Symptomatology Of Schizophrenia Research Articles

Tobacco status, impulsivity, and the five-factor of the PANSS in paranoid schizophrenia

There is consistent evidence that impulsivity is linked to tobacco consumption and to symptomatology in schizophrenia. In the current study, we propose a new integrative model of the relationship between impulsivity, psychopathological symptoms, and tobacco status in patients with paranoid schizophrenia. We investigated 33 paranoid schizophrenia patients and 37 healthy controls using a battery of psychopathological scales included the Structured Clinical Interview for DSM-IV (SCID), the five-factor model of the Positive and Negative Symptom Scale (PANSS), the Barratt Impulsiveness Scale (BIS-10), and the UPPS Impulsive Behavior scale (UPPS). Step-wise regression analysis revealed that positive factor of the PANSS and tobacco status contributed positively and significantly to the explained variance of impulsivity. In addition, non-planning impulsivity and sensation-seeking emerged as significant predictors of tobacco status, while smoking predicted non-planning impulsivity and sensation-seeking. Our results suggest that the relationship between sensation-seeking and tobacco use is reciprocal and proposes a new integrative model of the relationship between impulsivity, positive symptoms and tobacco status in patients with paranoid schizophrenia. However, the exact mechanisms for these relationships deserve further investigation.

Childhood trauma, depression, and sleep quality and their association with psychotic symptoms and suicidality in schizophrenia

This study involved the examination of the relationship between childhood trauma and both psychotic symptoms and suicidality in patients with schizophrenia after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality. The Childhood Trauma Questionnaire-Short Form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Pittsburgh Sleep Quality Index (PSQI), and the suicidality subscale of Mini-International Neuropsychiatric Interview (MINI) were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology, total symptoms of schizophrenia, and suicidality were dependent variables.Depressive symptomatology and childhood physical abuse significantly contributed to positive, negative, general psychopathology, and global schizophrenia symptomatology. Interestingly, general psychopathology scores were negatively associated with childhood physical neglect. Also, subjective sleep quality significantly contributed to positive schizophrenia symptoms. Although prior suicide attempts and depression were significant antecedents of suicidal ideation, no association between suicidality and both childhood trauma and sleep was found. Childhood physical abuse could have an impact on psychopathology in schizophrenia. In addition to childhood trauma, depression, sleep disturbances, and clinical features should be considered and inquired about in the course of clinical care of schizophrenia patients.

Elucidation of shared and specific white matter findings underlying psychopathology clusters in schizophrenia.

Schizophrenia is associated with diverse white matter (WM) brain abnormalities. In this study, we sought to examine the WM microstructural findings which underlie clinical psychopathology clusters in schizophrenia and hypothesized that these symptom clusters are associated with common and unique WM tracts. Overall, 76 healthy controls (HC), and 148 patients with schizophrenia (SZ) were recruited and severity of symptomatology in schizophrenia was assessed using the Positive and Negative Syndrome Scale. WM fractional anisotropy (FA) values were extracted from their diffusion tensor images. Psychopathology clusters were first determined using factor analysis and the relationship between these symptom factors and FA values were then assessed with structural equation modelling, which included covariates such as age, sex, duration of illness and medications prescribed. Patients with schizophrenia had reduced FA in the genu of corpus callosum (gCC) compared to HC. A three-factor model, namely Positive, Negative, Disorganised factors, was determined as the best fit for the data. All three psychopathology factors were associated with decreased FA in the gCC and bilateral cingulate gyrus. Higher Negative factor scores were uniquely associated with decreased FA in the right sagittal striatum and right superior longitudinal fasciculus. This study found shared and specific WM changes and their associations with specific symptom clusters, which potentially allows for monitoring of such white matter findings associated with clinical presentations in schizophrenia over treatment and illness course.

Schizophrenia with prominent catatonic features: A selective review

A widely accepted consensus holds that a variety of motor symptoms subsumed under the term ‘catatonia’ have been an integral part of the symptomatology of schizophrenia since 1896, when Kraepelin proposed the concept of dementia praecox (schizophrenia). Until recently, psychiatric classifications included catatonic schizophrenia mainly through tradition, without compelling evidence of its validity as a schizophrenia subtype. This selective review briefly summarizes the history, psychopathology, demographic and epidemiological data, and treatment options for schizophrenia with prominent catatonic features. Although most catatonic signs and symptoms are easy to observe and measure, the lack of conceptual clarity of catatonia and consensus about the threshold and criteria for its diagnosis have hampered our understanding of how catatonia contributes to the pathophysiology of schizophrenic psychoses. Diverse study samples and methodologies have further hindered research on schizophrenia with prominent catatonic features. A focus on the motor aspects of broadly defined schizophrenia using modern methods of detecting and quantifying catatonic signs and symptoms coupled with sophisticated neuroimaging techniques offers a new approach to research in this long-overlooked field.

Imbalance between abstract and concrete repetitive thinking modes in schizophrenia

ObjectiveRepetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. MethodsThirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. ResultsCompared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). ConclusionThis imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes.

P50 suppression deficits and psychopathology in Han Chinese patients with schizophrenia.

Numerous studies have reported P50 gating deficits in schizophrenia, though with mixed results. Moreover, few studies have explored the association between P50 gating deficits and psychopathology in Chinese patients with schizophrenia. In the present study, we investigated the P50 auditory sensory gating patterns and their correlations with clinical symptoms in a large sample of Han Chinese patients with schizophrenia. We assessed P50 sensory gating with a 64-channel electroencephalography system in 133 patients with schizophrenia and 148 healthy controls. The schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Patients with schizophrenia had a significantly higher P50 gating ratio (p<0.001), longer S1 latency (p<0.05), lower S1 amplitude (p<0.01), and lower P50 difference (p<0.001) than did controls. No significant correlations were found between the P50 gating measures and the PANSS total score or subscale scores in patients with schizophrenia. These findings suggest that the P50 sensory gating deficits identified in Chinese patients with schizophrenia may not be involved in the psychopathology of the illness.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Relationship between childhood trauma and psychotic symptoms in patients with schizophrenia

IntroductionThe association between childhood trauma and psychotic symptoms is still not clearly understood. Findings for positive and negative symptoms are confounding. This symptomatic response may differ according to the type of childhood trauma, for example childhood abuse was associated with positive symptoms while childhood neglect was associated with negative symptoms.ObjectivesThis study examined the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality.MethodsThe childhood trauma questionnaire – short form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia, Pittsburgh sleep quality index, and the suicidality subscale of mini-international neuropsychiatric interview were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology and total symptoms of schizophrenia were dependent variables.ResultsDepressive symptomatology and childhood physical abuse (CPA) significantly contributed to positive, negative, general psychopathology and global schizophrenia symptomatology. Stepwise regression analysis results are presented in Table 1.ConclusionsOur findings suggest that CPA during childhood could have an impact on psychopathology in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Association Study of Tumor Necrosis Factor Receptor 1 (TNFR1) Gene Polymorphisms with Schizophrenia in the Polish Population.

Schizophrenia is a devastating mental disorder with undetermined aetiology. Previous research has suggested that dysregulation of proinflammatory cytokines and their receptors plays a role in developing schizophrenia. We examined the association of the three single nucleotide polymorphisms (SNPs; rs4149576, rs4149577, and rs1860545) in the tumor necrosis factor receptor 1 (TNFR1) gene with the development and psychopathology of paranoid schizophrenia in the Polish Caucasian sample consisting of 388 patients and 657 control subjects. The psychopathology was assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). SNPs were genotyped using the TaqMan 5′-exonuclease allelic discrimination assay. The SNPs tested were not associated with a predisposition to paranoid schizophrenia in either the entire sample or after stratification according to gender. However, rs4149577 and rs1860545 SNPs were associated with the intensity of the PANSS excitement symptoms in men, which may contribute to the risk of violent behavior. Polymorphisms in the TNFR1 gene may have an impact on the symptomatology of schizophrenia in men.

Self is "other", other is "self": poor self-other discriminability explains schizotypal twisted agency judgment.

Anomalous agency has been reported clinically and empirically for people with schizophrenia. This finding is expected to contribute to understanding positive symptomatology in schizophrenia in terms of a general neurocomputational model of motor control, because anomalous agency has also been reported in schizotypal traits in the general population. However, superficially opposite conclusions have been suggested: over-attributed or under-attributed agency in patients. In this work, healthy participants (N=104) were presented continuous morphed self-other visual feedback of their reaching movements and rated the agency they felt for it. The slope of the regression line in stimuli-response coordination as a function of self-other discriminability was estimated for each participant. The estimated slopes were significantly associated with positive schizotypal symptomatology. Higher schizotypal participants exhibited a lower slope, indicating poorer discriminability between their own and others' movements. Furthermore, the estimated regression lines in the high and low groups are predicted to cross at the approximately center point in the coordinates, which should produce both over-attribution and under-attribution errors for the high group compared with low group. The pattern of schizotypal attribution error depends on the S/N (signal-to-noise) ratio of the given stimuli within our sensorimotor system where the self-originated stimulus is the signal to be detected. The current study, for the first time, suggests both over- and under-attribution within participants scoring high on schizotypy.

Association of the BDNF Val66Met polymorphism with BMI in chronic schizophrenic patients and healthy controls.

Several lines of evidence suggest that a functional variant of the brain-derived neurotrophic factor gene (BDNF Val66Met) correlates with a number of eating disorders. Studies have also shown that the BDNF Val66Met polymorphism was associated with weight gain in patients with schizophrenia on long-term antipsychotic treatment. This study aimed to determine whether there was a relationship between the BDNF Val66Met polymorphism and BMI values in patients with chronic schizophrenia. We compared 308 Han Chinese patients with schizophrenia on long-term antipsychotic medication with 304 healthy normal controls on BDNF polymorphism. Body weight and BMI were measured before breakfast on the day blood samples were taken. The symptomatology of schizophrenia was assessed using the Positive and Negative Syndrome Scale. The results showed that the BDNF Val66Met polymorphism was associated with the BMI value, with genotype having a strong effect on the mean BMI value in male but not in female patients. Our results suggest that variation in the BDNF gene may be a risk factor for weight gain in male patients with schizophrenia on long-term antipsychotic treatment.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Differential blood-based biomarkers of psychopathological dimensions of schizophrenia

Symptomatology of schizophrenia is heterogeneous, there is not any pathognomonic symptom. Moreover, the diagnosis is difficult, since it is based on subjective information, instead of markers. The purpose of this study is to provide a review of the current status of blood-based biomarkers of psychopathological dimensions of schizophrenia. Inflammatory, hormonal or metabolic dysfunctions have been identified in patients with schizophrenia and it has attempted to establish biomarkers responsible for these dysfunctions. The identification of these biomarkers could contribute to the diagnosis and treatment of schizophrenia.

Modelling the cognitive and neuropathological features of schizophrenia with phencyclidine.

Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology. The animal model, using a sub-chronic dosing regimen (sc) with the non-competitive NMDA receptor antagonist PCP (phencyclidine), evolved from previous work in rats (for PCP) and primates (for cognition). The hypothesis of a PV deficit came from emerging evidence for a GABAergic dysfunction in schizophrenia, in particular a deficit in PV-containing GABA interneurons. Since this original publication, a PV deficit has been identified in other animal models for schizophrenia, and the PV field has expanded considerably. This includes mechanistic work attempting to identify the link between oxidative stress and GABAergic dysfunction using this scPCP model, and assessment of the potential of the PV neuron as a target for new antipsychotic drugs. The latter has included development of a molecule targeting KV3.1 channels located on PV-containing GABA interneurons which can restore both PV expression and cognitive deficits in the scPCP model.

The relationship between self-reported childhood adversities, adulthood psychopathology and psychological stress markers in patients with schizophrenia

BackgroundChildhood adversity is a well-established risk factor for the development of schizophrenia. In particular, there is evidence that childhood adversity increases the occurrence of positive symptoms, possibly through glucocorticoid influences on dopaminergic neurotransmission. AimsTo compare levels of childhood trauma in schizophrenia patients vs. healthy control persons, and to study the association between childhood adversity and the symptomatology of adulthood schizophrenia, as well as subjective and biological markers of psychological stress. MethodsThirty-seven patients fulfilling ICD-10 criteria for schizophrenia and 39 healthy control persons filled out the comprehensive Childhood Abuse and Trauma Scale (CATS). Data were analyzed after a data-driven dichotomization into two groups of either high or low CATS score in patients and controls, respectively. The psychopathology of the patients was measured by the Positive and Negative Syndrome Scale (PANSS) and analyzed by a five-factor PANSS model. Measures of perceived stress (Perceived Stress Scale) and hypothalamic-pituitary-adrenal (HPA)-axis activity (9AM plasma cortisol and daytime salivary cortisol output) were recorded. ResultsAs expected, patients had significantly higher total CATS scores than the control persons (>3-fold, P<0.001), reflecting significantly higher scores across all subscales of the CATS. In patients, the total PANSS score did not significantly differ between the high and the low CATS score group (P=0.2). However, there was a statistically significant higher level of positive symptoms in the high CATS group (P=0.014), and no difference in other psychopathological domains. Correspondingly, when using the CATS score as a continuous variable, a strong association with positive PANSS scores was found (P=0.009). The high CATS score group showed higher levels of perceived stress (P=0.02), but there was no difference between the high vs. low CATS group in HPA-axis activity. ConclusionAlthough causal inferences cannot be made from this cross-sectional study, the study adds support to the suggestion that childhood adversity specifically increases the occurrence of positive symptoms in adulthood schizophrenia in a manner that appears to leave HPA-axis activity unaltered.

Maternal immune activation alters sensitivity to action-outcome contingency in adult rat offspring

Epidemiological studies have provided convincing evidence for a role of maternal immune activation in the pathogenesis of neurodevelopmental disorders such as autism and schizophrenia. In recent years, several research groups have capitalised on this discovery and developed animal models such as the maternal immune activation (MIA) model that emulates many phenotypes characteristic of disorders such as schizophrenia. In the present series of experiments we used the MIA model to examine motivation, a core component of the negative symptomatology in schizophrenia. Contrary to what we expected, in the progressive ratio task, which assesses an animals’ willingness to work for a reward under increasing effort requirements, we found that MIA rats appeared more motivated than controls. Subsequent tests showed that this seemingly enhanced motivation was not due to an overall increase in responding, nor due to enhanced attribution of incentive salience to reward associated responses. Instead, we found that the increased willingness to work exhibited by MIA animals was due to an inability to detect changes in the contingency between their behaviour and the resulting rewarding outcome. With regard to motivation, the experiments reported here are the first to subject the MIA model to a rigorous experimental analysis of behaviour by parsing underlying processes that give rise to the overt symptoms in psychiatric disease.

Influence of Family and Childhood Memories in the Development and Manifestation of Paranoid Ideation.

Memories of family dynamics characterized by behaviours of antipathy from both parental figures, submissiveness and bullying victimization are important predictors of paranoid ideation in adult life. The study highlights the importance of exploring subjective recalls of feelings and behaviours associated with early rearing experiences, peer relationships and themes related to social rank theory in the roots of internal models of relationship with the self and others in the general sample, patients diagnosed with schizophrenia and their first-degree relatives. Our findings indicate that schizophrenic patients in active phase differ regarding memories of threat and submission and are more likely to remember childhood experiences perceived as threatening during an active phase than when in remission. It is possible that by changing these internal models and social interaction styles, patients may be able to get involved in more cooperating and affiliative interactions, disconfirming these early beliefs about others being rejecting, critical or hostile towards the self, and more effectively reducing the invalidation caused by positive and negative symptomatology of schizophrenia on social functioning.

Implicit Timing as the Missing Link between Neurobiological and Self Disorders in Schizophrenia?

Disorders of consciousness and the self are at the forefront of schizophrenia symptomatology. Patients are impaired in feeling themselves as the authors of their thoughts and actions. In addition, their flow of consciousness is disrupted, and thought fragmentation has been suggested to be involved in the patients’ difficulties in feeling as being one unique, unchanging self across time. Both impairments are related to self disorders, and both have been investigated at the experimental level. Here we review evidence that both mechanisms of motor control and the temporal structure of signal processing are impaired in schizophrenia patients. Based on this review, we propose that the sequencing of action and perception plays a key role in the patients’ impairments. Furthermore, the millisecond time scale of the disorders, as well as the impaired sequencing, highlights the cooperation between brain networks including the cerebellum, as proposed by Andreasen (1999). We examine this possibility in the light of recent knowledge on the anatomical and physiological properties of the cerebellum, its role in timing, and its involvement in known physiological impairments in patients with schizophrenia, e.g., resting states and brain dynamics. A disruption in communication between networks involving the cerebellum, related to known impairments in dopamine, glutamate and GABA transmission, may help to better explain why patients experience reduced attunement with the external world and possibly with themselves.

Differential blood-based biomarkers of psychopathological dimensions of schizophrenia.

Symptomatology of schizophrenia is heterogeneous, there is not any pathognomonic symptom. Moreover, the diagnosis is difficult, since it is based on subjective information, instead of markers. The purpose of this study is to provide a review of the current status of blood-based biomarkers of psychopathological dimensions of schizophrenia. Inflammatory, hormonal or metabolic dysfunctions have been identified in patients with schizophrenia and it has attempted to establish biomarkers responsible for these dysfunctions. The identification of these biomarkers could contribute to the diagnosis and treatment of schizophrenia.

Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia

Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to chronic medicated patients with schizophrenia and examined the association of IL-3 with their psychopathological symptoms. Serum IL-3 levels were assessed in 55 FEDN patients, 52 chronic medicated patients and 43 healthy controls. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). We found significantly lower IL-3 levels in FEDN patients than both chronic patients and healthy controls (both p<0.001), while IL-3 levels in chronic patients were markedly higher than in healthy controls. No significant association was observed between IL-3 and any clinical psychopathology in FEDN patients; however, we found a significant correlation between serum IL-3 levels and the PANSS general psychopathology subscore in chronic medicated patients (p<0.05). Decreased IL-3 levels in FEDN patients suggest that suppressed immune function may be associated with developing schizophrenia, but as the disease progresses IL-3 levels increase perhaps related to medication treatment or other factors that occur during chronic illness.