Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria

The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.     

A simple method for large-scale generation of dopamine neurons from human embryonic stem cells

Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are potentially valuable in drug screening and as a possible source of donor tissue for transplantation in Parkinson's disease. However, existing culture protocols that promote the differentiation of DA neurons from hESCs are complex, involving multiple steps and having unreliable results between cultures. Here we report a simple and highly reproducible culture protocol that induces expandable DA neuron progenitors from hESCs in attached cultures. We found that the hESC-derived neuronal progenitors retain their full capacity to generate DA neurons after repeated passaging in the presence of basic fibroblast growth factor (bFGF) and medium conditioned with PA6 stromal cells. Using immunocytochemistry and RT-PCR, we found that the differentiated DA neurons exhibit a midbrain phenotype and express, e.g., Aldh1a, Ptx3, Nurr1, and Lmx1a. Using HPLC, we monitored their production of DA. We then demonstrated that the expanded progenitors are possible to cryopreserve without loosing the dopaminergic phenotype. With our protocol, we obtained large and homogeneous populations of dopaminergic progenitors and neurons. We conclude that our protocol can be used to generate human DA neurons suitable for the study of disease mechanisms, toxicology, drug screening, and intracerebral transplantation.     

Prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty

Labuda A, Papaioannou A, Pritchard J, Kennedy C, DeBeer J, Adachi JD. Prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty.

Objective

To determine the prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty.

Design

Cross-sectional study.

Setting

The Specialized Outpatient Rehabilitation Service's (SORS) Pre-surgical Arthroplasty Service located at the Chedoke Hospital, Hamilton Health Sciences, Hamilton, ON, Canada.

Participants

SORS outpatients (N=364), from the period of March 2006 to March 2007.

Interventions

Not applicable.

Main Outcome Measures

Prevalence of osteoporosis was determined by review of a self-reported survey, and defined by (1) self-reported diagnosis of osteoporosis, (2) history of fragility fracture (defined by a bone fracture occuring as a result of a fall from standing height or less after the age of 50), or (3) current treatment for osteoporosis using bisphosphonates.

Results

Of the study cohort, 26% were classified as having osteoporosis, according to our criteria. Of the patients with self-reported osteoporosis or a history of fragility fractures, only 37% and 17% reported current treatment with bisphosphonates, respectively.

Conclusions

Osteoporosis is common in the osteoarthritic arthroplasty population, with a prevalence at least equal to that in the general population. Due to the self-reported nature of the study, the prevalence of osteoporosis in this population is likely significantly higher. Results from this study indicate need for further research, specifically in formal assessment for osteoporosis in patients undergoing a joint replacement.     

Autism spectrum traits in children and adolescents with obsessive-compulsive disorder (OCD)

OBJECTIVE: Assess the prevalence of autistic traits (AST) in pediatric obsessive-compulsive disorder (OCD) and relate them to OCD co-morbidity and compare them with published normative data. METHODS: Pediatric patients with obsessive-compulsive disorder (n=109) according to the DSM-IV were studied using parent ratings of the Autistic Symptom/Syndrome Questionnaire to assess AST symptoms as a continuous rather than categorical trait. The KSADS, a semi-structured psychiatric interview, was used for the psychiatric diagnostic evaluation. Also, the Children's Yale-Brown Obsessive-Compulsive Scale was used to assess OCD severity and other clinical features. RESULTS: AST was common among our patients. Symptom scores were highest in cases with co-morbid Autistic Spectrum Disorders, but cases with other co-morbidities as tics/Tourette and attention/behavioral disorders also scored higher. All sub-groups, including OCD without these co-morbidities scored higher than the Swedish normative group. Using ANOVA, co-morbid ASD and tics/Tourette (plus a term for gender by tic interaction indicating that girls with tics scored high, otherwise low) and pathological doubt contributed (R2=.41) to the AST-traits, while OCD severity and co-morbid anxiety- and depressive disorders did not. CONCLUSION: AST traits are prevalent in OCD and seem to be intricately associated with the co-morbidities as well as the OCD syndrome itself. The findings might have implication for our nosological understanding of OCD which currently is discussed.     

Normative data for the Multidimensional Anxiety Scale for Children (MASC) in Swedish adolescents

The Swedish translation of a new scale developed for childhood and adolescent anxiety, the Multidimensional Anxiety Scale for Children (MASC), was studied regarding reliability and convergent validity and to obtain norms in a general population. Four hundred and five adolescents, reasonably representative of Swedish adolescents, were asked to rate their anxiety symptoms on the MASC. In order to study the convergent validity, they also rated their depressive symptoms on the Children's Depression Inventory (CDI), their attitude to their body on the Body Esteem Scale for Adolescents and Adults (BESAA) and filled in demographical data on themselves. The MASC showed adequate internal consistency both for the whole scale (alpha = 0.87) and for subscales (range 0.64-0.84). The scale showed convergent validity through a moderate correlation with the CDI (r=0.400, P=0.0001) and the BESAA (r= - 0.29, P=0001). Girls scored higher (mean = 38.9) than boys (mean = 31.9) on the MASC total score (t(385) = 5.14, P=0.0001) and on the subscales, except Harm avoidance. Using the MASC as a general screen for anxiety, scores of 48 for boys and 56 for girls using MASC total scores, or scores of 15 for boys and 17 for girls using the Anxiety Disorders Index could be employed (both representing the 90th percentiles). The MASC appears to be a reliable and valid scale both on the global and on the subscale level.     

Resolution of peri‐implantitis following treatment. An experimental study in the dog.

The aim of the present experiment was i) to study the effect of anti-microbial therapy of experimentally induced peri-implantitis lesions and ii) to assess features of bone regrowth following treatment. Four beagle dogs were used. Three titanium fixtures (Brånemark System®) were installed in each quadrant of the mandible (premolars previously extracted). Abutment connection was performed 5 months later and ligature induced break-down was initiated. The ligatures were removed when approximately 50% of the initial bone support was lost. A 3-week antibiotic regimen (amoxi-cillin and metronidazole) was initiated 1 month later. Two days after the start of the antibiotic administration, the experimental implant sites were exposed to local therapy. The abutments were removed and the exposed fixture surfaces were treated with an abrasive (pumice) administered via a rotating brush (left side) or cleaned with cotton pellets soaked in saline (right side). Cover screws were attached to the fixtures and the implants were submerged. Fluorochromes were injected intravenously 2 weeks, 4 weeks and 12 weeks after surgery. The animals were killed 7-months after surgery and block biopsies of each implant site were dissected and prepared for histological analysis. The findings of the examinations disclosed that the inflammatory lesion was resolved and new bone formation had occurred in the previous defect following antimicrobial and local therapy. The amount of “re-osseointegration” that had taken place, however, was small. Indeed, at all experimental implant sites, a thin connective tissue capsule was found to separate the implant surface from the newly formed bone.     

Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms

Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics-metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females.     

Weight concerns, body image, depression and anxiety in Swedish adolescents

OBJECTIVES: To assess weight problems and correlates in respect of body image, depression, anxiety and demographic background factors. METHOD: 405 Swedish adolescents were assessed in respect of Body Mass Index (BMI), biographical data, the Body Esteem Scale for Adolescents and Adults (BESAA), the Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression Inventory (CDI). RESULTS: Boys were in the positive and girls in the negative direction from ideal BMI for age and gender. Girls and boys differed in respect of CDI, MASC and of BESAA where girls generally were shifted in the "pathological" direction. DISCUSSION: The adolescents' own positive attitude to slimness, negative mood (girls), and anxiety symptoms that reflect social fears (boys) and physical aspects of anxiety (girls and boys) were important correlates of lower BMI than ideal. Adolescent cultural norms need to be addressed in preventive work. However, in girls' separation anxiety might be a protective factor against underweight. In girls, overweight seems to be associated with negative self-esteem.