Schizophrenic Cohort Research Articles

Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It "Blowin' in the Wind"?

Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive and impulsive behaviors. Described as an octopus of behavioral dysfunction, RDS refers to abnormal behavior caused by a breakdown of the cascade of reward in neurotransmission due to genetic and epigenetic influences. The resultant reward neurotransmission deficiencies interfere with the pleasure derived from satisfying powerful human physiological drives. Epigenetic repair may be possible with precision gene-guided therapy using formulations of KB220, a nutraceutical that has demonstrated pro-dopamine regulatory function in animal and human neuroimaging and clinical trials. Recently, large GWAS studies have revealed a significant dopaminergic gene risk polymorphic allele overlap between depressed and schizophrenic cohorts. A large volume of literature has also identified ADHD, PTSD, and spectrum disorders as having the known neurogenetic and psychological underpinnings of RDS. The hypothesis is that the true phenotype is RDS, and behavioral disorders are endophenotypes. Is it logical to wonder if RDS exists everywhere? Although complex, “the answer is blowin’ in the wind,” and rather than intangible, RDS may be foundational in species evolution and survival, with an array of many neurotransmitters and polymorphic loci influencing behavioral functionality.

Differences in the Opioid Consumption of Terminally Ill Schizophrenic and Nonschizophrenic Cancer Patients: Analysis of Secondary National Population Data

ContextIt is uncertain whether terminally ill schizophrenic cancer patients are hypoalgesic or have disparities in pain management. ObjectivesThe objective of this study was to analyze the dosage of opioids used in terminally ill cancer patients with and without schizophrenia. MethodsThis is a population-based retrospective cohort study based on data derived from the Taiwan National Health Insurance Research Database. Patients aged >20 years and newly diagnosed between 2000 and 2012 with at least one of the six most common cancers were included. After 1:4 matching, 1001 schizophrenic cancer patients comprised the schizophrenia cohort, while 4004 cancer patients without schizophrenia comprised the nonschizophrenia cohort. The percentage of opioid use, accumulated dose, and average daily dose near the end of life were analyzed for each cohort using multiple logistic and linear regression models. ResultsThe percentage of opioid use was lower in the schizophrenic cohort than the nonschizophrenic cohort during the last month before death (69.6% vs. 84.8%, odds ratio = 0.40, 95% CI = 0.34–0.48). The accumulated dose of opioid consumption was also lower in the schizophrenic cohort (2407 mg vs. 3694 mg, P value < 0.05). ConclusionNear the end of life, cancer patients with schizophrenia use less opioid than their nonschizophrenic counterparts. Cognitive impairment may be a cause in the disparity in end-of-life care for terminally ill schizophrenic cancer patients. Thus, we should formulate a more accurate pain scale system and pay attention to their need for pain treatment.

Estimation of life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for schizophrenia in Taiwan

By employing a novel semi-parametric extrapolation method, the life expectancies after the first hospitalization for schizophrenia and the associated lifetime healthcare expenditures were both estimated. Based on the linkage between the National Health Insurance Research Database and the National Mortality Registry of Taiwan, we have established a schizophrenic cohort for 2000–2010 and followed up to 2011. Survival function was estimated through Kaplan–Meier's method and extrapolated throughout life. We applied a simple linear regression to the logit-transformed survival ratio between the schizophrenic cohort and the sex-, age-matched referents via Monte Carlo simulation from the national life table. The monthly survival probability was multiplied by the average healthcare expenditures and summed throughout life to estimate the lifelong cost reimbursed by the National Health Insurance. The results showed that patients diagnosed at age 20–29 had the highest expected years of life lost (EYLL), 15 and 9years, in men and women, respectively, with corresponding lifetime healthcare expenditures of USD 48,000 and 53,000. Males generally had higher health cost per life-year than their female counterparts across their lifespan. We applied the same method to the first 6years of the cohort and extrapolated to 12years, which showed that the relative biases for different age strata were less than 5%. We thus concluded that the semi-parametric extrapolation method might provide a timely estimation of lifetime outcomes for health care planning of schizophrenia.

Use of Antipsychotics and Risk of Cerebrovascular Events in Schizophrenic Patients

This nested case-control study assessed the association between antipsychotic use and cerebrovascular adverse events among schizophrenic patients. Using Taiwan's National Health Insurance Research Database, we identified 9715 newly diagnosed schizophrenic patients during 2001 to 2009. Within the schizophrenic cohort, 386 cases of cerebrovascular events and 772 matched control subjects (1:2 ratio) were further identified. Conditional logistic regression models were used to examine the association between the use of antipsychotics (timing, duration, and type) and risk of cerebrovascular events. Current users of antipsychotics were associated with a 2-fold risk of stroke (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-1.39; P = 0.02) as compared with nonusers. Among current users, patients who used antipsychotics less than 15 days (adjusted OR, 9.41; 95% CI, 3.08-28.71; P < 0.01) and 16 to 30 days (adjusted OR, 6.90; 95% CI, 1.09-43.69; P = 0.04) were associated with an extremely high risk of stroke. The risk of stroke was greater for patients who used first-generation antipsychotics alone or combination of first- and second-generation antipsychotics, with adjusted ORs of 2.75 (95% CI, 1.34-5.64; P < 0.01) and 2.37 (95% CI, 1.20-4.68; P = 0.01), respectively, but not in patients who used second-generation antipsychotic alone. This population-based study extends previous evidence by documenting the increased cerebrovascular events associated with antipsychotic use in a schizophrenic cohort. A temporal association of such risk was reported in our study. Further studies are needed to assess the risk-benefit profile of first- and second-generation antipsychotics in this patient population.

Social Cognitive Role of Schizophrenia Candidate Gene GABRB2

The occurrence of positive selection in schizophrenia-associated GABRB2 suggests a broader impact of the gene product on population fitness. The present study considered the possibility of cognition-related GABRB2 involvement by examining the association of GABRB2 with psychosis and altruism, respectively representing psychiatric and psychological facets of social cognition. Four single nucleotide polymorphisms (SNPs) were genotyped for quantitative trait analyses and population-based association studies. Psychosis was measured by either the Positive and Negative Syndrome Scale (PANSS) or antipsychotics dosage, and altruism was based on a self-report altruism scale. The minor alleles of SNPs rs6556547, rs1816071 and rs187269 in GABRB2 were correlated with high PANSS score for positive symptoms in a Han Chinese schizophrenic cohort, whereas those of rs1816071 and rs1816072 were associated with high antipsychotics dosage in a US Caucasian schizophrenic cohort. Moreover, strongly significant GABRB2-disease associations were found among schizophrenics with severe psychosis based on high PANSS positive score, but no significant association was observed for schizophrenics with only mild psychosis. Interestingly, in addition to association with psychosis in schizophrenics, rs187269 was also associated with altruism in healthy Han Chinese. Furthermore, parallel to correlation with severe psychosis, its minor allele was correlated with high altruism scores. These findings revealed that GABRB2 is associated with psychosis, the core symptom and an endophenotype of schizophrenia. Importantly, the association was found across the breadth of the psychiatric (psychosis) to psychological (altruism) spectrum of social cognition suggesting GABRB2 involvement in human cognition.

Increases in Two Truncated TrkB Isoforms in the Prefrontal Cortex of People With Schizophrenia

The truncated brain-derived neurotrophic factor (BDNF) receptors (truncated TrkB [TrkB-TK-] and sarc homology containing TrkB [TrkB-Shc]) are alternative transcripts of the full-length TrkB receptor (TrkB-TK+) that produce isoforms capable of binding to BDNF but not being able to mediate the classic neurotrophic response via tyrosine kinase signaling. We hypothesized that in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia, truncated TrkB receptors (TK- and Shc) would be altered and may contribute to deficits in BDNF function. Using a large cohort of controls and schizophrenics (n = 72/72), we measured mRNA expression of the full-length TrkB receptor, TrkB-TK+ and the truncated TrkB receptors, TrkB-TK- and TrkB-Shc, by quantitative real-time polymerase chain reaction and protein expression by western blotting. We found highly significant increases in mRNA expression of both truncated TrkB receptor isoforms in people with schizophrenia. When we examined the full-length TrkB-TK+:truncated TrkB ratios, we observed significant decreases in schizophrenia both on the mRNA and protein level. We found a slight reduction in TrkB-TK+ mRNA and a significant reduction in TrkB-TK+ protein expression in schizophrenia, which was evident in females. No gender-specific changes were found for the truncated TrkB receptors. Diagnostic changes in TrkB-TK+ mRNA and protein may be subtle and/or gender-specific, whereas changes in TrkB-TK- and TrkB-Shc expression are robust and may generalize to both males and females with schizophrenia. Increased truncated TrkB receptors may contribute to reduced overall BDNF/tyrosine receptor kinase B (TrkB) signaling and lead to reduced neuronal plasticity in the DLPFC in schizophrenia suggesting that therapies aimed at ameliorating neurotrophin deficits may need to consider blocking excessive truncated TrkB function.

A Recombination Hotspot in a Schizophrenia-Associated Region of GABRB2

BackgroundSchizophrenia is a major disorder with complex genetic mechanisms. Earlier, population genetic studies revealed the occurrence of strong positive selection in the GABRB2 gene encoding the β2 subunit of GABAA receptors, within a segment of 3,551 bp harboring twenty-nine single nucleotide polymorphisms (SNPs) and containing schizophrenia-associated SNPs and haplotypes.Methodology/Principal FindingsIn the present study, the possible occurrence of recombination in this ‘S1–S29’ segment was assessed. The occurrence of hotspot recombination was indicated by high resolution recombination rate estimation, haplotype diversity, abundance of rare haplotypes, recurrent mutations and torsos in haplotype networks, and experimental haplotyping of somatic and sperm DNA. The sub-segment distribution of relative recombination strength, measured by the ratio of haplotype diversity (Hd) over mutation rate (θ), was indicative of a human specific Alu-Yi6 insertion serving as a central recombining sequence facilitating homologous recombination. Local anomalous DNA conformation attributable to the Alu-Yi6 element, as suggested by enhanced DNase I sensitivity and obstruction to DNA sequencing, could be a contributing factor of the increased sequence diversity. Linkage disequilibrium (LD) analysis yielded prominent low LD points that supported ongoing recombination. LD contrast revealed significant dissimilarity between control and schizophrenic cohorts. Among the large array of inferred haplotypes, H26 and H73 were identified to be protective, and H19 and H81 risk-conferring, toward the development of schizophrenia.Conclusions/SignificanceThe co-occurrence of hotspot recombination and positive selection in the S1–S29 segment of GABRB2 has provided a plausible contribution to the molecular genetics mechanisms for schizophrenia. The present findings therefore suggest that genome regions characterized by the co-occurrence of positive selection and hotspot recombination, two interacting factors both affecting genetic diversity, merit close scrutiny with respect to the etiology of common complex disorders.

A comparative study of MAP2 immunostaining in areas 9 and 17 in schizophrenia and Huntington chorea

Increasing evidence suggests that there may be significant morphological changes in the neuropil of the dorsolateral prefrontal cortex in schizophrenia. A controversial issue surrounding these deficits in the cortical neuropil is the confounding effects of antipsychotic (neuroleptic) medication as well as the question of generality to psychiatric disorders. To begin to address these issues we examined brains from Huntington’s patients matched to a cohort of schizophrenics and controls. Many Huntington’s patients take neuroleptics similar to schizophrenics; therefore, by comparing the two groups to controls we can begin to determine if neuroleptics play a role in the deficits reported in schizophrenia. Using MAP2 immunohistochemistry and thionin staining eight matched triplets of Huntington, schizophrenia and control, in areas 9 and 17 layers III and V were analyzed. Our results confirmed previous published data showing a schizophrenia-associated decrease in MAP2 in area 9 with no change in area 17. Similarly the Huntington’s patients showed no change in area 9 layer III and no change in area 17. There was however, a modest decrease observed in layer V area 9 of the Huntington’s patients. Neuron density measurements showed no change in either layer or brain region in any of the diagnostic categories. These observations suggest that antipsychotic medication may not be responsible for some of the morphological changes observed in the neuropil of the PFC in schizophrenia.

A link between schizophrenia and diabetes?: Insights from the pre-antipsychotic era

Background: Because type II diabetes is currently more prevalent in schizophrenics than non-schizophrenics, some investigators have postulated a more fundamental association between these two disorders. However, there is a paucity of evidence concerning the association between diabetes and schizophrenia that is not confounded by the use of antipsychotic drugs, many of which have been linked to diabetes or pre-diabetes. Clinical literature from the pre-antipsychotic era (PAPE) may provide insights that help better define the risks currently associated with antipsychotic drugs. Aims and methods: After reviewing approximately 140 articles that addressed metabolic derangements in serious mental illness, we analyzed 20 English language clinical studies from the PAPE (all pre-1950 to assure that none of the patients had been exposed to neuroleptics) that specifically commented on glucose regulation in patients with schizophrenia and severe depression. From these, data from 5 studies that used uniform methodology and presented blood glucose (BG) data en toto were selected for quantitative evaluation. Fasting blood glucose (FBG) values and results from oral glucose tolerance tests (OGTTs), corrected by a factor of 20 mg% for the presence of non-glucose reducing substances, were pooled from patients with schizophrenia, schizophrenia sub-classified as catatonic, patients with psychotic depression and age-matched controls. BG data were evaluated with reference to current diagnostic standards for diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) from the American Diabetes Association. Results: The mean FBG from the schizophrenic group (n = 148; 88.1 ± 17.8 mg% (range 50-140 mg%)) was not materially different from the mean FBG of contemporaneous age-matched healthy controls (n = 27; 82.3 ± 10.4 mg% (range 58- 105 mg%); p> 0.05). Descriptions of patients by the original authors did not indicate clinical signs of DM. However, these acutely ill schizophrenics were nearly 4 times as likely as controls (relative risk 3.74) to manifest a moderate elevation in FBG not inconsistent with IFG according to current diagnostic standards (i.e., FBG 100-125 mg%), and were also approximately 3 times as likely as controls (relative risk 2.9) to have fastinghypoglycemia (i.e., FBG < 65 mg%). With the notable exception of a subgroup with active catatonia, OGTT results from schizophrenics provided equivocal evidence of IGT. Evidence is presented which suggests that, in the setting of acute or sub-acute serious mental illness, hyperglycemia was often transitory, tending to resolve spontaneously or in apparent response to non-pharmacologic psychotherapy. Summary and conclusions: Insights from studies performed in the PAPE cast doubt on the clinical relevance and putative specificity of association between diabetes or pre-diabetes and schizophrenia. Moderate fasting hyperglycemia, moderate fasting hypoglycemia and equivocally abnormal OGTTs were present in substantial minorities of schizophrenics early in the course of hospitalization, but these findings were nonspecific and appear to have been transitory in many instances. We conclude that it is inappropriate to refer to available BG data from the PAPE as supporting the hypothesis that a diagnosis of schizophrenia per se is an independent risk factor for diabetes. Additional research is needed to better define environmental and iatrogenic factors that may explain the higher rates of true diabetes and related morbidity that have been reported recently in schizophrenic cohorts, and in particular the attributable risk of antipsychotic drugs.

The PsyGrid Experience

The key aim of the PsyGrid project was the creation of an information system to ascertain and characterise a large, representative cohort of schizophrenics, beginning from their first episode of psychosis. The cohort was to be drawn from eight geographically dispersed regions of Eng-land, covering in total one-sixth of the entire population. In order to meet the current and future requirements we needed to build a secure distributed system, which not only could support remote data collection, but could also be integrated with other data sets, applications, and workflows for statistical analysis. We concluded that a service-oriented architecture was required and that the implementation technology should be Web services. In this article we present the design, deployment and operation of the PsyGrid data collection system as a case study in applying Web services to health informatics. The major problems we faced were related to the deployment of Web services into an existing network infrastructure, but overall found Web services to be the most suitable middleware technology.

Disconnection and Cognitive Dysmetria in Schizophrenia

Disconnection and Cognitive Dysmetria in Schizophrenia

Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation

Background: Acetylcholine is important to hippocampal function, including the processes of learning and memory. Patients with schizophrenia show impaired learning and memory and hippocampal dysfunction. Thus, acetylcholinergic systems may be primarily or secondarily disrupted in the hippocampal formation of schizophrenic patients. The present study tested the hypothesis that [ 3H]pirenzepine-labeled muscarinic cholinergic receptor levels are altered in the hippocampal formation of patients with schizophrenia. Methods: We have used quantitative autoradiography to measure [ 3H]pirenzepine binding to M 1 and M 4 receptors in the hippocampal formation from 15 schizophrenic and 18 nonschizophrenic subjects. Results: The mean density of [ 3H]pirenzepine binding was reduced in all regions studied, including the dentate gyrus, subdivisions of Ammon’s Horn (CA1–CA4), subiculum, and the parahippocampal gyrus, of the schizophrenic cohort. Moreover, unlike controls, there was no significant variation between the mean levels of [ 3H]pirenzepine binding across the subregions of the hippocampal formation from schizophrenic subjects. Conclusions: These findings provide support for a possible involvement of the muscarinic cholinergic system in the pathology and/or treatment of schizophrenia.

Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a three-dimensional, stereologic counting method

Neuropsychologic testing in schizophrenic patients has underscored the prominence of dysfunction in cognitive processes associated with the dorsolateral prefrontal cortex. Quantitative cytometric analysis of area 46 was undertaken in brains from schizophrenic patients to determine whether there are morphologic changes underlying these cognitive deficits. Postmortem brain specimens from 9 schizophrenic patients, 10 normal subjects, and 8 Huntington's diseased patients were fixed in formalin and celloidin embedded. A direct, three-dimensional counting method was used to determine cell density and cortical thickness in Nissl-stained sections of area 46. Overall neuronal density was 21% greater in brains from schizophrenic patients in comparison to normal controls. Significant elevations in neuronal density were observed in layers II, III, IV, and VI. The cortical ribbon was slightly (8%) but not significantly thinner. However, layer II exhibited disproportionate thinning compared with all other layers. In brains from Huntington's diseased patients, increases in neuronal (35%) and glial (61%) density with substantial cortical thinning (30%) were observed. The neuropathology of area 46 in schizophrenia is similar in direction and magnitude to that previously described in area 9 (Selemon et al. [1995] Arch. Gen. Psychiatry 52:805-818), except for the abnormalities in layer II, which are specific to area 46. In contrast to Huntington's disease, in which cortical atrophy and gliosis are present, no evidence for cortical cell loss was uncovered in the schizophrenic cohort. The observed elevation in neuronal density suggests that a reduction in interneuronal neuropil may constitute the anatomical substrate for prefrontal cortical dysfunction in schizophrenia.

Schizophrenia among patients treated for rheumatoid arthritis and appendicitis

The widely accepted negative association between schizophrenia and rheumatoid arthritis (RA) is based on the results of investigations which sought RA in large samples of schizophrenic patients. Using a discharge register, we examined the frequency of schizophrenia in a sample of 5626 RA patients. Appendicitis patients ( n = 5330) were used as a comparison group. The cumulative incidence of hospital care with the diagnosis of schizophrenia during 8 years was higher in the RA group (0.64%) than in the appendicitis group (0.47%). Schizophrenia was significantly more common in the RA group than in the appendicitis group among the young. The age-adjusted prevalence of schizophrenia was 0.96% in the RA group and 0.51% in the appendicitis group. Because of this unexpected finding, we examined the incidence of RA and appendicitis among a birth cohort born in 1966. The frequencies of RA and appendicitis among schizophrenic cohort members ( n = 76), cohort members with psychiatric diagnosis other than schizophrenia ( n = 438), and members without psychiatric diagnosis ( n = 10503) were similar. These findings do not support the negative association between schizophrenia and RA. Prolonged institutionalization per se may have been the protective factor against RA in the previous studies. The findings also raise the hypothesis that genes that predispose to schizophrenia provide protection from appendicitis, historically a common cause of mortality.

Prediction of suicide in a first episode schizophrenic cohort

Prediction of suicide in a first episode schizophrenic cohort

Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics

NMDA receptor antagonists can induce a schizophrenia-like psychosis, but the role of NMDA receptors in the pathophysiology of schizophrenia remains unclear. Expression patterns of mRNAs for five NMDA receptor subunits (NR1/NR2A-D) were determined by in situ hybridization in prefrontal, parieto-temporal, and cerebellar cortex of brains from schizophrenics and from neuroleptic-treated and nonmedicated controls. In the cerebral cortex of both schizophrenics and controls, mRNAs for NR1, NR2A, NR2B, and NR2D subunits were preferentially expressed in layers II/III, Va, and VIa, with much higher levels in the prefrontal than in the parieto-temporal cortex. Levels of mRNA for the NR2C subunit were very low overall. By contrast, the cerebellar cortex of both schizophrenics and controls contained very high levels of NR2C subunit mRNA, whereas levels for the other subunit mRNAs were very low, except NR1, for which levels were moderate. Significant alterations in the schizophrenic cohort were confined to the prefrontal cortex. Here there was a shift in the relative proportions of mRNAs for the NR2 subunit family, with a 53% relative increase in expression of the NR2D subunit mRNA. No comparable changes were found in neuroleptic-treated or untreated controls. These findings indicate regional heterogeneity of NMDA receptor subunit expression in human cerebral and cerebellar cortex. In schizophrenics, the alterations in expression of NR2 subunit mRNA in prefrontal cortex are potential indicators of deficits in NMDA receptor-mediated neurotransmission accompanying functional hypoactivity of the frontal lobes.

Lack of sex differences in the neuropsychological performance of patients with schizophrenia.

While a number of studies have suggested that women with schizophrenia have a less severe form of the disorder than men, the issue has been examined with neuropsychological measures only infrequently. The authors compared neuropsychological test performances of men and women from four independent schizophrenic cohorts: two groups of inpatients with chronic courses at a research hospital (N = 128 and N = 63), one group of consecutive admissions to a private psychiatric hospital (N = 57), and one group of schizophrenic twins from discordant monozygotic pairs (N = 20). Nearly 100 comparisons of neuropsychological test performances were made between men and women. Not one comparison significantly favored women, and few were even significantly different between the sexes. It cannot be ruled out that the disproportionate number of men in the chronic cohorts may have reflected either more frequent intellectual deterioration in men or a bias toward more severely impaired women. Yet, men and women in all groups performed similarly, including the groups in which the sex ratios were nearly equal and were not skewed toward chronicity. These results provide little support for the hypothesis that gender is associated with a unique pathogenesis of schizophrenia or is a marker for a distinct subtype of schizophrenia, at least to the extent that cognitive impairment is a primary manifestation of the underlying disease process. However, given the lack of female patients with later ages at onset and more affective symptoms, the results in this study should be considered relevant only for chronic patients with onset of schizophrenia before age 30.

Committed Suicide in a Total Schizophrenic Cohort: In Search of the Suicidal Process

In an epidemiologic case-finding study of 341 persons diagnosed as having “long-term functional psychosis”, 7 persons with schizophrenia had committed suicide during a follow-up period of 3 years. Data about the seven cases were retrospectively gathered through studies of medical case records and through interviews with significant others and care personnel/psychotherapists. All seven persons had been chronically ill. Most of them were in a state of remission from their illness before the suicide and even showed signs of lasting improvement. The individuals had premorbidly been functioning rather well, with normal ambitions. Late in their illness they expressed a sense of loss of a former self and feelings of being hopelessly handicapped and separated from what they considered to be normal life. All seven persons had also experienced negative life events shortly before the suicide. The time perspective of having lived with a chronic mental illness for many years seems to have been of major importance in t...

Brain Atrophy or Dystrophy in Schizophrenia: When Did It Happen?

B et al, 1 reporting on a quantitative magnetic resonance imaging investigation of 44 neuroleptic-treated schizophrenic patients and 29 healthy volunteers, found a decrease in volume of left and right amygdalahippocampal complex and a smaller volume of right and left prefrontal white matter in the schizophrenic group. These findings support and extend similar results by others from previous imaging and quantitative postmortem studies. 2-6 This study 1 also measured total cerebral and cerebrospinal fluid volume based on an outline of the dura on serial magnetic resonance imaging slices, excluding the brain stem and cerebellum. There was no significant difference between the schizophrenic cohort and controls in this measure of total cerebral volume, which may be considered to be equivalent to the measurement of head circumference. Many investigators consider that a reduction in the volume of the medial temporal lobe and other structures in schizophrenia represents a neurodevelopmental disorder, ie, a

Cortical cholinergic markers in schizophrenia

Cortical cholinergic deficits have been implicated in the cognitive deficits produced by a variety of neurodegenerative diseases including Alzheimer's disease (AD). Recent studies have suggested that many of the chronically institutionalized geriatric schizophrenic patients are also cognitvely impaired. In this postmortem study we compared cholinergic marker activity in six different cortical regions derived from elderly controls, chronically institutionalized geriatric schizophrenic patients, and AD patients. All of the Alzheimer's disease cases met neuropathological criteria for AD, while none of the schizophrenic cases met criteria for AD. Cholinergic marker activity (choline acetyltransferase and acetylcholinesterase) was significantly diminished in the AD cohort but not in the schizophrenic cohort. Additionally, cortical choline acetyltransferase activity was significantly and negatively correlated with Clinical Dementia Rating scores (CDR), whereas no such correlations were evident in the schizophrenic cohort. These results suggest that cognitive deficits in geriatric schizophrenics are not due to diminished cortical cholinergic activity.