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P Falkai

Publications and source records attributed to P Falkai.

At least 19 recordsLinked to original sources
PubMed2007

[Cortical excitability in schizophrenia. Studies using transcranial magnetic stimulation].

Abnormalities in brain plasticity, including abnormal information processing by disturbed cortical inhibition and facilitation in schizophrenia, have been described several times in the past. Transcranial magnetic stimulation (TMS) provides a neurophysiological technique for the measurement of cortical excitability, especially of the motoneural system. With TMS it is possible to explore important aspects of the pathophysiological mechanisms underlying schizophrenia using recently developed paradigms (paired pulse method, cortical silent period). This review summarizes the results of available diagnostic TMS studies in schizophrenia. Studies investigating the efficacy of therapeutic repetitive magnetic stimulation in patients with treatment resistant hallucinations or predominantly negative symptoms were not considered. The reviewed studies support the assumption of reduced cortical inhibition, probably caused by GABAergic deficit, in schizophrenia. Factors influencing the study results, the limitations of this promising technique in schizophrenia, and further research options are discussed.

Evoked Potentials, Motor↗
PubMed2007

Impulsiveness in obsessive-compulsive disorder: results from a family study.

OBJECTIVE: Although obsessive-compulsive disorder (OCD) is usually conceptualized as an anxiety disorder some studies suggested it to be a deficit of impulse control. The purpose of this study was to assess impulsiveness in OCD families and compare it to control families. METHOD: Seventy cases and their 139 relatives were compared with 70 controls and their 134 relatives from a German family study on OCD (German Epidemiologic Network for OCD Studies). All subjects were interviewed and diagnosed according DSM-IV criteria and were administered the Barratt Impulsiveness Scale (BIS) and PADUA-Inventory to assess obsessive-compulsive symptoms. RESULTS: OCD subjects had significantly higher scores of cognitive impulsiveness. However, first-degree relatives of OCD cases and of controls had comparable BIS-11 scores. Significant associations of aggressive obsessions and checking with cognitive impulsiveness were found. CONCLUSION: OCD is a severe mental disorder that is characterized by a lack of cognitive inhibition. However, impulsiveness does not represent a familial trait in families of OCD subjects.

Adult↗
PubMed2006

How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

Brain↗
PubMed2006

Altered NMDA receptor expression and behavior following postnatal hypoxia: potential relevance to schizophrenia.

The present study investigated the effects of chronic, repeated hypoxia during a postnatal vulnerable period. Acoustic startle response in adult rats was measured along with NMDA receptor binding and mRNA expression of subunits at postnatal days (PND) 11 and 120. Rats at PND 120 exhibited a deficit in prepulse inhibition of acoustic startle response. In PND 11 rats, chronic hypoxia decreased NMDA receptor binding and increased transcript expression of NR1 subunit in frontal and temporal regions, nucleus accumbens and hippocampus, while NR2A subunit expression was downregulated in hippocampal subregions. At PND 120, gene expression of NR1 was still increased in hippocampal, frontal and temporal subregions as well as nucleus accumbens. A prepulse inhibition deficit points to schizophrenia-like behavior in adult (PND 120) rats. Compensatory upregulation of NR1 expression may occur due to NMDA receptor hypofunction. We discuss this animal model to further analyze effects of hypoxia as a factor of obstetric complications in the pathophysiology of schizophrenia.

Animals↗
PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗
PubMed2006

[Pharmacological treatment options in frontotemporal dementia].

In contrast to Alzheimer's disease, there are only few systematic trials for drug therapy of frontotemporal dementia (FTD). Neurochemically, a strong serotonergic deficit is supposed in FTD. This is the rationale for treatment, especially of behavioral abnormalities, with serotonergic antidepressants. However, only paroxetine and trazodone have been studied in trials with class I and II evidence so far. The results of paroxetine are inconsistent; and for trazodone a number of potential side-effects must be considered. Moreover, there is class II evidence for rivastigmine in FTD, even though a cholinergic deficit in this type of dementia is questionable. There are no published data from controlled trials for the use of memantine in FTD so far.

Aged↗
PubMed2006

Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease.

Increasing evidence links Alzheimer's disease (AD) with misbalanced Cu homeostasis. Recently, we have shown that dietary Cu supplementation in a transgenic mouse model for AD increases bioavailable brain Cu levels, restores Cu, Zn-super oxide-1 activity, prevents premature death, and lowers A beta levels. In the present report we investigated AD patients with normal levels of A beta 42, Tau and Phospho-Tau in the cerebrospinal fluid (CSF) in comparison with AD patients exhibiting aberrant levels in these CSF biomarkers. The influence of these cerebrospinal fluid (CSF) diagnostic markers with primary dependent variables blood Cu, Zn and ceruloplasmin (CB) and secondary with CSF profiles of Cu, Zn and neurotransmitters was determined. Multivariate tests revealed a significant effect of factor diagnostic group (no AD diagnosis in CSF or AD diagnosis in CSF) for variables plasma Cu and CB (F=4.80; df=2, 23; p=0.018). Subsequent univariate tests revealed significantly reduced plasma Cu (-12.7%; F=7.05; df=1, 25; p=0.014) and CB (-14.1%; F=9.44; df=1, 24; p=0.005) levels in patients with aberrant CSF biomarker concentrations. Although only AD patients were included, the reduced plasma Cu and CB levels in patients with a CSF diagnosis of advanced AD supports previous observations that a mild Cu deficiency might contribute to AD progression.

Aged↗
PubMed2006

Cholesterol synthesis rate in human hippocampus declines with aging.

During the last three to four decades, interest in the interaction of circulating and brain cholesterol has increased. As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain is expected to decline. We measured cholesterol, its precursors and its brain specific metabolite 24S-hydroxycholesterol in hippocampus from 7 female and 13 male corpses by highly sensitive and specific gas chromatography-mass spectrometry. Two age groups (young, n=10; elderly, n=10) were formed with a cut-off at the median age of 38 years. The amount of cholesterol was comparable in young and elderly subjects. The concentrations of the cholesterol precursors lanosterol and lathosterol were significantly higher in young (P=0.036 and 0.005, respectively) than in elderly subjects. In accordance, there was a significantly negative correlation between age and lathosterol concentrations (r=-0.505; P=0.023). Absolute levels of 24S-hydroxycholesterol in the brain were slightly, but not significantly, lower in the hippocampal specimens from the elderly subjects. We conclude that during aging, cholesterol synthesis is decreased in the hippocampus, while absolute cholesterol content remains at a stable level.

Adolescent↗
PubMed2006

Cognitive changes after carotid artery stenting.

INTRODUCTION: We aimed to test changes in cognitive performance after carotid artery stenting (CAS). METHOD: Ten patients were neuropsychologically tested at least 24 h before and 48 h after CAS. To diminish thromboembolic events, we used a proximal protection device. The following neuropsychological tests were selected: The Mini Mental State Examination (MMSE), symbol digit test and subtests of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (verbal fluency, constructional practice, word list memory and delayed recall). Affective state was determined by the Beck Depression Score (BDS). RESULTS: No patient suffered from depression (BDS <1) or dementia (MMSE 29.9+/-1.5). Nine of the ten patients (P=0.12) showed increased speed in the Number Connection Test (NCT) (corresponding to trail making test). Most patients showed better or similar results concerning delayed recall (P=0.31). No change was observed in the symbol digit test, word list memory, verbal fluency or constructional practice. Better results concerning NCT and delayed recall after carotid stenting might be due to improved brain perfusion. CONCLUSION: After CAS, cognitive and memory performance seem to improve. Further studies with different time intervals and more refined testing, as well as perfusion-weighted imaging, are needed.

Aged↗
PubMed2006

Neural mechanisms of advance preparation in task switching.

The preparation effect in task switching can be interpreted to reflect cognitive control processes during the interval between task-cue onset and the trial-stimulus onset which support the flexible and rapid configuration of response dispositions. However, it is an open issue what neural processes underlie this effect. In the present study, healthy volunteers underwent functional magnetic resonance imaging (fMRI) while performing a cued task switching paradigm, in which geometric objects had to be classified according to either color or shape. By manipulating the duration of the cue-target-interval (CTI) in the range between 0 and 1500 ms, we were able to dissociate brain activity changes related to the processing of either the cue or the target. A network of frontal and parietal brain areas was activated during advance preparation for the upcoming task independent of whether the task was switched or repeated. The same brain regions also showed increased neural activity in response to targets without advance preparation in contrast to targets with advance preparation which only elicited activations in areas involved in visual processing and motor execution. These findings strongly argue for a 'task-set activation perspective' on advance preparation in task switching [Altmann, E.M., 2004. Advance preparation in task switching: what work is being done? Psychol. Sci. 15, 616-622.], whereas no empirical support could be found for the 'mental gear changing model' of task switching as no significant brain activity changes were observable in association with task switches, switch costs, or the interaction effect of advance preparation on switch costs. Finally, in the light of previous behavioral studies on interference effects of articulatory suppression on task preparation in humans, the present findings are compatible with the assumption that verbalization mechanisms, e.g., the retrieval of a verbal task or goal representation into working memory may be a functional component of advance configuration of task-sets.

Adult↗
PubMed2006

[Advances in neurobiological understanding of schizophrenia. Perspectives for new therapeutic concepts].

Causal treatment options for schizophrenia are lacking due to our restricted knowledge of its etiology and pathogenesis. However, recently three postulated disposition genes for schizophrenia have been increasingly better confirmed: dysbindin, neuregulin-1, and G(72)/DAOA genes. These genes code proteins involved in processes ranging from brain development to the maintenance of glutamatergic transmission in the mature brain. Current interpretation of neuroanatomical findings points at reminiscences of disturbed brain development and a loss of nonneuronal elements, the so-called neuropil, as a correlate of brain atrophy. This reduction in neuropil is mainly caused by synaptic elements. Biochemical findings supporting this show that besides the dopaminergic and serotonergic system, glutamatergic transmission is also disturbed in schizophrenia. All these findings fit very well with the presumed functions of the disposition genes. Hypothesis-free approaches in structural brain imaging and the combination of functional imaging with relevant gene variants open new avenues for using markers from brain imaging to improve the diagnosis of schizophrenia and judge the response to neuroleptic treatment. Despite the enormous increase in knowledge for example in genetic research, the risk variants known until now provide no contribution to early diagnosis of schizophrenia. Furthermore, pharmacogenetics is currently unable to give a clear answer as to whether a single patient is responding to treatment or not.

Animals↗
PubMed2006

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↗
PubMed2005

Traumatic brain injury: cause or risk of Alzheimer's disease? A review of experimental studies.

Traumatic Brain Injury is the leading cause of death and disability among young individuals in our society. Moreover, according to some epidemiological studies, head trauma is one of the most potent environmental risk factors for subsequent development of Alzheimer's disease. Interestingly, pathological features that are present also in Alzheimer's disease (in particular deposition of beta-amyloid protein) were observed in traumatised brains already a few hours after the initial insult. The primary objective of this review is to present methodology and results of numerous recent human and animal studies dealing with this issue. Special emphasis was placed on head trauma experiments in transgenic mouse models of Alzheimer's disease. We further evaluate the connection between traumatic brain insults and subsequent development of dementia and try to differentiate between primary and secondary pathological mechanisms.

Alzheimer Disease↗
PubMed2005

[The role of copper in the pathophysiology of Alzheimer's disease].

Alzheimer's dementia (AD) is a chronically progressive neurodegenerative disease. The key protein in the pathophysiology of AD is the amyloid precursor protein (APP) which releases the amyloid-beta peptide (Abeta) by proteolytic cleavage. APP is probably involved in the homeostasis of cellular copper (Cu) metabolism, because significantly changed Cu levels in the brain were found in AD patients as well as in mouse models. In vivo studies with transgenic mice showed that oral Cu supplements can restore lowered Cu levels in the brain to normal, can reduce Abeta production, and can reduce mortality of the animals. Currently, the influence of oral Cu supplementation (in addition to an established acetylcholinesterase inhibitor) on the progression of the disease is being studied in a prospective, double-blind, randomized and placebo-controlled longitudinal clinical trial in patients with mild AD.

Alzheimer Disease↗
PubMed2005

[Neural correlates of working memory deficits in schizophrenic patients. Ways to establish neurocognitive endophenotypes of psychiatric disorders].

This article briefly reviews some methodological limitations of functional neuroimaging studies in psychiatric patients. We argue that the investigation of the neural substrates of cognitive deficits in psychiatric disorders requires a combination of functional neuroimaging studies in healthy subjects with corresponding behavioral experiments in patients. In order to exemplify this methodological approach we review recent findings regarding the functional neuroanatomy of distinct components of human working memory and provide evidence for selective dysfunctions of cortical networks that underlie specific working memory deficits in schizophrenia. This identification of subgroups of schizophrenic patients according to neurocognitive parameters may facilitate the establishment of behavioral and neurophysiological endophenotypes and the development of a neurobiological classification of psychiatric disorders.

Brain Mapping↗
PubMed2005

[Magnetic resonance spectroscopy in schizophrenia. Possibilities and limitations].

Magnetic resonance spectroscopy is a noninvasive investigative technique for in vivo detection of biochemical changes in neuropsychiatric disorders for which especially proton (1H-MRS) and phosphorus (31P-MRS) magnetic resonance spectroscopy have been used. In this review we explain the principles of MRS and summarize the studies in schizophrenia. A systematic literature review was carried out for 1H-MRS studies investigating schizophrenic patients compared to controls. The inconsistent results in the cited studies may be due to different study population, specific neuroimaging technique, and selected brain regions. Frequent findings are decreased PME and increased PDE concentrations (31P-MRS) linked to altered metabolism of membrane phospholipids and decreased N-acetylaspartate (NAA) or NAA/choline ratio (1H-MRS) linked to neuronal damage in frontal (DLPFC) or temporal regions in patients with schizophrenia. These results contribute to the disturbed frontotemporal-thalamic network assumed in schizophrenia and are supported by additional functional neuroimaging, MRI morphometry, and neuropsychological evaluation. The combination of the described investigative techniques with MRS in follow-up studies may provide more specific clues for understanding the pathogenesis and disease course in schizophrenia.

Brain↗