Paranoid Subgroup Research Articles

TLR4 Polymorphisms (T399I/D299G) Association with Schizophrenia and Bipolar Disorder in a Tunisian Population.

Immune dysregulation has been widely described in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Particularly, TLR4-altered activation was proposed as one of the underlying processes of psychosis onset. Since TLR4 activation was altered by T399I and D299G polymorphisms, we hypothesized that those variants could present common genetic factors of SCZ and BD. A total of 293 healthy volunteers and 335 psychotic patients were genotyped using PCR-RFLP. Genotype, allele, and haplotype distribution between controls and patients were evaluated according to clinical parameters. Statistical analyses were adjusted by logistic regression. In dominant model, T399I CT + TT and allele frequency were significantly higher in controls compared to psychotic population (p = 0.004, p = 0.002, respectively), SCZ (p = 0.02, p = 0.01, respectively), and BD (p = 0.03, p = 0.02, respectively). Similarly, D299G AG + GG and allele frequency were significantly higher in controls compared to psychotic population (p = 0.04, p = 0.04, respectively) and SCZ (p = 0.04, p = 0.03, respectively). T399I CT + TT and T allele were overrepresented in controls compared to paranoid subgroup (Padjusted = 0.04, p = 0.04, respectively) and type I BD (p = 0.04). Moreover, T399I and D299G were less prevalent in SCZ late-onset age (p = 0.03, p = 0.02, respectively). TA haplotype was associated with protection from psychoses (p = 0.02) and particularly from schizophrenia (p = 0.04). In conclusion, TLR4 polymorphisms could present a preventive genetic background against psychoses onset in a Tunisian population. While T399I could be associated with protection against SCZ and BD, presenting an overlapping genetic factor between those psychoses, D299G was suggested to be associated with protection only from schizophrenia.

Cortical surface complexity in frontal and temporal areas varies across subgroups of schizophrenia

Schizophrenia is assumed to be a neurodevelopmental disorder, which might involve disturbed development of the cerebral cortex, especially in frontal and medial temporal areas. Based on a novel spherical harmonics approach to measuring complexity of cortical folding, we applied a measure based on fractal dimension (FD) to investigate the heterogeneity of regional cortical surface abnormalities across subgroups of schizophrenia defined by symptom profiles. A sample of 87 patients with DSM-IV schizophrenia was divided into three subgroups (based on symptom profiles) with predominantly negative (n = 31), disorganized (n = 23), and paranoid (n = 33) symptoms and each compared to 108 matched healthy controls. While global FD measures were reduced in the right hemisphere of the negative and paranoid subgroups, regional analysis revealed marked heterogeneity of regional FD alterations. The negative subgroup showed most prominent reductions in left anterior cingulate, superior frontal, frontopolar, as well as right superior frontal and superior parietal cortices. The disorganized subgroup showed reductions in bilateral ventrolateral/orbitofrontal cortices, and several increases in the left hemisphere, including inferior parietal, middle temporal, and midcingulate areas. The paranoid subgroup showed only few changes, including decreases in the right superior parietal and left fusiform region, and increase in the left posterior cingulate cortex. Our findings suggest regional heterogeneity of cortical folding complexity, which might be related to biological subgroups of schizophrenia with differing degrees of altered cortical developmental pathology.

Evidence for association between the 5' flank of the NOS1 gene and schizophrenia in the Chinese population

Nitric oxide (NO) plays an important role in the dopaminergic and serotonergic system as the second messenger of the NMDA receptor and has possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. There is also genetic evidence to support the human NOS1 (neuronal nitric oxide synthase 1) gene as a promising candidate gene associated with schizophrenia. In this paper we conducted a case-control association study involving 1705 Chinese subjects and 12 genetic markers [11 single nucleotide polymorphisms (SNPs) and 1 microsatellite] mainly in the 5' flank region of the gene by direct sequencing and capillary electrophoresis. We identified SNP rs3782206 and several haplotypes derived from it as being significantly associated with schizophrenia and, specifically, in a paranoid subgroup. Our results strongly support a previous hypothesis that NOS1 contributes to the genetic risk of schizophrenia and suggest that further research on more NOS1 variants and its regular elements are warranted.

Prolactin and estradiol serum levels in unmedicated male paranoid schizophrenia patients

There is evidence for the involvement of the endocrine system in schizophrenia. This involment was widely investigated in female patients. In the current study, we examined prolactin and estradiol serum levels in hospitalized unmedicated men with first-episode and recurrent schizophrenia and then tested possible correlation with various subtypes of the disease. In addition, the estradiol and prolactin levels were compared with a healthy control group. The serum samples were assessed the morning following admission in fifty-seven schizophrenia male patients. There was a significant difference in prolactin serum levels between the paranoid and “nonparanoid” schizophrenia subgroups. However, no significant differences were found in estradiol serum levels between schizophrenia subtypes or between the patients and their healthy counterparts. Finally, a significant and positive correlation was found between the prolactin and estradiol levels in the paranoid subgroup alone. Thus, it appears that low estradiol levels are associated with low prolactin levels, alleged hyperdopaminergic tone and psychotic breakdown in paranoid schizophrenia. The results of the present study further support our previous report of the association between prolactin serum levels and the schizophrenia cluster subtypes, indicating a different dopaminergic activity for the various forms of the disease.

Facial affect decoding in schizophrenic disorders: A study using event-related potentials

Deficits in emotional processing are evident in schizophrenia, but the underlying processes are still under debate. In this study we tried to replicate findings of diminished prefrontal electroencephalographic response during facial affect recognition in healthy controls and subsequently in schizophrenic patients. As a first step, we analysed the event-related potentials (ERPs) of 36 healthy subjects during emotional expression decoding compared with neutral face viewing. Subsequently, the ERPs of 22 patients with schizophrenia were compared with the ERPs of 22 healthy subjects matched for age and sex. The hypothesised increase in the negative component at 200 ms over frontal brain regions during facial affect decoding was not found in this study. Instead we found increased positive amplitudes at 300 ms over parietal brain areas for the active affect-decoding task compared with the passive neutral face-viewing task. Interestingly, schizophrenic patients had higher amplitudes in the neutral condition than did healthy controls. This effect was more pronounced in the paranoid subgroup of patients.

The effect of TRH administration during ect on seizure threshold and seizure duration : M.A. Theodoropoulou, I.M. Zervas, M. Markianos, N. Vaidakis, and Y.G. Papakostas. Department of Psychiatry, Athens University Medical School, Eginition Hospital, 72-74 Vas Sophias Avenue, Athens 115 28, Greece

We have previously reported that the activity in platelets of the important antioxidant enzyme glutathione peroxidase (GPx) is inversely correlated with computed tomographic (CT) measures of brain atrophy in a population of patients with chronic schizophrenia, suggesting that low GPx may be a vulnerability factor in those schizophrenic patients with structural brain abnormalities. The significance of this finding has now been explored in a larger clinical population by examining the relation of GPx and CT parameters to psychosocial variables and to the activity of platelet monoamine oxidase (MAO), which has also been reported to be altered in certain schizophrenic populations. In the present study, low platelet GPx and high brain atrophy were found to be associated with DSM-III diagnoses of nonparanoid schizophrenia, a high degree of chronicity, and a predominance of negative symptoms. Contrary to some literature reports, atrophy also correlated with age and length of illness among the schizophrenic patients, although the contribution of these factors was less than that of low GPx, which was itself not age dependent. The ventricle-brain ratio (VBR) and atrophy were highly correlated in a control group of affective disorder patients, but not in the schizophrenic group, where large VBRs were found predominantly in the DSM-III undifferentiated subgroup. The low-GPx/high-atrophy schizophrenic patients had normal platelet MAO levels, and MAO was significantly lower only in the paranoid subgroup, consistent with reported observations. There was no evidence for a neuroleptic-induced effect on either enzyme.

Automatic versus controlled semantic priming in schizophrenia.

Schizophrenic individuals (n = 31), including paranoid and nonparanoid diagnostic subgroups, and normal controls (n = 20) participated in a semantic priming experiment involving a single-choice lexical decision task. For the automatic priming blocks, a 260-ms stimulus onset asynchrony (SOA) was used; for the controlled priming blocks, 1,000-ms SOA was used. The paranoid subgroup showed significantly less priming than did the control group. The nonparanoid subgroup showed a decrease in priming compared with the control group that approached significance. There was an increased priming effect for the controlled compared with the automatic priming condition; this difference was not modulated by participant group. Nonsignificant semantic priming (equal to 0) occurred only for schizophrenic subgroups and only in automatic priming conditions.

The Ego Impairment Index and schizophrenia: a validation study.

This study is an extension of our work on a new scale, the Ego Impairment Index (EII; Perry & Viglione, 1991). The index is theoretically based on Beres's (1956) model of ego assessment and was empirically developed on a sample of melancholic, depressed outpatients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed. [DSM-III]; American Psychiatric Association, 1980). The EII is derived from the Rorschach Inkblot Test and offers a single composite score of ego impairment. This study validates the use of the EII with a heterogeneous sample of schizophrenic patients. In support of the trait-like characteristics of the scale, the EII continues to be expressed as a single factor, with a correlation of .98 when comparing the original factor derived from a melancholic population with this sample of schizophrenic patients. Significant correlations were also found between the EII and other clinical indices, including the Magical Ideation Scale, the Schizophrenia Index, and the Minnesota Multiphasic Personality Inventory (MMPI). Finally, the EII was found to differentiate between a paranoid subgroup and a mixed undifferentiated/disorganized subgroup who theoretically have more ego impairment. These results offer support for the use of the EII as an empirical means of quantitatively and qualitatively assessing thought disorder within a theoretical framework. Further research is needed to understand the application of the EII across different diagnostic groups and its relationship to other indices of psychological disturbance.

Natural autoantibodies in schizophrenia.

Autoantibodies reacting with cell constituents other than antinuclear antibodies have seldom been reported in the literature on schizophrenia. Serum of 41 DSM-III-R schizophrenic patients was examined for the presence of various autoantibodies and compared with that of healthy volunteers (n = 10) and hospitalized controls. Titers of IgG, IgA and IgM autoantibodies directed against actin, tubulin, myosin, DNA, thyroglobulin, elastin, albumin, DNA and trinitrophenyl groups were determined using enzyme immunoassay. IgG and IgA titers were significantly decreased in schizophrenic patients. These results contrast with those obtained with various other autoimmune and nonautoimmune diseases in which titers are either unchanged or increased. A significant increase of various autoantibody levels was observed in the paranoid subgroup of schizophrenics compared with the disorganized subgroup. These autoantibodies possess characteristics similar to those of natural autoantibodies, which seem to play several biological roles.

Plasma phenylethylamine in schizophrenic patients

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.

Phenylacetic acid in CSF and serum in Indian schizophrenic patients

Davis, Bruce A., Satish Shrikhande, Vasudev P. Paralikar, Steven R. Hirsch, David A. Durden and Alan A. Boulton: Phenylacetic Acid in CSF and Serum in Indian Schizophrenic Patients. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1991, 15 (1): 41–47. 1. 1. It has been proposed that an increase in the concentration of the neuromodulator phenylethylamine at the post-synaptic dopamine receptor may be involved in the etiology of schizophrenia. If this increase is the case, a reduction in the CSF and/or serum concentrations of phenylacetic acid, its major metabolite, might be anticipated. 2. 2. The authors have found in hospitalized Indian schizophrenic patients ingesting antipsychotic drugs, that the paranoid subgroup did indeed exhibit lower levels of unconjugated, conjugated and total phenylacetic acid in both serum and CSF.

Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: Relation to psychosocial variables

We have previously reported that the activity in platelets of the important antioxidant enzyme glutathione peroxidase (GPx) is inversely correlated with computed tomographic (CT) measures of brain atrophy in a population of patients with chronic schizophrenia, suggesting that low GPx may be a vulnerability factor in those schizophrenic patients with structural brain abnormalities. The significance of this finding has now been explored in a larger clinical population by examining the relation of GPx and CT parameters to psychosocial variables and to the activity of platelet monoamine oxidase (MAO), which has also been reported to be altered in certain schizophrenic populations. In the present study, low platelet GPx and high brain atrophy were found to be associated with DSM-III diagnoses of nonparanoid schizophrenia, a high degree of chronicity, and a predominance of negative symptoms. Contrary to some literature reports, atrophy also correlated with age and length of illness among the schizophrenic patients, although the contribution of these factors was less than that of low GPx, which was itself not age dependent. The ventricle-brain ratio (VBR) and atrophy were highly correlated in a control group of affective disorder patients, but not in the schizophrenic group, where large VBRs were found predominantly in the DSM-III undifferentiated subgroup. The low-GPx/high-atrophy schizophrenic patients had normal platelet MAO levels, and MAO was significantly lower only in the paranoid subgroup, consistent with reported observations. There was no evidence for a neuroleptic-induced effect on either enzyme.

Differences between paranoid and nonparanoid schizophrenic patients on the somatosensory P300 event-related potential.

Event-related potentials were recorded from schizophrenic patients (n = 30) and healthy controls (n = 30) using a somatosensory-reaction-time version of the oddball paradigm, by stimulating the right and the left median nerve. Latency, amplitude, duration and area of the P300 were measured. The patient group was subdivided into a paranoid (n = 16) and a nonparanoid (n = 14) subgroup and each was compared to controls. After stimulation of the right median nerve the nonparanoid group had a significantly prolonged P300 latency and a normal amplitude. The paranoid subgroup had a trend toward reduction of the P300 amplitude; its P300 latency was normal. After stimulation of the left median nerve, a prolongation of the P300 latency was observed in the paranoid subgroup. This subgroup had also a reduced P300 amplitude, while the nonparanoid patients had both values comparable to those of the controls. Duration and area were not significantly different between the two subgroups of patients and controls. Paranoid and nonparanoid patients showed a different behavior on reaction time parameters. No relationship was observed between P300 parameters and clinical ratings, neuroleptic dose and demographic data. The P300 parameters did not correlate with the reaction time measures. These results are discussed in terms of a disturbance of CNS inhibitory mechanisms in cognitive processes of paranoid schizophrenic patients and could be a further indication that different subtypes of schizophrenia may have different biological substrates.

HLA antigens and neuroleptic response in clinical subtypes of schizophrenia

The frequency of HLA antigens of A and B loci was examined in a carefully selected sample of 91 schizophrenic patients from central Italy. This population showed no increase in antigens compared with the control group. However, in agreement with previous studies, a slight increase in A1 was observed in the hebephrenic subgroup and, in a lesser extent, an increase of A2 was found in the paranoid subgroup. Although these increases are more prominent when the subgroups are compared and tend to support the case for genetic heterogeneity, they fail to reach statistical significance. Response to neuroleptic treatment was studied in an attempt to further subdivide the clinical subgroups. A1-negative and A2-positive paranoid patients demonstrated a statistical better response to neuroleptics. The findings suggest that schizophrenia should be considered a heterogenous disease and that response to neuroleptics can be employed as an instrument of biological subclassification.

Aggression control and structuring of social relations among recently admitted schizophrenics

As part of a study using an ethological conceptual approach, three scales were constructed to reflect adaptive success in the structuring of social relations. Twenty recently admitted schizophrenics were studied longitudinally in an active therapeutic milieu, drug-free, and during neuroleptic treatment. Patients showed substantial failures in the ritualization of agonistic behavior, manifest in more overt flight and fight. Poor group integration and absence of bond formation characterized the sample and were correlated with social withdrawal and elevated resting pulse rate—a pattern highly reminiscent of that seen in monkeys after bilateral amygdalectomy. The paranoid subgroup was the least impaired. Four-month long intensive treatment, including neuroleptics and psychosocial therapies, produced significant but modest improvements. Considerable maladaptive functioning remained.