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J Thome

Publications and source records attributed to J Thome.

At least 19 recordsLinked to original sources

Psychopathological rating scales for diagnostic use in adults with attention-deficit/hyperactivity disorder (ADHD).

The diagnosis of attention-deficit hyperactivity disorder (ADHD) in adults is a complex procedure which should include retrospective assessment of childhood ADHD symptoms either by patient recall or third party information, diagnostic criteria according to DSM-IV, current adult ADHD psychopathology including symptom severity and pervasiveness, functional impairment, quality of life and comorbidity. In order to obtain a systematic database for the diagnosis and evaluation of the course ADHD rating scales can be very useful. This article reviews rating instruments that have found general acceptance. The Wender-Utah Rating Scale (WURS) and the Childhood Symptoms Scale by Barkley and Murphy try to make a retrospective assessment of childhood ADHD symptoms. The Connors Adult ADHD Rating Scales (CAARS), the Current Symptoms Scales by Barkley and Murphy (CSS), the Adult Self Report Scale (ASRS) by Adler et al. and Kessler et al. or the Attention Deficit Hyperactivity Disorder--Self Report Scale (ADHD-SR by Rösler et al.) are self report rating scales focusing mainly on the DSM-IV criteria. The CAARS and the CSS have other report forms too. The Brown ADD Rating Scale (Brown ADD-RS) and the Attention Deficit Hyperactivity Disorder--Other Report Scale (ADHD-OR by Rösler et al.) are instruments for use by clinicians or significant others. Both self rating scales and observer report scales quantify the ADHD symptoms by use of a Likert scale mostly ranging from 0 to 3. This makes the instruments useful to follow the course of the disease quantitatively. Comprehensive diagnostic interviews not only evaluate diagnostic criteria, but also assess different psychopathological syndrome scores, functional disability measures, indices of pervasiveness and information about comorbid disorders. The most comprehensive procedures are the Brown ADD Diagnostic Form and the Adult Interview (AI) by Barkley and Murphy. An instrument of particular interest is the Wender Reimherr Interview (WRI) which follows a diagnostic algorithm different from DSM-IV. The interview contains only items delineated from adult psychopathology and not derived from symptoms originally designed for use in children. Other instruments focus on functional impairment, quality of life, comorbid disorders, gender effects and specific psychopathological models.

Adult↗

Kinematic analysis of dopaminergic effects on skilled handwriting movements in Parkinson's disease.

Patients with Parkinson's disease (PD) exhibit impairments in the execution of highly practiced and skilled motor actions such as handwriting. The analysis of kinematic aspects of handwriting movements has demonstrated that size, speed, acceleration and stroke duration are affected in PD. Although beneficial effects of dopaminergic therapy in regard to execution of movements have been reported, the effects of pharmacological therapy on these measures have not been examined in detail. The present study has compared kinematic aspects of handwriting movements of 27 healthy subjects and 27 patients with PD both on their usual dopaminergic treatment and following withdrawal of dopaminergic medication. Healthy subjects were matched with PD patients according to age, sex, handedness and education level. A digitising tablet was used for the assessment of handwriting movements. Subjects were asked to perform a simple writing task. Movement time, distance, velocity, acceleration and measures of fluency of handwriting movements were measured. Compared with healthy subjects, the kinematics of handwriting movements in PD patients were markedly disturbed following withdrawal of dopaminergic medication. Although dopaminergic treatment in PD patients resulted in marked improvements in the kinematics of handwriting movements, PD patients did not reach an undisturbed level of performance. The results suggest that dopamine medication results in partial restoration of automatic movement execution.

Aged↗

[Neurogenesis. Relevance for pathophysiology and pharmacotherapy of psychiatric diseases].

Research into neurogenesis, i.e., the growth of new neurons in the adult brain, is leaving the area of pure basic science and gaining relevance for clinical disciplines such as psychopharmacology and molecular psychiatry. Neurogenesis is proposed to play a crucial role in psychiatric disorders which exhibit degenerative alterations, neural maldevelopment, and changes in neural plasticity as potentially important pathophysiological factors. Especially in dementia, drug addiction, and schizophrenic and affective psychoses, disruption of adult neurogenesis could thus represent a considerable pathogenetic element. Interestingly, several psychotropic drugs (e.g., antidepressants, atypical antipsychotics) are able to modify neurogenesis significantly. Further elucidation of the importance and implications of neurogenesis may concomitantly result in better understanding of the etiopathogenesis of mental disorders and increased knowledge of the mechanisms of action of psychotropic substances. Furthermore, this may support the development of promising innovative therapeutic approaches in clinical practice.

Adult↗

Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis.

Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disorders served for control. Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged. Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.

Adult↗

[Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist].

We report on the development of a German self-rating behaviour questionnaire (ADHD-SR) and diagnostic checklist (ADHD-DC) for the diagnosis of attention-deficit/hyperactivity disorder in adults according to DSM IV and ICD 10 research criteria. When comparing self-rating with expert rating, we found good concordance measured by intraclass coefficients on the level of single symptoms and syndrome scores. High retest reliability of the ADHD-SR demonstrated the ability to assess time-stable behaviour traits. Evaluation of the psychometric properties revealed good internal consistency and adequate convergent and divergent validity measured by the "big five" derived from the NEO-FFI and the constructs impulsivity, venturesomeness, and empathy of Eysenck's impulsiveness questionnaire. We detected a remarkable correlation with the Wender Utah Rating Scale, which targets the detection of childhood ADHD symptoms. Diagnostic sensitivity for different cutoff points was calculated by ROC analysis at 65--88%. Specificity was 67% to 92%.

Adult↗

[Synaptic vesicle proteins and psychiatric disorders].

Synaptic vesicle proteins modulate the release of neurotransmitters in the synaptic cleft via regulation of vesicle transport, membrane fusion and exocytosis. Due to their relevance for neural and synaptic plasticity, they represent an important object of molecular psychiatric research. There is increasing evidence that they play a significant role in the pathophysiology of several psychiatric disorders. Furthermore, psychotropic drugs differentially modify the expression of synaptic vesicle proteins; thus, this group of molecules is also of considerable interest from a therapeutic point of view.

Brain↗

Differential regulation of synaptic vesicle proteins by antidepressant drugs.

Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release and neural plasticity, and have been implicated in the pathophysiology of psychiatric disorders such as depression. Antidepressant drugs not only alter the level of neurotransmitters, but also modulate de novo gene transcription and synthesis of proteins involved in neural plasticity. In order to investigate the effects of antidepressant compounds on SVP-mRNA levels, the expressions of synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline. The results demonstrate that chronic treatment with fluoxetine and tranylcypromine leads to an increased expression of synaptophysin, but decreased expression of synaptotagmin and VAMP in the hippocampus and cerebral cortex. Additionally, synapsin I-mRNA levels in the hippocampus and cerebral cortex are significantly reduced in tranylcypromine-treated animals. This identifies SVP genes as target genes of antidepressant treatment.

Animals↗

Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology.

Several lines of evidence indicate that dopaminergic neurotransmission is involved in the regulation of impulsive aggression and violence and that genetically determined variability in dopaminergic gene expression modifies complex traits including that of impulsivity and aggression. In this study we report an association of the dopamine D3 receptor (DRD3) polymorphism with impulsiveness according to Eysenck's EIQ and scores on the German short version of the Wender Utah Rating Scale (WURS-k), which we used for the assessment of a history of ADHD-related symptoms. This association was detected in a group of violent offenders, but not in non-violent individuals. Highest scores of EIQ impulsiveness and of the WURS-k were found in heterozygous violent individuals, while homozygotes showed significant lower rating scores, suggesting an heterosis effect. The results of our study suggest that variations of the DRD3 gene are likely involved in the regulation of impulsivity and some psychopathological aspects of ADHD related to violent behavior.

Adult↗

[The concept of liberty in Jaspers' psychopathology].

The debate on conceptional problems represents a fundamental and inevitable challenge also for contemporary biological psychiatry. Especially questions concerning liberty, loss of liberty and regaining liberty are relevant for daily psychiatric practice. This study attempts to critically and systematically investigate the answers given in the philosophy and psychopathology of Karl Jaspers. Thereby, the key term "Grenzsituation" (border situation) plays a significant role. The interpretation of psychiatric disorder as an exceptional state of existence, possibly converting "Alltagssituationen" (situations of daily life) to "Grenzsituationen", sheds new light on Jaspers' thoughts about the concept of liberty which, thus, turn out to be of crucial relevance for the necessary discussions of ethical principles in the era of molecular psychiatry.

Freedom↗

[Molecular aspects of antidepressive therapy. Transsynaptic effects on signal transduction, gene expression and neuronal plasticity].

Simple neurotransmitter theories cannot sufficiently explain the mode of action of antidepressant drugs. Molecular pharmacological studies demonstrate that antidepressive treatment initially modulates the neurotransmitter-receptor interaction, subsequently influences signal transduction cascades beyond the synapse and gene transcription mechanisms, and ultimately triggers the expression of specific target genes. Such genes often code for molecules which play an important role in the maintenance of neural and synaptic plasticity. Chronic (but not acute) treatment with antidepressants modulates, for example, the cAMP-second-messenger system and increases the expression of neurotrophic factors. Furthermore, antidepressants promote hippocampal neurogenesis. Stress, an important risk factor for psychiatric disorders, often induces opposite effects. A better understanding of the molecular and cellular effects of stress and therapy with psychotropic drugs will stimulate the development of innovative treatment strategies for which an optimised antidepressant efficacy with a simultaneously improved tolerance is expected.

Antidepressive Agents↗

[Augmentation of selective serotonin reuptake inhibitors (SSRI) with atypical antipsychotics in the treatment of depression].

The treatment of severe depression represents a difficult task in the daily psychiatric practice. In certain cases, augmentation therapies in order to improve the efficacy of SSRIs can be useful. Recently, it has become possible to use atypical antipsychotics for SSRI augmentation. This option adds to the existing strategies in the treatment of depression and primary systematic studies show encouraging results. In this review, the possibility of a SSRI augmentation by additionally administering risperidone or olanzapine is critically discussed.

Antipsychotic Agents↗

Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus.

BACKGROUND: In view of the effects of stress on synaptic plasticity, the regulation of synaptophysin and synaptotagmin expression by immobilization was analyzed by in situ hybridization. METHODS: Rats were exposed to immobilization stress, which induced typical behavioral alterations, such as reduced locomotor activity after stress exposure. Determination of mRNA levels of the integral synaptic vesicle proteins was performed immediately after acute or chronic immobilization. RESULTS: The results demonstrate that stress exposure leads to reduced expression of synaptophysin but increased expression of synaptotagmin in the hippocampus. CONCLUSIONS: This rapid and differential regulation of synaptic vesicle proteins could be responsible for some of the morphological, biochemical, and behavioral changes observed after stress exposure. These changes may be relevant to such clinical disorders as psychoses, depression, and posttraumatic stress disorder that are sensitive to stress and involve changes in neural and synaptic plasticity.

Animals↗

Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses.

Disturbed neural development has been postulated as a crucial factor in the pathophysiology of schizophrenic psychoses. The neurobiochemical basis for such changes of cytoarchitecture and changed neural plasticity could involve an alteration in the regulation of neurotrophic factors. In order to test this hypothesis, BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic patients were determined by ELISA. There was a significant increase in BDNF concentrations in cortical areas and a significant decrease of this neurotrophin in hippocampus of patients when compared with controls. NT-3 concentrations of frontal and parietal cortical areas were significantly lower in patients than in controls. These findings lend further evidence to the neurotrophin hypothesis of schizophrenic psychoses which proposes that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity, thus being an important event in the etiopathogenesis of schizophrenic psychoses.

Aged↗

Association analysis of HTR6 and HTR2A polymorphisms in sporadic Alzheimer's disease.

In order to identify gene variants related to the serotonergic neurotransmitter system that possibly represent a hereditary risk factor for sporadic Alzheimer's disease (AD), patients suffering from AD and non-demented psychiatric inpatients without symptoms of dementia were genotyped for polymorphisms of HTR6 (267C/T) and HTR2A (-1438G/A). Although there was a tendency toward an increased number of the genotype TT of the 5-HT6 receptor polymorphism in AD patients when compared to controls (2.8% vs. 1.3%), neither this nor the 5-HT2A promoter polymorphism showed significant differences in their genotypic or allelic distribution among patients and controls. These polymorphisms probably do not represent major genetic risk factors of AD. However, further studies including other genetic variants of the serotonergic neurotransmitter system are needed in order to elucidate their role in AD.

Alleles↗

[Symptoms from the spectrum of Attention-Deficit/Hyperactivity Disorder (ADHD) in sexual delinquents].

The implications of ADHD for sexual delinquent behavior were investigated in a sample of 127 male sexual delinquents for whom social, forensic and psychiatric data were collected. For the retrospective evaluation of ADHD-symptoms, we used the Wender Utah Rating Scale (WURS, 61-item version). We also used the Eysenck Impulsiveness Questionnaire for the assessment of impulsivity. The prevalence of ADHD within the group of sexual delinquents was 27.6 % with a persistence rate of 14.2 % at a cut-off point of 90 in the WURS. The prevalence of ADHD within the control group was 7.8 % with a persistence rate of 3.0 %. The prevalence within the group of sexual delinquents dropped to 15.7 % for childhood ADHD-symptoms and 11.0 % for partial ADHD persistence in adulthood using a cut-off score of 100. In the control group the rates were 4.8 % and 2.4 % respectively. Based on ICD-10 criteria, 35.4 % of the sexual delinquents had no psychiatric disorder. We found personality disorders of the antisocial type (22.1 % of the sample) and paraphilias in 25.2 %. Approximately, half of the delinquents with paraphilia met the criteria of pedophilia. We also found schizophrenia, organic psychiatric disorders and mental retardations in less than 5 %. The criminal careers of the sexual delinquent group with a history of childhood ADHD symptoms started 10 years earlier. We also found a significant correlation between previous convictions and the retrospective diagnosis of ADHD symptoms. This was more prominent when a previous sexual offence could be found in their criminal record. These results illustrate the hypothesis, that in addition to paraphilias the presence of ADHD-symptoms might be an important vulnerability factor for sexual delinquency, esp. when there is a persistence into adulthood. This demonstrates the need for an early therapeutical intervention, since 44.1 % of the sample had previously undergone psychiatric treatment.

Adult↗

[Paroxetine augmentation with risperidone in therapy-resistant depression].

In a 71 years-old patient, a severe therapy-resistant depressive episode without psychotic symptoms was successfully treated by a combination of paroxetine and risperidone. Previously, several different antidepressants were not effective in ameliorating the depressive symptoms which occurred repeatedly over a period of more than ten years.

Aged↗

Potential genetic markers of sporadic Alzheimer's dementia.

Polymorphisms within the genes encoding apolipoprotein E (ApoE), apolipoprotein CI (ApoCI), alpha1-antichymotrypsin (ACT), the low-density lipoprotein (LDL) receptor and lipoprotein lipase were investigated in patients suffering from Alzheimer's dementia and non-demented psychiatric patients as control subjects. The ApoE allele 4, well known as a risk factor in Alzheimer's disease, and the ApoCI allele A2, which is closely linked to the ApoE allele 4, were found elevated in the index group. Concerning the polymorphism within exon 8 of the LDL receptor (alanin/threonin), there was also a predominance of the allele carrying threonin in the index group, which barely missed significance. Distribution of the polymorphisms of ACT and lipoprotein lipase were similar in both groups investigated. We conclude that, apart from the ApoE allele 4, other genetically regulated factors like ApoCI and the LDL receptor modulate the individual risk for Alzheimer's disease.

Aged↗