| 1 | Int J Psychophysiol 2003 Aug 49: 139-46 |
|---|---|
| PMID | 12919716 |
| Title | Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives. |
| Abstract | Several forms of eye movement dysfunction (EMD) have been widely regarded as candidate endophenotypes of schizophrenia, ultimately capable of identifying individuals carrying schizophrenia susceptibility genes and elucidating the pathophysiology of schizophrenia. As an indication of their trait-like status, candidate endophenotypes optimally evidence stability over time. However, there have been few published reports of test-retest reliability of several forms of EMD in schizophrenia patients and their relatives. In the current investigation, schizophrenia patients and the first-degree biological relatives of schizophrenia patients (n=15) were administered by an eye movement battery including smooth pursuit, antisaccade and prosaccade tasks, and re-tested after an average of 1.82 years (range=14-24 months). Adequate test-retest reliabilities of smooth pursuit closed-loop gain (Pearson r=0.72), antisaccade error rate (r=0.73), saccade reaction time to correct antisaccade responses (r=0.73), and prosaccade hypometria (r=0.72) were observed. Lower reliabilities were obtained for smooth pursuit open-loop gain (r=0.52) and prosaccade reaction time (r=0.43). The results are supportive of the trait-like characteristics of particular forms of EMD in schizophrenia families and of the candidacy of EMD as an endophenotypic marker of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 2 | World J. Biol. Psychiatry 2004 Apr 5: 100-6 |
| PMID | 15179669 |
| Title | Antipsychotic drugs influence transport of the beta-adrenergic antagonist [3H]-dihydroalprenolol into neuronal and blood cells. |
| Abstract | The amine hypothesis suggests that the cause of schizophrenic or depressive psychosis is dysfunction of noradrenergic or serotonergic neurotransmission. We investigated pharmacological properties of [3H]-dihydroalprenolol (DHA) transport into C6, IMR32, native lymphocytes, B-lymphoblastoids and MOLT-3 cells. DHA transport was inhibited by a heterogeneous group of structurally related compounds exhibiting an amine group and various aromatic ring structures. It was verified on cells of neuronal/glial and blood cell origin but in detail on B-lymphoblastoids. The latter once showed strongest inhibition of DHA transport using tricyclic antidepressants (amitriptyline: IC50 = 2.86 microM, imipramine: IC50 = 3.33 microM) and haloperidol (IC50 = 3.98 microM) as a neuroleptic. Antipsychotics like clozapine (IC50 = 11 microM), olanzapine (IC50 = 15 microM), spiperone (IC50 = 66 microM) and EMD 49980 (ICso > 100 microM) were less effective. In contrast to cells of blood origin, a stimulation of DHA transport by antipsychotics was not detectable using neuronal cells. As antipsychotics showed a distinct inhibition and, concerning cells of blood origin, a stimulation of transport after pre-incubation, further investigations seem to be of interest in respect to its involvement in the cellular uptake of drugs and therefore its impact on the quality of therapy of psychiatric patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 3 | Neuropsychobiology 2005 -1 51: 204-10 |
| PMID | 15870510 |
| Title | Relationship between class I and II HLA antigens in schizophrenia and eye movement disturbances: a preliminary study. |
| Abstract | The region coding human leukocyte antigen (HLA) on chromosome 6q21 was shown to be associated with both the vulnerability to schizophrenia and presence of eye movement disturbances (EMD). The aim of this preliminary study was to investigate how individual class I and II HLA antigens in schizophrenic patients may be related to schizophrenia and to the intensity of two kinds of EMD: fixation and smooth pursuit. The incidence of HLA antigens was compared between 40 schizophrenic patients (17 male, 23 female) and 198 healthy control subjects (112 male, 86 female). In schizophrenic patients, the intensity of EMD assessed by infrared reflectometry and quantified on a scale from 0 to 3 was correlated with the incidence of HLA antigens. A number of differences regarding HLA antigens were found between schizophrenic patients and healthy subjects. Significant correlation was also obtained between some EMD and a number of HLA antigens. Antigens A24 and A28 were found to occur in different frequencies in schizophrenic patients and healthy control subjects. They also correlated with EMD on the fixation and smooth pursuit tests. The results obtained show an association between HLA antigens and EMD as an endophenotypic marker of schizophrenia, and may add to other findings on susceptibility loci for schizophrenia on chromosome 6p21. A limitation of this study is a small number of investigated patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 4 | Neuropsychobiology 2005 -1 51: 204-10 |
| PMID | 15870510 |
| Title | Relationship between class I and II HLA antigens in schizophrenia and eye movement disturbances: a preliminary study. |
| Abstract | The region coding human leukocyte antigen (HLA) on chromosome 6q21 was shown to be associated with both the vulnerability to schizophrenia and presence of eye movement disturbances (EMD). The aim of this preliminary study was to investigate how individual class I and II HLA antigens in schizophrenic patients may be related to schizophrenia and to the intensity of two kinds of EMD: fixation and smooth pursuit. The incidence of HLA antigens was compared between 40 schizophrenic patients (17 male, 23 female) and 198 healthy control subjects (112 male, 86 female). In schizophrenic patients, the intensity of EMD assessed by infrared reflectometry and quantified on a scale from 0 to 3 was correlated with the incidence of HLA antigens. A number of differences regarding HLA antigens were found between schizophrenic patients and healthy subjects. Significant correlation was also obtained between some EMD and a number of HLA antigens. Antigens A24 and A28 were found to occur in different frequencies in schizophrenic patients and healthy control subjects. They also correlated with EMD on the fixation and smooth pursuit tests. The results obtained show an association between HLA antigens and EMD as an endophenotypic marker of schizophrenia, and may add to other findings on susceptibility loci for schizophrenia on chromosome 6p21. A limitation of this study is a small number of investigated patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 5 | Psychopharmacology (Berl.) 2005 Jun 179: 725-32 |
| PMID | 15619109 |
| Title | Selective serotonin 5-HT2A receptor antagonist EMD 281014 improves delayed matching performance in young and aged rhesus monkeys. |
| Abstract | The superior cognitive effects of atypical neuroleptics over typical agents reported in the schizophrenia literature are often attributed to the more prominent antagonist activity of the atypical drugs at serotonin 5HT(2A) receptors. However, atypical neuroleptics also have activity at many additional neurotransmitter receptors and few studies have specifically (and prospectively) tested the hypothesis that 5HT(2A) antagonism alone results in enhanced cognitive function. The purpose of this study was to evaluate the selective 5-HT(2A) antagonist, 7-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl}-1H-indole-3-carbonitrile HCl (EMD 281014) in young and aged monkeys in a test designed to assess working memory function. Four oral doses (0.1, 1.0, 3.0, and 10.0 mg/kg) of EMD 281014 were evaluated in six young adult (mean age=9.2 years) and eight aged rhesus macaques (mean age=24.9 years) trained to perform a computer-assisted delayed matching-to-sample (DMTS) task. Depending on dose, EMD 281014 improved DMTS accuracy in young and aged monkeys primarily at either the medium or long retention intervals. While the latencies associated with incorrect color selections (choices latencies) tended to be longer than those associated with correct selections (particularly in the aged subjects) under baseline conditions, there were no significant effects of EMD 281014 on either sample or choice latencies in either age group. In addition, no adverse effects were observed across the range of doses evaluated in either cohort of animals. These experiments, conducted in a non-human primate model, suggest that selective 5HT(2A) antagonists such as EMD 281014 could offer therapeutic benefit to younger and older psychiatric patients by improving working memory function. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 6 | Brain Cogn 2008 Dec 68: 436-61 |
| PMID | 18930572 |
| Title | Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. |
| Abstract | Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 7 | Prz. Lek. 2010 -1 67: 674-6 |
| PMID | 21387803 |
| Title | [The empirical mode decomposition and Lempel-Ziv complexity. The new possibility in diagnosis of EEG in schizophrenic patients?]. |
| Abstract | Over the last few decades, numerous attempts have been made to identify electroencephalographic (EEG) manifestations of schizophrenia. However, clinical applicability of these studies has not been demonstrated. A novel approach to EEG analysis which is based on combination of two methods of time series analysis was presented. Empirical mode decomposition is used to decompose a signal into several independent mode functions (IMF). Then, Lempel-Ziv complexity is used to quantify variability of such modes. We dub this approach EMD-LZC analysis. We carry out EMD-LZC analysis of EEG (performed according to 10-20 standard) of 21 healthy volunteers and 19 schizophrenic patients who were not medicated for at least a week. We find that variability of the third IMF mode is lower in the patients. The statistically significant differences were observed in 14 channels. Interestingly enough, the Fourier power spectra of both cohorts were not statistically different in any of 19 EEG channels. Unlike traditional spectral analysis, the combination of empirical mode decomposition and Lempel-Ziv complexity enabled us to identify the properties of EEG that are affected by schizophrenia. The future, more extensive, studies should verify the applicability of the proposed algorithm to diagnostics of schizophrenia. Moreover, we would like to link the observed differences in EEG variability to the pathogenesis of this disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 8 | Prz. Lek. 2010 -1 67: 674-6 |
| PMID | 21387803 |
| Title | [The empirical mode decomposition and Lempel-Ziv complexity. The new possibility in diagnosis of EEG in schizophrenic patients?]. |
| Abstract | Over the last few decades, numerous attempts have been made to identify electroencephalographic (EEG) manifestations of schizophrenia. However, clinical applicability of these studies has not been demonstrated. A novel approach to EEG analysis which is based on combination of two methods of time series analysis was presented. Empirical mode decomposition is used to decompose a signal into several independent mode functions (IMF). Then, Lempel-Ziv complexity is used to quantify variability of such modes. We dub this approach EMD-LZC analysis. We carry out EMD-LZC analysis of EEG (performed according to 10-20 standard) of 21 healthy volunteers and 19 schizophrenic patients who were not medicated for at least a week. We find that variability of the third IMF mode is lower in the patients. The statistically significant differences were observed in 14 channels. Interestingly enough, the Fourier power spectra of both cohorts were not statistically different in any of 19 EEG channels. Unlike traditional spectral analysis, the combination of empirical mode decomposition and Lempel-Ziv complexity enabled us to identify the properties of EEG that are affected by schizophrenia. The future, more extensive, studies should verify the applicability of the proposed algorithm to diagnostics of schizophrenia. Moreover, we would like to link the observed differences in EEG variability to the pathogenesis of this disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 9 | Br. J. Pharmacol. 2012 Sep 167: 436-49 |
| PMID | 22568655 |
| Title | 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. |
| Abstract | 5-HT(6) receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT(6) receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT(6) receptor agonists have been found to enhance and impair memory. The conditioned emotion response (CER) paradigm was validated in rats. Then we examined the effect of the 5-HT(6) receptor antagonist, EMD 386088 (10 mg·kg(-1) , i.p.), and agonists, E-6801 (2.5 mg·kg(-1) , i.p.) and EMD 386088 (5 mg·kg(-1) , i.p.) on CER-induced behaviour either alone or after induction of memory impairment by the muscarinic receptor antagonist, scopolamine (0.3 mg·kg(-1) , i.p) or the NMDA receptor antagonist, MK-801 (0.1 mg·kg(-1) , i.p). Pairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory when the rat was returned to the shock chamber 24 h later. Pretreatment (-20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT(6) receptor antagonist, SB-270146, and agonists, EMD 386088 and E-6801, had little effect on CER freezing when given alone, but all significantly reversed scopolamine- and MK-801-induced reduction in freezing. CONCLUSION AND IMPLICATIONS Both the 5-HT(6) receptor agonists and antagonist reversed cholinergic- and glutamatergic-induced deficits in associative learning. These findings support the therapeutic potential of 5-HT(6) receptor compounds in the treatment of cognitive dysfunction, such as seen in Alzheimer's disease and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 10 | J. Psychopharmacol. (Oxford) 2013 May 27: 469-76 |
| PMID | 23479455 |
| Title | The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats. |
| Abstract | Preclinical data suggest that the 5-hydroxytryptamine (serotonin) 6 (5-HT6) receptor may be a potential target for the development of new therapies for treating cognitive dysfunctions in schizophrenia and other central nervous system disorders. Recent evidence indicates that not only blockade but also activation of 5-HT6 receptors exerts procognitive effects. Nevertheless, little is known about the potential efficacy of 5-HT6 receptor agonists in models of schizophrenia-like cognitive deficits. The aim of the present study was to evaluate the effects of the 5-HT6 receptor agonist, EMD 386088, on the ketamine-induced deficits in the attentional set-shifting task (ASST), novel object recognition (NOR) task and prepulse inhibition (PPI) task in rats. Acute administration of EMD 386088 (2.5 and 5 mg/kg, intraperitoneally) to Sprague-Dawley rats reversed the deficit in the ASST induced by repeated ketamine administration. Moreover, the ketamine-induced deficit in the NOR task was ameliorated by EMD 386088 at a dose of 5 mg/kg. However, in contrast to the antipsychotic drug clozapine, the 5-HT6 agonist did not affect PPI disrupted by ketamine. The present study demonstrated the beneficial effects of the 5-HT6 agonist in ameliorating some of the ketamine-induced deficits relevant to schizophrenia. It thus seems likely that the 5-HT6 receptor activation may represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 11 | Schizophr. Res. 2014 Jun 156: 60-2 |
| PMID | 24768130 |
| Title | It is all in the factors: effects of cognitive remediation on symptom dimensions. |
| Abstract | Cognitive remediation (CR) aims primarily to improve cognition and functional outcomes. However, a limited number of studies reported a positive effect on symptoms. This limited effect may be because the symptom clusters considered are too broad and heterogeneous. This study explores, for the first time, the effect of CR on five empirically defined symptom dimensions of schizophrenia. Participants were patients with schizophrenia taking part in a randomised controlled trial comparing CR plus treatment as usual (CR, N=43) to treatment as usual (TAU, N=42). All participants were assessed at baseline and 14-weeks (i.e. at the conclusion of treatment for the CR group) with the Positive and Negative Symptoms Scale (PANSS). Five symptom dimensions were derived from the PANSS scores: Positive (POS), Negative (NEG), Disorganised (DIS), Excited (EXC) and Emotional Distressed (EMD). After CR, the therapy group had a significant reduction in DIS and NEG symptom dimensions compared to the TAU group. The traditional PANSS factors showed no effect of CR on symptoms. CR can have not only a positive effect on disorganisation but also on negative symptoms. Using detailed symptom dimensions can characterise more accurately the effect of CR on symptom of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |