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At least 19 recordsLinked to original sources

PubMed2026

Whole-Exome and Whole-Genome Sequencing of Candidate Pharmacogenomic and Schizophrenia-Related Genes in Sudanese Families with Schizophrenia.

BACKGROUND: Schizophrenia is considered a neuro-developmental disorder leading to disastrous lifelong disability of the patients and their families. There is a lack of data regarding pharmacogenomics of schizophrenia in Sudan. This study aimed to identify different genes affecting the treatment outcomes in Sudanese patients with schizophrenia. METHODS: A case-control study was conducted on seven families having more than one member diagnosed with schizophrenia. This was a small exploratory family-based sequencing study involving 18 affected individuals and 8 controls from seven families. Ethical clearance and informed consent were obtained. Demographic data were collected using a standardized data collection sheet. DNA was extracted from blood samples collected from patients and control groups. Then, whole-exome and genome sequencing were performed. Sixty-six genes associated with schizophrenia, treatment, and treatment resistance were selected from the variant calling file. Variants showing single-nucleotide polymorphisms (SNPs) were identified. These variants were then classified based on their impact on the protein-coding sequence into high- and moderate-impact. Moreover, indel mutations were also identified. RESULTS: Twelve variants of seven genes (COMT, FMO1, LPL, CYP2E1, ABCC1, GRM3, CYP2C9) were identified as genes with impact and potential association with schizophrenia (p-value=0.006632). Forty-three genes had a moderate impact, and they showed a potential association with schizophrenia (p-value=0.0004436). Two variants were indel mutations (CYP2D6, DTNBP1) and showed association with schizophrenia (p-value=0.004741). The p-values were generated from different databases. CONCLUSION: This exploratory family-based sequencing study identified several potentially relevant pharmacogenomic and schizophrenia-associated variants in Sudanese families, warranting validation in larger and ethnically diverse cohorts.

antipsychotics↗

PubMed2026

Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia.

The genetic mechanisms underlying heterogeneity in symptom presentation and antipsychotic response in schizophrenia remain unclear, limiting the development of personalized treatment. We integrated genome-wide schizophrenia polygenic risk scores (SZ-PRS) and pathway-specific PRSs (pPRSs) for four major neurotransmitter systems to examine their associations with clinical phenotypes across the course of illness. Primary analyses were conducted in 394 drug-naïve, first-episode patients from the Chinese First-Episode Schizophrenia Trial (CNFEST) to investigate associations with baseline symptom severity, neurocognitive impairment, and longitudinal treatment response. The CNFEST cohort included 52-week longitudinal assessments of symptoms and neurocognition using the Positive and Negative Syndrome Scale and a modified version of the MATRICS Consensus Cognitive Battery. An independent case-control cohort evaluated associations with schizophrenia diagnosis, while a cohort of 514 healthy adults assessed whether PRS-cognition associations are specific to schizophrenia. Higher SZ-PRS predicted schizophrenia diagnosis (OR = 2.28, Pfdr = 0.003) and poorer baseline executive function (β = -0.44, Pfdr = 0.006) and working memory (β = -0.49, Pfdr = 0.018), but these associations were absent in healthy adults. In contrast, pPRSs showed weaker associations with diagnosis and baseline cognition but were more informative for treatment outcomes: higher serotonin-pPRS predicted greater improvement in depressive symptoms (Pfdr = 0.023-0.032), and higher GABA-pPRS predicted greater improvement in overall symptoms (Pfdr = 0.038-0.043) during weeks 4-24. Exploratory drug-specific analyses further suggested that treatment response varied across antipsychotics and was differentially associated with pPRSs. These findings demonstrate that genome-wide and pathway-specific PRSs contribute distinctly to schizophrenia phenotypes, supporting their integration for personalized stratification and treatment.

Humans↗

PubMed1976

A study of "atypical schizophrenia". Comparison with schizophrenia and affective disorder by sex, age of admission, precipitant, outcome, and family history.

Eighty-five cases of atypical schizophrenia were compared with 200 of schizophrenia, 100 of bipolar (mania), and 225 of unipolar (depression) affective disorder. Comparisons were made on the basis of sex, age at admission, precipitating factors, outcome, and a family history of schizophrenia or of affective disorder. The atypical schizophrenia differed remarkably from the schizophrenia and most closely resembled the bipolar affective disorder when allowance was made for a younger age at onset and a higher frequency of precipitants. An analysis of symptoms verified the predominance of schizophrenic features in the atypical schizophrenia, but also showed a high percentage (80%) of patients who had one or more manic symptoms at index admission. It is concluded that great care should be taken in diagnosing schizophrenia in a patient who also has manic symptoms.

Adult↗

PubMed1976

Another view of schizophrenia subtypes. A report from the international pilot study of schizophrenia.

Schizophrenia subtypes are defined predominantly my manifest symptoms and behavior. This report, based on sign and symptom data from the International Pilot Study of Schizophrenia, addresses three questions: (1) Are traditional subtype diagnoses applied similarly across cultures? (2) Are the various traditional subtypes symptomatically distinguishable from one another? (3) Can cluster analytic techniques define a more distinctive set of schizophrenic subgroups? Present State Examination data were reduced to 27 psychopathologic signs and symptoms. Profile analysis of variance results indicate that each subtype appears similar, regardless of center of origin. However, this is based on a lack of distinguishing features between different subtypes. On the other hand, when a cluster analytic technique was used, it showed one large and three small subgroups, each readilty distinguishable from the others. These subgroups, labeled "usual," "flagrant," "insightful," and "hypochondriacal," are described clinically. If replicated or validated, such subgroups may prove meaningful in future considerations of subdivisions of the schizophrenia syndrome.

Culture↗

PubMed1978

[Age-related dynamics of outpatient forms of schizophrenia (on the age-related dynamics of so-called latent schizophrenia in light of late catamneses in senescence)].

The report contains a study of 45 patients aged 60--84 in whom during the entire life there were gradually increasing subclinical symptoms of schizophrenia: emotional shallowness, oddness, episodic rudimentary affective or paranoial disturbances. However, the level of adaptation and mental activity did not suffer significantly. The age-specific dynamics of such forms corresponded to general regularities in the development of schizophrenia: in the involutional period there was revivification of the above-mentioned symptoms of schizophrenia while in senescence only paranoial disorders and an increase of deficitary changes remained. The author discusses the question of justified diagnosis of latent schizophrenia in such cases.

Affective Symptoms↗

PubMed1977

Very short-term memory dysfunction in schizophrenia. Defective short time constant information processing in schizophrenia.

Disordered, very short-term memory (VSTM) has been hypothesized as the fundamental cognitive deficit in schizophrenia. We describe a method that measures VSTM using self-stimulated auditory average evoked potentials. This paradigm allows the VSTM hyothesis to be tested relatively free of superficial attentional and motivational artifacts. The experimental results are consistent with a VSTM dysfunction in schizophrenia. Very short-term memory dysfunction is discussed in light of recent blink reflex evidence that there is a short time constant information processing system with a time base similar to VSTM (ie, 1 to 1,000 msec). This leads to new testable hypotheses about information processing and VSTM in schizophrenia. It also lays the basis for interpreting this phenomenon as a pathologic exaggeration of an adaptive neurophysiologic mechanism.

Adaptation, Psychological↗

PubMed1992

Schizophrenia, genetic retrenchment, and epidemiologic renaissance. The Sixth Biennial Winter Workshop on Schizophrenia, Badgastein, Austria, January 26-February 1, 1992.

A distinctive feature of these workshops, in addition to those noted in the introductory overview, is the selection of a relatively isolated location for a 1-week period. This, together with a rich and varied program and an ethos of informality, encourages participants to discuss not only the work presented but also their unpublished work and their intuitions based on preliminary data and analyses. Such an interchange is of inestimable value to the schizophrenia research community. In scientific terms, a panel of concluding discussants (Drs Kendell, Torrey, and Waddington) were in some measure of agreement that genetics, particularly molecular genetics, appears to be experiencing a period of retrenchment, while epidemiology is experiencing something of a renaissance. Maternal influenza was a prominent theme, although the data were far from consistent. It was argued by Dr Wessely that risk for schizophrenia putatively attributable to maternal influenza might be 5% to 10% of all cases, indicating a modest effect. Eclectically, Dr Kendell believed the effect to be "real" but slight and fragile, it being sought against large aggregates that almost inevitably result in differing findings from differing countries or from different data bases within a given country. Gender differences were also among the more prominent themes, not just in an epidemiologic context but also in a variety of other studies. This points anew to disturbances in schizophrenia of factors that regulate, or are intimately associated with, sexual dimorphism in brain development. Abnormalities in cerebral asymmetry continue to pervade a variety of research findings and point further to neurodevelopmental anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1975

Diagnostic criteria and five-year outcome in schizophrenia. A report from the International Pilot Study of schizophrenia.

Systematic psychiatric assessment was undertaken on 131 patients (the American cohort of the International Pilot Study of Schizophrenia). Nine areas of outcome functioning were assessed five years later at follow-up evaluation on 63% of these patients. An analysis of 66 clinical and demographic variables established that the patients sucessfully followed-up were representatives of the entire cohort. Diagnostic data from initial evaluations and follow-up outcome assessment were used to examine the relationship between diagnostic criteria and outcome in schizophrenia. Applying the criteria for schizophrenic diagnosis defined by Langfeldt, by Schneider, and Carpenter et al failed to define a poor outcome group. No difference in outcome was found when traditional schizophrenic subtypes were contrasted. Overall outcome in 61 patients with conditions diagnosed as schizophrenic was heterogeneous. However, despite overlap, the mean outcome in the schizophrenic cohort was poorer than in the 19 nonschizophrenic patients.

Activities of Daily Living↗

PubMed1975

Discriminating symptoms in schizophrenia. A report from the international pilot study of schizophrenia.

Schizophrenia is recognized by the presence of one or more clinical syndromes, but there is disagreement as to how far the boundaries of the concept should be extended. During the course of a World Health Organization study, using the Present State Examination and a computerized classification program, a nuclear schizophrenic syndrome was nearly always (95.1%) associated with a diagnosis of schizophrenic or paranoid psychosis. The only substantial exception was that 13 out of 79 patients diagnosed as manic were said to show the nuclear syndrome. The computer classification was concordant with a clinical diagnosis of schizophrenic or paranoid psychosis, manic psychosis, or depressive disorder, in 90% of cases. If appropriate precautions are taken, many of the sources of noncomparability in epidemiological, therapeutic, and prognostic studies can be brought under control.

Adjustment Disorders↗

PubMed1976

Neurologic soft signs in schizophrenia and character disorders. Organicity in schizophrenia with premorbid asociality and emotionally unstable character disorders.

Previous studies indicated that for two subgroups of patients, schizophrenics with premorbid asociality (SPA) and individuals with emotionally unstable character disorders (EUCD), central nervous system damage may have etiologic significance. It was hypothesized that these two patient groups would also have an increased number of neurologic soft signs. The relationship of neurologic examination, tests of auditory-visual integration, and intelligence quotient, and diagnoses was studied for 350 patients. Tests of reliability and persistence for all observed signs were performed. The EUCD and SPA groups had increased evidence of neurologic soft signs. Differences in patterns of IQ scores also suggest that different forms of brain damage may be present in these two groups. When the two groups were removed from the larger patient sample, those patients with other types of schizophrenia and character disorder did not exhibit evidence of neurologic impairment. This study of neurologic soft signs adds to the validity of considering SPA and EUCD as separate diagnostic entities.

Central Nervous System Diseases↗

PubMedDate not supplied

Schizophrenia and tardive dyskinesia: is schizophrenia also a "denervation hypersensitivity"?

In human beings, amphetamine can induce both schizophreniform psychosis and oral-facial dyskinesia resembling tardive dyskinesia, while neuroleptic agents reduce the manifestations of both conditions. This suggests that such psychosis and movement disorder may occur by the same or very similar mechanisms. It is thought that tardive dyskinesia may result from neuroleptic-induced denervation hypersensitivity to dopamine. The author cites evidence suggesting that amphetamine may act on dopaminergic pathways in the CNS to produce a denervation hypersensitivity like that caused by neuroleptic agents. Clinical evidence compatible with a denervation hypersensitivity hypothesis of schizophrenia is then discussed.

Animals↗

PubMed1975