1Schizophr. Res. 2006 Jul 85: 12-9
PMID16624531
TitleThree dimensions of clinical symptoms in elderly patients with schizophrenia: prediction of six-year cognitive and functional status.
AbstractA three-syndrome categorization of schizophrenia has been recently proposed [Arndt, S., Alliger R.J., Andreasen, N.C., 1991. The distinction of positive and negative symptoms: the failure of a two-dimensional model. Br. J. Psychiatry 158, 317-322; Miller, D.D., Arndt, S., Andreasen, N.C., 1993. Alogia, attentional impairment, and inappropriate affect: their status in the dimensions of schizophrenia. COMP. Psychiatry 34, 221-226; Gur, R.E., Mozley, D., Resnick, S.M., Levick, S., Erwin, R., Saykin, A.J., Gur, R.C., 1991. Relations among clinical scales in schizophrenia. Am. J. Psychiatry 148, 472-478. Brown, K.W., White, T., 1992. Syndromes of chronic schizophrenia and some clinical correlates. Br. J. Psychiatry 161, pp. 317-322].
Chronic, elderly, schizophrenia patients with deficit (N = 111), nondeficit with High reality distortion/Low conceptual disorganization (nondeficit-delusional) (N = 40) and nondeficit with Low reality distortion/High conceptual disorganization (nondeficit-disorganized) (N = 56) were followed-up for 6 years. Assessment included the Positive and Negative Syndrome Scale (PANSS), the Mini-mental Status Examination (MMSE) and the Alzheimer's Disease Assessment-Late Stage Cognitive and Non-Cognitive Subscale (ADAS-L Cog and ADAS-L Self care).
At initial assessment, MMSE scores were significantly lower, while the ADAS-L Cog and Negative symptoms were significantly higher in the deficit and nondeficit-disorganized groups COMPared with the nondeficit-delusional group (all p values <0.05). Positive symptoms were significantly lower in the deficit group than in both nondeficit syndrome groups (p < 0.05). On the ADAS-L Self Care scale the nondeficit-delusional group was the most impaired while the nondeficit-disorganized was the least impaired. There was a significant decline over time in MMSE scores in the deficit and the nondeficit-delusional groups (p < 0.01), but no change in the nondeficit-disorganized group. ADAS-L Cog and ADAS-L Self Care functions worsened over time in all three groups (p < 0.0001). Severity of negative symptoms was stable over time in deficit patients and in nondeficit-disorganized patients but worsened in nondeficit-delusional patients (p < 0.001). There was also a significant worsening of positive symptoms over time in deficit patients (p = 0.04).
Deficit, nondeficit-delusional and nondeficit-disorganized patients with schizophrenia may represent distinct subgroups discriminated by different courses in negative and positive symptoms and cognitive status.
SCZ Keywordsschizophrenia, schizophrenic
2J. Comp. Neurol. 2009 Aug 515: 454-64
PMID19459221
TitleSelective reduction of neuron number and volume of the mediodorsal nucleus of the thalamus in macaques following irradiation at early gestational ages.
AbstractNeurons in the macaque brain arise from progenitors located near the cerebral ventricles in a temporally segregated manner such that lethal doses of ionizing irradiation, if administered over a discrete time interval, can deplete individual nuclei selectively. A previous study showed that neuron number in the dorsal lateral geniculate nucleus is reduced following early gestational exposure to x-irradiation (Algan and Rakic [1997] J. COMP. Neurol. 12:335-352). Here we examine whether similarly timed irradiation decreases neuron number in three associational thalamic nuclei: mediodorsal (MD), anterior, and pulvinar. Ten macaques were exposed to multiple doses of x-rays (total exposure (175-350 cGy) in early gestation (E33-E42) or midgestation (E70-E90); eight nonirradiated macaques were controls. Only the early-irradiated monkeys, not the midgestationally irradiated animals, exhibited deficits in whole-thalamic neuron (-15%) and glia numbers (-21%) COMPared with controls. Reduction of neuron number (-26%) and volume (-29%) was particularly pronounced in MD. In contrast, cell number and volume were not significantly decreased in the anterior or pulvinar nuclei following early gestational irradiation. Thus, reduced thalamic neuron number was associated specifically with irradiation in early gestation. Persistence of the thalamic neuronal deficit in adult animals indicates that prenatally deleted neurons had not been replenished during maturation or in adulthood. The selective reduction of MD neuron number also supports the protomap hypothesis that neurons of each thalamic nucleus originate sequentially from separate lines of neuronal stem cells (Rakic [1977a] J. COMP. Neurol. 176:23-52). The early gestationally irradiated macaque is discussed as a potentially useful model for studying the neurodevelopmental pathogenesis of schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic
3J. Biomol. Struct. Dyn. 2011 Apr 28: 695-715
PMID21294583
TitleIn search of allosteric modulators of a7-nAChR by solvent density guided virtual screening.
AbstractNicotinic acetylcholine receptors (nAChR) are pentameric ligand gated ion channels whose activity can be modulated by endogenous neurotransmitters as well as by synthetic ligands that bind the same or distinct sites from the natural ligand. The subtype of ?7 nAChR has been considered as a potenial therapeutic target for Alzheimer's disease, schizophrenia and other neurological and psychiatric disorders. Here we have developed a homology model of ?7 nAChR based on two high resolution crystal structures with Brookhaven Protein Data Bank (PDB) codes 2QC1 and 2WN9 for threading on one monomer and then for building a pentamer, respectively. A number of small molecule binding sites are identified using Pocket Finder (J. An, M. Tortov, and R. Abagyan, Molecular & Cellular Proteomics, 4.6, 752-761 (2005)) of Internal Coordinate Mechanics (ICM). Remarkably, these COMPuter-identified sites match perfectly with ordered solvent densities found in the high-resolution crystal structure of ?1 nAChR, suggesting that the surface cavities in the ?7 nAChR model are likely binding sites of small molecules. A high throughput virtual screening by flexible ligand docking of 5008 small molecule COMPounds was performed at three potential allosteric modulator (AM) binding sites of ?7 nAChR using Molsoft ICM software (R. Abagyan, M. Tortov and D. Kuznetsov, J COMPut Chem 15, 488-506, (1994)). Some experimentally verified allosteric modulators of ?7 like CCMI COMP-6, LY 7082101, 5-HI, TQS, PNU-120596, genistein, and NS-1738 ranked among top 100 COMPounds, while the rest of the COMPounds in the list could guide further search for new allosteric modulators.
SCZ Keywordsschizophrenia, schizophrenic
4J Pers Assess 2013 -1 95: 471-8
PMID23844937
TitleA comparison of new and revised Rorschach measures of schizophrenic functioning in a Serbian clinical sample.
AbstractWe empirically evaluated indexes derived from the Rorschach COMPrehensive System (CS) and the Rorschach Performance Assessment System (R-PAS) that are used for the assessment of psychotic functioning in schizophrenia. We COMPared the Perceptual Thinking Index (PTI) and the Ego Impairment Index (EII-2) with their revised versions: Thought and Perception COMPosite (TP-COMP) and EII-3. We evaluated their predictive validity for differentiating schizophrenic from nonschizophrenic patients in a Serbian sample. The sample consisted of 211 (109 men and 102 women, 18-50years old) inpatients in Serbia who were divided into 2 groups: schizophrenic (100) and nonschizophrenic (111). Test administration, coding, and form quality classification followed CS guidelines. Logistic regression analysis indicated that the new indexes TP-COMP and EII-3 have slightly better predictive power than their counterparts, PTI and EII-2, in identification of schizophrenia, and that TP-COMP performed better than other indexes, although all 4 indexes were successful in differentiating these groups. The results supported the use of TP-COMP in diagnosis of schizophrenia and generally provided evidence for the utility of the Rorschach in evaluating psychosis and for its use in a cross-national context.
SCZ Keywordsschizophrenia, schizophrenic
5J Pers Assess 2013 -1 95: 471-8
PMID23844937
TitleA comparison of new and revised Rorschach measures of schizophrenic functioning in a Serbian clinical sample.
AbstractWe empirically evaluated indexes derived from the Rorschach COMPrehensive System (CS) and the Rorschach Performance Assessment System (R-PAS) that are used for the assessment of psychotic functioning in schizophrenia. We COMPared the Perceptual Thinking Index (PTI) and the Ego Impairment Index (EII-2) with their revised versions: Thought and Perception COMPosite (TP-COMP) and EII-3. We evaluated their predictive validity for differentiating schizophrenic from nonschizophrenic patients in a Serbian sample. The sample consisted of 211 (109 men and 102 women, 18-50years old) inpatients in Serbia who were divided into 2 groups: schizophrenic (100) and nonschizophrenic (111). Test administration, coding, and form quality classification followed CS guidelines. Logistic regression analysis indicated that the new indexes TP-COMP and EII-3 have slightly better predictive power than their counterparts, PTI and EII-2, in identification of schizophrenia, and that TP-COMP performed better than other indexes, although all 4 indexes were successful in differentiating these groups. The results supported the use of TP-COMP in diagnosis of schizophrenia and generally provided evidence for the utility of the Rorschach in evaluating psychosis and for its use in a cross-national context.
SCZ Keywordsschizophrenia, schizophrenic
6J. Comp. Neurol. 2016 Aug 524: 2281-99
PMID26669716
TitleImmunocytochemical heterogeneity of somatostatin-expressing GABAergic interneurons in layers II and III of the mouse cingulate cortex: A combined immunofluorescence/design-based stereologic study.
AbstractMany neurological diseases including major depression and schizophrenia manifest as dysfunction of the GABAergic system within the cingulate cortex. However, relatively little is known about the properties of GABAergic interneurons in the cingulate cortex. Therefore, we investigated the neurochemical properties of GABAergic interneurons in the cingulate cortex of FVB-Tg(GadGFP)45704Swn/J mice expressing green fluorescent protein (GFP) in a subset of GABAergic interneurons (GFP-expressing inhibitory interneurons [GINs]) by means of immunocytochemical and design-based stereologic techniques. We found that GINs represent around 12% of all GABAergic interneurons in the cingulate cortex. In contrast to other neocortical areas, GINs were only found in cortical layers II and III. More than 98% of GINs coexpressed the neuropeptide somatostatin (SOM), but only 50% of all SOM?+?neurons were GINs. By analyzing the expression of calretinin (CR), calbindin (CB), parvalbumin, and various neuropeptides, we identified several distinct GIN subgroups. In particular, we observed coexpression of SOM with CR and CB. In addition, we found neuropeptide Y expression almost exclusively in those GINs that coexpressed SOM and CR. Thus, with respect to the expression of calcium-binding proteins and neuropeptides, GINs are surprisingly heterogeneous in the mouse cingulate cortex, and the minority of GINs express only one marker protein or peptide. Furthermore, our observation of overlap between the SOM?+?and CR?+?interneuron population was in contrast to earlier findings of non-overlapping SOM?+?and CR?+?interneuron populations in the human cortex. This might indicate that findings in mouse models of neuropsychiatric diseases may not be directly transferred to human patients. J. COMP. Neurol. 524:2281-2299, 2016. 2015 Wiley Periodicals, Inc.
SCZ Keywordsschizophrenia, schizophrenic