3H-spiperone binding in platelet membranes: a possible biological marker for schizophrenia

High-affinity-specific 3H-spiperone binding to platelet membranes was carried out in 30 schizophrenic patients, without prior antipsychotic medication, fulfilling the Research Diagnostic Criteria, and in 30 matched control subjects. The psychosis was rated on the Modified Brief Psychiatric Rating Scale. Compared with healthy subjects, schizophrenic patients had significantly higher 3H-spiperone binding due to a lower dissociation constant (38%), i.e. increased affinity. No significant difference was observed in the maximum number of binding sites (Bmax) between the two groups. It is our contention that 3H-spiperone binding to platelets may be a biological marker for schizophrenia.     

Uptake of H-spiperone by lymphocytes in schizophrenia

Uptake of ³H-spiperone into lymphocytes obtained from control subjects (N = 22), chronic schizophrenics (N = 20), relatives with psychiatric disorder (N = 11) and unaffected relatives (N = 17) was studied. No differences were observed in spiperone uptake among any of the groups examined. Although previous investigations reported marked differences in ³H-spiperone uptake between schizophrenic and control subjects, we were unable to replicate their findings: the failure to replicate those of Bondy and colleagues may well be due to our inability to duplicate in our laboratory the exact biochemical methodology described by these investigators. Saturation curves could not be determined for most subjects. In addition, chronicity of illness and long-term exposure to neuroleptic medication among the schizophrenic subjects may partially account for the contradictory results reported by different investigators.     

Alpha-2-adrenoreceptor binding as a possible vulnerability marker for affective disorders

The affinity (1/Kd) and density (Bmax) of alpha 2-adrenoreceptors in platelet membranes were studied in patients with major depressed illness (n = 10), affected first-degree relatives (n = 17), nonaffected first-degree relatives (n = 44) and controls (n = 31). The alpha 2 selective antagonist 3H-yohimbine was used as the radioligand. The mean Bmax values of affected subjects (probands and relatives) were significantly lower than those of controls. There was no difference in Kd values between the controls and affected subjects. There was a positive gradient of the mean Bmax values from the groups of probands to affected relatives, unaffected relatives and control subjects. A familial effect of Bmax values between members of the same families confirms a genetic control of alpha-receptor affinity. These results support the hypothesis that the density of alpha 2-adrenoreceptors, evaluated by 3H-yohimbine binding on human platelets, could be a potential vulnerability marker for affective disorder.     

Peculiar word use as a possible trait marker in schizophrenia

Peculiar word use in schizophrenia has been emphasized by many authors, however the definition or the linguistic and clinical correlates of this phenomenon are not clear. We propose a new, standard and reliable method to extract a numerical measure of peculiar word use with operationalized definitions. We applied a modified version of the Controlled Word Association Test (Turkish version) to a pool of healthy subjects (N=55) and used the data as norm to compare the degree of peculiarity and patterns of word association among patients with schizophrenia (N=33), their healthy siblings (N=31) and healthy controls (N=32). We also explored the relationship of peculiar word use with patterns of word association (semantic versus phonologic) and formal thought disorder. Patients and their siblings performed worse on measures of verbal fluency. They also generated more peculiar words and relied less on semantic associations, compared to healthy controls. Peculiar word use was associated with the severity of formal thought disorder and the tendency to make use of phonologic associations in the patient group and their siblings, whereas neither of the word association patterns predicted peculiar word use in the control group. Our results provide empirical support to previous observations about the peculiarity of schizophrenic speech. Peculiar word use could be associated with a deficit to employ semantic classifications in verbal fluency tasks and thus relying more on sound-based associations. Excess use of phonologic associations may be playing a mediating role between semantic processing abnormalities and formal thought disorder.     

3H-spiperone binding to lymphocytes in neuroleptic-naive-schizophrenia and the effect of neuroleptic treatment

The aim of this study was to determine whether spiperone binding to lymphocytes could serve as a biological marker of susceptibility to schizophrenia and schizophrenic spectrum disorders or as a measure of response to neuroleptic treatment. Lymphocyte spiperone binding parameters (Bmax, KD) were assessed in 13 patients with schizophrenia and 4 patients with schizotypal personality disorder, all neuroleptic naive, and in 19 age- and sex-matched control subjects. A repeated determination was carried out in 11 of the schizophrenic subjects after several months of neuroleptic treatment. In addition, the binding characteristics of 12 of the schizophrenic/schizotypal patients were compared with those of 13 healthy family members and normal unrelated controls. No significant differences were detected between the schizophrenic subjects and controls before or after neuroleptic treatment or between the patients and their non-affected family members and controls.     

Binding of H-spiperone to human peripheral lymphocytes: Absence of stereospecific high-affinity binding

The binding of ³H-spiperone to human peripheral lymphocytes (PBL) was characterized. The (+)-butaclamol displaceable binding of ³H-spiperone was not saturable, and both (+) and (-)-butaclamol were equally potent in displacing ³H-spiperone binding. We did not find evidence for the existence of a high-affinity specific binding site of ³H-spiperone on human PBL.     

High-affinity 3H-imipramine binding sites: a possible state-dependent marker for major depression

Ten patients with DSM-III diagnoses of nonbipolar recurrent major depression were studied in an attempt to assess the relationship between 3H-imipramine binding site density and clinical depressive state. They were compared with eight healthy controls who had no past or family history of affective disorders. Evaluations with the Hamilton Rating Scale for Depression and the Self-Rated Scale for Depression were done on the same day as platelet collection at baseline, and also at 2 and 5 weeks after the beginning of treatment with tricyclic antidepressants. The number (Bmax) and the affinity (Kd) of platelet 3H-imipramine binding sites were highly correlated with the improvement of the clinical depression. These results raise the interesting possibility that a decrease in 3H-imipramine binding sites may be a state-dependent marker in patients suffering from nonbipolar recurrent major depression.     

ERPs changes during neuroleptic treatment in schizophrenia--a vulnerability marker in schizophrenia]

P300 amplitude reduction and P300 latency prolongation are consistent findings in schizophrenia, but it is unclear if these abnormalities were the effect of current or past neuroleptic treatment or were present at the onset of illness. We previously recorded ERPs in drug free schizophrenic patients (45 neuroleptic-naive and 56 previously treated with neuroleptics). In that study, P300 amplitude reduction was observed in both the neuroleptic-naive and the previously treated patients. However, both N200 and P300 latencies were prolonged only in the previously treated schizophrenic patients. In this study, we investigated ERPs in 60 drug free schizophrenic patients before and after neuroleptic treatment was begun. According to DSM-IV, schizophrenia subtype classification, 26 cases were paranoid type, 14 were disorganized, 2 catatonic and 18 undifferentiated. Twenty six of the patients were neuroleptic-naive and 34 had been previously treated. Sixty gender- and age-matched healthy controls were also investigated. ERPs were recorded during an auditory oddball task. The scalp EEGs were recorded from AgAgCl electrodes at 16 sites according to the international 10-20 system. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Before treatment, all schizophrenic patients displayed larger N200 amplitudes than the controls; however, increases in N200 amplitudes were not observed after neuroleptic treatment was begun. Both N200 and P300 latencies in the patients before treatment were prolonged only in those previously treated. Neuroleptic-naive patients demonstrated prolongation of both N200 and P300 latencies only after treatment. P300 amplitudes in patients were increased by neuroleptic treatment; but patients had smaller P300 amplitudes than the controls even after treatment. The change in P300 amplitudes (Pz) and the change in total BPRS scores by neuroleptic treatment were positively correlated in the patients whose duration of illness was six months or less (mean: 2.4 months). However, no correlation was observed for patients whose duration of illness was over six months (mean: 49.7 months). There were no significant differences in ERPs changes among subtypes. These results suggested that the P300 amplitude should be considered a vulnerability marker in schizophrenia and that both N200 and P300 latencies might be markers for neuroleptic exposure.     

Familial risk for depression and p3b component as a possible neurocognitive vulnerability marker

OBJECTIVE: Complex genetic mechanisms are involved in the vulnerability to depressive disorders and cognitive dysfunctions found in depression. This study was performed to explore the effect of the familial risk for depression on electrophysiological correlates of attentional functions as demonstrated by an event-related potential (ERP) go/no-go experiment. METHODS: The component P3b as an indicator of target detection processing was investigated in two groups of healthy subjects with or without a family history of depression (n = 14 each). An electrophysiological source localization method (LORETA) was employed to allow a neuro-anatomical interpretation for the ERP data. RESULTS: The group with a familial risk for depression showed a reduced P3b amplitude over left temporal areas in contrast to the control group. This two-dimensional effect was associated with a significantly reduced activation of the left middle temporal gyrus. CONCLUSIONS: The P3b amplitude decrement might represent a neurocognitive vulnerability marker for the development of depression.     

Smooth pursuit eye tracking and neuro-psychological performance in healthy volunteers. Exploring a possible genetic marker for vulnerability to schizophrenia

Eye movement dysfunction (EMD) has been repeatedly found in schizophrenics and their first-degree relatives. In the present study, smooth pursuit eye tracking was measured in healthy subjects and related to performance on computerized neuropsychological tasks assumed to involve frontal or frontoparietal functions: monitoring perspective fluctuations (Necker cube), finger tapping, trail making, reaction time (RT) and a perceptual maze test. Poor trackers performed worse on tasks requiring parallel processing (trail making with letters and digits and RT with random auditory signals for response inhibition) and made more errors and cancellations on the mazes. Results are in line with our earlier EMD results on schizophrenics, showing poor performance on frontal tasks. However, their deficiency was more pervasive, whereas the present healthy EMD subjects only had difficulties with more complex tasks. The results are of interest in view of the recent evidence that EMD may be a genetic marker for vulnerability to schizophrenia.     

Dermatoglyphic a-b ridge count as a possible marker for developmental disturbance in schizophrenia: replication in two samples

The aim of this study was to conduct an epidemiological analysis of quantitative dermatoglyphic traits as a marker of prenatal disturbance during the second trimester of life in schizophrenic patients. TFRC (Total Finger Ridge Count) and TABRC (Total a-b Ridge Count) were studied in a sample of 38 schizophrenic patients and 69 healthy individuals. A significant decrease of the a-b ridge count was found in patients compared to controls, with a significant linear trend across the population distribution (OR linear trend = 1.6; 95% CI = 1.0–2.4), indicating that the effect was not confined to a subgroup of cases with values in the lowest range. This finding was replicated in a second, larger sample (OR linear trend = 1.3; 95% CI = 1.0–1.8). The suggestion that a-b ridge count is associated with genetic risk for schizophrenia needs to be investigated further. TFRC did not distinguish between patients and controls. The a-b ridge count may be a continuous risk factor for later schizophrenia, pointing towards a disturbance occurring during the second trimester of prenatal life, a period of critical CNS growth.     

Characterization of opiate binding sites on membranes of rat lymphocytes

In view of the importance of membrane receptors for the interconnection between the central nervous system and the immune system, we carried out a study to characterize opiate binding sites on membranes of rat lymphocytes. We found that mitogen-activated spleen cells, but not thymocytes, possess specific and displaceable binding sites for [3H]naloxone. The binding was equally effective and intense while using B-cell-depleted spleen cells. The binding showed two sites of saturation, one at 10 nM and the other at concentrations greater than 20 nM of [3H]naloxone. Computer analysis of the binding data obtained with the lowest concentrations of naloxone revealed a unique site with high affinity binding to opiates. Displacement was achieved with morphine sulphate and naloxone but not with opioid peptides. The binding of the antagonist, [3H]naloxone, was profoundly inhibited by the co-presence of 120 mM NaCl and up to 100 microM guanosine 5'-O-(3-thiotriphosphate (GTP gamma S). Other metal ions and cyclic nucleotides were not able to interfere with the specific binding. This specificity for GTP analogues is consistent with the hypothesis that a GTP-binding regulatory protein that couples receptors to adenylate cyclase is involved in the process of binding of opiates to lymphocytes. The existence of binding sites on lymphoid cells, analogous to receptors for agents known to affect brain functions, may be another link between the immune system and the central nervous system.     

Stimulated lymphocytes in schizophrenia

This study examines the effect of neuroleptic medication on the distribution of the reported atypical lymphocytes of schizophrenia. The predominant atypical type in schizophrenia was termed the P-type atypical lymphocyte to differentiate the cell from other types of peripheral lymphocytes. Such P cells showed stimulated features: clear cytoplasmic basophilia and an irregularly shaped nucleus with a leptochromatic structure and occasionally one or two nucleoli, but the cell size ranged from small to large. P cells were found in all 42 schizophrenic patients examined and ranged from 5% to 45% of lymphocytes. Patients receiving neuroleptic medication had a lower mean percentage of P cells (17.8%) compared with patients not receiving neuroleptic medication (28.7%). The findings indicate that neuroleptic medication in not likely to be inducing the P-cell reaction.