bluuebunny/crossref_metadata_2025_split huggingface dataset:
S28-01 - Pharmacogenetics of the Metabolic Consequences of Antipsychotic Drug Treatment
Authors: Reynolds G. 
Published: June 2010

IntroductionSeveral antipsychotic drugs cause profound weight gain which can lead to further morbidity as indicated by the development of metabolic syndrome. These metabolic consequences of antipsychotic drug treatment show substantial variability between individuals, due in part to genetic factors.ObjectivesTo identify genetic polymorphisms contributing to individual variability in the metabolic consequences of antipsychotic drug treatment.MethodsCommon functional polymorphisms in several candidate genes implicated in the control of body weight have been investigated for association with weight gain in subjects initiating antipsychotic drug treatment, and with metabolic pathology in chronic schizophrenia.ResultsIn two studies of initially drug-free patients, we reported a strong association with antipsychotic-induced weight gain of a promoter region polymorphism of the 5-HT2C receptor, which is known to influence gene expression. The gene for leptin, a hormone controlling food intake, also has a functional promoter polymorphism which is associated with antipsychotic-induced weight gain, particularly in the longer term. Both polymorphisms are associated with circulating concentrations of leptin. Findings in chronically-treated patients have revealed association of the leptin gene polymorphism with the incidence of metabolic syndrome, while we find the obesity-related FTO gene is associated with measures of obesity in these subjects, and also interacts with the 5-HT2C gene in influencing weight gain in drug-naive subjects.ConclusionsIdentifying common genetic factors associated drug-induced weight gain and its metabolic consequences may provide clues as to the underlying mechanisms as well as providing opportunities for personalized medicine in the predictive assessment of metabolic risk.
S28-03 - Pharmacogenetics of Therapy Response in Schizophrenia
Authors: Spellmann I. , Rujescu D. , Musil R. , Mayr A. , Giegling I. , Genius J. , Zill P. , Dehning S. , Hartmann A.M. , Bondy B. , Müller N. , Möller H.-J. , Riedel M. 
Published: June 2010

Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
S28-04 - Pharmacogenetics of Extrapyramidal Motor Side Effects in the Treatment of Schizophrenia
Authors: Musil R. , Rujescu D. , Spellmann I. , Mayr A. , Zill P. , Giegling I. , Bondy B. , Müller N. , Möller H.-J. , Riedel M. 
Published: June 2010

IntroductionSince the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.ObjectivesIn this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.AimsTo identify new genes and show their relevance in the treatment of schizophrenic patients.MethodsRats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.ResultsWe found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.ConclusionsWe could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
S38-01 - The Effects of Recreational Coffee Consumption on Alcohol Withdrawal
Authors: Wiesbeck G.A. 
Published: June 2010

The vast majority of alcoholics consumes coffee as well as tobacco in addition to alcohol. The present study investigated the effects of these two psychotropic substances on the alcohol withdrawal syndrome. Therefore, personal structured interviews were performed in 128 alcohol-dependent women and men who were admitted to hospital for alcohol detoxification. They all regularly consumed tobacco and caffeinated coffee. Quantity and frequency of their consumption patterns were recorded. The severity of their alcohol withdrawal syndrome was measured using a validated scale.A multiple regression analysis revealed a significant positive correlation between quantity of alcohol and the severity of alcohol withdrawal. In addition, we could demonstrate that not only the quantity of alcohol consumed, but also tobacco and coffee consumption influenced the severity of the alcohol withdrawal syndrome. The more the patients smoked and the more coffee they drank, the less they suffered from withdrawal symptoms during alcohol detoxification.
S38-03 - Circadian Rhythmicity, ADHD and Addiction
Authors: Thome J. 
Published: June 2010

IntroductionAttention-deficit hyperactivity disorder (ADHD), specifically in adult patients, is often associated with a plethora of comorbid conditions including substance use and addiction. Interestingly, for bot conditions alterations of circadian rhythmicity have been described and variants in so-called CLOCK genes been implicated in their pathophysiology.Objectives, aims and methodsIn order to further clarify the role of CLOCK genes in these conditions, genotyping and quantitative reverse-transcriptase PCR were used to detect possible associations with CLOCK gene variants (polymorphisms) and possibly altered expression patterns of the gene products.ResultsPreliminary data suggest that certain CLOCK gene variants might be associated with both adult ADHD and addiction. Additionally, the circadian gene expression pattern in patients seems to significantly differ from that of controls.ConclusionsAlterations of CLOCK systems - on the DNA as well as the RNA level - might be a common pathophysiological phenomenon of ADHD and addiction, and represent the molecular basis for fundamental changes in circadian rhythmicity often observed on the clinical level. This may have far-reaching prognostic and therapeutic consequences.
S40-01 - Psychiatry During Pregnancy
Authors: Passov V. , Friedman C. , Passov L. , Alt J. 
Published: June 2010

1.Psychotropic medications and use of other treatment modalities for major psychiatric disorders in pregnancy. Victoria Passov, M.D.2.Chemical dependency issues in pregnancy and treatment modalities currently available. Catherine Friedman, M.D.3.Developmental outcomes on children born to mothers with psychiatric illness: complications in children of mothers who received treatment for their psychiatric conditions during pregnancy, as well as developmental and psychological consequences in kids born to untreated mothers will be discussed. Leo Passov, M.D.4.Psychology of reproductive loss and guidelines for helping families cope with the trauma of a miscarriage or stillbirth. We will discuss what makes reproductive loss unique and the physical and psychological sequelae that women experience after the loss of a pregnancy. Jennifer Alt, M.D.
S27-01 - Sleep Timing and Sleep Manipulation as Antidepressants
Authors: Wirz-Justice A. 
Published: June 2010

Disturbed sleep is an intrinsic symptom of depression and may precede or even initiate it. Thus, it is surprising that depriving a patient of sleep can induce improvement, often within hours - however usually with relapse following recovery sleep. Clinical trials of early and late partial sleep deprivation, or shifting sleep earlier, suggest a critical circadian phase where wakefulness is necessary for the antidepressant response. Combination with medication or light therapy can maintain improvement. There is now sufficient evidence for many chronotherapeutic combinations (Table) to support the use of “wake therapy” - the fastest antidepressant modality known - in general psychiatric practice (1).THERAPEUTIC RESPONSELATENCYDURATIONTotal (TSD) or partial (PSD) sleep deprivationhours∼ 1 dayPhase advance of the sleep-wake cycle∼ 2 days∼ 2 weeksTSD followed by phase advancehours∼ 2 weeksRepeated TSD or PSDhoursdays/weeksRepeated TSD or PSD + ADshoursweeks/monthsSingle or repeated TSD or PSD + light therapy; phase advance & light therapyhoursweeks/monthsSingle or repeated TSD or PSD + lithium, pindolol, or SSRIshoursmonthsLight therapy (SAD + non-seasonal MD)week(s)weeks/monthsLight therapy + SSRIs (non-seasonal MD)daysmonths[Circadian and Sleep Therapies of Major Depression]
S27-04 - Sleep Disorders, Mental Health and Quality of Life
Authors: Novak M. 
Published: June 2010

Sleep difficulties are often leading symptoms of psychiatric disorders. Furthermore, several longitudinal studies have demonstrated that untreated insomnia predicts the onset of mental health disorders. Other sleep disorders also often cause mood and/or anxiety symptoms. Furthermore, overlapping symptoms of sleep apnea, a sleep disorder with undoubted public health significance, and depression merits special attention.Sleep disorders have profound effect on daytime functioning causing daytime sleepiness, tiredness, fatigue and impaired cognitive functioning. These symptoms may severely affect both the quality of life of the patient and also the sleep and quality of life of their bedpartners and family members, as well.It is increasingly appreciated that the majority of medically ill patients suffer from sleep disorders and sleep complaints, which contribute to their impaired quality of life and clinical outcomes. “Sleep Health” is an important aspect of everyone's life but has a special relevance in mentally or medically ill patients.In our studies focusing on patients with various stages of chronic kidney disease (moderate to severe chronic renal failure, patients on dialysis and kidney transplant recipients) we have found high prevalence of sleep disorders (insomnia, Restless Legs Syndrome, Periodic Leg Movements in Sleep, Sleep apnea). We have shown that they are associated with the presence of depressive symptoms, increased illness intrusiveness and worse quality of life. Furthermore, RLS predicted mortality of kidney transplant recipients.In my presentation I will cover the most important aspects of the complex relationship between sleep disorders, mental and physical health and quality of life.
S34-01 - Gray Matter Volume in Monozygotic Twins Concordant and Discordant for Schizophrenia
Authors: Borgwardt S.J. , Picchioni M.M. , Ettinger U. , Toulopoulou T. , Murray R. , McGuire P.K. 
Published: June 2010

IntroductionAlterations in gray matter volume (GMV) are a robust feature of schizophrenia. However, it is not clear to what extent these abnormalities are correlates of the genetic liability to the disorder, as opposed to environmental factors and the disorder itself.ObjectivesWe investigated the influence of genetic risk and illness on GMV in monozygotic (MZ) twin pairs concordant and discordant for schizophrenia.MethodTotal and regional GMVs were measured from magnetic resonance images of 80 twins: 14 MZ pairs concordant for schizophrenia, 9 pairs discordant for schizophrenia, and 17 healthy MZ twin pairs. The three groups were matched for age, gender, handedness, level of education, parental socioeconomic status, and ethnicity.ResultsTotal GMV was smaller in twins with schizophrenia (t=-3.17, p= 0.003) and non-psychotic co-twins from discordant pairs (t=-2.66, p= 0.011) than in healthy control twins. Twin pairs concordant for schizophrenia displayed reduced regional GMV in the inferior frontal, medial frontal, and anterior cingulate gyri, the caudate, lingual gyrus and cerebellum relative to healthy twins (p< 0.05, corrected). Within discordant pairs, twins with schizophrenia had less GMV than their non-psychotic co-twins in the insula, superior/medial frontal, pre/postcentral, cingulate and superior temporal gyri, and the paracentral lobule. There were no significant differences in regional GMV between non-psychotic co-twins and healthy controls.ConclusionsThe presence of schizophrenia was specifically related to reduced GMV in frontal, insular, cingulate, medial parietal and temporal cortex, over and above effects of genetic risk for the disorder.
S34-03 - Iffusion Tensor Imaging Analyses of Twins with and Without Schizophrenia
Authors: Kanaan R. , Carletti F. , Picchioni M. , Kane F. , Ettinger U. , McGuire P. 
Published: June 2010

DTI studies in schizophrenia have consistently reported decreased fractional anisotropy (FA, an index of white matter microstructure) in patients. There is little evidence as to the genetic or environmental determinants of this difference however. Studies of twins with schizophrenia allow us to estimate these influences. We report a cross-sectional case control study of twins with and without schizophrenia.We recruited mono- and di-zygotic twins concordant and discordant for DSM schizophrenia from across the United Kingdom, referred by their treating psychiatrists. We recruited healthy control twins from the Institute of Psychiatry Volunteer Twin Register and by national media advertisements. Clinical diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (Spitzer and Endicott, 1978). Zygosity was confirmed by DNA analysis. Eleven pairs of monozygotic twins concordant for schizophrenia, 10 pairs of monozygotic and seven pairs of dizygotic twins discordant for schizophrenia, 24 pairs of healthy monozygotic twins and 20 pairs of healthy dizygotic twins were recruited.Subjects were scanned with an optimized DTI sequence at 1.5T. Scans were warp-corrected, masked, and FA calculated at each voxel. FA maps were then co-registered to a study-specific FA template using SPM2 and group differences calculated on segmented white-matter FA maps using non-parametric XBAM_v3.4.Results are presented of analyses comparing twins with schizophrenia with their well co-twin, linear trend analyses comparing healthy controls with well di and mono-zygotic co-twins, and a heritability analysis of the healthy controls.
S05-04 - Conceptual Aspects and Recent Data on the Prodrome to First Episode Mania
Authors: Conus P. , Ward J. , Cotton S. , Yung A.R. , Berk M. , McGorry P.D. 
Published: June 2010

BackgroundLittle is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative “high-risk” studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a subgroup of at-risk subjects.MethodsRetrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.ResultsBefore onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania.LimitationsThis is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies.ConclusionsEarly identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD may be a sign of impending first episode mania.
S31-01 - Cortex Gyrification and Auditory Hallucinations in Schizophrenia
Authors: Cachia A. 
Published: June 2010

IntroductionOne century ago, Elmer Southard investigated developmental brain lesions in schizophrenia from the analysis of cortex macroscopic anatomy. So far, a number of epidemiologic, genetic, and brain imaging studies have further supported the hypothesis that abnormal brain development could be a risk factor for schizophrenia. However, the mechanisms underlying its symptomatological expression are still debated, in particular for the auditory verbal hallucinations (AVH).Objectives and aimsBrain imaging studies in schizophrenia patients with AVH have reported both functional and anatomical deviations in language-related cortical regions but it is still unclear whether these deviations relate to neurodevelopmental impairments. We investigated the cortex gyrification in schizophrenia patients with AVH as gyrification can be considered an indirect marker of gyration and sulcation, namely the development of gyri and sulci.Methods and resultsUsing recent sophisticated computer-based morphometry methods, we detected abnormal gyrification in the language-related cortex in schizophrenia patients with persistent AVH. In addition, in comparison to healthy subjects, opposite displacements of the junction between the superior temporal sulcus and its anterior branch were found in patients with AVH heard inside the head in comparison to patients with AVH heard outside the head.ConclusionsSuch sulcal abnormalities support a neurodevelopmental component to AVH in schizophrenia. Furthermore, the “sulcal dysjunction” suggests impairments during early brain maturation, when the STS and its anterior branch appear and merge. Recent results on the genetic, neurochemical and biomechanical processes involved on the cortex gyrification will provide new insight into the pathophysiology of AVH in schizophrenia.
S03-01 - The Immunological Background of Major Depression: a Genetic Study
Authors: Claes S. , Myint A. , Domschke K. , Rothermundt M. 
Published: June 2010

Immune system dusfunction is a consistent finding in mood disorder research. One of the relevant metabolic pathways in this regard is the kynurenine pathway which forms a bridge between immune activation, serotonergic deficiency and disturbed NMDA-R function. Given the potential importance of the kynurenine pathway in the pathogenesis of MDD, a SNP based gene association analysis was undertaken, focusing on three major players in this pathway: the genes coding for Trytophan Hydroxylase 2 (neuronal THP, TPH2), Kynurenine-3-MonoOxygenase (K3MO), and Kynurenine AminoTransferase III (KATIII). In order to assess the potential role of these three genes, SNP maps covering the gene were constructed, and single SNP and haplotype association analyses were performed in a sample of 338 German patients with mood disorders and 310 control individuals matched for age, ethnicity and gender.At the single SNP level, SNP rs1053230 in the K3MO gene shows borderline significant evidence for association. Looking at the haplotype analysis (using the Plink program), the KATIII gene showed significantly different overall haplotype distributions (OMNIBUS) between patients and control individuals for all windows (p-values between 1.75 × 10−5 and 0.006). These findings were mainly due to an overrepreseantation of the CGCTCT risk haplotype, with a frequency of 7,1% in bipolar patients, 5,3% in MDD patients and 1,9% in healthy control individuals.The identification of a KATIII risk haplotype for mood disorders should be considered preliminary. A next step would be to completely sequence the KATIII promoter, exons and intron-exon-boundaries in patients carrying the risk haplotype.
S03-02 - Immune-Tryptophan Pathway Interaction: Possible Pathophysiological Role in Major Depressive Disorder
Authors: Myint A.-M. , Schwarz M. 
Published: June 2010

BackgroundThe involvement of immune mechanism in psychiatric disorders was proposed in macrophage theories of depression and schizophrenia. Later, the involvement of the inflammatory related changes beyond the cytokines including the interaction between inflammatory response system and neurotransmitters was considered in pathophysiology of neuropsychiatric disorders. The neurodegeneration hypothesis of depression stressed the importance of imbalance between the pro- and anti-inflammatory cytokines that leads to another imbalance in neuroprotective kynurenic acid arm and neurodegenerative 3-hydroxykynurenine and quinolinic acid arm of the tryptophan catabolic pathway.MethodA series of studies on human plasma and CSF changes and their associations to clinical symptoms and response to treatment and certain SNPs polymorphisms were carried out. Some studies were also done in cell culture system and post mortem morphology.ResultsIt was observed that the neuroprotective, kynurenic acid was significantly lower and one of the neurodegenerative metabolites 3-hydroxykynurenine was significantly higher in the plasma of drug naïve depressed patients. The plasma kynurenic acid concentration and neuroprotective ratio gave clear discrimination between the patients and controls with reasonable sensitivity and the specificity. The CSF findings showed similar direction. The findings were also supported by the findings from SNPs polymorphism and post-mortem studies.ConclusionThe major depressive disorder is associated with imbalanced immune-metabolic-neurochemical systems.