Anomalous visual experiences, negative symptoms, perceptual organization and the magnocellular pathway in schizophrenia: a shared construct?

It is difficult to come away from review of pharmacologic and metabolite studies without concluding that dopaminergic mechanisms play a significant role in mediating both negative and positive symptoms. Nevertheless, the characteristics of dopaminergic involvement are unclear. Whereas compelling evidence continues to link the mechanism of action of neuroleptic drugs, including therapeutic effects on negative and positive symptoms, to blockade of D2 receptors, neuroleptic-induced alterations in dopaminergic function are time-dependent and may include reductions in variability as well as in net dopamine activity. Moreover, pharmacologic enhancement of dopaminergic function may at least transiently improve symptomatology (negative greater than positive) and levels of CSF HVA appear to be reduced or are negatively correlated with symptoms in some schizophrenic patients. Thus, there is support for both increased and decreased dopamine function in schizophrenia. Functional brain imaging has, after only a few years of application, made significant contributions to our understanding of the pathophysiology of schizophrenia. Studies of cerebral metabolism and regional CBF have shown remarkable consistency in their identification of abnormal function of the frontal cortex in schizophrenia. It should be pointed out, however, that agreement across studies remains largely conceptual with significant discrepancies still existing with regard to the precise localization of dysfunction and its relationship to cognitive activation. Although less well documented than 'hypofrontality' itself, negative symptomatology appears to bear some relationship to this defect. The idea that positive symptoms might be associated with increased subcortical and/or metabolism is less well supported. The recent advances in our understanding of structure and function of CNS dopaminergic systems may help to integrate these two bodies of data into more dynamic models of dopaminergic defects in schizophrenia. For example, the concept that diminished mesocortical coupled with increased subcortical dopaminergic activity might be a 'substrate' for psychosis is compatible with neurochemical evidence suggesting both diminished and enhanced dopaminergic processes as well as with metabolic hypofrontality. Better understanding of the regulatory mechanisms involved in establishing functional balance between cortical and subcortical systems might, therefore, identify new possibilities for biological dysfunction in schizophrenia. The recent study by Weinberger et al. which correlates CSF HVA levels with neuropsychologically induced frontal CBF is an example of how neurochemistry can enhance brain imaging data.(ABSTRACT TRUNCATED AT 400 WORDS)

Objective To investigate the impairment of intertemporal choices in adolescents with positive and negative schizophrenic symptoms. Methods 30 adolescent schizophrenia patients with positive symptoms (positive symptoms group), 30 adolescent schizophrenia patients with negative symptoms (negative symptoms group)and 30 healthy controls were selected. All the subjects were investigated with intertemporal-choice Test. Results (1) Under now conditions ((37.22±30.92)%, (19.67±16.35)%, P 0.05). (2)Pearson correlation analysis showed that the Vocabulary Fluency Test of negative symptoms group was positively correlated with LL selection ratio under now conditions(r=0.411, P=0.024). Conclusion The ability of intertemporal choices in adolescents schizophrenia patients with negative symptoms is impaired remarkably, while this kind of ability is impaired unremarkable in adolescence with negative symptoms. The ability of intertemporal choices in adolescents schizophrenic patients with negative symptoms is correlated with cognitive executive function. Key words: Positive symptoms; Negative symptoms; Schizophrenia; Adolescents; Intertemporal-choice

The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.

Differential relationships between positive and negative symptoms and neuropsychological deficits in schizophrenia

This study compared the effect of clozapine and haloperidol on positive and negative symptoms of schizophrenia and in patients with high levels of negative symptoms or the deficit syndrome. Patients were participants in a 15-site double-blind, random-assignment Veterans Administration trial comparing clozapine (N=205) and haloperidol (N=217) in hospitalized patients with refractory schizophrenia. Analysis of covariance examining change at 6 weeks, 3 months, and 1 year evaluated 1) clozapine's effect on positive and negative syndromes; 2) clozapine's effect on each syndrome, statistically controlling for the other; and 3) the interaction of clozapine treatment and the presence or absence of high levels of negative symptoms at baseline and the deficit syndrome. Patients treated with clozapine showed significantly greater improvement than control subjects on positive symptoms at all time points and on negative symptoms at 3 months. Clozapine had no independent effect on negative symptoms at any time after control for positive symptoms, but its effects on positive symptoms persisted after control for negative symptoms at 6 weeks only. There were no significant differences in response to clozapine between patients with high and low levels of negative symptoms at baseline or between patients with and without the deficit syndrome. The greater effectiveness of clozapine as compared to conventional medications in refractory schizophrenia is not specific to either negative clinical symptoms or clinical subtypes defined by prominent negative symptoms or evidence of the deficit syndrome.

A state-independent network of depressive, negative and positive symptoms in male patients with schizophrenia spectrum disorders

The interrelationship between schizotypy, clinical high risk for psychosis and related symptoms: Cognitive disturbances matter

To investigate the determinants of family burden in a sample of patients with schizophrenia and their caregivers. Thirty-one stable patients with schizophrenia and their main caregivers were recruited. Sociodemographic variables were assessed in a semi-structured interview, and positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed with the Schizophrenia Cognition Rating Scale (SCoRS). Levels of burden on caregivers were assessed with the Family Burden Interview Schedule (FBIS). Interactions among variables were analyzed using Pearson correlations and linear regression analysis. Objective and subjective FBIS scores were 1.9 (standard deviation [SD] = 0.5) and 2.4 (SD = 0.6) respectively. Objective burden correlated positively with positive and negative symptoms, and cognitive impairment. Subjective burden correlated positively with positive symptoms and negatively with mean age of disease onset. Positive, negative and cognitive symptoms accounted for 47.6% of the variance of objective burden, with negative symptoms accounting independently for 30.3%. Age of onset, parents as caregivers and positive symptoms accounted for 28% of the variance of subjective burden, with age of onset independently explaining 20.3%. Patients' clinical and sociodemographic variables are important determinants of family burden in schizophrenia. Objective burden is predicted by symptoms, particularly negative ones. Subjective burden is predicted by symptoms and sociodemographic variables, particularly age of disease onset.

Background: It is approximately that the prevalence of schizophrenia in Indonesia is 1% out of total population. Within the total population of 205 million, the number of schizophrenia cases in Indonesia is 2 million.This number should be considered as the burden of disease impact on the whole family and its environment, not only the patient itself. Objectives: To know the demographic characteristics of schizophrenia among Puri Nirmala Mental Hospital in-patients, to assess the efficacy of therapy on decreasing positive and negative symptoms manifested by Schizophrenia patients; and to assess the contribution of demographic characteristics and treatments toward decreasing symptoms. Methods: A hospital based retrospective study cohort was used as the design of this study. Samples of this study were 750 Puri Nirmala Mental Hospital in-patients from January 2000 to December 2002. Samples were chosen based on schizophrenia diagnosis established by Psychiatrists based on PPDGJ III. Outcome variable is the absence of negative and positive symptoms, whereas study factors are demographic and treatments variables. Descriptive analysis, paired t-test and logistic regression were used for data analysis. Results: Subjects mostly males (63.3%), living in Yogyakarta province (69,5%), age 21-30 years old (42,3%), high school educations (50,7%), and jobless (68,9%). There was a significantly statistics difference of the positive and negative symptoms before and after treatment manifested among subjects. Jobless, less visit, and both treatments (pharmacotherapy and pharmacotherapy added with electrical convulsion therapy (ECT) were associated with the decreasing of positive and negative symptoms. Conclussion: Treatments with pharmacotherapy and pharmacotherapy added with ECT are effective for decreasing positive and negative symptoms manifested of Schizophrenia patients. Keywords: Schizophrenia; Demographic-factor; Pharmacotherapy; Treatment; Electrical-convulsion-therapy

The relationships of positive and negative symptoms with neuropsychological functioning and their ability to predict verbal memory in psychotic major depression

Background: Schizophrenia is a chronic mental disorder with a relapsing course with generally incomplete remissions and functional decline with varying positive and negative symptoms along with cognitive impairments. Despite the widespread availability of medications to suppress psychosis and prevent relapse, schizophrenia patients continue to remain disabled in different functional aspects in the community. Disability can hence be termed as one of the consequences of schizophrenia. Aims: The aim of this study was to evaluate the frequency of mental disability among patients with schizophrenia and to evaluate the association between clinical features and disabilities among them. Methods: Fifty-three patients who came to psychiatry outpatients in a government tertiary health care hospital who fulfill diagnostic criteria for schizophrenia with at least 2 years of duration of illness and have been on pharmacotherapy for at least 8 weeks before the day of assessment were considered into the study after obtaining an informed consent. The Mini-international neuropsychiatric interview screening for psychiatric diagnosis was applied. The Positive and Negative Syndrome Scale was applied to know the illness severity of schizophrenia. The Indian Disability Evaluation and Assessment Scale is applied to all to assess the disability among the participants. The Clinician Rating Scale is applied to determine the treatment compliance with psychiatric medications. The Montreal Cognitive Assessment Scale (MoCA) was applied to all participants to assess their cognitive functioning. Results: Mild disability was more prevalent followed by moderate and severe disability. The percentage of disability was found to be positively correlated with negative (r = 0.73) and general psychopathology symptoms (r = 0.67) than with positive symptoms (r = 0.39) and was found to be negatively correlated with total MoCA scores (r = −0.5). All these associations were significant. Conclusions: Disability is found to increase with increase in positive, negative, and general psychopathology symptoms and declining cognitive function. Out of all the symptoms, the negative symptoms are found to strongly influence the severity of disability.

From “under” to “over” social cognition in schizophrenia: Is there distinct profiles of impairments according to negative and positive symptoms?

IntroductionClinical high risk for psychosis (CHR) is associated with mild cognitive impairments. Symptoms are clustered into positive, negative and disorganization symptoms. The association between specific symptom dimensions and cognitive functions remains unclear. The aim of this study was to investigate the associations between cognitive functions and positive, negative, and disorganization symptoms. Method53 CHR subjects fulfilling criteria for attenuated psychotic syndrome in the Structural Interview for Prodromal Syndromes (SIPS) were assessed for cognitive function. Five cognitive domain z-scores were defined by contrasting with observed scores of a group of healthy controls (n = 40). Principal Components Analyses were performed to construct general cognitive composite scores; one using all subtests and one using the cognitive domains. Associations between cognitive functions and symptoms are presented as Spearman's rank correlations and partial Spearman's rank correlations adjusted for age and gender. ResultsPositive symptoms were negatively associated with executive functions and verbal memory, and disorganization symptoms with poorer verbal fluency. Negative symptoms were associated with better executive functioning. There were no significant associations between the general cognitive composites and any of the symptom domains, except for a trend for positive symptoms. ConclusionIn line with previous research, data indicated associations between positive symptoms and poorer executive functioning. Negative symptoms may not be related to executive functions in CHR the same way as in psychosis. Our results could indicate that attenuated positive symptoms are more related to cognitive deficits in CHR than positive symptoms in schizophrenia and FEP.

Objective To investigate the clinical features of psychopathology symptoms and function in individuals with attenuated psychosis syndrome (APS) in China. Method Seventy-six individuals with APS were identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS) from 7 research centers. Sixty-two controls in communities were recruited. Participants were administered measures of psychosis risk symptoms Scale of Psychosis-Risk Symptoms (SOPS), depressive symptoms Montgomery-sberg Depression Rating Scale (MADRS) and function status Global Assessment of Functioning (GAF). The above clinical characteristics were compared between the two groups, and the correlation between these features were also explored. Results Compared with health controls, the APS subjects had higher scores of SOPS (26.25±11.73 vs. 1.48±1.66) and it′s subscales of (positive symptoms (8.75±3.69 vs. 0.31±0.56), negative symptoms (8.06±6.15 vs. 0.33±0.59), disorganized symptoms (3.67±2.84 vs. 0.36±0.66), and general symptoms (5.76±3.40 vs. 0.48±0.67)), and MADRS (12.42±9.39 vs. 0.39±0.98), and a lower score of GAF (62.28±13.25 vs. 88.61±4.74;Z=10.08,10.29,9.19,8.10,8.93,9.69,9.94，all P<0.01）. In the individuals with APS, the most common psychosis risk symptoms were unusual thought content (68.4%, 52/76), suspiciousness/persecutory ideas (56.6%, 43/76) and dysphoric mood (48.7%, 37/76). There were 51.3%（39/76）subjects with APS having concurrent depressive symptoms, which were significantly related with negative symptoms（r=0.444, P<0.01）and general symptoms（r=0.571, P<0.01）. The GAF significantly negatively correlated with all the psychosis risk symptoms（r=-0.377--0.700, P<0.01） and the depressive symptom（r=-0.370，P<0.01）. Moreover, a higher score of the positive symptom （t=-3.19，P=0.002）or the negative symptom （t=-3.81，P<0.01） could significantly predicted a lower score of GAF. Conclusions The positive risk symptoms, negative risk symptoms and the social function impairment may be the core clinical symptoms of APS, and the nonspecific risk symptoms and the concurrent depressive symptoms are common as well. Key words: Attenuated psychosis syndrome; Clinical features; Preliminary study

AimsThis case study investigates a rare occurrence of symptom transition in a chronic schizophrenia patient following high-frequency repetitive transcranial magnetic stimulation (rTMS), aiming to understand the unexpected shift from predominantly negative to positive symptoms.rTMS, known for inducing changes in neuronal activity based on Faraday's law, is believed to enhance cortical excitability through high-frequency stimulation.Schizophrenia, a severe and chronic mental disorder, presents with both positive (e.g., delusions, hallucinations) and negative symptoms (e.g., apathy). Current treatments, predominantly antipsychotic drugs, often show limited efficacy, especially for negative symptoms. Non-invasive neuromodulation techniques like rTMS are emerging as potential interventions.MethodsThis case involves a 27-year-old banking executive with a 30 months illness duration primarily marked by negative symptoms over the past 3 months. Despite various antipsychotics, there was no improvement, leading to the initiation of high-frequency rTMS on the left dorsolateral prefrontal cortex (DLPFC) as an adjunct strategy for persistent negative symptoms. Surprisingly, after the 5th rTMS session, positive symptoms like delusions and hallucinations emerged. Serial assessments demonstrated a decrease in negative symptom domain scores on PANSS but an increase in positive symptom domain scores on PANSS.ResultsResults suggest that 5 Hz rTMS over the left DLPFC may have contributed to the transition to positive symptoms. The discussion explores limited literature on rTMS-induced positive symptoms, with case reports dating back to 2004 indicating the possibility of such induction. Studies propose a link between higher pulse frequency, motor threshold intensity, left prefrontal cortex stimulation, and longer trial durations with the exacerbation of positive symptoms, possibly linked to dopamine changes in specific brain tracts.Recent trials indicate potential improvement in positive symptoms, such as excitement, with low frequency rTMS of the temporo parietal area. However, the efficacy of rTMS varies with the stimulation site, with left prefrontal rTMS showing promise for negative symptoms and left temporo-parietal junction stimulation possibly reducing auditory hallucinations.ConclusionThis case report suggests that a subset of schizophrenia patients may experience a transient exacerbation of positive symptoms following rTMS. This underscores the need for increased awareness of potential side effects, serving as an exploratory study that calls for future research to refine these findings for a clearer understanding of rTMS-induced symptom switches in schizophrenia.