Drug-naive Schizophrenia Patients Research Articles

Deficient associative learning in drug-naive first-episode schizophrenia: Results obtained using a new visual within-subjects learned irrelevance paradigm

One of the key features of schizophrenia is the inability to filter out irrelevant stimuli which consequently leads to stimulus overload. There are different methods which aim at investigating these deficient filter mechanisms; one of these is the learned irrelevance (LIrr) paradigm. LIrr refers to the retardation of associative learning that occurs if the conditioned stimulus (CS) and the unconditioned stimulus (US) are preexposed in an explicitly unpaired manner prior to the establishment of the association between the stimuli. In the present study we used a recently developed computerized within-subject visual LIrr test. We measured 11 drug-naive first-episode schizophrenia patients and compared their performance to that of 17 healthy control subjects. LIrr was observed to be intact in normal individuals but disrupted in drug-naive first-episode schizophrenia patients. After one month elapsed, 5 of the 11 patients and 16 of the 17 control subjects were retested in a follow-up study. By this time, patients had been medicated with antipsychotic drugs for at least 3 weeks. While healthy controls exhibited a robust LIrr effect, patients still failed to show LIrr. Correlations were found between the performance of unmedicated patients and the depression component of the PANSS psychopathology scale.

Independent protein-profiling studies show a decrease in apolipoprotein A1 levels in schizophrenia CSF, brain and peripheral tissues

Although some insights into the etiology of schizophrenia have been gained, an understanding of the illness at the molecular level remains elusive. Recent advances in proteomic profiling offer great promise for the discovery of markers underlying pathophysiology of diseases. In the present study, we employed two high-throughput proteomic techniques together with traditional methods to investigate cerebrospinal fluid (CSF), brain and peripheral tissues (liver, red blood cells and serum) of schizophrenia patients in an attempt to identify peripheral/surrogate disease markers. The cohorts used to investigate each tissue were largely independent, although some CSF and serum samples were collected from the same patient. To address the major confounding factor of antipsychotic drug treatment, we also included a large cohort of first-onset drug-naive patients. Apolipoprotein A1 (apoA1) showed a significant decrease in expression in schizophrenia patients compared to controls in all five tissues examined. Specifically, using SELDI-TOF mass spectrometry, apoA1 was found decreased in CSF from schizophrenia patients (-35%, P=0.00001) and, using 2D-DIGE, apoA1 was also found downregulated in liver (-30%, P=0.02) and RBCs (-60%, P=0.003). Furthermore, we found a significant reduction of apoA1 in sera of first-onset drug-naive schizophrenia patients using enzyme-linked immunosorbent assay (-18%, P=0.00008) and in two investigations of post-mortem brain tissue using western blot analysis (-35%, P=0.05; -51%, P=0.05). These results show that apoA1 is consistently downregulated in the central nervous system as well as peripheral tissues of schizophrenia patients and may be linked to the underlying disease mechanism.

Regional frontal abnormalities in schizophrenia: a quantitative gray matter volume and cortical surface size study

Background: Previous structural studies of the frontal lobe in schizophrenia have had somewhat inconsistent results, but most of them have measured the frontal lobe as a single brain structure. To investigate more specific abnormalities in frontal subregions, we measured gray matter volume and cortical surface size in 10 subregions in drug-naive patients during the early stages of the illness. Methods: Magnetic resonance imaging was used to measure frontal subregions in 34 healthy male volunteers, and 26 male, drug-naive schizophrenia patients at early stages of the illness. Frontal subregions were manually traced using our locally developed parcellation method. Results: Patients with schizophrenia had a significant deficit in cortical surface size in the right straight gyrus and left orbitofrontal cortex. No differences were found in gray matter volumes. Conclusions: Frontal structural abnormalities found in drug-naive schizophrenic patients appear to be subtle and circumscribed to ventral portions. Anomalies in the cortical surface size suggest neurodevelopmental abnormalities might occur during the early stages of the gyrogenesis. Further investigations are needed to explore the implications of paralimbic ventral frontal regions (i.e., straight gyrus and orbitofrontal cortex) in the pathophysiology of schizophrenia.

Pharmacological Manipulation of D1-Dopamine Receptor Function in Schizophrenia

The most widely accepted hypothesis concerning the pathophysiology of schizophrenia, the dopamine hypothesis, suggests that the symptoms of schizophrenia are mediated in part by a functional hyperactivity in the dopamine system in the brain, primarily at D2-dopamine receptors. Recent data suggest that D1-dopamine receptors may also play a major role in the pathophysiology of schizophrenia. Using positron emission tomography (PET), increased variability and reduced D1-receptor binding have been observed in the basal ganglia and frontal cortex of drug-naive schizophrenia patients. Such alterations have also been found in some in vitro studies. These results suggest that the ratio of D1- over D2-regulated dopamine signaling in some brain regions is reduced in schizophrenia. A clinical trial of SCH 39166, a selective D1-dopamine receptor antagonist, showed no evidence of antipsychotic activity in schizophrenic patients. Instead, it appeared that selective D1-receptor antagonism may have aggravated symptoms. Although these findings do not support the prediction that selective D1-dopamine receptor antagonism produces antipsychotic effects, they do not preclude the possibility that combined D1- and D2-receptor antagonism may act synergistically to ameliorate symptoms in schizophrenia. In addition, clinical evaluation of D1 agonists in schizophrenia should be undertaken.

Symptoms in neuroleptic-naive, first-episode schizophrenia: response to risperidone

Analysis of the treatment response of different groups of patients with schizophrenia may further define the range of applications and specificity of novel therapies. Clinical trials of risperidone have focused on patients with exacerbations of chronic illness, largely having had multiple previous admissions and years of prior treatment (Chouinard et al 1993; Lindstrom and von Knorring 1994; Marder and Meibach 1994). Other investigators have reported the response to clozapine by first-episode, treatment-refractory patients with schizophrenia (Szymanski et al 1994); however, no prior studies document the response of first-episode, drug-naive schizophrenia patients to another novel antipsychotic, risperidone.

Abnormal photic driving responses in never-medicated schizophrenia patients.

The present study was conducted to compare electroencephalogram (EEG) driving responses to 10 hertz photic stimulation in 14 drug-naive schizophrenia patients and 16 sex- and age-matched control subjects. The amplitude of photic driving responses (PDRs) recorded from the occipital region was significantly lower in schizophrenia patients than in controls. In eight schizophrenia patients (vs. none in the control group) the PDR amplitudes recorded at the frontal region were higher than those at the occipital region, and frontal to occipital PDR ratios were significantly larger in schizophrenia subjects than in controls. Quantitative analysis of the resting EEG showed that the patients also had a significantly lower amplitude for the alpha frequency band. These findings suggest that the PDRs of schizophrenia patients are abnormal in their amplitude and distribution.