Does sex influence the relation between symptoms and neurocognitive functions in schizophrenia?

OBJECTIVE: A secondary analysis of our data to investigate if sex influences the specificity of the relationship between each of the 3 clinical syndromes (i.e., reality distortion, disorganization and psychomotor poverty) in schizophrenia and the neurocognitive functions that are thought to represent regional brain functions. PATIENTS AND DESIGN: Fifty-seven male and 30 female patients with a DSM-III-R diagnosis of schizophrenia were rated on the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms to derive scores for psychomotor poverty, disorganization, and reality distortion syndromes. All subjects completed a battery of neuropsychological tests purported to assess functioning of left temporal, right temporal, left basal frontal, right basal frontal, and dorsolateral prefrontal cortex. RESULTS: Correlation coefficients between syndrome scores and neuropsychological measures showed only word fluency (left frontal functioning) to have a statistically significant association with psychomotor poverty in women (p < 0.01). This relation was specific to psychomotor poverty syndrome. No relations between neurocognitive measures and symptoms were seen in men. CONCLUSIONS: The lack of specific relations between symptom dimensions in schizophrenia may be influenced by the fact that the neuronal circuitry associated with particular symptom dimensions may differ in men and women.     

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.     

Error-related negativity and correct response negativity in schizophrenia.

OBJECTIVES: To examine error-related negativity (ERN) and correct response negativity (CRN) in schizophrenia in light of two previous conflicting reports, and to determine their relation to disorganization, psychomotor poverty and reality distortion. METHODS: Event-related potentials were recorded from 21 schizophrenic and 21 control participants who performed a simple go/no-go task. Response-locked potentials were computed for errors of commission and for correct-hits. Scores for reality distortion syndrome, psychomotor poverty syndrome and disorganization syndrome were determined for each schizophrenic participant using the Signs and Symptoms of Psychotic Illness (SSPI) scale. RESULTS: ERN produced during error trials and CRN produced during correct trials were significantly larger in the control participant group than in the schizophrenic participant group. In the schizophrenic patients, ERN amplitude was negatively correlated with psychomotor poverty syndrome score and CRN amplitude was negatively correlated with disorganization syndrome score. CONCLUSIONS: Decreased ERN and CRN in the schizophrenic participant group suggests abnormal internal behavior monitoring in schizophrenic patients. Patients with high disorganization symptoms may employ an abnormal strategy for comparing actual response outcome with desired response outcome, while patients with psychomotor poverty may be less emotionally responsive to errors.     

Psychopathological and SPECT findings in never-treated schizophrenia

A total of 24 never-treated (i.e. drug-naive) actively psychotic schizophrenic patients, operationalized according to DSM-III-R, were examined in a pre-post-treatment design using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and ^99mTc-HMPAO-single photon emission computed tomography (SPECT) to assess regional cerebral blood flow (rCBF). The control subjects were 20 patients free of neurological and psychiatric symptoms. Before treatment there was only a slight hypofrontality, and hypoperfusion was observed in the left temporal superior region. After treatment, hypofrontality was reduced to one region and temporal hypoperfusion disappeared. Formal thought disorders were accompanied by increased rCBF in the bilateral frontal interior and left temporal superior regions. Delusions were associated with hypoperfusion in the anterior cingulate cortex. Negative symptoms showed no linkage to hypofrontality, either before or after treatment. Factor analysis showed delusions and hallucinations loading on different dimensions. The disorganized dimension correlated positively with all regions of interest, whereas these were negatively correlated with reality distortion.     

Scanning eye movements in schizophrenic patients. Relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT.

Eye movements during the Benton Visual Retention Test were examined using an eye-mark recorder in 32 schizophrenic patients and 32 normal controls. The patients had significantly fewer eye fixations, longer mean duration of fixation and shorter length of mean scan path than the controls. In the patients, these eye movement parameters were significantly correlated with the negative symptom score but not with the positive symptom score on the Positive and Negative Syndrome Scale. These parameters had a significant correlation with the composite score on the Scale for the Assessment of Negative Symptoms (SANS). In particular, they were highly correlated with avolition-apathy and affective flattening or blunting scores on SANS subscales. Thus, examination of scanning eye movements seemed to be a good objective index of negative symptoms. Secondly, regional cerebral blood flow (rCBF) was examined using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and single photon emission computer tomography in 17 of 32 patients. With regard to the relationship between the eye movement parameters and rCBF, the mean duration of fixation was negatively correlated with 123I-IMP uptake in the left superior frontal area and left basal ganglia. The mean length of the scan path was correlated with uptake in the left superior frontal area. These findings suggest that the characteristic eye movements of schizophrenic patients are likely to be related with dysfunction of the frontal-basal ganglia neural circuit.     

SPECT study of Chinese schizophrenic patients suggests that cerebral hypoperfusion and laterality exist in different ethnic groups.

Hypofrontality is a common finding in schizophrenia in many countries. To date, there have been few studies on Chinese patients with schizophrenia. We thus wondered whether hypofrontality exists in Chinese patients with schizophrenia. We investigated 45 patients with schizophrenia and 21 healthy controls using brain perfusion single photon emission computed tomography (SPECT). Subjects were also administered the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Halstead-Reitan Neuropsychological Battery (HRNB) and the Wechsler Memory Scale-Revised (WMS-R). Images were analyzed using a semi-quantitative reading and a quantified region of interest analysis. We found that schizophrenic patients showed hypoperfusion in the frontal and temporal lobes and hyperperfusion in the basal ganglia. Schizophrenic patients with both negative and positive symptoms showed asymmetric perfusion in the temporal lobe. Schizophrenic patients with prominent negative symptoms also showed asymmetric perfusion in the prefrontal lobes. Negative symptoms showed a significantly negative correlation with regional cerebral blood flow (rCBF) in the left frontal lobe. Improved memory quotient (MQ) was significantly correlated with increased rCBF in the left temporal lobe. These findings from Chinese patients confirm a similar regional neuroanatomic dysfunction as in Western patients with the disease.     

Neuropsychological correlates of schizophrenic syndromes in patients treated with atypical neuroleptics.

There is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.     

Regional cerebral blood flow and abnormal eating behavior in Prader–Willi syndrome

Background: Prader–Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Methods: Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[¹²³I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. Results: The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. Conclusions: These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS.     

Relationship between neurological 'soft signs’and syndromes of schizophrenia

Past research on the importance of 'soft’neurological signs in schizophrenia has often not examined the relationship between specific groups of neurological signs and different dimensions of schizophrenia psychopathology. Gender differences in the reported relationships have never been explored. In this paper we describe a study of 100 DSM-III-R (65 male and 35 female) schizophrenic patients who were rated for neurological 'soft signs’with the Neurological Evaluation Scale (NES) (1), and for schizophrenic symptomatology with the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Following a factor analysis of NES items, differential relationships were examined between the five derived NES factors and three well-established dimensions of schizophrenic symptomatology, namely psychomotor poverty, disorganization and reality distortion. Our results failed to show any relationship between NES dimensions and either the reality distortion or disorganization dimensions. There was a modest but differentially significant relationship between psychomotor poverty and an extrapyramidal factor on the NES. This relationship was shown only by male subjects, and was influenced by duration of illness but not by age or neuroleptic medication. On the other hand, female subjects showed a significant relationship between psychomotor poverty and an NES factor reflecting attention and initiative, and between reality distortion and coordination/sequencing of motor activity. These relationships in female subjects were, relative to relationships for male subjects, more independent of the effect of medication and duration of illness.     

Regional cerebral blood flow changes in a patient with delusional parasitosis before and after successful treatment with risperidone: a case report

The pathophysiology and appropriate pharmacological interventions for delusional parasitosis (DP) remain unknown. Here, we present a case of DP following brain infarction of the right temporoparietal region. Pharmacotherapy with risperidone resulted in a dramatic therapeutic response over a short period. In a sequential N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked increase of rCBF in the large areas including the bilateral frontal and left temporoparietal regions, the right parietal operculum and the bilateral basal ganglia, in contrast to pre-treatment SPECT images showing a global decrease of rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for treatment of DP and that both dopaminergic and serotonergic dysfunction may play a role in DP. Our sequential SPECT findings suggest that psychiatric improvement of DP is associated with increased rCBF.