Environmental Factors Influence Language Development in Children with Autism Spectrum Disorders

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Is Ankyrin a genetic risk factor for psychiatric phenotypes?

Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases

Transplacental Passage of Interleukins 4 and 13?

The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Die selbstquälerische Depression: eine Form monopolarer endogener Depression

Anhand von drei exemplarischen fällen wird. das Krankheitsbild der selbstquälerischen Depression, eine Form der reinen Depressionen Leonhards, dargestellt. Im Zentrum stehen die Ideen der Selbsterniedrigung und Selbstentwertung und der sich daran entwickelnde ängstlich-depressive Affekt. Charakteristisch ist auch die Angst um die nächsten Angehörigen. In ihren Selbstanklagen erwarten und fordern die Patienten für sich die schrecklichsten Strafen. Diese wenigen Leitsymptome kehren in jeder Krankheitsphase gleichförmig wieder. Andere depressive Symptome wie Denkhemmung und psychomotorische Hemmung treten dagegen völlig in den Hintergrund. Der Krankheitsverlauf ist streng monopolar. Die Dauer der Krankheitsphasen wurde von Leonhard mit durchschnittlich 5,8 Monaten angegeben. Sie betrug bei unseren Patienten durchschnittlich 4,1 Monate. Das klinische Erscheinungsbild ist durch moderne Behandlungsstrategien nicht wesentlich zu beeinflussen. Eine familiäre Belastung mit affektiven Psychosen findet sich nur sehr selten.Three ease reports will be used to describe the self-torturing depression, one form of Leonhard's monopolar depressive disorders. The main symptomatology consists of marked feelings of guilt, as weil as ideas of self-abasement and self-depreciation. The severe anxious-depressive affect developes on the grounds of these symptoms. Worries of the patients about their family are also characteristic. Excessive self-reproach results in the expectation of and demand for heaviest punishment. These symptoms repeatedly occur during each episode. Other depressive symptoms like inhibited thinking and motor retardation are lacking. The course of the disease is strictly monopolar. In Leonhard's original description the mean duration of the episodes was found to be 5.8 months. We noticed a mean duration of 25 episodes of 4.1 months. The clinical manifestation of the episodes can only insignificantly be influenced by modern therapy. There is little evidence for familial loading with affective psychoses

Schwangerschafts- und Geburtskomplikationen - ihr Stellenwert in der Entstehung schizophrener Psychosen

In a retrospective study of 80 chronic DSM 111-R schizophrenics and 80 controls, the occurrence of obstetric complications (OCs) into the development of chronic schizophrenias was investigated using Leonhard s distinction in systematic schizophrenia (no obvious familial loading) and unsystematic schizophrenia (mainly genetically determined according to Leonhard). The Lewis & Murray and Fuchs scales were used for evaluation. In both scales, unsystematic schizophrenias did not differ from controls, but those with OCs were significantly (p < 0.01) earlier hospitalized (20.5 years) than those without OCs (25.6 years). Systematic schizophrenics had an increased frequency, severity and total score of OCs compared to controls in the Fuchs scale (p < 0.0 I). Likewise, in the Lewis & Murray scale systematic schizophrenia showed an increased presence ofOCs compared to controls (p < 0.05) and to unsystematic schizophrenia (p < 0.1 ). Systematic schizophrenias were significantly allocated to matemal infectious diseases during mid-gestation. Patients with matemal infections showed moreadditional OCs than those without (p < 0.05; Lewis & Murray scale). In systematic schizophrenia, a history of OC was not associated with an early onset of the disease. In the genetic determined schizophrenias prenatal and perinatal disturbanccs Iead to an early onset of the disease, however, in systematic schizophrenias they seem to be of causal importance for the development of the disease.Auf der Grundlage von Leonhards Unterteilung in systematische Schizophrenien (niedriges genetisches Risiko) und unsystematische Schizophrenien (nach Leonhardr Befunden hauptsächlich genetisch determiniert) wurden in einer retrospektiven Studie bei 80 Patienten mit chronischen DSM 111-R Schizophrenien und 80 Kontrollen die Häufigkeit von Schwangerschafts- und Geburtskomplikationen untersucht. Zur Auswertung wurden die Skalen von Lewis & Murray sowie von Fuchs verwandt. Unsystematische Schizophrenien unterschieden sich in beiden Skalen nicht von den Kontrollen. Diejenigen mit Komplikationen wurden jedoch signifikant früher als diejenigen ohne Komplikationen ersthospitalisiert (p < 0,01 ). Bei systematischen Schizophrenen waren in ; der Skala von Fuchs Häufigkeit, Schweregrad sowie der Summenwert der Komplikationen gegenüber den Kontrollen erhöht (p < 0,0 I). Auch in der Skala von Lewis & Murray traten häufiger obstetrische Komplikationen auf als bei Kontrollen (p < 0,05) und unsystematischen Schizophrenen (p < 0,1 ). Systematische Schizophrenien waren auch assoziiert mit Schwangerschaftsinfektionen im zweiten Trimenon. Mütter mit Schwangerschaftsinfektionen zeigten gehäuft weitere perinatala Komplikationen (p < 0,05). Geburtskomplikationen hatten bei systematischen Schizophrenen jedoch keinen Einfluß auf den Zeitpunkt des Krankheitsbeginns. Während pdi und perinatale Störungen bei genetisch determinierten Schizophrenien lediglich einen frühen Krankheitsbeginn bewirken, scheinen sie bei den systematischen Schizophrenien von ursächlicher Bedeutung fiir die Krankheitsentstehung zu sein

Die frühkindliche Form einer negativistischen Katatonie

Es wird ein Krankheitsbild negativistischer Katatonie nach Leonhard mit nachweislichem Beginn in der frühen Kindheit beschrieben. Dieses zeichnet sich durch Negativismus, negativistische Erregungen mit (Auto)aggressivität und triebhaften Durchbrüchen aus. Die expressive Sprachentwicklung fehlt oder sie bleibt auf dem erreichten Entwicklungsstand stehen. Die körperliche Gesamtreifung ist retardiert. Zumeist nicht als frühkindliche Katatonien erkannt, werden diese Krankheiten fälschlich als "Schwachsinn bei frühkindlichem Hirnschaden" oder unspezifisch als "tiefgreifende Entwicklungsstörung" (DSM III-R, ICD 10) diagnostiziert.In a case report the clinical manifestation of negativistic catatonia with its modified symptomatology by first onset in early childhood is presented. The symptomatology consists of negativism, negativistic excitations with (auto)aggressivity and impulsive behaviour. Development of expressive language is lacking or is arrested. Physical development is retarded. These conditions are seldom recognized but diagnosed as organic brain syndrome or more unspecifically as "pervasive developmental disorder" (DSM III-R, ICD 10)