Biomedical subjects

Rebekka Lencer

Publications and source records attributed to Rebekka Lencer.

11 recordsLinked to original sources

PubMed2007

Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations.

OBJECTIVE: To investigate a possible association of mutations in the PTEN-induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism. METHOD: 20 members of a family (4 homozygous, 11 heterozygous and 5 non-mutation carriers) were investigated for the presence of psychiatric disorders using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); information on three additional heterozygous mutation carriers was obtained according to the family history research diagnostic criteria. RESULTS: We found predominantly affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation carriers and in 1 (20%) of the 5 mutation-negative cases. CONCLUSIONS: First, affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations. Second, patients with familial movement disorders associated with psychiatric conditions may serve as a valuable study population to explore (genetic) causes of neuropsychiatric disease.

Adult↗

PubMed2006

Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: An fMRI study.

Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM velocity is reduced. In this study we were interested in identifying the cortical mechanisms associated with extraretinal processing of SPEM in schizophrenic patients. During condition A, patients and healthy subjects had to pursue a constantly visible target (10 degrees /s). During condition B the target was blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye movement data were assessed during scanning sessions by a limbus tracker. During condition A, reduced SPEM velocity in patients was associated with reduced activation of the right ventral premotor cortex and increased activation of the left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a similar extent in both groups. While in patients a decrease in activation was observed in the right cerebellar area VIIIA, the activation of the right anterior cingulate, the right superior temporal cortex, and the bilateral frontal eye fields was increased. The results implicate that schizophrenic patients employ different strategies during SPEM both with and without target blanking than healthy subjects. These strategies predominantly involve extraretinal mechanisms.

Adult↗

PubMed2006

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive-compulsive disorder.

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.

Adult↗

PubMed2006

Clinical spectrum of homozygous and heterozygous PINK1 mutations in a large German family with Parkinson disease: role of a single hit?

BACKGROUND: Although homozygous mutations in the PTEN-induced putative kinase 1 (PINK1) gene have been unequivocally associated with early-onset Parkinson disease (PD), the role of single heterozygous PINK1 mutations is less clear. OBJECTIVE: To investigate the role of homozygous and heterozygous PINK1 mutations in a large German pedigree (family W). DESIGN: Mutation analysis of PINK1 and results of standardized neurological and motor examination by 3 independent movement disorder specialists, including blinded video rating. SETTINGS: University of Lübeck. PARTICIPANTS: Twenty family members. MAIN OUTCOME MEASURES: The PINK1 genotype and PD status of all family members. RESULTS: The index patient of family W carried a homozygous nonsense mutation (c.1366C>T; p.Q456X) and presented with a phenotype closely resembling idiopathic PD but with an onset at 39 years of age. The family included a total of 4 affected homozygous members (age, 60-71 years; age at onset, 39-61 years), 6 members with slight or mild signs of PD (affected) and a heterozygous mutation (age, 31-49 years), and 5 unaffected heterozygous mutation carriers (age, 34-44 years). Although none of the heterozygous affected family members was aware of their signs (asymptomatic), the clinical findings were unequivocal and predominantly or exclusively present on their dominant right-hand side, eg, unilaterally reduced or absent arm swing and unilateral rigidity. The heterozygous members were all considerably younger than the affected homozygous mutation carriers. CONCLUSIONS: Heterozygous PINK1 mutations may predispose to PD, as was previously suggested by the presence of dopamine hypometabolism in asymptomatic mutation carriers. Long-term follow-up of our large family W provides an excellent opportunity to further evaluate the role of single heterozygous PINK1 mutations later in life, which will have major implications on genetic counseling.

Adult↗

PubMed2005

Parametric modulation of cortical activation during smooth pursuit with and without target blanking. an fMRI study.

Smooth pursuit eye movements (SPEM) are performed to track slowly moving visual targets and are accompanied by saccades whenever foveal representation is lost. In the present study, we correlated the cerebral activation as assessed by functional magnetic resonance imaging with parameters of eye movement performance in order to determine the cortical areas involved in the retinal and extraretinal processing of maintaining smooth pursuit velocity (SPV) and generating saccades in 16 healthy males. The stimulus consisted of a target moving at a constant velocity of 10 degrees/s with and without target blanking. During constant target presentation, SPV was positively correlated with the BOLD signal in the right V5 complex and negatively correlated with the BOLD response in the left dorsolateral prefrontal cortex (DLPFC). In the condition with target blanking, additional negative correlations with SPV were found in the left frontal eye field (FEF), the left parietoinsular vestibular cortex (PIVC) and the left angular gyrus. Saccadic frequency was negatively correlated with activations of the right mesial intraparietal sulcus (IPS) during both conditions and the right premotor area during continuous target presentation. We conclude that V5 is directly related to the maintenance of an optimal smooth pursuit velocity during visual feedback, whereas the FEF, PFC, angular gyrus and PIVC are involved in reconstitution and prediction whenever SPV decreases, especially during maintenance of smooth pursuit in the absence of a visual target. Furthermore, we suggest that parietal areas are related to the suppression of saccades during smooth pursuit.

Adult↗

PubMed2004

Reduced neuronal activity in the V5 complex underlies smooth-pursuit deficit in schizophrenia: evidence from an fMRI study.

Smooth-pursuit eye movements are the essential tool for a clear and stable visual perception of our environment by matching eye velocity to the velocity of moving objects. However, in about 50% of schizophrenic patients, this ability is disturbed. To reveal the cortical mechanisms that underlie this deficit, eye velocity-related neuronal activity was analyzed by functional magnetic resonance imaging (fMRI). Blocks of constant velocity ramps (10 degrees/s) were presented to 17 patients with schizophrenia and 16 matched controls while assessing smooth-pursuit velocity (SPV) during scanning sessions. Using random-effects analysis, the parametric modulation of brain hemodynamic responses related to SPV was compared between both groups. In schizophrenic patients, reduced SPV was significantly correlated with a focal decrease of the hemodynamic response in the V5 complex (t = 4.21, P(FWE-corrected) = 0.005). Our results provide direct evidence for reduced neuronal activity in V5 as one major factor underlying abnormal SPV in schizophrenia and suggest impaired motion perception. They confirm hypotheses about a V5 deficit derived from psychophysiological studies with schizophrenic patients in which deficient motion perception (especially velocity discrimination) was associated with impaired smooth-pursuit performance.

Adult↗

PubMed2004

Botulinum toxin as an effective treatment of clozapine-induced hypersalivation.

Hypersalivation is a common and frequently disabling side effect of atypical neuroleptics such as clozapine. Current treatment options of this adverse advent are limited by lack of efficacy or additional side effects. Botulinum toxin (BTX) injections into the parotid glands have been shown to be very effective in treating sialorrhea in the context of various neurological disorders, such as Parkinson's and motor neuron disease. Surprisingly, BTX treatment of drug-induced sialorrhea has not yet been described. We here report a patient with clozapine-induced hypersalivation and a good response to BTX injections lasting for more than 12 weeks, resulting in a marked reduction of the hypersalivation and consequently of his social withdrawal. Our patient serves to alert clinicians to the frequent problem of drug-induced sialorrhea and suggests that BTX injections should be considered as an effective and safe treatment for hypersalivation in psychiatric patients treated with clozapine.

Anti-Dyskinesia Agents↗

PubMed2004

Eye movements and psychiatric disease.

PURPOSE OF REVIEW: During the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. RECENT FINDINGS: A few studies addressed impaired smooth pursuit eye movements (eye tracking dysfunction) in unaffected relatives of psychiatric patients, and were important in excluding non-specific effects (e.g. medication) and isolating genetic predisposition to the disease. This predisposition could be demonstrated in families of schizophrenic patients irrespective of whether the index case was sporadic or familial. One large study demonstrated pathological distributions of various parameters of smooth pursuit eye movement performance in groups of schizophrenic patients and their relatives. However, another study challenged the specificity of eye tracking dysfunction as a trait marker for schizophrenia by showing that its prevalence was identical among relatives of patients with affective disorder and schizophrenia. Eye tracking dysfunction was associated with two gene polymorphisms that interfere with dopamine metabolism and are thus reasonable candidate genes for the predisposition to schizophrenia. The influence of nicotine and neuroleptic drugs on eye movement performance was studied in schizophrenic patients. Nicotine improved smooth pursuit performance in three studies, one of which attributed this finding to enhanced attention. Two groups of schizophrenic patients treated with two different atypical neuroleptic drugs, risperidone and olanzapine, did not differ in a battery of saccadic tasks. SUMMARY: Eye movements provide an important tool to measure pharmacological effects in patients and unravel genetic traits in psychiatric disease.

Dopamine↗

PubMed2004

Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study.

Smooth pursuit eye movements are evoked by retinal image motion of visible moving objects and can also be driven by the internal representation of a target due to extraretinal mechanisms (e.g. efference copy). To delineate the corresponding neuronal correlates, functional magnetic resonance imaging at 1.5 T was applied during smooth pursuit at 10 degrees /s with continuous target presentation and target blanking for 1 s to 16 right-handed healthy males. Eye movements were assessed during scanning sessions by infra-red reflection oculography. Smooth pursuit performance was optimal when the target was visible but decreased to a residual velocity of about 30% of the velocity observed during continuous target presentation. Random effects analysis of the imaging data yielded an activation pattern for smooth pursuit in the absence of a visual target (in contrast to continuous target presentation) which included a number of cortical areas in which extraretinal information is available such as the frontal eye field, the superior parietal lobe, the anterior and the posterior intraparietal sulcus and the premotor cortex, and also the supplementary and the presupplementary eye field, the supramarginal gyrus, the dorsolateral prefrontal cortex, cerebellar areas and the basal ganglia. We suggest that cortical mechanisms such as prediction, visuo-spatial attention and transformation, multimodal visuomotor control and working memory are of special importance for maintaining smooth pursuit eye movements in the absence of a visible target.

Adult↗

PubMed2004

Family history of primary movement disorders as a predictor for neuroleptic-induced extrapyramidal symptoms.

BACKGROUND: A genetic susceptibility to extrapyramidal symptoms caused by treatment with neuroleptic medication has been suggested. AIMS: To identify predictor variables for neuroleptic-induced extrapyramidal symptoms, particularly considering family history of primary movement disorders. METHOD: We investigated 100 in-patients receiving a stable neuroleptic medication with regard to occurrence of extrapyramidal symptoms, drug history and detailed family history of primary movement disorders. RESULTS: Step-wise logistic regression analysis revealed that a positive family history was a significant predictor for lifetime prevalence of extrapyramidal symptoms, including reported and currently observed symptoms. The duration of exposure to neuroleptic medication and age were further predictors. CONCLUSIONS: Our findings underline the notion of genetic susceptibility for secondary extrapyramidal symptoms and suggest possible shared genetic factors in primary and secondary movement disorders as well as psychotic disorders.

Adolescent↗

PubMed2003

Schizophrenia spectrum disorders and eye tracking dysfunction in singleton and multiplex schizophrenia families.

One line of research which is helping to unravel the genetic susceptibility to schizophrenia (SZ) is the analysis of eye tracking dysfunction (ETD), a quantifiable phenotypic marker. To investigate if such a biological marker is also present in singleton schizophrenia families, we examined eye tracking in members of singleton families (N=53) and compared it to members of multiplex (N=76) and nonpsychiatric families (N=71) using high resolution infrared oculography. The prevalence of ETD defined by gain values (eye/target velocity) and saccadic frequencies during smooth pursuit at 15 degrees /s did not differ between multiplex and singleton families in either the schizophrenic index patients or their relatives, but was significantly different from nonpsychotic families. ETD rate was higher in those relatives with compared to those without a diagnosis of a schizophrenia spectrum disorder. In relatives with a spectrum disorder, ETD appeared to be associated with traits for "sensitivity" and "suspiciousness". In the group of relatives from singleton families without a schizophrenia spectrum disorder, we still found a higher prevalence of ETD than in nonpsychotic families. Our results suggest that eye tracking dysfunction is a very sensitive biological marker for the vulnerability to schizophrenia, even in those cases where no psychopathological symptoms or signs are obvious. ETD in schizophrenia is suggested to serve as a neurophysiological type model, indicating a perception deficit.

Adult↗