Current Issue : January - March Volume : 2012 Issue Number : 1 Articles : 8 Articles
Background: The catecholaminergic and serotonergic neurotransmitter systems are implicated in the\r\npathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for\r\nsynthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin.\r\nA disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric\r\ndisorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim\r\nof this study was to explore whether children with ADHD may have disturbed amino acid transport.\r\nMethods: Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from\r\n13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine,\r\ntryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic\r\nparameters, maximal transport capacity (Vmax) and affinity constant (Km) were determined. Any difference between\r\nthe two groups was analyzed by Student�s unpaired t-test or the Mann Whitney U test.\r\nResults: The ADHD group had significantly decreased Vmax (p = 0.039) and Km (increased affinity) (p = 0.010) of\r\ntryptophan transport in comparison to controls. They also had a significantly higher Vmaxof alanine transport (p =\r\n0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of\r\nthe kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group.\r\nConclusions: Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB).\r\nHence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB\r\nin the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both\r\nthe serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected.\r\nThe physiological importance of an elevated transport capacity of alanine to the brain is not known to date....
Background: Monoamine oxidases (MAOs) catalyze the metabolism of dopaminergic neurotransmitters.\r\nPolymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as\r\nschizophrenia. Association studies detected these polymorphisms in several populations, however the data have\r\nnot been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with\r\nschizophrenia in a Han Chinese population.\r\nMethods: Two functional single nucleotide polymorphisms (SNPs), rs6323 of MAOA and rs1799836 of MAOB, were\r\nselected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and\r\nHaplotype associations were calculated.\r\nResults: No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as\r\na risk factor in the development of schizophrenia (P = 0.00001). The risk haplotype rs6323T-rs1799836G was\r\nassociated with schizophrenia in female patients (P = 0.0002), but the frequency difference was not significant\r\namong male groups.\r\nConclusions: Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant\r\nassociations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data\r\nsupport further investigation of the role of MAO genes in schizophrenia....
Background: Fatigue is a common symptom in both sick and healthy people. We examined autonomic nervous\r\nalterations associated with fatigue to clarify the mechanisms underlying fatigue.\r\nMethods: The study group consisted of 19 healthy participants who performed a 2-back test for 30 min as a\r\nfatigue-inducing mental task session. Before and after the session, they completed the advanced trail making test\r\n(ATMT) for 30 min for mental fatigue evaluation, subjective scales to measure fatigue sensation, and underwent\r\nelectrocardiography to allow assessment of autonomic nerve activities.\r\nResults: After the fatigue-inducing task, the total error counts on the ATMT tended to increase (P = 0.076); the\r\nATMT for total trial counts (P = 0.001), the subjective level of fatigue (P < 0.001), and the % low-frequency power\r\n(%LF) (P = 0.035) increased significantly; and the % high-frequency power (%HF) decreased compared with before\r\nthe fatigue-inducing task although this did not reach the statistical significance (P = 0.170). Although LF measured\r\nin absolute units did not change significantly before and after the fatigue-inducing task (P = 0.771), and HF\r\nmeasured in absolute units decreased after the task (P = 0.020). The %LF and LF/HF ratio were positively associated\r\nwith the daily level of fatigue evaluated using Chalder�s fatigue scale. In addition, %HF was negatively associated\r\nwith the fatigue score.\r\nConclusions: Increased sympathetic activity and decreased parasympathetic activity may be characteristic features\r\nof both acute and daily levels of fatigue. Our findings provide new perspectives on the mechanisms underlying\r\nfatigue....
Physiological and environmental variables, or covariates, can account for an important portion of the variability\r\nobserved in behavioural/physiological results from different laboratories even when using the same type of animals\r\nand phenotyping procedures. We present the results of a behavioural study with a sample of 1456 genetically\r\nheterogeneous N/Nih-HS rats, including males and females, which are part of a larger genome-wide fine-mapping\r\nQTL (Quantitative Trait Loci) study. N/Nih-HS rats have been derived from 8 inbred strains and provide very small\r\ndistance between genetic recombinations, which makes them a unique tool for fine-mapping QTL studies. The\r\nbehavioural test battery comprised the elevated zero-maze test for anxiety, novel-cage (open-field like) activity,\r\ntwo-way active avoidance acquisition (related to conditioned anxiety) and context-conditioned freezing (i.e.\r\nclassically conditioned fear). Using factorial analyses of variance (ANOVAs) we aimed to analyse sex differences in\r\nanxiety and fear in this N/Nih-HS rat sample, as well as to assess the effects of (and interactions with) other\r\nindependent factors, such as batch, season, coat colour and experimenter. Body weight was taken as a quantitative\r\ncovariate and analysed by covariance analysis (ANCOVA). Obliquely-rotated factor analyses were also performed\r\nseparately for each sex, in order to evaluate associations among the most relevant variables from each behavioural\r\ntest and the common dimensions (i.e. factors) underlying the different behavioural responses. ANOVA analyses\r\nshowed a consistent pattern of sex effects, with females showing less signs of anxiety and fear than males across\r\nall tests. There were also significant main effects of batch, season, colour and experimenter on almost all\r\nbehavioural variables, as well as ââ?¬Å?sex Ã?â?? batchââ?¬Â, ââ?¬Å?sex Ã?â?? seasonââ?¬Â and ââ?¬Å?sex Ã?â?? experimenterââ?¬Â interactions. Body weight\r\nshowed significant effects in the ANCOVAs of most behavioural measures, but sex effects were still present in spite\r\nof (and after controlling for) these ââ?¬Å?body weightââ?¬Â effects. Factor analyses of relevant variables from each test\r\nshowed a two-fold factor structure in both sexes, with the first factor mainly representing anxiety and conditioned\r\nfear in males, while in females the first factor was dominated by loadings of activity measures. Thus, besides\r\nshowing consistent sex differences in anxiety-, fear- and activity-related responses in N/Nih-HS rats, the present\r\nstudy shows that femalesââ?¬â?¢ behaviour is predominantly influenced by activity while males are more influenced by\r\nanxiety. Moreover, the results point out that, besides ââ?¬Å?sexââ?¬Â effects, physiological variables such as colour and body weight, and environmental factors as batch/season or ââ?¬Å?experimenterââ?¬Â, have to be taken into account in both\r\nbehavioural and quantitative genetic studies because of their demonstrated influences on phenotypic outcomes....
Rationale: Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development\r\ncauses lasting effects remains unresolved.\r\nObjective: Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when\r\non-drug.\r\nMethods: Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or\r\n10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half\r\nafter 60 days off-drug (20 litters).\r\nResults: The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week posttreatment.\r\nOn-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries,\r\nor latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N = 20/\r\ngroup). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI)\r\nalthough a trend (p < 0.10) was seen, which after combining dose levels, showed a significant increase in ASR\r\namplitude for both fluoxetine and paroxetine (N = 20-21/group). No differences on immobility time were seen in\r\nthe Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no\r\neffects were seen in the elevated plus maze (N = 16/group), ASR/PPI (N = 20/group), forced swim (N = 19-20/\r\ngroup), or plasma corticosterone (N = 19/group). At the doses tested, fluoxetine and paroxetine induced minor\r\neffects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation.\r\nConclusions: The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the\r\nbehaviors measured here after adolescent to young adult exposure....
Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be\r\nperformed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro.\r\nIn macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with\r\nstreptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation,\r\nconditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in\r\nthe learning phase (p�s < .05), regardless whether they received the conditioned stimulus or not at evocation.\r\nHowever, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If\r\nfurther experiments confirm that simple learning can occur in immune cells, this may have bearings not only on\r\nimmune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly,\r\nwhether capacities for simple learning in single cells extend beyond habituation, and how this would be\r\ndemonstrated, remain open questions....
Background: Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in\r\nnoise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated\r\nwith language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical\r\nskill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill\r\nand neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and\r\nregularity in music. Here, we aimed to define relationships between the subcortical processing of speech\r\nregularities, music aptitude, and reading abilities in children with and without reading impairment. We\r\nhypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing\r\nspeech provides a common biological mechanism underlying the development of music and reading abilities.\r\nMethods: We assessed auditory working memory and attention, music aptitude, reading ability, and neural\r\nsensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity\r\nto acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in\r\npredictable and variable speech streams.\r\nResults: Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy\r\nboth relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory\r\nworking memory and attention. Relationships between music and speech processing are specifically driven by\r\nperformance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and\r\nmusic.\r\nConclusions: These data indicate common brain mechanisms underlying reading and music abilities that relate to\r\nhow the nervous system responds to regularities in auditory input. Definition of common biological underpinnings\r\nfor music and reading supports the usefulness of music for promoting child literacy, with the potential to improve\r\nreading remediation....
Introduction: Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To\r\novercome this state of uncertainty, the SZGene database has been established by including all published casecontrol\r\ngenetic association studies appearing in peer-reviewed journals. In the current study, we aimed to\r\ndetermine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our casecontrol\r\nsamples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of\r\nseven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative\r\ndiagnostic manual, the DSM-IV.\r\nMethods: Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven\r\ntop-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February,\r\n2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the\r\ndisorder based on the participantsââ?¬â?¢ genetic information, we calculated the ââ?¬Å?risk-indexââ?¬Â by adding the number of\r\ngenetic risk factors.\r\nResults: No statistically significant deviation between cases and controls was observed in the genetic risk-index\r\nderived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the\r\nschizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39).\r\nConclusion: The current work illustrates the difficulty in identifying universal and definitive risk-conferring\r\npolymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the\r\npossibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is\r\nalso important to aggregate the updated positive variants in the SZGene database when the replication work is\r\nconducted....
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