Modification of Cognitive Performance in Schizophrenia by Complexin 2 Gene Polymorphisms

Begemann, Martin; Grube, Sabrina; Papiol, Sergi; Malzahn, Dörthe; Krampe, Henning; Ribbe, Katja; Friedrichs, Heidi; Radyushkin, Konstantin; El-Kordi, Ahmed; Benseler, Fritz; Hannke, Kathrin; Sperling, Swetlana; Schwerdtfeger, Dayana; Thanhäuser, Ivonne; Gerchen, Martin Fungisai; Ghorbani, Mohammad; Gutwinski, Stefan; Hilmes, Constanze; Leppert, Richard; Ronnenberg, Anja; Sowislo, Julia F.; Stawicki, Sabina; Stödtke, Maren; Szuszies, Christoph; Reim, Kerstin; Riggert, Joachim; Eckstein, Fritz; Falkai, Peter; Bickeböller, Heike; Nave, Klaus‐Armin; Brose, Nils; Ehrenreich, Hannelore

doi:10.1001/archgenpsychiatry.2010.107

Cited by 89 publications

(117 citation statements)

References 73 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Regarding the discovery sample (total of N = 2,495), subject selection was unbiased, that is, sera collection was concluded before specific serological analysis was planned: Schizophrenic patients (N = 1,076) were recruited between 2005 and 2011 at 23 German sites for the Göttin-gen Research Association for Schizophrenia (GRAS) data collection. Patients fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (11) criteria for schizophrenia (81.4%) or schizoaffective disorder (18.6%) were included regardless of disease stage (8,12). Healthy GRAS controls were anonymized blood donors (N = 1,271; Transfusion Medicine, Göttingen, Department of Transfusion Medicine, University Medicine of Göttingen).…”

Section: Participantsmentioning

confidence: 99%

“…Of all schizophrenic (GRAS) patients, extensive phenotypical characterization was conducted as referenced previously (8,12). Age of onset, age at first psychotic episode, positive and negative syndrome scale (PANSS) scores, chlorpromazine equivalents (CPZ), neurological symptoms (Cambridge Neurological Inventory [CNI]) including fine motor skills (MacQuarrie dotting/tapping), current cognitive functioning (composite score comprising reasoning, executive function, verbal learning and memory), global assessment of functioning (GAF), Parkinsonism, hard neurological signs, motor coordination, sensory integration and gait were employed as disease characteristics.…”

Section: Phenotypical Analysesmentioning

confidence: 99%

See 1 more Smart Citation

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Hammer

Wanitchakool

Sirianant

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding Cl -channels and phospholipid scram-

show abstract

Section: Participantsmentioning

confidence: 99%

Section: Phenotypical Analysesmentioning

confidence: 99%

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Hammer

Wanitchakool

Sirianant

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Complexins are conserved in invertebrates, which usually also express soluble and membrane-anchored forms (5,6). In human patients, significant evidence links complexin expression to schizophrenia, although it is unclear whether the observed changes are cause or consequence of the disorder (7)(8)(9)(10).…”

mentioning

confidence: 99%

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Yang

Cao

Südhof

2013

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

Complexin, a presynaptic protein that avidly binds to assembled SNARE complexes, is widely acknowledged to activate Ca 2+ -triggered exocytosis. In addition, studies of invertebrate complexin mutants and of mouse neurons with a double knockdown (DKD) of complexin-1 and -2 suggested that complexin maintains the readily releasable pool (RRP) of vesicles and clamps spontaneous exocytosis. In contrast, studies of mouse neurons with a double knockout (DKO) of complexin-1 and -2, largely carried out in hippocampal autapses, did not detect changes in the RRP size or in spontaneous exocytosis. To clarify complexin function, we here directly compared in two different preparations, cultured cortical and olfactory bulb neurons, the phenotypes of complexin DKD and DKO neurons. We find that complexin-deficient DKD and DKO neurons invariably exhibit a ∼50% decrease in vesicle priming. Moreover, the DKD consistently increased spontaneous exocytosis, but the DKO did so in cortical but not olfactory bulb neurons. Furthermore, the complexin DKD but not the complexin DKO caused a compensatory increase in complexin-3 and -4 mRNA levels; overexpression of complexin-3 but not complexin-1 increased spontaneous exocytosis. Complexin-3 but not complexin-1 contains a C-terminal lipid anchor attaching it to the plasma membrane; addition of a similar lipid anchor to complexin-1 converted complexin-1 from a clamp into an activator of spontaneous exocytosis. Viewed together, our data suggest that complexin generally functions in priming and Ca 2+ triggering of exocytosis, and additionally contributes to the control of spontaneous exocytosis dependent on the developmental history of a neuron and on the subcellular localization of the complexin. synaptic transmission | neurotransmitter release | synaptotagmin | SNARE protein | membrane fusion

show abstract

“…The schizophrenic patient sample (n = 1,086) was recruited across 23 sites throughout Germany in the cross-sectional GRAS study and most comprehensively phenotyped (31,32). The study was approved by the Ethics Committee of the GeorgAugust-University (Göttingen, Germany) and the review boards of participating centers and complies with the Declaration of Helsinki.…”

Section: Human Samplementioning

confidence: 99%

“…To explore the function of Baiap3, we combined the behavioral analysis of Baiap3 knockout (KO) mice with a phenotype-based genetic association study (PGAS) of the human BAIAP3 gene by using the Göttingen Research Association for Schizophrenia (GRAS) database (31,32). Using this two-pronged approach, we identify Baiap3/BAIAP3 as the first genetic risk marker for anxiety and benzodiazepine abuse in both mice and humans.…”

Section: Introductionmentioning

confidence: 99%

Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

Wojcik

Tantra

Stepniak

et al. 2013

Mol Med

Self Cite

View full text Add to dashboard Cite

Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders.

show abstract

Modification of Cognitive Performance in Schizophrenia by Complexin 2 Gene Polymorphisms

Abstract: The PGAS allows identification of marker-associated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression.

Cited by 89 publications

References 73 publications

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

Contact Info

Product

Resources

About

Modification of Cognitive Performance in Schizophrenia by Complexin 2 Gene Polymorphisms

Abstract: The PGAS allows identification of marker-associated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression.

Cited by 89 publications

References 73 publications

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Deconstructing complexin function in activating and clamping Ca 2+ -triggered exocytosis by comparing knockout and knockdown phenotypes

Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

Contact Info

Product

Resources

About

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes