The distinction between positive and negative symptoms has gained prominence in schizophrenia research, but the construct has not been unequivocally validated. The authors report preliminary findings of investigations in which symptomatic and neuropsychological assessments were conducted in a sample of 32 chronic schizophrenic inpatients. Three distinct clusters of symptoms were identified in correlative analyses. One cluster of symptoms (alogia, attentional impairment, positive formal though disorder, and bizarre behavior) appeared to reflect primarily a disorganization of though independent of current definitions of the positive/negative symptom construct. A second cluster of symptoms (affective flattening, avolition/apathy, and anhedonia) appeared to reflect predominantly blunting of affect and volition. A third cluster (delusions, hallucinations, and "breadth of psychosis") seemed to represent only the florid psychotic features. The first and (to a lesser extent) second clusters of symptoms were selectively associated with neuropsychological impairment. The patterns of neuropsychological deficits correlated with the first cluster of symptoms appeared to be consistent with a process characterized by failure in the development of a normal repertoire of cognitive abilities. It is suggested that the "defect state" may not be a monothetic construct, and that within the domain of "type II" schizophrenia, disturbances of thought may be distinguished from those of affect and motivation.
"The symptoms of SZ have different dimensions that usually occur together and can reflect substantial variation among patient phenotypes
[8-10]. Different researchers have formulated various models of these dimensions but the most widely appreciated 3D models were first proposed by Bilder et al. and Liddle
[9,11]. These authors concluded that the main symptoms are poverty of speech, formal thought disorder, decreased voluntary movement, psychomotor impairment, bizarre behavior, hallucinations, abnormal acts, inappropriate affects, flat affects, flattening, avolition, and alogia. "
[Show abstract][Hide abstract] ABSTRACT: Background
Schizophrenia is a neurodegenerative disorder that occurs worldwide and can be difficult to diagnose. It is the foremost neurological disorder leading to suicide among patients in both developed and underdeveloped countries. D-amino acid oxidase activator (DAOA), also known as G72, is directly implicated in the glutamateric hypothesis of schizophrenia. It activates D-amino acid oxidase, which oxidizes D-serine, leading to modulation of the N-methyl-D-aspartate receptor.
MODELLER (9v10) was utilized to generate three dimensional structures of the DAOA candidate gene. The HOPE server was used for mutational analysis. The Molecular Evolutionary Genetics Analysis (MEGA5) tool was utilized to reconstruct the evolutionary history of the candidate gene DAOA. AutoDock was used for protein-ligand docking and Gramm-X and PatchDock for protein-protein docking.
A suitable template (1ZCA) was selected by employing BLASTp on the basis of 33% query coverage, 27% identity and E-value 4.9. The Rampage evaluation tool showed 91.1% favored region, 4.9% allowed region and 4.1% outlier region in DAOA. ERRAT demonstrated that the predicted model had a 50.909% quality factor. Mutational analysis of DAOA revealed significant effects on hydrogen bonding and correct folding of the DAOA protein, which in turn affect protein conformation. Ciona was inferred as the outgroup. Tetrapods were in their appropriate clusters with bifurcations. Human amino acid sequences are conserved, with chimpanzee and gorilla showing more than 80% homology and bootstrap value based on 1000 replications. Molecular docking analysis was employed to elucidate the binding mode of the reported ligand complex for DAOA. The docking experiment demonstrated that DAOA is involved in major amino acid interactions: the residues that interact most strongly with the ligand C28H28N3O5PS2 are polar but uncharged (Gln36, Asn38, Thr 122) and non-polar hydrophobic (Ile119, Ser171, Ser21, Ala31). Protein-protein docking simulation demonstrated two ionic bonds and one hydrogen bond involving DAOA. Lys-7 of the receptor protein interacted with Lys-163 and Asp-2037. Tyr-03 interacted with Arg-286 of the ligand protein and formed a hydrogen bond.
The predicted interactions might serve to inhibit the disease-related allele. It is assumed that current bioinformatics methods will contribute significantly to identifying, analyzing and curing schizophrenia. There is an urgent need to develop effective drugs for schizophrenia, and tools for examining candidate genes more accurately and efficiently are required.
Theoretical Biology and Medical Modelling 01/2013; 10(1):3. DOI:10.1186/1742-4682-10-3 · 0.95 Impact Factor
"Several authors have drawn attention to the striking resemblance between the exploratory and confirmatory factorial solutions of the signs and symptoms of schizotypy and those observed in schizophrenia. Thus, the dimensions of positive, negative and disorganisation symptoms reported in schizophrenia (Bilder et al., 1985; Liddle, 1987; Peralta et al., 1992) are comparable to similarly construed dimensions in schizotypy (Bentall et al., 1989; Claridge, 1990; Gruzelier, 1996; Raine et al., 1994; Venables & Bailes, 1994; Vollema & Hoijtink, 2000; Vollema & van den Bosch, 1995). These findings suggest that psychosis may exist as a continuum of variation along various comorbid symptom dimensions (van Os et al., 1999). "
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a severe mental illness that affects 1% of the population. The diagnosis is made according to current diagnostic systems of DSM-IV (American Psychiatric Association, 1994) and ICD-10 (World Health Organisation, 1992), on the basis of characteristic 'positive' and 'negative' symptoms. The traditional model assumes a categorical view of the schizophrenia syndrome and its core symptoms, in which differences between psychotic symptoms and their normal counterparts are considered to be qualitative. An alternative, dimensional approach assumes that schizophrenia is not a discrete illness entity, but that psychotic symptoms differ in quantitative ways from normal experiences and behaviours. This paper reviews evidence for the continuity of psychotic symptoms with normal experiences, focusing on the symptoms of hallucinations and delusions.
A qualitative review of the relevant literature.
The literature suggests that although current epidemiological approaches yield substantial evidence for a continuum view, it is rarely interpreted as such.
The traditional concept of schizophrenia as a homogeneous disease entity has become outdated and is in dire need of a more valid and clinically useful successor.
"Negative schizotypy and schizophrenia are characterized by deficits such as affective flattening, anhedonia , social disinterest, and diminution of cognitive functioning . While there is not a universally agreed upon latent structure of schizotypy, the proposed factors appear consistent with those hypothesized to comprise schizophrenia (Bilder et al., 1985; Liddle, 1987; Peralta et al., 1992), supporting the hypothesis that the vulnerability to schizophrenia is expressed across the continuum of schizotypy. "
[Show abstract][Hide abstract] ABSTRACT: Personality traits such as neuroticism are associated with schizophrenia and schizotypy. However, studies thus far have not clarified the differential association of neuroticism with individual schizotypy dimensions and the role it plays in the expression of schizophrenia-spectrum psychopathology. 204 nonclinically ascertained participants completed self-report questionnaires assessing neuroticism and the positive and negative schizotypy dimensions, and underwent structured interviews assessing schizophrenia-spectrum psychopathology (psychotic-like experiences, negative symptoms, cluster A personality disorders and traits), mood episodes, substance abuse, and global functioning. Results indicated that neuroticism predicted positive symptoms of schizophrenia and depression, over-and-above the effects of both schizotypy dimensions. Also, neuroticism moderated the association of positive schizotypy with interview measures of psychopathology and functioning. The results of this study are consistent with other research indicating that neuroticism is etiologically relevant for schizophrenia-spectrum psychopathology and that it cannot be considered solely a 'secondary effect' of spectrum disorders. Current psychological models of psychosis can accomodate the finding of neuroticism being a shared vulnerability factor for affective and psychotic disorders.
Schizophrenia Research 10/2009; 115(2-3):303-9. DOI:10.1016/j.schres.2009.09.021 · 3.92 Impact Factor
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