Nondeficit Syndrome Research Articles

ROI-based analysis of diffusion indices in healthy subjects and subjects with deficit or non-deficit syndrome schizophrenia

We analyzed DTI data involving 22 healthy subjects (HC), 15 patients with deficit syndrome schizophrenia (DSZ), and 25 patients with non-deficit syndrome schizophrenia (NDSZ). We used a 1.5-T MRI scanner to collect diffusion-weighted images and T1 images, which were employed to correct distortions and deformations within the diffusion-weighted images. For 156 regions of interest (ROI), we calculated the average fractional anisotropy (FA), mean diffusion (MD), and radial diffusion (RD). Each ROI underwent a group-wise comparison using permutation F-test, followed by post hoc pairwise comparisons with Bonferroni correction. In general, we observed lower FA in both schizophrenia groups compared to HC (i.e., HC>(DSZ=NDSZ)), while MD and RD showed the opposite pattern. Notably, specific ROIs with reduced FA in schizophrenia patients included bilateral nucleus accumbens, left fusiform area, brain stem, anterior corpus callosum, left rostral and caudal anterior cingulate, right posterior cingulate, left thalamus, left hippocampus, left inferior temporal cortex, right superior temporal cortex, left pars triangularis and right lingual gyrus. Significantly, the right cuneus exhibited lower FA in the DSZ group compared to other groups ((HC=NDSZ)>DSZ), without affecting MD and RD. These results indicate that compromised neural integrity in the cuneus may contribute to the pathophysiological distinctions between DSZ and NDSZ.

Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Corpus callosum in schizophrenia with deficit and non-deficit syndrome: a statistical shape analysis

BackgroundThe corpus callosum (CC) is the most targeted region in the cerebrum that integrates cognitive data between homologous areas in the right and left hemispheres.AimsOur study used statistical analysis to...

Predicting Persisting Disability in Schizophrenia: The Potential of Neuroimaging

SEE CORRESPONDING ARTICLE ON PAGE 665 Resting-State Connectivity Biomarkers of Cognitive Performance and Social Function in Individuals With Schizophrenia Spectrum Disorder and Healthy Control SubjectsBiological PsychiatryVol. 84Issue 9PreviewDeficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome). Full-Text PDF

Affective modulation of target detection in deficit and non-deficit schizophrenia

Emotional deficits are an integral feature of schizophrenia (SZ), but our understanding of these deficits is limited. In the present study, we examined whether the severity of emotional deficits reflects difficulty in the cognitive processing of affectively valenced stimuli. Healthy controls (HC; N = 170) and stable outpatients with SZ (N = 245), characterized as either deficit syndrome (DS; N = 62) or non-deficit syndrome (NDS; N = 183), completed an Affective Go/NoGo task requiring discrimination of positively, negatively or neutrally valenced words. Accuracy (d′) and response bias (c) were calculated for each of the three conditions, and a series of ANOVAs were carried out to examine group differences. Examination of accuracy revealed significant main effects of group and valence and a significant valence × group interaction, indicating that while affective valence impacted accuracy for the HC and NDS groups, the DS group maintained the same low level of accuracy across all levels of affective valence. Examination of response bias also revealed significant main effects of group and valence and a significant valence × group interaction. Specifically, within the HC and NDS groups, response bias did not differ between negatively and positively valenced words while response bias in the DS group was lowest for neutral, higher for negatively valenced and higher still for positively valenced words. These results suggest that emotional deficits in DS may be directly related to deficits in processing affective information. Moreover, although this deficit is observed across both positively and negatively valenced stimuli, it is most pronounced for positively valenced material.

Resting-State Connectivity Biomarkers of Cognitive Performance and Social Function in Individuals With Schizophrenia Spectrum Disorder and Healthy Control Subjects

BackgroundDeficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome). MethodsWe evaluated a fully data-driven approach to do the same by building and validating a brain connectivity–based biomarker of social cognitive and neurocognitive performance in a sample using resting-state and task-based functional magnetic resonance imaging (n = 74 healthy control participants, n = 114 persons with schizophrenia spectrum disorder, 188 total). We used canonical correlation analysis followed by clustering to identify a functional connectivity signature of normal and poor social cognitive and neurocognitive performance. ResultsPersons with poor social cognitive and neurocognitive performance were differentiated from those with normal performance by greater resting-state connectivity in the mirror neuron and mentalizing systems. We validated our findings by showing that poor performers also scored lower on functional outcome measures not included in the original analysis and by demonstrating neuroanatomical differences between the normal and poorly performing groups. We used a support vector machine classifier to demonstrate that functional connectivity alone is enough to distinguish normal and poorly performing participants, and we replicated our findings in an independent sample (n = 75). ConclusionsA brief functional magnetic resonance imaging scan may ultimately be useful in future studies aimed at characterizing long-term illness trajectories and treatments that target specific brain circuitry in those with impaired cognition and function

P.3.d.036 - Are there differences in the antipsychotic load between deficit and non-deficit syndrome in first-episode schizophrenia?

The aim of the present study is to develop novel approach for the green synthesis of titanium oxide nanoparticles (TiO2 NPs) using Eichhornia crassipes extract and calcined at different temperatures for evaluate the wound healing activity in the femoral fracture. The synthesized TiO2 are formed different (plate and rod-like) nanostructures at various calcination temperatures. These samples were characterized by X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), Field emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). Microscopic studies of TiO2 NPs revealed that the synthesized TiO2 NPs are formed well-defined rod-like structures at 400 °C with size ranged from 200 nm to 500 nm. The characterized plate and rod-like TiO2 NPs are combined with human morphogenetic protein (HbMP) to improving its wound healing activity and osteoblast properties on femoral fractures. The biocompatibility was tested by using human bone marrow mesenchymal stem cells (BMSC) cells and antibacterial efficacy analyzed using human pathogenica bacteria Staphylococcus aureus and Escherichia coli through agar well diffusion assay. The green synthesized rod-like TiO2 NPs combined with HbMP has been exhibited effective bone fusion behaviors with biomechanical properties and also improved antibacterial activity against pathogenic bacteria. From this study results, it is suggested that green synthesized TiO2NPs could be used effectively in biomedical application.

Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome.

BackgroundBrain-derived neurotrophic factor (BDNF) is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls.MethodsAfter fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23) and nondeficit syndrome (N=35) according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels.ResultsThe groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls.ConclusionThis study suggests that decreased BDNF levels may play a role in the pathophysiology of schizophrenic patients with deficit syndrome. Nonetheless, additional studies using a larger patient sample size are needed to investigate the serum BDNF levels in schizophrenic patients with deficit syndrome.

Impaired processing speed and attention in first-episode drug naive schizophrenia with deficit syndrome

Although first-episode drug naive patients with schizophrenia are known to show cognitive impairment, the cognitive performances of these patients, who suffer deficit syndrome, compared with those who suffer non-deficit syndrome is undetermined. The aim of this study was to compare cognitive performances in first-episode drug-naive schizophrenia with deficit syndrome or non-deficit syndrome. First-episode drug naive patients (n=49) and medicated patients (n=108) with schizophrenia, and age, sex, and education matched healthy controls (n=57 for the first-episode group, and n=128 for the medicated group) were enrolled. Patients were divided into deficit or non-deficit syndrome groups, using the Schedule for Deficit Syndrome. Cognitive performance was assessed using the CogState computerized cognitive battery. All cognitive domains in first-episode drug naive and medicated patients showed significant impairment compared with their respective control groups. Furthermore, cognitive performance in first-episode drug naive patients was significantly worse than in medicated patients. Interestingly, the cognitive performance markers of processing speed and attention, in first-episode drug naive patients with deficit syndrome, were both significantly worse than in equivalent patients without deficit syndrome. In contrast, no differences in cognitive performance were found between the two groups of medicated patients. In conclusion, this study found that first-episode drug naive schizophrenia with deficit syndrome showed significantly impaired processing speed and attention, compared with patients with non-deficit syndrome. These findings highlight processing speed and attention as potential targets for pharmacological and psychosocial interventions in first-episode schizophrenia with deficit syndrome, since these domains are associated with social outcomes.

Comparison of serum BDNF levels in deficit and nondeficit chronic schizophrenia and healthy controls

The aim of this study was to compare serum BDNF levels of chronic schizophrenic patients, with or without deficit syndrome, and healthy controls. A comparative study of serum BDNF levels, determined by ELISA, was performed in 47 chronic patients with schizophrenia matched with 47 healthy controls. A part of the chronic schizophrenic sample was further divided into patients with a deficit (n=14) and a nondeficit syndrome (n=20), according to the Proxy for the Deficit Syndrome Scale. A significant difference was observed in decreased serum BDNF levels between chronic schizophrenia and healthy controls. No statistical significant differences in BDNF levels between deficit and nondeficit chronic schizophrenic patients were found. Our study confirms differences of serum BDNF levels of chronic schizophrenia and healthy controls, which correspond to the clinical progression of the disease. Our results do not support a relation between deficit profile in chronic schizophrenia and lower serum BDNF levels.

Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia

Research investigating the association between negative symptoms and plasma cortisol levels in individuals with schizophrenia has produced inconsistent findings. This study investigated whether deficit syndrome schizophrenia (characterized by high levels of primary negative symptoms) is associated with comparatively high morning plasma cortisol levels, more negative appraisals about illness and higher levels of depression. Participants were 85 individuals diagnosed with schizophrenia and 85 individuals with no history of contact with psychiatric services matched for age and gender. All participants provided fasting 9.00a.m. plasma cortisol samples. There were no significant differences between the schizophrenia and control participants in plasma cortisol levels. The Proximal Deficit Syndrome method was used to identify individuals with deficit syndrome schizophrenia. Contrary to what had been hypothesized, participants with deficit syndrome schizophrenia had significantly lower plasma cortisol levels than both non-deficit syndrome participants and control participants. Participants with the deficit syndrome reported significantly less negative appraisals about illness (assessed by PBIQ) and lower levels of depression (assessed by BDI-II). Differences in cortisol levels continued to trend toward significance when levels of depression were controlled for. The patterns of illness-related appraisals and plasma cortisol levels raise the possibility that the deficit syndrome could be a form of adaptation syndrome.

Using negative feedback to guide behavior: Impairments on the first 4 cards of the Wisconsin Card Sorting Test predict negative symptoms of schizophrenia

Research has demonstrated that individuals with schizophrenia fail to appropriately use negative feedback to guide learning. These learning deficits are thought to arise from abnormalities in midbrain dopamine activity. Primary and enduring negative symptoms are also associated with abnormal dopamine activity and are expected to produce more severe deficits in learning when they present in individuals with schizophrenia. The current study examines this matter by comparing individuals with deficit syndrome schizophrenia, which is characterized by primary and enduring negative symptoms, to individuals with nondeficit syndrome schizophrenia and to normal controls in their use of positive feedback and negative feedback to guide learning on the first four cards of the WCST. Participants included 67 individuals with schizophrenia (15 deficit; 52 nondeficit syndrome) and 51 healthy controls. Accuracy data from the first 4 cards of the WCST and measures of global test performance were examined. Individuals with schizophrenia were significantly less accurate than controls in their performance on early (pre-shift) WCST trials, and this impairment was significantly greater in patients with deficit than nondeficit schizophrenia. Additionally, accuracy across the first 4 WCST cards significantly predicted the number of categories completed and percentage of perseverative errors across the entire test. These findings suggest that negative symptoms of schizophrenia are associated with difficulty using negative feedback to adaptively guide behavior, and are consistent with the notion that abnormal DA signaling contributes to the higher-order executive functioning impairments seen in schizophrenia with severe negative symptoms.

Orbitofrontal cortex abnormality and deficit schizophrenia

Deficit syndrome, which is characterized by primary and enduring negative symptoms, is a homogeneous subtype within schizophrenia. Negative symptoms in schizophrenia are currently considered to be closely linked with frontal lobe impairment. However, the etiology in the frontal lobe of people with deficit syndrome is not fully understood. We measured regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) in 33 patients with deficit syndrome, 40 patients with nondeficit syndrome, and 45 healthy controls, and we compared groups using the voxel-wise method. Schizophrenia combined group, the deficit syndrome and the nondeficit syndrome presented hypoperfusion in mainly the medial and lateral prefrontal cortices. The deficit syndrome group showed a significant decrease in rCBF in the right orbitofrontal cortex (OFC) compared to the nondeficit group. These results demonstrated that at-rest hypofrontality was a common feature within the disease group and suggested that the OFC might play an important role in the development of severe negative symptoms in people with deficit syndrome.

A new nosology of psychosis and the pharmacological basis of affective and negative symptom dimensions in schizophrenia.

Although first rank symptoms focus on positive symptoms of psychosis they are shared by a number of psychiatric conditions. The difficulty in differentiating bipolar disorder from schizophrenia with affective features has led to a third category of patients often loosely labeled as schizoaffective. Research in schizophrenia has attempted to render the presence or absence of negative symptoms and their relation to etiology and prognosis more explicit. A dichotomous population is a recurring theme in experimental paradigms. Thus, schizophrenia is defined as process or reactive, deficit or non-deficit and by the presence or absence of affective symptoms. Laboratory tests confirm the clinical impression showing conflicting responses to dexamethasone suppression and clearly defined differences in autonomic responsiveness, but their patho-physiological significance eludes mainstream theory. Added to this is the difficulty in agreeing to what exactly constitutes useful clinical features differentiating, for example, negative symptoms of a true deficit syndrome from features of depression. Two recent papers proposed that the general and specific cognitive features of schizophrenia and major depression result from a monoamine-cholinergic imbalance, the former due to a relative muscarinic receptor hypofunction and the latter, in contrast, to a muscarinic hypersensitivity exacerbated by monoamine depletion. Further development of these ideas will provide pharmacological principles for what is currently an incomplete and largely, descriptive nosology of psychosis. It will propose a dimensional view of affective and negative symptoms based on relative muscarinic integrity and is supported by several exciting intracellular signaling and gene expression studies. Bipolar disorder manifests both muscarinic and dopaminergic hypersensitivity. The greater the imbalance between these two receptor signaling systems, the more the clinical picture will resemble schizophrenia with bizarre, incongruent delusions and increasingly disorganized thought. The capacity for affective expression, by definition a non-deficit syndrome, will remain contingent on the degree of preservation of muscarinic signaling, which itself may be unstable and vary between trait and state examinations. At the extreme end of muscarinic impairment, a deficit schizophrenia subpopulation is proposed with a primary and fixed muscarinic receptor hypofunction.The genomic profile of bipolar disorder and schizophrenia overlap and both have a common dopaminergic intracellular signaling which is hypersensitive to various stressors. It is proposed that the concomitant muscarinic receptor upregulation differentiates the syndromes, being marked in bipolar disorder and rather less so in schizophrenia. From a behavioral point of view non-deficit syndromes and bipolar disorder appear most proximate and could be reclassified as a spectrum of affective psychosis or schizoaffective disorders. Because of a profound malfunction of the muscarinic receptor, the deficit subgroup cannot express a comparable stress response. Nonetheless, a convergent principle of psychotic features across psychiatric disorders is a relative monoaminergic-muscarinic imbalance in signal transduction.

Olfactory Hedonic Judgment in Patients With Deficit Syndrome Schizophrenia

Olfactory perception was examined in deficit syndrome (DS) and nondeficit syndrome (ND) schizophrenia patients. Participants included 22 controls (CN) and 41 patients with schizophrenia who were divided into DS (n = 15) and ND (n = 26) subtypes using the Schedule for the Deficit Syndrome (SDS). Olfactory perception for pleasant and unpleasant odors was assessed using the Brief Smell Identification Test. Participants were instructed to identifying each smell as well as provide hedonic judgment ratings of each smell on a 7-point scale (1 = extremely pleasant, 4 = neutral, and 7 = extremely unpleasant). Results indicated that when compared with the ND patients, the DS patients rated pleasant smells as being significantly less pleasant, although no difference between the groups was present for unpleasant smells, and both ND and DS groups significantly differed from CN on rating and identifying pleasant and unpleasant items. Additionally, lower smell identification accuracy was negatively correlated with SDS symptom severity, and valence ratings for pleasant odors were positively correlated with SDS diminished emotional range. Findings suggest that the DS is characterized by a unique pattern of olfactory valence judgment that is characterized by abnormalities in processing positively valenced stimuli.

Periods of Recovery in Deficit Syndrome Schizophrenia: A 20-Year Multi-follow-up Longitudinal Study

Periods of recovery were examined in patients with and without deficit syndrome schizophrenia. Fifty-six patients with schizophrenia were studied, 39 of whom were divided into deficit and nondeficit syndrome schizophrenia subtypes using a proxy method. We also studied 39 nonpsychotic depressive comparison patients. Patients were evaluated as part of the Chicago Follow-up Study, which prospectively examined patients at regular intervals over a 20-year period. Using standardized instruments, patients were evaluated for the deficit syndrome, global recovery, rehospitalization, social dysfunction, occupational disability, and symptom presentation. Recovery was examined at 6 time points measured at 2-, 4.5-, 7.5-, 10-, 15-, and 20-year postindex hospitalization. Cumulatively, over the 20-year period, 13% of patients classified as meeting criteria for the deficit syndrome showed 1 or more 1-year periods of global recovery, in comparison to 63% of nondeficit schizophrenia patients and 77% of depressed patient controls. Results indicate that the deficit syndrome represents a persistently impaired subsample of schizophrenia patients, with continuous social, occupational, and symptom impairment. In contrast, nondeficit syndrome schizophrenia patients showed at least some periods of remission or recovery, with the likelihood of these periods increasing as they became older. Findings provide further support for the validity of the deficit syndrome concept and suggest that deficit status is characterized by a more persistently impaired course of illness and particularly poor long-term prognosis.

Automatic affective processing impairments in patients with deficit syndrome schizophrenia

Affective impairments were examined in patients with and without deficit syndrome schizophrenia. Two Emotional Stroop tasks designed to measure automatic processing of emotional information were administered to deficit ( n = 15) and non-deficit syndrome ( n = 26) schizophrenia patients classified according to the Schedule for the Deficit Syndrome, and matched non-patient control subjects ( n = 22). In comparison to non-deficit patients and controls, deficit syndrome patients demonstrated a lack of attention bias for positive information, and an elevated attentional lingering effect for negative information. These findings suggest that positive information fails to automatically capture attention of deficit syndrome patients, and that when negative information captures attention, it produces difficulty in disengagement Attentional abnormalities were significantly correlated with negative symptoms, such that more severe symptoms were associated with less attention bias for positive emotion and a greater lingering effect for negative information. Results are generally consistent with a mood-congruent processing abnormality and suggest that impaired automatic processing may be core to diminished emotional experience symptoms exhibited in deficit syndrome patients.

P.3.a.002 Deficits in reward sensitivity and reversal learning in chronic schizophrenia during decision-making tasks

Research has demonstrated that individuals with schizophrenia fail to appropriately use negative feedback to guide learning. These learning deficits are thought to arise from abnormalities in midbrain dopamine activity. Primary and enduring negative symptoms are also associated with abnormal dopamine activity and are expected to produce more severe deficits in learning when they present in individuals with schizophrenia. The current study examines this matter by comparing individuals with deficit syndrome schizophrenia, which is characterized by primary and enduring negative symptoms, to individuals with nondeficit syndrome schizophrenia and to normal controls in their use of positive feedback and negative feedback to guide learning on the first four cards of the WCST. Participants included 67 individuals with schizophrenia (15 deficit; 52 nondeficit syndrome) and 51 healthy controls. Accuracy data from the first 4 cards of the WCST and measures of global test performance were examined. Individuals with schizophrenia were significantly less accurate than controls in their performance on early (pre-shift) WCST trials, and this impairment was significantly greater in patients with deficit than nondeficit schizophrenia. Additionally, accuracy across the first 4 WCST cards significantly predicted the number of categories completed and percentage of perseverative errors across the entire test. These findings suggest that negative symptoms of schizophrenia are associated with difficulty using negative feedback to adaptively guide behavior, and are consistent with the notion that abnormal DA signaling contributes to the higher-order executive functioning impairments seen in schizophrenia with severe negative symptoms.

P.3.a.027 Splitting of nondeficit syndrome by the boundries of two clusters identified by cognitive neuropsychiatric mapping

Schizophrenia is associated with reduced cardio-respiratory fitness (CRF), and impaired cognition is a core feature of the disorder. Despite their particular significance to schizophrenia disparately, the relationship between these two variables has not yet been thoroughly assessed. In this study we aimed to investigate naturally occurring associations between CRF and all cognitive domains within this patient population.Eighty outpatients with schizophrenia spectrum disorders participated in the study. Neurocognition was assessed with the Wechsler Adult Intelligence Scale version 4 General Ability Index (WAIS GAI) and the MATRICS Consensus Cognitive Battery (MCCB). Oxygen uptake was measured directly by analyzing O2 and CO2 content in expired air during a maximum exercise session on a treadmill using a modified Balke protocol. Clinical symptom load was assessed with the Positive and Negative Syndrome Scale (PANSS). Hierarchical multiple regression analyses were conducted, controlling for sex and age, and negative psychotic symptom levels.CRF explained a significant 8.2% and 9.1% of the variance in general intellectual ability and state-sensitive cognitive functioning respectively, beyond the impact of negative psychotic symptom load.The study indicates a direct relation between CRF and cognition in schizophrenia. Impaired cognition is a difficult-to-treat expression of the disorder, and identifying modifiable factors possibly mediating cognition, such as CRF, is of great clinical value.

Lack of association between COMT gene and deficit/nondeficit schizophrenia

BackgroundThe dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients.MethodsEighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val158Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65).ResultsThere was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases.ConclusionResults from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia.