Psychopathological and auditory evoked potential correlates of ketamine psychosis--a single case report.
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RATIONALE: A serotonergic dysfunction is supposed to play a pathogenetic role in depression, but there is a considerable number of non-responders in the acute treatment of depression with serotonergic agents like SSRI. Thus, an indicator of central serotonergic activity could lead to a more specific pharmacological treatment of depression. In animal and human data there is a growing amount of evidence that a strong loudness dependency of late auditory evoked potentials (LDAEP) is an indicator of low serotonergic activity and vice versa. OBJECTIVE: In 29 depressive inpatients (DSM-III-R diagnosis 296.x in 28 patients, 300.4 in one patient), the hypothesis was tested that a strong LDAEP prior to treatment can predict a better clinical outcome under SSRI treatment over 4 weeks. RESULTS: Patients with a strong pre-treatment LDAEP had a significantly greater decrease of depressive symptoms (Hamilton Scale for Depression) after 4 weeks than patients with a flat LDAEP. Significantly more responders fell into the group with a high LDAEP. Contrary to what might be expected, a second recording in a subsample of 19 patients after 4 weeks of treatment failed to show changes in the LDAEP. CONCLUSION: Our finding confirms the hypothesis that a strong LDAEP, indicating a low serotonergic activity, is related to a favorable response to acute SSRI treatment in depression. The LDAEP is a promising tool for the prediction of response to serotonin agonists in depression and it seems to be of clinical importance.
Gamma-aminobutyric acid (GABA)A-receptors play a crucial role in the generation of electroencephalogram (EEG) oscillations and evoked potentials (ERPs). The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA beta2 (GABRB2) and gamma2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotide substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed in 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/ P200-complex). No genotypic association was found for the GABRB2 nucleotide exchange polymorphism with any electrophysiological parameter. A significant association was found between the genotype of the intronic GABRG2 G-->A nucleotide exchange and the event-related N100/P200 (ANOVA: F=3.81; df=2; P=0.026). A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002). Post hoc analysis of this association with current density analysis in three-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefrontal cortex. Taking into account the risk of false-positive association findings attributable to multiple testing, our results encourage further replication studies to examine the phenotype-genotype relationship of GABRG2 gene variants and event-related prefrontal activity.
At present, our understanding of how normal aging affects in vivo brain function is rudimentary. Therefore, the aim of the present study was to investigate age effects on auditory P300 topography. A recently developed dipole source model for P300 distinguishes overlapping P300 subcomponents and enhances reliability as well as validity of the measurement. 67 healthy subjects were examined using the P300 dipole model in addition to the scalp data measurement. The results show that P300 subcomponents reflect functionally different processes concerning age changes of P300 activities. Temporo-parietal P300 is smaller in older subjects, whereas frontal P300 is not attenuated. Age affected both P300 subcomponents' latencies. Therefore, the functionally different alteration of P300 subcomponents might be the reason for P300 topography changes with the P300 maximum more frontally in older age.
BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood.
Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.
BACKGROUND: The aim of the study was to investigate abnormalities of P300 subcomponents in schizophrenic patients as well as relationships between these subcomponents and positive versus negative schizophrenic symptoms. METHODS: Nineteen schizophrenic patients and 19 healthy controls were tested with an auditory event-related potential oddball paradigm designed to elicit the P300. The P300 data were analyzed by separating P300 subcomponents with a recently developed dipole source model. RESULTS: Compared to healthy controls, schizophrenic patients showed reduced P300 amplitudes of the temporo-basal dipoles, corresponding mainly to P3b. Positive symptoms of the Positive and Negative Syndrome Scale correlated positively with the temporo-basal but not with temporo-superior dipole P300 activities, whereas negative symptoms correlated positively with the temporo-superior but not with temporo-basal dipole activities. CONCLUSIONS: The P300 subcomponents separated with the dipole model are affected in a different manner by positive versus negative symptoms. Furthermore, the positive correlation between the severity of psychopathology and the P300 amplitudes of the different dipole activities appears to be a state-dependent effect, which has to be separated from the P300 amplitude reduction as a trait marker in schizophrenic patients.
After surgical operations delirium can occur as a serious and possible lethal complication in about 5-15% of patients. Additionally, risk factors such as old age, polymedication, organic and psychiatric diseases raise the incidence. After open-heart and orthopedic surgery more than half of the patients are affected. Delirium has negative effects on postoperative mobilization and reconvalescence and prolongs treatment on the ward. It is discussed in the literature that delirium may induce dementia in older patients. The correction of metabolic and electrolyte imbalances, as well as the therapy of neurologic and psychiatric diseases, belongs to prophylactic treatment. Environmental conditions which facilitate reorientation of the patient after operation have beneficial effects. Some success has been achieved by using the nootropic substance piracetam as a prophylactic. In acute treatment, the butyrophenon-neuroleptic haloperidol is the drug of choice. In delirium caused by intoxication with anticholinergic agents, physostigmin is indicated. Benzodiazepines, clonidine and clomethiazole are used in particular for the treatment of withdrawal delirium.
Episodes of anxiety have been reported to be the most common psychological symptoms in patients with partial seizures. They may occur before, during and after seizures and can also appear in isolation without any convulsive symptoms. The epileptic anxiety syndrome is strikingly similar to panic attacks, and panic disorder is an important differential diagnosis. The close relationship between epileptic seizures and panic attacks is of special interest for a better pathophysiological understanding of panic attacks. In the literature an epileptiform neuronal activity is discussed as a possible underlying mechanism for panic disorder. The finding that anxiety was the most common experiential phenomenon produced by electrical stimulation of amygdala and hippocampus with depth electrodes points in this direction. PET has demonstrated abnormalities of hippocampal structures during the nonpanic state of patients with panic disorder. In addition, some EEG studies have demonstrated a high incidence of epileptiform EEG patterns in patients with panic disorder with or without agoraphobia. This was the reason why several investigators proposed that a subset of panic attacks may be related to abnormal epileptiform neuronal activity in the limbic system. The size of this subset is difficult to determine because discharges in the depth of the limbic system often cannot be seen in the scalp EEG. Concerning the hypothetical pathophysiological mechanism of panic disorder therapeutic measures were taken with antiepileptic agents. The best results were obtained for valproic acid. It seems to be reasonable to make a therapeutic trial with antiepileptic medication after nonresponse to standard pharmacotherapy.
Delirium is a serious postoperative complication after general anaesthesia. The incidence is estimated to be about 10-15%. In the case of additional risk factors, such as old age, previously existing cerebral-vasculous and psychic deficiencies, and anaesthesia of long duration the incidence is much higher. Delirium impairs postoperative mobilisation and convalescence of the patient, can lead to a longer hospital stay and is associated with higher mortality rates. In a series of clinical studies it could be shown that the perioperative administration of the nootropic piracetam led to a shorter recovery period after anaesthesia and had a favourable influence on the delirious symptoms. Especially patients with risk factors for postoperative delirium profited from prophylactic application of piracetam. The success of this medication can be explained by a protective influence of the substance on central neurons against hypoxia, ischemia and intoxication, all of which are discussed as possible causes for postoperative delirium. Next to the pathogenetic mechanisms of postoperative delirium, the mode of action of piracetam is shown in a review and a summary of references on the clinical use in anaesthesia is given.
As a modification of the diagnostic criteria of the serotonin syndrome proposed by Sternbach, we developed the Serotonin syndrome scale for the operationalized assessment of both the presence and the severity of the core symptoms of the serotonin syndrome. In a first study on the validity of this scale, the relationships between the serotonin syndrome score (SSS) and both the paroxetine plasma levels (n = 42) and the loudness dependence of the auditory evoked potentials (LDAEP; n = 24) were investigated in depressed patients treated with paroxetine. A strong LDAEP is supposed to indicate low central serotonergic neurotransmission, and vice versa. The SSS was positively related to paroxetine plasma levels and negatively to the LDAEP. Both results support the validity of the serotonin syndrome scale. Using a SSS > 6 as diagnostic criterion, mild serotonin syndromes were diagnosed in 5 of our 42 patients. The Serotonin syndrome scale may become a useful tool for clinicians and scientists dealing with the serotonin syndrome.
Event-related potentials (ERPs) can serve as markers for cognitive processing stages. Identification of those ERPs altered in schizophrenia offer information about cognitive dysfunction. Auditory evoked potentials (AEPs) were elicited within an oddball paradigm in 35 schizophrenic patients and compared with 35 healthy controls. N100 and P200, as well as N200, frontal P300 and parietal P300 subcomponents, were separated using dipole source analysis. The amplitudes of the N100 and the parietal P300 measured in schizophrenics were diminished. The input-related processing stages (N100 and P200) were not altered, whereas later, the deviant and task-related processes (N200, frontal P300, parietal P300 and reaction time) were significantly prolonged in schizophrenia.
Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor "sleep disturbance". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.
Action-oriented personality traits such as sensation seeking, extraversion, and impulsivity have been related to a pronounced amplitude increase of auditory evoked scalp potentials with increasing stimulus intensity. Dipole source analysis represents a crucial methodological progress in this context, because overlapping subcomponents of the scalp potentials can be separated and can be related to their generating cortical structures. In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex. These results support the concept that the serotonergic brain system, which is supposed to modulate sensory processing in primary auditory cortices, is an important factor underlying individual differences in sensation seeking.
The spatio-temporal approach of dipole source analysis represents a crucial methodological progress in research on individual differences in the dependence of auditory evoked potential amplitude on stimulus intensity (augmenting/reducing) because overlapping subcomponents of the N1/P2-component can be separated and can be related to their generating cortical structures. Basic aspects of the intensity dependence of auditory evoked dipole source activity were analysed in 40 healthy subjects. The evoked responses to binaural 1000-Hz tones at five levels of intensity (60, 70, 80, 90, 100 dB sound pressure level) were recorded at 33 sites across the scalp. The dipole source analysis of the grand average data confirms the reports in the literature that the N1/P2 potentials at the scalp can be explained by two dipoles per hemisphere: a tangential dipole, representing activity of the superior temporal cortex (including primary auditory cortex), and a radial dipole, representing activity of the lateral temporal cortex (secondary auditory areas). The intensity dependence of the tangential dipole activity was significantly more pronounced than that of the radial dipoles, supporting the assumption that radial and tangential dipoles represent different physiological processes. A high reliability of the intensity dependence of the tangential dipole (Pearson correlation: r = 0.88) was found when retesting the subjects after three weeks. Age was negatively correlated with the intensity dependence of the tangential dipole. Dipole source analysis proved to be a reliable method which allows, at least in part, to study separately the intensity dependence of the evoked responses from primary and secondary auditory cortices. This is of importance with regard to the hypothesis that the central serotonergic system modulates the intensity dependence of the evoked N1/P2-response of primary auditory cortex.
The spatiotemporal approach of dipole source analysis is a crucial methodological advance in event-related potential research, as overlapping subcomponents of cortical evoked potentials can be separated and related to their generating structures. This enhances the reliability and validity of event-related potential parameters and facilitates the link to underlying neurochemical processes. The present paper presents methodological aspects of the dipole source analysis of auditory-evoked potentials to different stimulus intensities.
The relationship between auditory-evoked potentials and the ethanol withdrawal syndrome was investigated in alcoholic inpatients using dipole source analysis. It was found that the increase in N1/P2 amplitude during withdrawal was positively correlated to the general severity of the withdrawal, but not to single symptoms such as seizures. Monitoring of initial changes in the auditory-evoked N1/P2 amplitude may be of predictive value concerning the withdrawal severity of alcoholic patients.
Decrement of the auditory P300 component of the event-related potentials (ERP) is a robust finding in schizophrenic patients and seems to be most pronounced in the left temporal region. Structural MRI studies support the hypothesis that regional structural brain differences in this patient group include reduced volume in temporal lobe structures. The aim of the presented study was to investigate the possible gray matter volume reductions in the left posterior superior temporal gyrus (STG) and the P300 reduction and left <right topographic asymmetry in schizophrenic patients. Therefore, in 50 male schizophrenic patients and 50 age- and educational level-matched male controls, auditory ERPs and structural MRI measurements of the gray matter volume of the STG were assessed. In the group of patients, the psychopathological symptom of thought disorder was correlated with the electrode site T3 and underlying gray matter of the left posterior superior temporal gyrus. The subgroup of patients with pronounced negative symptoms was analyzed with respect to ERP and structural MRI measurements. Our data revealed no evidence for a reduction of P300 amplitude or left STG gray matter volume in schizophrenic patients. However, the higher amount of thought disorders was related to a small T3 amplitude. No associations between the electrophysiological and structural measurements could be detected. There were also no significant reductions of ERP and MRI measurements within the subgroup of patients with pronounced negative symptoms.