Albert Putzhammer

Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: A generalization of Steen's study on DRD3 and tardive dyskinesia

Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug-induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.

Comorbidity of Alcohol Dependence With Attention-Deficit Hyperactivity Disorder: Differences in Phenotype With Increased Severity of the Substance Disorder, but Not in Genotype (Serotonin Transporter and 5-Hydroxytryptamine-2c Receptor)

BACKGROUND Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. METHODS We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. RESULTS There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. CONCLUSIONS Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Cerebrospinal fluid tau and β-amyloid in Alzheimer patients, disease controls and an age-matched random sample

We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)-beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p-tau181) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimers disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N=219). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%, tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181 (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics.

Association of the −141C Del variant of the dopamine D2 receptor (DRD2) with positive family history and suicidality in German alcoholics

Several lines of evidence indicate an involvement of the dopaminergic system in alcoholism, withdrawal, suicidality, and attention‐deficit hyperactivity disorder (ADHD). The functionally relevant −141C Ins/Del polymorphism located upstream to exon 1 in the 5′‐region of the dopamine D2 receptor (DRD2) gene might be an interesting candidate gene. We investigated a sample of 1,126 well‐characterized, primary chronic alcoholics of German descent according to a phenotype–genotype strategy, i.e., alcoholics suffering from severe withdrawal complications such as seizure or delirium, family history positive (FH+) alcoholics, alcoholics with an antisocial personality disorder (ASPD), alcoholics with an ADHD, and type 1 or type 2 alcoholics according to Cloningers typology. Compared to the control subjects, there was a significant excess of the −141C Del allele in alcoholics with a paternal and grandpaternal history of alcoholism and in alcoholic subgroups with suicidality or without a history of withdrawal symptoms. There were no significant differences in allele frequency between the entire group or subgroups of alcoholics and healthy controls. Therefore, the −141C Del variant of the DRD2 might be a protective factor against the development of withdrawal symptoms. However, it might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and it might contribute to the substantially higher likelihood of suicide in alcoholics.

Spatial and temporal parameters of gait disturbances in schizophrenic patients

This study assessed the locomotor patterns of gait in schizophrenic patients and differentiated intrinsic effects of the illness from those caused by conventional and atypical neuroleptic treatment. Gait parameters of drug-naïve, conventionally and atypically treated patients as well as control subjects were evaluated. Differences in gait velocity and in stride length between the four investigated groups were highly significant (ANOVA: p<0.001). Mean gait velocities of all patient groups were significantly slower than those of controls, with the most striking difference observed between the control group and patients treated with conventional neuroleptics (p <0.001). Amongst the patient groups, significant differences were detected between patients treated with conventional neuroleptics and both patients treated with atypical neuroleptics and drug-naïve patients (p < 0.05), but not between untreated and atypically treated patients. In all patient groups the reduction of gait velocity was due to a smaller mean stride length, while the cadence (steps per minute) was not changed. These results indicate that schizophrenia causes a primary disturbance of stride length regulation. Conventional antipsychotic treatment intensifies this deficit, whereas atypical antipsychotic treatment does not cause any additional gait disturbances. In contrast to the spatial parameters, the temporal structure of schizophrenic gait is not affected either by antipsychotic treatment or schizophrenia itself.

Evidence of a role for the 5-HTTLPR genotype in the modulation of motor response to antidepressant treatment.

RationaleSerotonergic mechanisms are thought to play an important role in the regulation of mood, motor activity and sleep patterns. Serotonin reuptake is controlled by the serotonin transporter (5-HTT) and by a common functional insertion/deletion polymorphism in the corresponding gene’s promoter region (5-HTTLPR). Homozygosity for the long variant may confer a favourable response to treatment with serotonin reuptake inhibitors (SSRIs), and to sleep deprivation.ObjectivesThe study assessed the role of the 5-HTTLPR genotype in determining motor side effects of antidepressant medication.MethodsMotor activity patterns of 62 patients with major depression who were being treated with either SSRIs or tricyclic antidepressants (TCAs) were monitored over a 24-h period using a wrist-actograph. Additionally, motor activity was rated in a semi-structured interview using the motor agitation and retardation scale (MARS).ResultsNight-time motor activity was significantly increased in homozygous carriers of the long 5-HTTLPR allele (LL-genotype) who were being treated with SSRIs in comparison to short allele carriers (LS-genotype and SS-genotype), regardless of the type of antidepressant treatment (P<0.001). It was also significantly increased in comparison to patients with the LL-genotype who were being treated with TCAs (P<0.01). Differences in actographic motor activity were most prominent between 11 p.m. and 4 a.m. Clinical ratings of motor activity also showed a trend toward higher agitation scores in patients with the LL-genotype who received SSRI treatment.ConclusionsHomozygosity for the long variant of the 5-HTTLPR may cause a predisposition to increased night-time motor activity in conjunction with SSRI treatment.

Gait disturbances in patients with schizophrenia and adaptation to treadmill walking

Abstract  This study evaluated the gait patterns of schizophrenic patients at free gait and at three fixed velocities on a treadmill. The effects of illness and antipsychotic treatment on gait parameters and on adaptation to treadmill walking were compared. Gait parameters of 14 drug‐naïve schizophrenic patients, 14 patients treated with conventional antipsychotics, 14 patients treated with olanzapine, as well as 14 matched controls were assessed on a walkway and on a treadmill at three different velocities (very slow, intermediately slow, and comfortable) using an ultrasonic movement analysis system. At free gait, all patients showed a significantly decreased gait velocity, predominantly due to a shorter stride length, when compared to the controls, with the most striking difference observed between the patients treated with conventional neuroleptics and the controls (anova, P ≤ 0.001). Cadence (steps per second) did not differ between the investigated groups. When gait was evaluated on the treadmill, differences in stride length and cadence were significant only at the very slow treadmill velocity (anova, P ≤ 0.05). In all patient groups, mean stride length was decreased and cadence compensationally increased. Significant differences between the patient groups were no longer detectable. With increasing treadmill velocities, gait parameters of all patient groups normalized. The results show that, like in patients with Parkinsons Disease, impaired gait parameters can also be normalized in schizophrenic patients by external stimulation via treadmill walking.

[The work of medical doctors on psychiatric wards: an analysis of everyday activities].

Die ökonomische Situation der psychiatrischen Kliniken war in den vergangenen Jahren starken Veränderungen unterworfen. Während die stationäre Verweildauer der Patienten kontinuierlich abund die Zahl der behandelten Fälle zunahm, mussten viele Kliniken wegen der angespannten fi nanziellen Lage Stellen beim therapeutisch tätigen Personal abbauen. Die in der Psychiatrie-Personalverordnung (PsychPV) formulierten Anforderungen an eine für die individuelle patientenorientierte Versorgung notwendige Personalausstattung werden häufi g nicht mehr erfüllt. Die vorliegende Studie untersucht die aus diesen Entwicklungen entstehenden Folgen für die ärztliche Tätigkeit. Dazu wurde auf insgesamt 16 allgemeinpsychiatrischen Stationen in vier Versor-

Die Entwicklung von Betreuungs- und Unterbringungsmaßnahmen in einer bayerischen Versorgungsregion im Vergleich zum Bundes- und Landestrend für den Zeitraum von 1999–2009

OBJECTIVE In this study trends in legal guardianship and involuntary treatment in a Bavarian catchment area in comparison to trends at federal state and federal level between 1999 and 2009 will be examined. METHODS Data from the federal department of justice, from the federal health monitoring system and data from a district court were used to compute rates, quotas and quotients. Regression analyses were conducted to analyse associations between time series. RESULTS In comparison to the federal state and the federal level the target region shows a significantly higher rate of new guardianships but a lower rate of judicial ordered mobility restrictions and at least in comparison to the federal state level a significantly lower rate of involuntary admissions according to guardianship law. CONCLUSIONS The obtained differences indicate significant differences in the legal guardianship and involuntary admission practise which cannot be explained by epidemiological developments. Therefore it is necessary to investigate potential socio-cultural and socioeconomic sources for these varieties.

Präsenile Demenz bei polyzystischer lipomembranöser Osteodysplasie

ZusammenfassungWir berichten über den ersten Fall von polyzystischer lipomembranöser Osteodysplasie oder “brain, bone and fat disease” in Deutschland. Die nach dem Erstbeschreibern auch als Morbus Järvi-Hakola-Nasu bezeichnete Erkrankung ist bisher vor allem in Japan und in Finnland beschrieben worden. Einzelne Fälle wurden aus Schweden, Norwegen, Italien, Südafrika, Belgien und den USA berichtet. Im deutschsprachigen Raum ist bisher ein Fall aus Ö veröffentlicht worden.SummaryWe present a 36-year-old woman with a 3-year history of cognitive decline followed by development of a small stepped gait and urinary and fecal incontinence. Workup revealed multiple bone cysts documented by X-ray and idiopathic hyperprolactinoma. An MRI confirmed the CT finding of massive bilateral basal ganglia calcification. This is the first case of polycystic lipomembranous osteodysplasia described in Germany. We conclude that patients with presenile dementia, psychosis, or early-onset Parkinsonism associated with basal ganglia calcification should undergo X-rays of hand and feet to rule out polycystic lipomembranous osteodysplasia.