bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sertraline treatment attenuates the sex differentiated behavioural stress response in the rat forced swim test
Authors: Kokras N. , Dalla C. , Antoniou K. , Papadopoulou-Daifoti Z. 
Published: May 2011

IntroductionSex differences have been described in depression and more recently in antidepressant response. Animal models and in particular the Forced Swim Test (FST), are widely used to investigate the behavioural response to stress and to antidepressant treatment.ObjectivesThe present study explored sex differences in the stress response during the FST and examined whether antidepressant treatment alleviates the sex-differentiated stress response.MethodsAdult male and female Wistar rats were subjected to a 15 min FST session and then treated with three injections of sertraline 10 mg/kg or vehicle at 0, 19 and 23 hours post-FST. Twenty-four hours after the first FST, they had a second 5 min FST session and their behaviour was recorded.ResultsVehicle-treated females exhibited 66% longer duration and 70% shorter latency of immobility than males, suggesting enhanced levels of despair. Sertraline did not significantly affect immobility, but exerted its antidepressant effect by elongating swimming duration in both sexes and shortening climbing behaviour in males only. In contrast, to vehicle-treated rats, no sex differences were observed in sertraline-treated rats in any of these behavioural parameters. However, sex-differences in head swinging behaviour, which is unaffected by sertraline treatment, were still observed in sertraline-treated rats.ConclusionsFemales appear more vulnerable than males to the FST, but the post-treatment organisation of FST behaviour is not sex-differentiated. Antidepressants seem to modulate the behavioural response in FST in a sex-specific way, due to sex differences in baseline FST performance. Consequently, the sex-differentiated stress response profile during FST is attenuated by antidepressant treatment.
Genetic addiction risk score analysis: hypodopaminergic polymorphic risk alleles in polydrug addicted males and meso-limbic dopaminergic agonistic activation by neuroadaptagen amino-acid therapy
Authors: Blum K. , Stice E. , Liu Y. , Giordano J. , Morse S. , Bailey J.A. , Thompson J. , Smolen A. , Oscar-Berman M. , Bowirrat A. , Allen C. , Manka M. , Downs B.W. , Fonari F. , Tan J. , Damle U.J. , Braverman E.R. 
Published: May 2011

IntroductionThere is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to chemical dependency programs.MethodsThe prevalence of seven risk alleles (DRD2 = A1; SLC6A3 (DAT) = 10R; DRD4 = 3R or 7R; 5HTTLPR = L or LA; MAO = 3R; COMT = G) and corresponding severity risk score (Low (LS) = 1–36%, moderate (MS) = 37–50%, and high (HS) = 51–100%) were calculated. Group 1 consisted of 16 Caucasian male psycho-stimulant addicts, and Group 2 consisted of 10 Chinese male heroin addicts (9 were genotyped). qEEG and fMRI visualized the impact of Neuroadaptagen Amino-Acid Therapy complex on mesolimbic system activation.Results[Findings by Group]74% of the combined groups had a moderate to high genetic addiction risk score (GARS). One acute dose of KB220-IV variant in heroin addicts having brain abnormalities was found to normalize qEEG. Additionally, a randomized double-blind placebo controlled study involving oral KB220-Z variant established qEEG normalization of reward circuitry in abstinent psycho-stimulant abusers (P < 0.03).ConclusionsWe cautiously suggest that long-term activation of dopaminergic receptors will lead to D2 receptor proliferation and enhanced “dopamine sensitivity,” thus reducing aberrant craving behavior especially in carriers of the DRD2 A1 allele. Although supported by 20 clinical trials, KB220-Z awaits PET scanning to determine its chronic effects on D2 receptor numbers.
BDNF and DISC1 are associated with cognitive dysfunction but not with schizophrenia in a hungarian sample
Authors: Farkas K. , Réthelyi J. , Polgár P. , Benkovits J. , Fábián Á. , Czobor P. , Bitter I. 
Published: May 2011

IntroductionPrevious studies have found association between several schizophrenia candidate genes and neurocognition in schizophrenia patients and healthy individuals. Both brain-derived neurotrophic factor (BDNF) and disrupted in schizophrenia 1 (DISC1) are important for neurodevelopmental processes and have been implicated as schizophrenia candidate genes, as well as genes influencing neurocognition.Objectives and aimsTo test for the previously described association of these genes with schizophrenia and neurocognition.MethodsDNA samples from a homogeneous sample of 280 schizophrenia patients and 230 healthy controls were genotyped for polymorphisms in schizophrenia candidate genes DISC1 (rs821597 and rs821616) and BDNF (rs6265). Clinical assessment was performed using the Schedule for Deficit Syndrome and the Positive and Negative Symptom Scale. Neurocognitive functioning was assessed in a subsample of 263 patients and 135 healthy controls by a comprehensive neuropsychological test-battery. Based on the raw neuropsychological measures we calculated a global index of cognitive impairment and domain-specific composite z-scores. Association between the above composite scores and the SNPs was examined using GLM and GENMOD analysis.ResultsThe investigated SNPs were not associated with schizophrenia, nor with the deficit or non-deficit subgroups. However we found significant association between global cognitive impairment and rs821616 in DISC1 (F = 3.02, p = 0.05) and rs6265 in BDNF (F = 4.47, p = 0.01); moreover rs6265 was associated with working memory (F = 6.22, p = 0.002) and attention (F = 7.27, p = 0.0074)ConclusionUsing neurocognition as an endophenotype for psychotic disorders in genetic studies has the potential to determine common and separate genetic factors influencing disease risk and neurocognition.
THE -1021C/T polymorphism of the dopamine-B-hydroxylase (DBH) gene promoter affects personality traits in healthy subjects
Authors: Kamata M. , Suzuki A. , Matsumoto Y. , Shibuya N. , Togashi H. , Otani K. 
Published: May 2011

IntroductionDopamine and norepinephrine are implicated in the characterization of personality traits. Dopamine-β-hydroxylase (DBH) is the enzyme responsible for conversion of dopamine to norepinephrine. Previous studies have shown that the -1021C/T polymorphism of the DBH gene promoter influences plasma DBH activity. Few studies investigated the association between this polymorphism and personality traits.AimTo examine the association between the -1021C/T DBH polymorphism and personality traits in healthy volunteers.MethodsThe participants were 627 Japanese unrelated volunteers. The subjects with present psychiatric disorders or past history of psychiatric disorders according to the DSM-IV were excluded. The DBH genotypes were identified by a PCR-RFLP method, and personality traits were assessed by the Temperament and Character Inventory (TCI). The study protocol was approved by the Ethics Committee of Yamagata University School of Medicine, and all subjects provided written informed consent to participate.ResultsIn the two-factor analysis of covariance with the DBH genotype and sex as factors and with age as a covariate, there was no main effect of the DBH genotype on any TCI score, while the interaction between the factors was significant in harm avoidance. In the post-hoc analysis, the group with the T allele predictive of lower DBH activity had higher scores of harm avoidance than that without the T allele in females (p=0.006), but not in males.ConclusionThe present study suggests that the -1021C/T DBH polymorphism affects the personality trait of harm avoidance in healthy females.
Genetical realtions of social loneliness in geriatric patients
Authors: Kuzelova H. , Ptacek R. , Macek M. , Zukov I. , Eliasova I. 
Published: May 2011

Loneliness affects both psychical and physical health and among geriatric patients can be serious. Social loneliness, anxiety-related personality traits, risk of developing depression, alcoholism or suicidal behavior could be associated with a functional variant in the serotonin transporter. Serotonin transporter gene length polymorphism (5-HTTLPR) is associated with changes of serotonin transporter activity and is one of the major factors which contribute to the etiology of many psychiatric disorders. The aim of the study was to found possible differences in distribution of variants in two groups of geriatric patients (average age 80 years).Group of 300 probands were examined for 5-HTTLPR variants. Blood samples were randomly collected from 150 elderly males and 150 elderly females. The elderly individuals were not related and lived in the same geographic region as the control newborns and the young adults. Two groups were defined - ambulatory (apparently healthy, 65 males and 70 females) and non-ambulatory (have no people who could take care about them, having chronic diseases and depend on geriatric care, 85 males and 80 females) people. Bialelic and trialelic dividing of 5-HTTLPR was considered. Length polymorphism was analyzed (L or S variant) and single nucleotide polymorphism was detected (LA or LG variant).A significant difference was found in allele distribution of 5-HTTLPR in two groups of patients. Ambulatory group of patients had higher occurrence of L allele and also LA allele. The results of the study suggest that social loneliness may have some personality predictors that may have its genetical correlates.
Association study between glucocorticoid receptor polymorphisms and personality traits in healthy subjects
Authors: Matsumoto Y. , Suzuki A. , Shibuya N. , Sadahiro R. , Kamata M. , Goto K. , Otani K. 
Published: May 2011

AimsPrevious studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. Glucocorticoid receptor (GR) is the most important regulator of the HPA axis negative feedback system, and several polymorphisms of the GR gene are associated with altered glucocorticoid sensitivity. In the present study, we examined the associations between the GR polymorphisms and personality traits in healthy subjects.MethodsSubjects were 880 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI). Two polymorphisms of the GR gene, i.e., G/C SNP in the intron 2 (BcII polymorphism, rs41423247) and A/G SNP in the exon 9β (9β polymorphism, rs6198), were detected by a real-time PCR and cycling probe technology for SNP typing.ResultsThe genotype distributions were G/G = 614, G/C = 240, and C/C = 26 for the BcII polymorphism, and A/A = 879 and A/G = 1 for the 9β polymorphism, respectively. There were no significant associations between the BcII genotype groups in any TCI dimension score.ConclusionThe present study suggests that these two GR polymorphisms (BcII and 9β polymorphism) are not involved in the characterization of personality traits in healthy subjects.
COMT in major depression - UK candidate gene association study
Authors: Schosser A. , Ng M.Y. , Butler A.W. , Cohen-Woods S. , Craddock N. , Owen M. , Craig I. , Farmer A.E. , Lewis C.M. , McGuffin P. 
Published: May 2011

Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.
Resequencing of the GAP-43 gene reveals some rare genetic variants that may increase the genetic burden in schizophrenia
Authors: Shen Y.-C. , Chen C.-H. 
Published: May 2011

ObjectivesGrowth-associated protein 43 (GAP-43) was critical for initial establishment or reorganization of synaptic connections, a process thought to be disrupted in schizophrenia. Abnormal GAP-43 expression has been linked to this disorder in numerous postmortem brain studies. The purpose of this study was to investigate the involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia.MethodsWe searched for genetic variants in the promoter region and 3 exons (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample of Han Chinese schizophrenic patients (n = 354) and non-psychotic controls (n = 338) from Taiwan, and conducted a case-control association study.ResultsWe identified 11 common SNPs in the GAP-43 gene. SNP and haplotype-based analyses showed no association with schizophrenia. Besides, we identified 4 rare variants in 4 out of 354 patients, including 1 variant located at the promoter region, 1 synonymous and 2 missense variants located at exon 2. No rare variants were found in the control subjects. Collectively, these rare variants were significantly overrepresented in the patient group (1.1% v.s 0; p value of Fisher’s exact test = 0.02), suggesting they may increase the genetic burden in schizophrenia.ConclusionAlthough the functional significance of these rare variants remained to be characterized, our study lent support to the hypothesis of multiple rare mutations in schizophrenia, and provided genetic clues to indicate the involvement of neurodevelopment defect in this disorder.
Interaction effects between the brain-derived neurotrophic factor Val66Met polymorphism and parental rearing on personality traits in healthy subjects
Authors: Suzuki A. , Matsumoto Y. , Shibuya N. , Sadahiro R. , Kamata M. , Goto K. , Otani K. 
Published: May 2011

AimsThere is a growing body of data suggesting the gene-environment interaction in the characterization of personality traits, but variation in ordinary parental rearing among environmental factors has not been focused yet. We examined the effects of the interaction between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on personality traits.MethodsSubjects were 710 Japanese healthy volunteers. Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. Personality assessment was performed by the Temperament and Character Inventory (TCI), which has 7 dimensions, i.e., novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence. The BDNF Val66Met polymorphism was detected by the PCR-RFLP method.ResultsParental rearing has significant main effects on all TCI dimensions except novelty seeking, while no significant main effects of the BDNF genotype on the TCI scores were found. The interaction between the BDNF genotype and maternal care of the PBI had significant effects on harm avoidance and self-directedness of the TCI. Post-hoc analyses showed that decreased maternal care was correlated with increased harm avoidance and decreased self-directedness in most of the genotype groups, and for both personality traits the correlation was highest in the Met/Met genotype and lowest in the Val/Val genotype and that for the Val/Met genotype was in between the two values.ConclusionThe present study suggests that the BDNF Val66Met polymorphism moderates the effects of parenting rearing, especially maternal care, on harm avoidance and self-directedness in healthy subjects.
Clinical phenomena of Charlevoix-Saguenay ataxia in two adult brothers
Authors: Verhoeven W.M.A. , Egger J.I.M. , Ahmed A.I.A. , Kremer B.P.H. , Vermeer S. , van Warrenburg B.P.C. 
Published: May 2011

IntroductionAutosomal recessive ataxia of Charlevoix-Saguenay (ARSACS) is characterized by early onset cerebellar ataxia, lower limb spasticity, and sensorimotor axonal polyneuropathy. Early atrophy of the superior cerebellar vermis is always present. Molecular linkage analysis found that the ARSACS gene is located on chromosome 13q12. Cloning of the gene, SACS, demonstrated that it encodes the protein sacsin.ObjectivesSystematic evaluation of neurological, neuropsychiatric and neuropsychological features in two male siblings.AimsInvestigation of the putative relationship between cerebellar dysfunction and affective symptoms.MethodsDetailed neuropsychiatric and neuropsychological assessment.ResultsThe first patient, aged 55, the disease started in early infancy and a severe progressive cerebellar syndrome with spasticity of the legs and axonal polyneuropathy developed. In his brother, aged 50, the debut of neurological symptoms was in preadolescence with a less severe deterioration over time. Cognitive functioning was only marginally impaired in the latter patient, whereas behavioural aberrations were present in the first patient only. Both patients showed a reduced cognitive and emotional responsivity to environmental events leading to impairments in several areas of daily life, such as lack of effort and strategic planning, as well as impulsivity and impoverished social interaction with emotional indifference. This symptom profile typically points towards the presence of an apathy syndrome.ConclusionsIn ARSACS, in addition to the motor impairments, it may be postulated that the cerebellar cognitive affective syndrome is present. Thus, this hereditary form of ataxia may be accompanied by a series of non-motor symptoms of which motivational and affective signs dominate. \
Kleefstra syndrome: neuropsychiatric sequelae
Authors: Verhoeven W.M.A. , Kleefstra T. , Egger J.I.M. 
Published: May 2011

IntroductionSubmicroscopic deletions of the distal long arm of chromosome 9q are relatively common and give rise to a clinically recognizable phenotype referred to as the Kleefstra Syndrome [OMIM 610253]. It was shown that haploinsufficiency of the EHMT1 (Euchromatic Histone Methyltransferase 1) gene is responsible for the core phenotype by identifying cases with intragenic EHMT1 loss of function mutations. Key features of the syndrome are mental retardation, childhood hypotonia and facial dysmorphisms. Congenital heart and renal defects, microcephaly, epilepsy, and behavioural problems are frequently present.ObjectivesDescription of the developmental, behavioural and neuropsychiatric characteristics in 4 middle aged patients with recently diagnosed Kleefstra syndromeAimsContributing to the putative behavioural phenotype of Kleefstra syndrome.MethodsDetailed neuropsychiatric and neuropsychological assessment.ResultsIn the 4 patients, conventional cytogenetic investigation showed normal karyotypes. With routine subtelomeric MLPA and additional 9q regional specific MLPA tests, a submicroscopic deletion of the long arm of chromosome 9 (9q34.3) was found. Both deletions comprised the EHMT1 gene, in agreement with the diagnosis of Kleefstra syndrome. In all patients a severe apathy and a marked dyssomnia were present. Although some motor symptoms could be assessed with a catatonia rating scale, these have to be considered as a consequence of the apathy and belong therefore not to the catatonic spectrum.ConclusionsKleefstra syndrome is constituted, in addition to its distinct phenotypic features, by a specific behavioural phenotype that comprises, apart from the absence of speech development, a specific sleep disturbance and severe apathy from the third decade on.
Behavioural phenotype of noonan syndrome in adulthood
Authors: Wingbermuehle E. , Egger J.I.M. , van der Burgt I. , Verhoeven W.M.A. 
Published: May 2011

IntroductionNoonan syndrome (NS) is an autosomal dominant genetic disorder with an estimated incidence of 1:1,500 live births and is characterized by short stature, facial dysmorphisms and congenital heart defects. At present, mutations in seven different genes have been identified. NS is associated with impaired affective processing and subsequently increased levels of anxiety.ObjectivesNeuropsychological investigation of social cognition.AimsThe use of neuropsychological assessment as a tool for studying the contribution of cognition and behaviour to the expression of the Noonan phenotype.MethodsForty adult NS-patients and a matched group of healthy controls underwent extensive neuropsychological assessment. Next to the standard cognitive domains (i.e. intelligence, attention, memory, executive functioning) several tests for social cognition were included to explore affective information processing. Correlation analysis and repeated measures MANCOVA were used.ResultsMarked problems were found in the recognition of own and other's emotions, as well as in the ability to verbally express feelings. Alexithymia was significantly more prevalent in the NS-group. In addition, NS-patients displayed more mood and anxiety complaints than controls. A tendency was found to social desirability and agreeableness.ConclusionsImpairments in social cognition are common elements of NS behavioural phenotype in adults. With neuropsychological assessment, psychosocial immaturity, amenable traits and alexithymia could be identified. The latter increases the vulnerability for the development of mood and anxiety disorders.
TPH2 Polymorphisms and alcohol-related suicide
Authors: Videtič Paska A. , Zupanc T. , Pregelj P. , Tomori M. , Komel R. 
Published: May 2011

IntroductionSubstantial evidence from family, twin, and adoption studies corroborates implication of genetic and environmental factors, as well as their interactions, on suicidal behavior and alcoholism risk. Serotonergic disfunction seems to be involved in the pathophysiology of substance abuse, and has also an important role in suicidal behavior.ObjectivesRecent studies of the tryptophan hydroxylase 2 (TPH2) showed mild or no association with suicide and alcohol-related suicide.AimsInvestigation of the role of five single nucleotide polymorphisms (SNPs), one functional (p.Arg441His), two in intron 5 (Rs1843809, Rs1386493), and two in the 5’ regulatory promoter region (Rs4131348, Rs11178997) of TPH2, in association with suicide and alcohol-related suicide on a population with one of the highest suicide rates in the world.MethodsWe performed qRT-PCR (Real-Time Polymerase Chain Reaction) genotyping analysis of SNPs and alcohol analysis on 388 suicide victims and 227 controls.ResultsThe results showed association between suicide (P(X2) = 0.043) and alcohol-related suicide (P(X2) = 0.021) for SNP Rs1843809. A tendency for association was determined also for polymorphism Rs1386493 (P(X2) = 0.055) and alcohol-related suicide. Data acquired from psychological autopsies in a subsample of suicide victims (n = 79) determined more impulsive behavior (P(X2) = 0.016) and verbal aggressive behavior (P(X2) = 0.025) in the subgroup with alcohol misuse or dependency.ConclusionsOur results suggest implication of polymorphisms in suicide and alcohol-related suicide, but further studies are needed to clarify the interplay among serotonergic system disfunction, suicide, alcohol dependence, impulsivity and the role of TPH2 enzyme.