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Christian Jacob

Publications and source records attributed to Christian Jacob.

11 recordsLinked to original sources
PubMed2006

Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation.

Variation in the tryptophan hydroxylase-2 gene (TPH2) coding for the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain modulates responses of limbic circuits to emotional stimuli and has been linked to a spectrum of clinical populations characterized by emotional dysregulation. Here, we tested a set of common single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of TPH2 for association with personality traits and with risk for personality disorders in two cohorts comprising of 336 healthy individuals and 420 patients with personality disorders. Personality dimensions were assessed by the Tridimensional Personality Questionnaire (TPQ) and the revised NEO Personality Inventory (NEO-PI-R). Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to clusters A, B, and C. Individual SNP and haplotype analyses revealed significant differences in genotype frequencies between controls and cluster B as well as cluster C patients, respectively. In both patient groups, we observed overrepresentation of T allele carriers of a functional polymorphism in the upstream regulatory region of TPH2 (SNP G-703T, rs4570625) which was previously shown to bias responsiveness of the amygdala, a structure critically involved in emotionality. Furthermore, significant effects of TPH2 variants on anxiety-related traits defined primarily by the TPQ Harm Avoidance were found in healthy individuals. The results link potentially functional TPH2 variants to personality traits related to emotional instability as well as to cluster B and cluster C personality disorders. These findings implicate alterations of 5-HT synthesis in emotion regulation and confirm TPH2 as a susceptibility and/or modifier gene of affective spectrum disorders.

Adolescent↗
PubMed2006

Facial affect decoding in schizophrenic disorders: a study using event-related potentials.

Deficits in emotional processing are evident in schizophrenia, but the underlying processes are still under debate. In this study we tried to replicate findings of diminished prefrontal electroencephalographic response during facial affect recognition in healthy controls and subsequently in schizophrenic patients. As a first step, we analysed the event-related potentials (ERPs) of 36 healthy subjects during emotional expression decoding compared with neutral face viewing. Subsequently, the ERPs of 22 patients with schizophrenia were compared with the ERPs of 22 healthy subjects matched for age and sex. The hypothesised increase in the negative component at 200 ms over frontal brain regions during facial affect decoding was not found in this study. Instead we found increased positive amplitudes at 300 ms over parietal brain areas for the active affect-decoding task compared with the passive neutral face-viewing task. Interestingly, schizophrenic patients had higher amplitudes in the neutral condition than did healthy controls. This effect was more pronounced in the paranoid subgroup of patients.

Adult↗
PubMed2006

The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder.

Panic disorder is a common psychiatric disorder characterized by recurrent anxiety attacks and anticipatory anxiety. Due to the severity of the symptoms of the panic attacks and the frequent additional occurrence of agoraphobia, panic disorder is an often debilitating disease. Elevation of central serotonin levels by drugs such as clomipramine represents one of the most effective treatment options for panic disorder. This points to an important role of dysregulation of the serotonergic system in the genetic etiology of panic disorder. The novel brain-specific 5-HT synthesizing enzyme, tryptophan hydroxylase-2 (TPH2), which represents the rate-limiting enzyme of 5-HT production in the brain, may therefore be of particular importance in panic disorder. We focused on the putative transcriptional control region of TPH2 and identified two novel common single nucleotide polymorphisms (SNPs) of TPH2 in and close to this region. Moreover, a recently described loss-of-function mutation of TPH2 which results in an 80% reduction of serotonin production, was assessed. In an analysis of the putative transcriptional control region SNPs in a sample of panic disorder patients and controls no association of the disorder with the TPH2 SNPs or haplotypes was found. Moreover, the loss-of-function R441H mutation of TPH2 was not present in the panic disorder patients. The results of this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder with or without agoraphobia.

Adult↗
PubMed2006

The Wuerzburg Research Initiative on Adult Attention-Deficit/Hyperactivity Disorder (WURIN-AADHD): multi-layered evaluation of long-term course.

Although the neurobiological basis of the clinical entity of attention-deficit/hyperactivity disorder (ADHD) is evident, data from studies on pathomechanism-phenotype correlations are inconsistent. There are several obvious limitations of the DSM-IV diagnostic criteria to describe an adequate phenotype of adult ADHD. A dimensional model of neurobiologically based endophenotypes is therefore more likely to be compatible with the genetic model of quantitative trait loci. The primary goal of the Wuerzburg Research Initiative on Adult Attention-Deficit/Hyperactivity Disorder (WURIN-AADHD) is to test the validity of two endophenotypes, deficit in response inhibition and impairment of working memory, using various psychometric and neurobiological strategies of investigation in adult patients with ADHD. An additional objective is the investigation of the long-term course of adult ADHD. The conclusive description of valid endophenotypes of ADHD is an ongoing process that may result in a comprehensive neurobiological model for ADHD or its symptom dimensions integrating genetic, neural, cognitive, and behavioral mechanisms. This model will eventually facilitate description of complete causal connections occurring across the lifespan from early development to adulthood and is also likely to accelerate development of more specific and efficient therapeutic strategies in adult ADHD.

Adult↗
PubMed2005

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in children and adolescents with obsessive-compulsive disorder.

Dysfunction of the central serotonergic system has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The genetic contribution to the development of OCD is particularly high in early-onset OCD. The aim of this study was to investigate the effect of polymorphic variants in the gene of the novel brain-specific tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in OCD with disease onset in childhood and adolescence. We analysed two common single nucleotide polymorphisms (SNPs) of TPH2 in the putative transcriptional control region and in intron 2 of the TPH2 gene in a unique family-based sample of OCD patients with onset of the disease in childhood and adolescence comprising 71 complete, independent trios. The transmission disequilibrium test was used to determine transmission of alleles and haplotypes from parents to offspring. In this first study of TPH2 in OCD, analysis of the SNPs, rs4570625 and rs4565946, revealed a significant preferential transmission of haplotype G-C to children and adolescents with OCD. Moreover, a trend towards preferential transmission of the C allele of SNP rs4565946 to the patients was found. The genotype relative-risk estimate for homozygous C allele carriers of SNP rs4565946 was 2.58 (95% CI 0.98-6.82). In conclusion, the results link TPH2 variations to the pathogenesis of early-onset OCD and further support the aetiological relevance of 5-HT signalling in OCD.

Adolescent↗
PubMed2005

Beneficial effect of atypical antipsychotics on prefrontal brain function in acute psychotic disorders.

Disturbance of prefrontal brain functions is assumed to be responsible for prominent psychopathological symptoms in psychotic disorders. Treatment with atypical, in contrast to typical antipsychotics is considered as a possible strategy for an improvement of prefrontal brain function. In the present study, response control as a specific prefrontal brain function was assessed by means of the Nogo-anteriorization (NGA) derived from the event-related potentials elicited during a Go-NoGo task in a consecutive sample of 39 patients suffering from acute psychotic disorders (brief psychotic disorders, 298.8, n = 34 and schizoaffective disorders, 295.70, n = 5; cycloid psychoses according to the Leonhard classification). A highly significant positive correlation between the amount of antipsychotic medication in terms of chlorpromazine equivalents per day and the NGA as a measure of prefrontal response control was only found in the subgroup of patients treated exclusively or predominantly with atypical antipsychotics but not for those treated with typical antipsychotics. These results are in line with the notion that atypical antipsychotics may exert a beneficial effect on prefrontal brain function.

Adult↗
PubMed2005

Evidence for unaltered brain electrical topography during prefrontal response control in cycloid psychoses.

OBJECTIVE: Prefrontal structures such as the anterior cingulate cortex (ACC) play a decisive role in processes of action monitoring and response control, functions often impaired in schizophrenia. Patients with cycloid psychoses exhibit some characteristic neurophysiological features not indicative of the cerebral hypofrontality observed in schizophrenia. This study aimed at examining if cycloid psychoses-unlike schizophrenias-involve a normal brain-electrical topography during a task demanding prefrontal response control. METHODS: Thirty-seven patients with cycloid psychoses and 37 healthy controls were investigated electrophysiologically while performing a Continuous Performance Test (CPT). Topographical analyses were conducted to individually quantify the Nogo-anteriorisation (NGA) as a neurophysiological index of prefrontal response control. RESULTS: The patients exhibited an unaltered topography with a mean NGA not significantly different from the controls. They did, however, differ from the control group regarding their Global Field Power (GFP), with a significantly reduced GFP (p<0.001) and decreased latencies (p<0.01) during Nogo trials. On a behavioral level, patients exhibited prolonged reaction times and an increased rate of omission errors. CONCLUSIONS: The investigated patients showed an activation of specific (presumably frontal) brain areas during Nogo trials, resulting in a frontalisation of the brain-electrical field comparable to the control group. However, the strength of this activation was apparently reduced. The patients' unaltered topographical pattern contrasts with previous findings in schizophrenic patients and supports the hypothesis that cycloid psychoses entail less severe prefrontal deficits than schizophrenias, which might be an indication of different biological backgrounds for both groups of endogenous psychoses.

Adult↗
PubMed2004

Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women.

Panic disorder is an anxiety disorder with an estimated heritability of up to 48%. Pharmacological and genetic studies suggest that genes coding for proteins involved in the catecholaminergic system might be relevant for the pathogenesis of the disease. In the present study, we genotyped a single nucleotide polymorphism (472G/A=V158M) in the coding region of the catechol-O-methyl-transferase (COMT) gene in 115 patients with panic disorder and age- and sex-matched controls. Association analysis revealed a significant excess of the more active COMT allele (472G=V158) in patients with panic disorder (p=0.04), particularly in female patients (p=0.01), but not in male patients (p=1.0). The assessment of a possible interaction of the COMT polymorphism with a previously reported functional 30-bp VNTR in the monoamine oxidase A promoter (MAOALPR) in female patients did not yield significant results. Our data support a role of the 472G/A (V158M) COMT polymorphism or a nearby locus in the pathogenesis of panic disorder in women.

Adult↗
PubMed2004

Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia.

Panic disorder is a common anxiety disorder which frequently co-occurs with agoraphobia. A functional promoter polymorphism in the serotonin receptor 1A (5-HT1A) gene has been found to be associated with major depression as well as anxiety- and depression-related personality traits. We investigated a possible association between this 5-HT1A gene promoter polymorphism and panic disorder by genotyping the 1019C>G single nucleotide polymorphism in 134 panic-disorder patients with and without agoraphobia and matched 134 controls. In our sample no significant evidence of allelic association in the combined panic-disorder group was found. However, our results show a significant association with the G allele in patients with panic disorder with agoraphobia (p=0.03, n=101). In conclusion, our findings do not support a major contribution of this polymorphism to the pathogenesis of panic disorder, but provide evidence for a possible role in the subgroup with agoraphobia.

Adult↗
PubMed2003

Reduced response-inhibition in obsessive-compulsive disorder measured with topographic evoked potential mapping.

Recent neuroimaging studies have suggested that a hyperactivity of the frontal-striate neuronal circuits, including the orbitofrontal cortex and the basal ganglia, mediates the symptomatology of obsessive-compulsive disorder (OCD). However, there is also some evidence that the superior frontal cortex is less activated in OCD, and this local hypoactivity has been shown to be negatively associated with the symptomatology. As the superior frontal cortex is believed to be involved in inhibitory control, this study investigated the brain electrical activity during response inhibition in OCD. Twelve patients with OCD and 12 healthy controls performed a cued Go-NoGo task (continuous performance test), while event-related potentials were registered with 21 electrodes. Patients reacted significantly faster than controls, but did not differ from controls regarding the error rate. As a main result, we found a reduced frontal activity during the NoGo condition in OCD, which was condensed in a reduced anteriorisation of the brain electrical field. We suggest that this inhibitory deficit in OCD has a major contribution to the pathophysiology of OCD, which is underscored by the fact that the anteriorisation during the NoGo condition (NGA) was negatively correlated with the symptomatology as measured by the Yale-Brown Obsessive-Compulsive Scale.

Adult↗