Effects of calcium-fortified ice cream on markers of bone health.

UNLABELLED: Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7 days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1 h of consuming ice cream. Body weight remained constant over 28 days. INTRODUCTION: Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. METHODS: Eighty women, ages 20-39 years (calcium intake <750 mg/day) were randomised to consume lower saturated fat/sugar ice cream containing 96, 244, 459 or 676 mg calcium daily for 28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h (n = 29 women). RESULTS: There were significant mean decreases by 7 days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change significantly between baseline and 28 days. CONCLUSIONS: Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244 mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women.

Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism.

OBJECTIVE: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. METHOD: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia-spectrum disorders and 77 inpatients with other non-psychotic disorders. RESULTS: First, age at first cannabis use correlates with age at onset in both schizophrenia-spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non-users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. CONCLUSION: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.

The role of schizotypal traits and the OXTR gene in theory of mind in schizophrenia: A family-based study.

BACKGROUND: There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals. METHODS: The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped. RESULTS: Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007). CONCLUSIONS: ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

New evidences of gene and environment interactions affecting prenatal neurodevelopment in schizophrenia-spectrum disorders: a family dermatoglyphic study.

BACKGROUND: Several studies have reported an increase of dermatoglyphic anomalies in schizophrenic patients compared to controls. However, the recognition of specific dermatoglyphic variables related to this disorder and their genetic and/or environmental component are still controversial. METHOD: We conducted a dermatoglyphic analysis in a new sample of 617 individuals: 205 patients with schizophrenia-spectrum disorders, 224 healthy first degree relatives and 188 healthy controls. The dermatoglyphic variables studied were: the total a-b ridge count (TABRC) and its fluctuating asymmetry (FAABRC), and the presence of ridge dissociations (RD) and abnormal palmar flexion creases (APFC). RESULTS: Patients, relatives and controls did not differ in TABRC. However, within the patients group those with a low birth weight or absence of psychiatric family history showed lower TABRC than the others. The frequency of ectodermic derivates abnormalities (RD and/or APFC) appeared to be higher in patients and relatives than in controls, while first degree relatives did not differ from patients. Males showed an increased rate of ectodermic derivates abnormalities compared to females in all groups and male patients also presented higher FAABRC than female patients. CONCLUSIONS: Our results suggest a different relative weight of genetic and environmental factors on each dermatoglyphic variable analyzed: i) TABRC may be a sensitive marker to environmental factors in schizophrenia, ii) ectodermal derivates abnormalities appear to be influenced by genetic risk factors, which could be involved both in the disrupted development of ectodermic derivates like dermatoglyphics and central nervous system and in the vulnerability for schizophrenia.

Familial aggregation of schizotypy in schizophrenia-spectrum disorders and its relation to clinical and neurodevelopmental characteristics.

INTRODUCTION: This study explored schizotypy as a familial liability marker for schizophrenia-spectrum disorders (SSD) by examining: 1) the aggregation of schizotypy in families with a SSD patient, 2) whether familial resemblance of schizotypy is associated with ridge dissociations (RD), another SSD liability marker, 3) whether schizotypy aggregation patterns influence patients' psychopathology. METHODS: The sample comprised 30 SSD patients and 82 healthy first-degree relatives. Schizotypy was assessed using the Structured Interview for Schizotypy-Revised (SIS-R). Patients' psychopathology was evaluated using the Comprehensive Assessment of Symptoms and History (CASH). RD were identified as anomalies of the dermal ridge junction. Familiality of SIS-R was investigated using a linear mixed model (LMM) and its strength was assessed using an intraclass correlation coefficient (ICC). Another LMM using the absolute differences in SIS-R scores between all possible pairs of relatives as the dependent variable was fitted to obtain an intra-family resemblance score, a family-specific indicator of resemblance of SIS-R scores within each family. RESULTS: 1) Schizotypy was familial (ICC = 0.30); families with high resemblance displayed low schizotypy, whereas families with low resemblance included at least one healthy relative with high schizotypy (p < 0.001). 2) Relatives with RD had higher SIS-R scores (p = 0.018) and belonged to families with discordant schizotypy scores among members (p < 0.001). 3) Patients from high schizotypy families showed more severe disorganized symptoms at the psychotic episode (p = 0.035) and 1 year later (p = 0.011). CONCLUSIONS: Schizotypy is a marker of vulnerability for SSD that runs within a subgroup of families. The schizotypy familial aggregation pattern correlates with RD in relatives and with patients' psychopathology.

Influence of DAOA and RGS4 genes on the risk for psychotic disorders and their associated executive dysfunctions: A family-based study.

BACKGROUND: Glutamatergic neurotransmission dysfunction has classically been related to the aetiology of psychotic disorders. A substantial polygenic component shared across these disorders has been reported and molecular genetics studies have associated glutamatergic-related genes, such as d-amino acid oxidase activator (DAOA) and regulator of G-protein signalling 4 (RGS4) with the risk for psychotic disorders. Our aims were to examine: (i) the relationship between DAOA and RGS4 and the risk for psychotic disorders using a family-based association approach, and (ii) whether variations in these genes are associated with differences in patients' cognitive performance. METHODS: The sample comprised 753 subjects (222 patients with psychotic disorders and 531 first-degree relatives). Six SNPs in DAOA and 5 SNPs in RGS4 were genotyped. Executive cognitive performance was assessed with Trail Making Test B (TMT-B) and Wisconsin Card Sorting Test (WCST). Genetic association analyses were conducted with PLINK, using the transmission disequilibrium test (TDT) for the family-based study and linear regression for cognitive performance analyses. RESULTS: The haplotype GAGACT at DAOA was under-transmitted to patients (P=0.0008), indicating its association with these disorders. With regards to cognitive performance, the DAOA haplotype GAGGCT was associated with worse scores in TMT-B (P=0.018) in SZ patients only. RGS4 analyses did not report significant results. CONCLUSIONS: Our findings suggest that the DAOA gene may contribute to the risk for psychotic disorders and that this gene may play a role as a modulator of executive function, probably through the dysregulation of the glutamatergic signalling.

Fish oil and oxidative stress by inflammatory leukocytes.

We investigated the effects of diets with different fatty acid composition upon the oxidative stress of inflammatory leukocytes of rats. After weaning, two groups of rats were fed isoenergetic semipurified diets for five weeks containing 5% of corn oil or menhaden oil. Polymorphonuclear leukocytes from rats fed menhaden oil diet incorporated n-3 polyunsaturated fatty acids into phospholipid membranes at the expense of arachidonic acid. These cells showed diminished superoxide production and, as a consequence, the total antioxidant status in the inflammatory exudate was increased. However, nitric oxide production was not affected by diet. Free malondialdeyde concentration increased in the exudate because of lower mitochondrial activity. These results add new aspects that help clarifying the anti-inflammatory mechanisms of n-3 polyunsaturated fatty acids.

[Medical and psychological status of one-year-old premature babies without severe disability. Case-control prospective study]. / Devenir médical, psychologique et affectif à l'âge d'un an des prématurés indemnes de handicap sévère. Etude prospective cas-témoins.

BACKGROUND: This case-control prospective study was conducted to determine whether and how medical, psychological and affective development differs from premature to full-term newborns without severe disability. POPULATION AND METHODS: Newborns under or at 33 weeks gestation (W) were included from December 1992 to January 1994 and were matched with two controls. The same examiners evaluated each infant at the effective postnatal age of nine to ten months. RESULTS: Fifty premature babies (average gestational age [GA] = 30.7 W) were compared to 100 controls. The main problems were bronchopulmonary (P = 0.03) and sleep (P = 0.027) disorders. Motor disability was suspected in 9% of the cases and none control (P = 0.00003, OR = 3.44). By multivariate analysis, cases differed from the controls by infant-mother relation disturbances (OR = 13.3), motherhood anxiety (OR = 13.3), poor expressiveness (OR = 5.6), peripheral tonus anomalies (OR = 39.5) and sleep troubles (OR = 5.8). CONCLUSION: Premature newborns had risks for the child-mother relation but not for psychoaffective development disturbances.

Neurodevelopmental liability to schizophrenia: the complex mediating role of age at onset and premorbid adjustment.

Large individual variation in the clinical presentation of schizophrenia-spectrum disorders raises key questions regarding their aetiological underpinnings. In this respect, age at onset of the disorder is a particularly interesting marker of liability, as it has been reported to be associated with other signs of developmental compromise, such as male gender, increased presence of familial history of psychosis and poor premorbid adjustment, as well as a more severe clinical outcome in terms of cognition and symptomatology. The association between these variables has encouraged a neurodevelopmental perspective of the aetiological mechanisms involved in the pathophysiology of schizophrenia. However, the complex relationships within neurobiological liability markers, and between these markers and clinical outcome, remain to be understood. In the present study, we used a path-analytic approach to explore: i) the fit of the model to observed data; and both ii) direct and iii) indirect associations between the variables. In a sample of 106 patients with schizophrenia-spectrum disorders, we found a good fit of the model to the observed data, providing further evidence that supports a neurodevelopmental pathway to the disease in a subgroup of patients. However, the most parsimonious model showed complex relationships, where age at onset and premorbid functioning acted as mediators between gender, familial history of psychosis and clinical outcome. These findings refine earlier explanations of the neurobiological basis of schizophrenia, with potential applications in genetic studies based on more homogeneous forms of the disease. We further discuss the putative implications of our results in clinical practice and prevention policies.

Family-based association study of neuregulin-1 gene and psychosis in a Spanish sample.

Neuregulin 1 (NRG1) is one of the most exciting candidate genes for schizophrenia since its first association with the disorder in an Icelandic population. Since then, many studies have analyzed allele and haplotype frequencies in European and Asian populations in cases and controls yielding varying results. We investigated the association of NRG1 with psychosis in a total sample set of 575 individuals from 151 Spanish nuclear families. We tested eight SNPs across 1.2 Mb along NRG1 including regions previously associated to schizophrenia in association studies. After correction for multiple testing, the TDT analysis for each marker did not show a significant over-transmission of alleles from the parents to the affected offspring for any of the markers (P > 0.05). The haplotypic analysis with TRANSMIT and PDT did not show preferential transmission for any of the haplotypes analyzed in our sample. These results do not seem to suggest that the investigated NRG1 markers play a role in schizophrenia in the Spanish population, although the finding of a trend for association with one SNP in the 3'of the gene warrants further investigation.

Effects of fish oil- and olive oil-rich diets on iron metabolism and oxidative stress in the rat.

The objective of the present study was to examine the effects of fish oil (FO)- and olive oil (OO)-rich diets on Fe metabolism and oxidative stress. Rats were fed for 16 weeks with diets containing 50 g lipids/kg; either OO, maize oil (MO) or FO. OO or MO diets contained a standard amount (100 mg/kg) of all-rac-alpha-tocopheryl acetate. FO diets were supplemented with 0, 100 or 200 mg all-rac-alpha-tocopheryl acetate/kg (FO-0, FO-1 or FO-2 diets, respectively). At the end of the feeding period, we measured non-haem Fe stores in liver and spleen, and erythrocyte and reticulocyte count. We also determined antioxidants and products derived from lipid peroxidation in plasma and erythrocytes. Our results showed reduced non-haem Fe stores in rats fed any of the FO diets. Reticulocyte percentage was higher in the rats fed FO-0 and FO-1. Plasma alpha-tocopherol was very low in rats fed the FO-0 diet. Rats fed the FO-1 and FO-2 diets showed higher alpha-tocopherol in plasma than the FO-0 group but lower than the MO or OO groups. We did not observe such differences in the alpha-tocopherol content in erythrocyte membranes. Superoxide dismutase and glutathione peroxidase activities were lower in the erythrocytes of rats fed the FO-0 diet. The products derived from lipid peroxidation were also higher in the FO groups. The administration of FO-rich diets increased lipid peroxidation and affected Fe metabolism. On the other hand, the OO-rich diet did not increase oxidative stress and did not alter Fe metabolism. Based on these results, we conclude that FO supplementation should be advised carefully.

Olive oil decreases both oxidative stress and the production of arachidonic acid metabolites by the prostaglandin G/H synthase pathway in rat macrophages.

Fish oil has a preventive role in cardiovascular and inflammatory diseases, but little is known about the effect of olive oil, which is widely consumed in Mediterranean regions. We examined the influence of dietary olive oil, corn oil and fish oil-rich diets on the production of superoxide anion (O2-) and nitric oxide (.NO) by resident macrophages stimulated by phorbol 12-myristate 13-acetate (PMA) and their effect on arachidonic acid release, prostaglandin G/H synthase-2 (PGHS-2) expression and the subsequent prostaglandin E(2) production. Resident peritoneal macrophages stimulated by PMA from rats fed with olive oil or corn oil had the same level of O2- production, but these levels were increased by the fish oil diet. Olive oil and the fish oil diets increased .NO and decreased arachidonic acid mobilization and the production of prostaglandin E(2). PGHS-2 expression, however, was not affected by diet. We conclude that although olive oil and fish oil reduce arachidonic acid mobilization and subsequent metabolism through the PGHS-2 pathway in PMA-stimulated macrophages, only olive oil offers an additional beneficial effect by increasing .NO/O2- production.

Molecular evidence for the role of a ferric reductase in iron transport.

Duodenal cytochrome b (Dcytb) is a haem protein similar to the cytochrome b561 protein family. Dcytb is highly expressed in duodenal brush-border membrane and is implicated in dietary iron absorption by reducing dietary ferric iron to the ferrous form for transport via Nramp2/DCT1 (divalent-cation transporter 1)/DMT1 (divalent metal-transporter 1). The protein is expressed in other tissues and may account for ferric reductase activity at other sites in the body.

A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.

Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells. Ireg1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA contains a functional iron-responsive element (IRE). IREG1 stimulates iron efflux following expression in Xenopus oocytes. We conclude that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease, hereditary hemochromatosis.