Cognition and autonomic function in schizophrenia: inferior cognitive test performance in electrodermal and niacin skin flush non-responders.

BACKGROUND: Patients with schizophrenia suffer from a broad range of cognitive disturbances. The impact in terms of functional outcome is significant. There are also several reports of disturbed autonomic regulation in the disease. The present study examined cognitive function as well as psychophysiological parameters in patients with schizophrenia and healthy controls. METHODS: Twenty-five patients and 14 controls were investigated with electrodermal activity (EDA), an oral niacin skin flush test and a comprehensive neurocognitive test program including the Wechsler battery (WAIS-R), Fingertapping Test, Trail Making Test, Verbal Fluency, Benton Visual Retention Test, Wisconsin Card Sorting Test and Rey Auditory Verbal Learning Test. RESULTS: The patients generally had inferior test results compared to controls. Further analysis revealed that the EDA non-responding patient group explained this variation with significant lower test results than controls. On executive tests, EDA non-responders also performed significantly worse than EDA responding patients. The small group of niacin non-responding patients exhibited an even lower overall test performance. Delayed niacin flush also correlated inversely with psychomotor function and IQ in the patients. CONCLUSION: The findings support the hypothesis of a neurodevelopment disturbance affecting both autonomic function and higher cortical function in schizophrenia.

Do we need a gender-specific total knee replacement? A randomised controlled trial comparing a high-flex and a gender-specific posterior design.

The purpose of this study was to investigate whether a gender-specific high-flexion posterior-stabilised (PS) total knee replacement (TKR) would offer advantages over a high-flex PS TKR regarding range of movement (ROM), 'feel' of the knee, pain and satisfaction, as well as during activity. A total of 24 female patients with bilateral osteoarthritis entered this prospective, blind randomised trial in which they received a high-flex PS TKR in one knee and a gender-specific high-flexion PS TKR in the other knee. At follow-up, patients were assessed clinically measuring ROM, and questioned about pain, satisfaction and daily 'feel' of each knee. Patients underwent gait analysis pre-operatively and at one year, which yielded kinematic, kinetic and temporospatial parameters indicative of knee function during gait. At final follow-up we found no statistically significant differences in ROM (p = 0.82). The median pain score was 0 (0 to 8) in both groups (p = 0.95). The median satisfaction score was 9 (4 to 10) in the high-flex group and 8 (0 to 10) in the gender-specific group (p = 0.98). The median 'feel' score was 9 (3 to 10) in the high-flex group and 8 (0 to 10) in the gender-specific group (p = 0.66). Gait analysis showed no statistically significant differences between the two prosthetic designs in any kinematic, kinetic or temporospatial parameters. Both designs produced good clinical results with significant improvements in several gait parameters without evidence of any advantage in the gender-specific design.

Fast-track surgery for bilateral total knee replacement.

Bilateral simultaneous total knee replacement (TKR) has been considered by some to be associated with increased morbidity and mortality. Our study analysed the outcome of 150 consecutive, but selected, bilateral simultaneous TKRs and compared them with that of 271 unilateral TKRs in a standardised fast-track setting. The procedures were performed between 2003 and 2009. Apart from staying longer in hospital (mean 4.7 days (2 to 16) versus 3.3 days (1 to 25)) and requiring more blood transfusions, the outcome at three months and two years was similar or better in the bilateral simultaneous TKR group in regard to morbidity, mortality, satisfaction, the range of movement, pain, the use of a walking aid and the ability to return to work and to perform activities of daily living. Bilateral simultaneous TKR can therefore be performed as a fast-track procedure with excellent results.

Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.

BACKGROUND: Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS: Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS: Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS: Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.

Genetic variability within the innate immune system influences personality traits in women.

Raised levels of inflammation markers have been associated with several mental disorders; however, studies regarding the relationship between inflammation or the immune system and various aspects of human behaviour are not numerous. The aim of the present study was to investigate whether an association exists between personality traits and two single nucleotide polymorphisms located in genes that are associated with the innate immune system. The studied population consisted of 42-year-old women recruited from the population registry that had been assessed by means of Karolinska Scales of Personality, a self-reported inventory. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation. The T-allele has previously been suggested to be linked to raised serum levels of CRP. The second polymorphism, Y402H (1277T>C, rs1061170), is located in the gene coding for complement factor H, an important regulator of the complement system. The C-allele has consistently been associated with age-related macular degeneration. While the +1444T allele was associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability, the 1277C polymorphism was associated with higher scores in verbal aggression and lower scores in social desirability. In conclusion, the associations between the personality traits and the studied polymorphisms further support the possible influence of the immune system on mental functions.

Rise in morning saliva cortisol is associated with abdominal obesity in men: a preliminary report.

An abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with risk factors for cardiovascular disease and Type 2 diabetes mellitus. The objective of this study was to examine if morning saliva cortisols show similar associations. Twenty-eight men, all 53 yr of age, delivered during an ordinary working day saliva cortisol samples immediately upon awakening and 15 min thereafter as well as at different times during the day, including after a standardized lunch. Dexamethasone (0.5 mg) suppression of cortisol was also measured. The rise of morning cortisol values was positively associated with body mass index (r: 0.45, p=0.016), waist/hip ratio (r: 0.54, p=0.003), abdominal sagittal diameter (r: 0.54, p=0.003), glucose (r: 0.54, p=0.003), insulin (r: 0.57, p=0.002) and triglycerides (r: 0.46, p=0.014). The morning rise also correlated positively with the elevation of cortisol following lunch (r: 0.45, p=0.043) but not with other cortisol measurements or dexamethasone suppression. Elevation of cortisol immediately after awakening has previously been found to provide a simple indicator of HPA axis regulation, as suggested also by the results of this study, and an elevated rise has been reported after exposure to frequent or chronic perceived stress. The rise of cortisol immediately after awakening might be an indicator of an increased risk of developing serious, prevalent diseases via the metabolic syndrome.

A 5-year follow-up study of disease incidence in men with an abnormal hormone pattern.

OBJECTIVES: Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases. To test this hypothesis, we conducted a 5-year follow-up study in middle-aged men. METHODS: A population-based cohort study conducted in 1995 amongst 141 Swedish men born in 1944, in whom a clinical examination supplemented by medical history aimed to disclose the presence of cardiovascular disease (CVD) (myocardial infarction, angina pectoris, stroke), type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000. In addition, salivary cortisol levels were measured repeatedly over the day. Serum testosterone concentrations were also determined. Using the baseline data, an algorithm was constructed, which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal. RESULTS: By the end of follow-up, men with an abnormal hormone secretion pattern (n = 73) had elevated mean arterial pressure (P = 0.003), fasting insulin (P = 0.009) and insulin : glucose ratio (P = 0.005) compared with men with a normal secretion pattern (n = 68). Body mass index, waist circumference, and waist : hip ratio were significantly elevated in both groups. However, the 5-year incidence of CVD, type 2 diabetes, and hypertension were significantly higher (P < 0.001) in men with an abnormal neuroendocrine secretory pattern compared to men with a normal pattern. CONCLUSIONS: These data suggest that an abnormal neuroendocrine secretory pattern is prospectively associated with an increased incidence of cardiovascular-related events and type 2 diabetes.

Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women.

Estrogens are known to play a key role in the regulation of various aspects of behavior. In order to study the potential contribution of genetic variation in the estrogen receptor (ER) alpha to specific personality traits, we investigated a repeat polymorphism in the ER alpha gene in 172 42-year-old women who had been assessed using the Karolinska Scales of Personality (KSP). Based on the hypothesis that there is a relationship between the length of a repeat polymorphism and gene function,(1) the alleles were divided into two groups: short and long. In order to elucidate the possible influence of the ER alpha gene on the different aspects of personality measured by means of the KSP, the possible association between this gene and four different factors ('neuroticism', 'psychoticism', 'non-conformity', and 'extraversion') was analysed. 'Neuroticism', 'psychoticism', and 'non-conformity' all appeared to be associated with the ER alpha gene. After correction for multiple comparisons by means of permutation analysis, the associations with the factor 'non-conformity'--including the subscales 'indirect aggression' and 'irritability'--and the factor 'psychoticism'--including the subscale 'suspicion'--remained significant. The results suggest that the studied dinucleotide repeat polymorphism of the ER alpha gene may contribute to specific components of personality.

Phenotypic and genotypic characteristics of women in relation to personality traits.

The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects. Women, all 42 years of age and premenopausal (n = 270), were recruited randomly. Conventional "masculine" and "feminine" personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by "masculinity" (M) or "femininity" (F) were 44.9%, respectively 15.0%, the rest consisting of a combination of M and F (33.2%) or "undifferentiated" (6.9%). M characteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of "tomboyism" as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showed M type of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene.

Antibody reactivities to skeletal muscle proteins in a patient with lambda light chain secreting multiple myeloma, generalised amyloidosis and rhabdomyolysis.

Rhabdomyolysis is a rare complication in haematological malignancies, and a diverse range of factors has been implicated in the etiology of the syndrome. In the present study we analysed muscle morphology and antibody reactivities to skeletal muscle proteins in a patient diagnosed with lambda (lambda) light chain-secreting multiple myeloma (MM) and amyloidosis, who developed a progressive rhabdomyolysis. The muscle tissue analysis showed focal amyloid depositions and a low degree of atrophy and inflammation. Antibody reactivities against muscle proteins of approximately 42, 51 and 66 kD, respectively, were present in the patient's serum. The antibody specificities were revealed by lambda light chain- or IgM-specific antibodies. The results indicate a possible etiologic link between antibody reactivities towards muscle proteins and muscle tissue disorder in a patient with the unique combination of rhabdomyolysis, amyloidosis and MM of the light chain type.

Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study.

OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.

Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women.

Several studies have reported an association between anxiety-related personality traits and a promoter polymorphism in the human serotonin transporter (5-HTT) gene (5-HTT gene-linked polymorphic region, 5-HTTLPR). In the present study, a population of 251 subjects was assessed with the Karolinska Scales of Personality (KSP) and genotyped both for the 5-HTTLPR and for a variable number of tandem repeats polymorphism in the second intron of the same gene. The interpretation of previous studies has to some extent been confounded by the studied subjects differing with respect to ethnicity, sex, and age. To circumvent this problem, all included subjects were Caucasians, women, and born in the same year (1956). Associations were found between the 5-HTTLPR and four of the five anxiety-related KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of assertiveness), subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype. In addition, an association was found between the intron 2 polymorphism and one anxiety-related personality trait (somatic anxiety).

Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women.

To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.

Circulating immune complexes induced by food proteins implicated in precocious myocardial infarction.

BACKGROUND: Circulating immune complexes (CIC) are frequently found in postinfarction patients. The constituents of these CIC are mostly unknown. AIM: The objective of the current study was to assess whether CIC containing alimentary proteins and antibodies against these proteins are implicated in precocious myocardial infarction (MI). METHODS: Seventy-six survivors (67 men and 9 women, mean age 39 years) of a first MI before the age of 45 years were enrolled in this study. Two control groups were included. One group consisted of age-matched, randomly selected, population-based healthy individuals, 79 men and 11 women, without features of coronary heart disease. An additional control group was used only for the determination of serum antibodies against some of the alimentary proteins and consisted of 139 healthy blood donors, 95 men and 44 women, with a mean age of 42 years. Sucrose density gradient centrifugation, gel filtration and precipitation by polyethylene glycol were used for the isolation of CIC, and enzyme-linked immunosorbent assay (ELISA) was used to measure the immunoglobulin levels and specific antibodies against alimentary proteins in both sera and isolated CIC. Sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis and Western blotting were used to determine alimentary proteins in the CIC. RESULTS: Alimentary antigens/antibodies were present in immune complex form in seven out of 14 (50%) postinfarction patients who had persistent high concentrations of CIC, the latter constituting 18% of the entire group. Antibodies of the IgG isotype predominated. A rise in CIC, signs of activation of the classical complement pathway, and a rise in plasma concentrations of von Willebrand factor antigen (vWFAg) were evident within 1 week in four patients subjected to a 2-week elimination diet followed by a single challenge with cow's milk. CONCLUSION: This study suggests that dietary proteins occasionally give rise to persistent CIC, which may predispose to MI at a young age.

Relationships between personality disorders and anthropometry, hormones and metabolism in women.

This study sought to examine the potential influence of personality disorders (PD) on anthropometry, hormones and metabolism in women. In a population sample of women born in 1956 (no.=270), estimates of PD:s by Structured Clinical Interview for DSM-III-R, Axis II, were correlated with anthropometric, endocrine, and metabolic factors. The PD:s were grouped into three thematic clusters: cluster A (characterized by oddness or eccentricity), cluster B (characterized by self-centeredness, emotionality, and erratic behavior) and cluster C (characterized by anxiety and fear). Subjects with cluster A PD:s had significantly increased body mass index (BMI, kg/m2) and abdominal sagittal diameter (cm) as well as lower salivary cortisol after dexamethasone (DEX) compared to controls. Subjects with cluster B also had a significantly higher abdominal sagittal diameter and significantly lower salivary cortisol levels after DEX than controls. In addition, subjects with cluster B PD:s had decreased levels of ACTH, and significantly higher concentrations of lactate and triglycerides, while high-density lipoprotein (HDL) cholesterol was significantly lower compared to controls. A significantly higher waist/hip ratio was seen among subjects with cluster C PD:s. In addition, these subjects had higher levels of insulin, glucose, lactate, triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol than controls. Moreover, IGF-I and HDL cholesterol were significantly decreased in the former group. These results suggest that PD:s are involved in the development of obesity and abdominal fat accumulation in women, with different endocrine and metabolic profiles depending on the type of PD.

Interleukin-10 gene promoter polymorphisms in multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of malignant plasma cells in the bone marrow. It is unclear whether genetic background could have an etiological impact on MM or influence the course of the disease. Interleukin-10 (IL-10) has been implicated in the growth and differentiation of normal B cells, and has also been shown to enhance the proliferation of MM cells. To address the putative involvement of IL-10 genetic variation in MM, we analyzed previously defined loci for bi-allelic polymorphism at position -1082 and two microsatellite loci (IL10.G and IL10.R) in the IL-10 promoter region. Seventy-three patients with MM, 27 with monoclonal gammopathy of undetermined significance, and 109 ethnically matched individuals as controls were included in the study. Significantly increased frequencies of the IL10.G genotype 136/136 and the IL10.R genotype 112/114, in addition to a decreased frequency of the IL10.R genotype 114/116, were found among the MM patients. Increased production of IL-10 was detected in the supernatants of lipopolysaccharide-stimulated peripheral blood mononuclear cells from MM patients who were homozygotes (136/136) and heterozygotes (136/non-136) for the IL10.G allele 136, as compared with the other IL10.G genotype carriers (non-136/non-136). These results suggest that the genetic variation in the IL-10 promoter region may play a role in the development of MM.

Telomerase activity in plasma cell dyscrasias.

Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM.