuse, specifically emotional and sexual abuse (χ 2 = 8.63, p = 0.003 and χ 2 = 7.55, p = 0.006, respectively). Cannabis abuse was significantly associated with earlier onset of the illness (z = -4.17, p < 0.001), lifetime history of at least one suicide attempt (χ 2 = 11.16, p = 0.001) and a trend for rapid cycling (χ 2 = 3.45, p = 0.06). Alcohol dependence was associated with suicide attempt (χ 2 = 10.28, p = 0.001), but not with age at onset or rapid cycling. After correcting for possible confounders and multiple testing, a trend was observed for an interaction between cannabis abuse and childhood abuse and suicide attempt (logistic regression: r 2 = 0.06, p = 0.039). Significant additive effects were also observed between cannabis abuse and childhood abuse on earlier age at onset (p < 0.001), increased rapid cycling and suicide attempt (logistic regression: r 2 = 0.03-0.04, p < 0.001). No mediation effects were observed; childhood abuse and cannabis abuse were independently associated with the disorder. CONCLUSIONS: Our study is the first to demonstrate significant additive effects, but no mediation effects, between childhood abuse and cannabis abuse on increased clinical expressions of bipolar disorders.

Dye lasing in optically manipulated liquid aerosols.

We report lasing in airborne, rhodamine B-doped glycerol-water droplets with diameters ranging between 7.7 and 11.0 µm, which were localized using optical tweezers. While being trapped near the focal point of an infrared laser, the droplets were pumped with a Q-switched green laser. Our experiments revealed nonlinear dependence of the intensity of the droplet whispering gallery modes (WGMs) on the pump laser fluence, indicating dye lasing. The average wavelength of the lasing WGMs could be tuned between 600 and 630 nm by changing the droplet size. These results may lead to new ways of probing airborne particles, exploiting the high sensitivity of stimulated emission to small perturbations in the droplet laser cavity and the gain medium.

Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis.

BACKGROUND: Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis. Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In turn, stress exposure and abnormal levels of the main HPA axis hormone cortisol are associated with cognitive impairments in a variety of clinical and experimental samples; however, this association has never been examined in first-episode psychosis (FEP). METHOD: In this study, 30 FEP patients and 26 controls completed assessment of the HPA axis (cortisol awakening response and cortisol levels during the day), perceived stress, recent life events, history of childhood trauma, and cognitive function. The neuropsychological battery comprised general cognitive function, verbal and non-verbal memory, executive function, perception, visuospatial abilities, processing speed, and general knowledge. RESULTS: Patients performed significantly worse on all cognitive domains compared to controls. In patients only, a more blunted cortisol awakening response (that is, more abnormal) was associated with a more severe deficit in verbal memory and processing speed. In controls only, higher levels of perceived stress and more recent life events were associated with a worse performance in executive function and perception and visuospatial abilities. CONCLUSIONS: These data support a role for the HPA axis, as measured by cortisol awakening response, in modulating cognitive function in patients with psychosis; however, this association does not seem to be related to the increased exposure to psychosocial stressors described in these patients.

[Surgery and sentinel node examination in early vulvar cancer]. / Kirurgi og undersøkelse av vaktpostlymfeknute ved tidlig vulvacancer.

BACKGROUND: Less than radical vulvectomy for primary vulvar cancer has been controversial. Less mutilating surgery without sacrificing benefits in prognosis is warranted. MATERIAL AND METHODS: Based on relevant literature and our own experience, we give a review of surgery and sentinel node examination in early vulvar cancer. RESULTS: Regional lymph node metastasis rarely occurs when tumour thickness is less than 1 mm. Smaller lesions (< 2 cm in diameter) should therefore be treated by wide excision only and without lymph node dissection. Other T1 lesions with deeper invasion should be radically excised with at least 2 cm margins and extend deep to the inferior fascia of the urogenital diaphragm. Complete inguinal-femoral lymphadenectomy should be performed in patients without groin metastases to avoid a small, but definite risk of recurrence, although the incidence of lymph node metastases for all clinical stage I patients is less than 10%. Lymphatic mapping with 99mTechnetium and patent blue technique is a potentially valuable intraoperative tool for assuring removal of the sentinel node most likely to have metastasis, defining the extent of the superficial inguinal lymphadenectomy and identifying uncommon anatomic variations. INTERPRETATION: Until reliable data on the benefits of selective lymphadenectomy using intraoperative lymphoscintigraphy are available, the procedure should only be performed in an approved research setting.

[Lymphedema and lymphangioscintigraphy]. / Lymfødem og lymfangioscintigrafi.

INTRODUCTION: The diagnoses of lymphoedema is generally based on clinical examination. Sometimes supplementary laboratory techniques are required. MATERIAL AND METHODS: A practical lymphangioscintigraphic method is described based on a survey of the literature and trial and error in a series of about 40 patients. The method gives an excellent picture of lymphatic pathology and the lymph stasis present in most lymphoedema patients. RESULTS: The use of the method in 48 patients is reported. An abnormal scintigraphic pattern was seen in 25 patients. In 20 cases with a well established clinical diagnose, the lymphangioscintigram was positive in 15 cases. INTERPRETATION: Lymphangioscintigraphy is a non-invasive method recommendable as first choice in supplementary examination of lymphoedema.

Internal radionuclide therapy of primary osteosarcoma in dogs, using 153Sm-ethylene-diamino-tetramethylene-phosphonate (EDTMP).

Fifteen dogs were referred because of a spontaneous bone tumor, lameness, and local pain. The osteosarcoma diagnosis was established by clinical examination, X-ray, bone scintigraphy, and histological examination of biopsy material. The tumors were located in the extremities (n = 12), scapula (n = 1), maxilla (n = 1), and the frontal bone (n = 1). The dogs were given one to four i.v. injections of 153Sm-labeled ethylene-diamino-tetramethylene-phosphonate (153Sm-EDTMP; 36-57 MBq/kg body weight). Three dogs had surgery in addition to the radionuclide treatment. Platelet and WBC counts showed a moderate and transient decrease. No other toxicity was observed. Average tumor doses after a single injection were approximately 20 Gy, considerably higher in some areas because of inhomogeneous uptake. Macroscopically distant metastases were detected in seven dogs at autopsy. One dog died from an intercurrent disease, free of cancer, 5 months after the radionuclide treatment. None of the dogs was cured. The median and mean survival times from the first treatment to death or euthanasia were 150 and 252 days, respectively. Nine of the dogs had obvious pain relief, and five of them seemed pain-free: one for 20 months and one for 48 months. It is concluded that high tumor doses may be deposited in dog osteosarcomas by 153Sm-EDTMP, and the ratio between tumor dose and the dose to surrounding tissues is favorable. The treatment gives pain relief and in some cases tumor growth delay. In combination with surgery, 153Sm-EDTMP may prolong life significantly and possibly cure the disease because the development of metastases are seemingly postponed. No serious side effects were observed.

Safety of the transpulmonary ultrasound contrast agent NC100100: a clinical and haemodynamic evaluation in patients with suspected or proved coronary artery disease.

OBJECTIVE: To evaluate the clinical and haemodynamic safety of NC100100, a new transpulmonary ultrasound contrast agent intended for vascular use. DESIGN: Pulmonary artery pressures and gas exchange, left ventricular and systemic blood pressure and ECG were measured at baseline, after saline injection, and after each of two increasing doses of NC100100 injected intravenously. PATIENTS: 30 patients who were evaluated for suspected coronary artery disease. RESULTS: No change was detected in any of the haemodynamic variables, or in haematological or clinical chemical parameters. Blood gases were unchanged, as were heart rhythm and arterial oxygen saturation. No serious adverse reactions were reported. CONCLUSIONS: NC100100 appeared to be haemodynamically inert and safe in patients with coronary artery disease.

[Measurement of glomerular filtration rate in connection with 99Tc-DTPA renography]. / Måling av glomerulaer filtrasjonshastighet i tilknytning til renografi med 99mTc-DTPA.

Glomerular filtration rate (GFR) was measured in two groups of cancer patients. In 20 patients, glomerular filtration rate was measured simultaneously with 51Cr-EDTA, 99mTc-DTPA and the X-ray contrast agent iohexol as markers, and with a complete set of eight blood samples during 24 hours. In a second group of 120 patients, we used 99mTc-DTPA only and tested various simplified methods, based on one or two blood samples. Glomerular filtration rate was also calculated from serum creatinine. There was excellent agreement between the values measured with the three markers, and, in the same group of patients, very good agreement with the results of simplified methods. The larger study carried out with 99mTc-DTPA on the second group of patients, confirmed a very good agreement between methods based on the slope of the plasma curve and a method based on one blood sample only. The correlation was worse between the values obtained by any of the radionuclide methods and those calculated from serum creatinine. The latter method should therefore not be used for determination of renal function.