Bruno Pfuhlmann

Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses

In the recent years, elevated homocysteine plasma levels have been reported to represent a risk factor not only for atherosclerosis, but also to be associated with dementia, depression and-in a gender-specific manner-schizophrenia. Here, we explored a possible association between homocysteinemia and psychiatric disorders. Fasting homocysteine, vitamin B12 and folate were determined in an ethnically homogeneous female population with different psychiatric disorders. Homocysteine was not elevated in females suffering from schizophrenia (mean, 11.6+/-5.8 micromol/l). As shown previously, increased homocysteine concentrations were associated not only with dementia of different aetiology (mean, 17.2+/-6.7 micromol/l; chi2=23.39, p<0.001, compared to the schizophrenia group), but also with depressive disorders (mean, 12.9+/-3.8 micromol/l; chi2=6.88, p=0.009). B12 and folate levels did not differ between different diagnostic groups. To further explore the connection between homocysteinemia and affective psychoses, a case-control study examining the C677T and the A1298C variants of methylenetetrahydrofolate reductase was conducted. The latter polymorphism not only was associated with affective psychoses in general, but also when divided in unipolar depression and bipolar affective disorder. In conclusion, we suggest that in females homocysteinemia is an unspecific risk factor for organic brain disorders like dementia, and possibly depression, but not for schizophrenia.

The different conceptions of catatonia: historical overview and critical discussion.

Abstract The present article outlines the different conception of catatonia from its initial description by Kahlbaum to current viewpoints. Originally considered to be an independent disease entity characterized by mental and motor abnormalities, catatonia was later viewed as a subtype of schizophrenia as it is the case in current classifications like ICD-10 and DSM-IV. Since catatonic symptoms were observable not only in schizophrenic psychoses, but also in affective, somatic or even psychogenic disorders, many researchers today consider catatonia as a nosologically unspecific syndrome. In the end, the traditional conceptions did not succeed in defining catatonia as a clinically homogeneous and valid diagnosis. An independent conception was elaborated by the Wernicke-Kleist-Leonhard school of psychiatry. Based on a precise differentiation of psychomotor disturbances, two essentially different forms of catatonic psychoses have been separated, systematic and periodic catatonias which differ in symptomatology, prognosis and treatment.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Authors C. Hiemke1, 2, N. Bergemann3, H. W. Clement4, A. Conca5, J. Deckert6, K. Domschke7, G. Eckermann8, K. Egberts9, M. Gerlach9, C. Greiner10, G. Gründer11, E. Haen12, U. Havemann-Reinecke13, G. Hefner14, R. Helmer15, G. Janssen16, E. Jaquenoud17, G. Laux18, T. Messer19, R. Mössner20, M. J. Müller21, M. Paulzen11, B. Pfuhlmann22, P. Riederer6, A. Saria23, B. Schoppek24, G. Schoretsanitis25, M. Schwarz26, M. Silva Gracia12, B. Stegmann12, W. Steimer27, J. C. Stingl10, M. Uhr28, S. Ulrich29, S. Unterecker6, R. Waschgler30, G. Zernig23, 31, G. Zurek32, P. Baumann33

ZDHHC8 as a candidate gene for schizophrenia: Analysis of a putative functional intronic marker in case-control and family-based association studies

BackgroundThe chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia.MethodsGiven the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186).ResultsIn the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity χ2 = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions.ConclusionThe findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.

Susceptibility to neuroleptic-induced parkinsonism: age and increased substantia nigra echogenicity as putative risk factors

OBJECTIVE Patients treated by neuroleptics often develop neuroleptic-induced parkinsonism (NIP) to a varying extent. The reasons for this are discussed controversially in the literature. Previous transcranial sonography (TCS) findings of the substantia nigra (SN) in patients with idiopathic Parkinsons disease suggest a correlation of echogenicity with nigrostriatal dysfunction. METHOD One hundred psychiatric patients receiving neuroleptics were included. They underwent clinical examination for NIP (Simpson and Angus-scale) and, independently, TCS of the SN. History of smoking habits and medication were taken from the patients chart. RESULTS We found a significant positive association of the prevalence of NIP with age (P < 0.01) and the echogenic area of the SN (P < 0.05). Neither type nor dosage of the neuroleptics was found to have any significant impact on the occurrence of NIP. Smokers displayed lower prevalence of NIP (P < 0.05) and lower EPS scores (P < 0.01). CONCLUSIONS These findings suggest that age and increased size of SN echogenicity are possible risk factors for NIP. In contrast, smoking seems to have a certain protecting effect.

On interrater reliability for Leonhard's classification of endogenous psychoses

Twenty-two patients with a diagnosis of schizophrenia according to DSM-III-R and ICD-10 criteria, for whom the long-term courses of illness were all well documented, were classified by 4 independent investigators using Leonhards classification of endogenous psychoses. With regard to the large nosological groups of cycloid psychoses (including the subtypes of anxiety-happiness psychosis, confusional psychosis and motility psychosis), of unsystematic schizophrenias (including the subtypes of affect-laden paraphrenia, cataphasia and periodic catatonia), and of systematic schizophrenias (divided into systematic catatonias, systematic paraphrenias, and hebephrenias), is was possible to reach a high level of agreement in the diagnosis, representing a Cohen kappa coefficient of 0.82 and 0.89, respectively. In only 2 out of 22 patients were discrepancies observed in the assignment to the above-mentioned groups. This clearly shows the high reliability of Leonhards classification, which allows a differentiated diagnostic and prognostic judgement of schizophrenic psychoses according to the DSM-III-R and ICD-10.

Correlation of QTc interval prolongation and serum level of citalopram after intoxication--a case report.

Citalopram (CIT) is a widely used antidepressant which acts by a selective serotonin reuptake inhibition. It is considered to be safer than tricyclic antidepressants at therapeutic levels, but also with respect to intoxications. We report the case of a 46-year-old woman, who ingested in suicidal intention 1400 mg CIT. During the following inpatient treatment repeatedly ECGs and determinations of the serum level of CIT were performed. Initially the patients serum level of CIT was 1231 ng/mL and QTc interval was 541.60 ms. It took 12 days until the serum level of CIT fell below the upper threshold of the recommended therapeutic range (130 ng/mL). The QTc interval on the sixth day after the intoxication for the first time was below 500 ms. The QTc interval correlated significantly with the serum level of CIT after intoxication (r=0.943; p<0.005). Although CIT is estimated as a safe antidepressant regarding serious adverse effects, toxic doses can lead to potentially hazardous ECG changes which according to our findings correlate strongly with the serum level of the drug.

The influence of smoking on the serum level of duloxetine.

Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high performance liquid chromatography (HPLC). The mean serum levels in 28 patients at the time of the first TDM analysis were 52.0+/-67 ng/mL. Eight of the patients were smokers and showed a considerably lower serum level of 24.3+/-18.8 ng/mL. In the further course of treatment the difference was compensated by application of higher doses in smokers. These findings suggest that smoking is associated with lower duloxetine serum levels due to an induction of CYP1A2 by polycylic hydrocarbons which are contained in tobacco smoke. Therefore in smokers higher doses of duloxetine (about 15%) seem to be necessary to reach adequate serum levels.

Is Ankyrin a genetic risk factor for psychiatric phenotypes

BackgroundGenome 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.MethodsWe 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 Leonhards classification featuring disease entities with specific combination of bipolar and psychotic syndromes.ResultsWe 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 Leonhards classification.ConclusionOur 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.

Long-Term Course and Outcome of Severe Postpartum Psychiatric Disorders

Thirty-nine women who had suffered from a severe first-episode postpartum psychiatric illness were re-examined after a period of 6–26 years (averaging 12.5 years). Diagnoses were established according to ICD-10 and Leonhard’s classification, revealing a marked predominance of cycloid psychoses (54%) according to Leonhard. There was no evidence of the nosological independence of postpartum psychosis. Only 4 patients (10%) had never recovered fully since the onset of the illness. In contrast, 6 patients had undergone a monophasic course without any further psychopathology. In 20 cases (51%) the illness had run a multiphasic course. The average number of episodes per patient was 2.5 (range 2–6). The course was not determinable in 4 patients (10%). Nineteen women (49%) had 22 further deliveries after the first manifestation of the illness. The frequency of a relapse in connection with further pregnancy or delivery was 50%. Applying the Strauss-Carpenter Outcome Scale, we found a favourable outcome for the total sample with a mean value of 14.1 (SD = 2.6). The vast majority of patients (75%) showed no persistent alterations. Our findings provide further evidence of a favourable prognosis of severe postpartum psychiatric disorder despite the remarkably high rate of puerperal relapses.