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Abstract Genetics constitute a crucial risk factor to schizophrenia. Introduction Despite a century of research, our knowledge of the etiology and pathogenetic unfolding of schizophrenia remains scarce. Models of Genetic Transmission It has for a long time been known that madness and many other human afflictions and characteristics runs in families. Molecular Genetics The Human Genome Project — has been instrumental in molecular genetic research in schizophrenia.
Limitations and Challenges As any research question, pre-molecular and molecular genetic studies in schizophrenia are based on certain assumptions and confront various limitations and challenges that must be made explicit if we are to properly appreciate the empirical findings. Conclusion Pre-molecular and molecular genetic studies have demonstrated that genetics form a strong risk factor for schizophrenia. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References Aberg K. A comprehensive family-based replication study of schizophrenia genes. JAMA Psychiatry 70 , — Diagnostic and Statistical Manual of Mental Disorders. Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Psychiatry , — Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Psychiatry 7 , — Genetics of schizophrenia and the new millennium: progress and pitfalls.
Molecular validation of the schizophrenia spectrum. Komplexe und Krankheitsursachen bei Dementia Praecox. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Replication analyses of four chromosomal deletions with schizophrenia via independent large-scale meta-analyses.
B Neuropsychiatr. Behavior genetics and postgenomics. Brain Sci. Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice. Genome Med. Power and predictive accuracy of polygenic risk scores. PLoS Genet. A neuroscientific perspective on the nature of altered self-other relationships in schizophrenia.
Genetic and environmental factors in schizophrenia. A study of schizophrenic twins and their families. Acta Psychiatr. De novo mutations in schizophrenia implicate synaptic networks. Nature , — Genetics of schizophrenia: new findings and challenges. Genomics Hum. Strong synaptic transmission impact by copy number variations in schizophrenia.
U S A , — Common genetic variation and human traits. Schizophrenia Genesis: The Origins of Madness. New York, NY: Freeman. Confirming unexpressed genotypes for schizophrenia. Psychiatry 46 , — A polygenic theory of schizophrenia. U S A 58 , — Developments in schizophrenia genetics: from linkage to microchips, deletions and duplications.
Psychiatry 65 , 82— New York, NY: Springer; , — Clinical manifestations of self-disorders and the Gestalt of schizophrenia. Psychiatric disorders in foster home reared children of schizophrenic mothers. Effects of child rearing by schizophrenic mothers: a follow-up. The use of eye movement dysfunctions in exploring the genetic transmission of schizophrenia. Psychiatry Neurol. Brain disorders? Science , — Rare chromosomal deletions and duplications increase risk of schizophrenia.
Purcell S. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Competing definitions of schizophrenia: what can be learned from polydiagnostic studies? Studien uber Vererbung und Entstehung geistiger Stfrungen. Schizoid und Schizophren im Erbgang. Berlin: Springer-Verlag. The Genetics of Schizophrenia. New York, NY: Augustin. The genetic theory of schizophrenia; an analysis of schizophrenic twin index families. Phenomenology of schizophrenia and the representativeness of modern diagnostic criteria.
JAMA Psychiatry 73 , — The roscommon family study. Methods, diagnosis of probands, and risk of schizophrenia in relatives. Psychiatry 50 , — Baltimore: John Hopkins University Press; , — Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the copenhagen study in the rest of Denmark.
Psychiatry 51 , — Neurexin 1 NRXN1 deletions in schizophrenia. Heredity and Environment in the Functional Psychoses. London: Heinemann Medical Books. Offspring of monozygotic twins discordant for schizophrenia. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study.
Lancet , — Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 72 , — Exome array analysis suggests an increased variant burden in families with schizophrenia. De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Psychiatry 19 , — Unlocking the treasure trove: from genes to schizophrenia biology.
Schizophrenia: a common disease caused by multiple rare alleles. The copenhagen high-risk project, — Schizotaxia, schizotypy, schizophrenia. Psychologist 17 , — Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Psychiatry 14 , — Meta-analysis of 32 genome-wide linkage studies of schizophrenia.
Self-disorders and schizophrenia-spectrum: A study of first hospital admissions. Temporal persistence of anomalous self-experience: A 5 years follow-up. The genetic deconstruction of psychosis. Premorbid self-disorders and lifetime diagnosis in the schizophrenia spectrum: a prospective high-risk study.
Early Interv. Psychiatry 10 , 45— Phenomenology of anomalous experiences in early schizophrenia. Psychiatry 44 , — EASE: Examination of anomalous self-experience. Psychopathology 38 , — Anomalous subjective experience among first-admitted schizophrenia spectrum patients: empirical investigation.
Anomalies of subjective experience in schizophrenia and psychotic bipolar illness. Disordered self in the schizophrenia spectrum: A clinical and research perspective. Psychiatry 22 , — Self-disorders: clinical and conceptual implications for the diagnostic concept of schizophrenia. Psychopathology 48 , — Self-experience in the early phases of schizophrenia: 5-year follow-up of the copenhagen prodromal study. World Psychiatry 10 , — Institutional rearing and diagnostic outcome in children of schizophrenic mothers.
A prospective high-risk study. Psychiatry 42 , — A polygenic burden of rare disruptive mutations in schizophrenia. The silent side of the spectrum: schizotypy and the schizotaxic self. Examination of anomalous self-experience: Initial study of the structure of self-disorders in schizophrenia spectrum. Looking at the schizophrenia spectrum through the prism of self-disorders: an empirical study.
Genetics of schizophrenia. Exome arrays capture polygenic rare variant contributions to schizophrenia. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Segregation analysis of schizophrenia and related disorders. The future of genetic studies of complex human diseases. Some factors associated with concordance and discordance with respect to schizophrenia in monozygotic twins.
Problems of sampling and diagnosis in the major twin studies of schizophrenia. Oxford: Pergamon Press; , — Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Patterns of genic intolerance of rare copy number variation in 59, human exomes. Zur Vererbung und Neuentstehung der Dementia Praecox. Berlin: Springer. Getting closer to the whole picture.
Zur Erbpathologie der Schizophrenic. Schizophrenia risk from complex variation of complement component 4. Sensing the worst: Neurophenomenological perspectives on neutral stimuli misperception in schizophrenia spectrum. Anomalous echo: Exploring abnormal experience correlates of emotional motor resonance in Schizophrenia Spectrum.
Psychiatry Res. Mirroring the self: testing neurophysiological correlates of disturbed self-experience in schizophrenia spectrum. Facial reactions in response to dynamic emotional stimuli in different modalities in patients suffering from schizophrenia: a behavioral and EMG study. Common variants on chromosome 6p Psychotic and neurotic illnesses in twins. Genome-wide association study identifies five new schizophrenia loci. Common variants conferring risk of schizophrenia.
Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. The Phenotypic Conundrum The definition of caseness is fundamental to research design decisions. Complex Genetics Our knowledge of the molecular mechanisms of schizophrenia pathophysiology remains very incomplete.
Evidence For Environmental Factors The longstanding and influential belief that the incidence of schizophrenia is unaffected by place and time has been recently disproven, opening a remarkably productive period for the study of schizophrenia epidemiology. The Evidence for Genetic Factors The modern twin and adoption studies were instrumental in rejecting psychological hypotheses of schizophrenia causation 37 and became the main foundation for the search of molecular genetic risk factors.
Twin studies Differences between monozygotic identical twins are attributed to the environment, and differences between dizygotic fraternal twins to both hereditary and environmental factors in twin studies. Adoption Studies Such studies allow dissection of genetic from environmental contributions to a disorder in ways that twin studies cannot see review 57 which also explores methodological strengths and weaknesses of these approaches.
Darwinian Paradox Schizophrenia has long been known to be associated with decreased fertility 39 , 71 , which is explained by the behavioral and social characteristics of schizophrenia. Open in a separate window. Figure 1. GWAS Genome-wide studies, in combination with system biology approaches, yield comprehensive information and have been demonstrated to be more useful to deal with complex phenotypes.
Figure 2. Table 2 Genes mentioned in review, and their functions. Table 3 Summary of recent genome-wide CNV studies of schizophrenia. Polygenic Contributions to Schizophrenia Many genetic variants, each with a very small effect, combined together, make substantial contributions to disorder risk under a polygenic model, first hypothesized for schizophrenia four decades ago Pleiotropy and Overlap with Bipolar Disorder and Autism Pleiotropy refers to the common phenomenon of variation in a gene simultaneously affecting different phenotypes.
Challenges for the Field of Schizophrenia Genetics After over a quarter century of molecular genetics work in schizophrenia, advances in biotechnology and statistics applied to the study of large and well characterized clinical samples have made possible the discovery of individual susceptibility loci with subsequent replication. Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. References 1. Psychiatric Genetics. Hoboken: Wiley; Schizophrenia: a concise overview of incidence, prevalence, and mortality.
Epidemiol Rev. Epidemiology of schizophrenia: review of findings and myths. Girard C, Simard M. Clinical characterization of late- and very late-onset first psychotic episode in psychiatric inpatients. Am J Geriatr Psychiatry. Remschmidt H, Theisen FM. Schizophrenia and related disorders in children and adolescents. J Neural Transm Suppl.
Leung A, Chue P. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl. Kraepelin E. Manic-Depressive Insanity and Paranoia. Edinburgh: E. Livingstone; English translation [ Google Scholar ].
Kasanin J. The acute schizoaffective psychoses. Am J Psychiatry. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry. The dichotomy of schizophrenia and affective disorders in extended pedigrees. Schizophr Res. A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands.
The Roscommon Family Study. Methods, diagnosis of probands, and risk of schizophrenia in relatives. Increased morbid risk for schizophrenia in families of in-patients with bipolar illness. Heckers S. Is schizoaffective disorder a useful diagnosis? Curr Psychiatry Rep. Research diagnostic criteria: rationale and reliability. Diagnostic interview for genetic studies. Rationale, unique features, and training. Meta-analysis of 32 genome-wide linkage studies of schizophrenia.
Mol Psychiatry. The human connectome: A structural description of the human brain. PLoS Comput Biol. Drachman DA. Do we have brain to spare? Kraft P, Hunter DJ. Genetic risk prediction--are we there yet? N Engl J Med. Schadt EE. Molecular networks as sensors and drivers of common human diseases. Petronis A.
The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biol Psychiatry. Epigenetic mechanisms in schizophrenia. Biochim Biophys Acta. Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications. Schizophr Bull. Advancing paternal age and the risk of schizophrenia.
Paternal age as a risk factor for schizophrenia: how important is it? The role of obstetric events in schizophrenia. Obstetric complications and schizophrenia: historical and meta-analytic review. Schizophrenia after prenatal exposure to the Dutch Hunger Winter of — Rates of adult schizophrenia following prenatal exposure to the Chinese famine of — Prenatal nutritional deficiency and risk of adult schizophrenia.
James WP. The epidemiology of obesity: the size of the problem. J Intern Med. Global prevalence of diabetes: estimates for the year and projections for Diabetes Care. Is schizophrenia really on the decrease? Eur Arch Psychiatry Clin Neurosci. Neill J. Whatever became of the schizophrenogenic mother? Am J Psychother. Gejman PV. Ernst Rudin and Nazi euthanasia: another stain on his career. Am J Med Genet. Zur Vererbung und Neuenstehung der Dementia Praecox.
Berlin: Springer; Gottesman II, Shields J. Schizophrenia: The Epigenetic Puzzle. Cambridge, England: Cambridge University Press; Risch N. Linkage strategies for genetically complex traits. Multilocus models.
Am J Hum Genet. Smalley SL. Sporadic cases are the norm for complex disease. Eur J Hum Genet. Kendler KS. Sporadic vs familial classification given etiologic heterogeneity: I. Sensitivity, specificity, and positive and negative predictive value. Genet Epidemiol. Cardno AG, Gottesman I. Twin studies of schizophrenia: From bow-and-arrow concordances to Star Wars Mx and functional genomics.
Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Rees J. Complex disease and the new clinical sciences. Increased occurrence of schizophrenia and other psychiatric illnesses among twins. Br J Psychiatry. The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Franzek E, Beckmann H. Different genetic background of schizophrenia spectrum psychoses: a twin study. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.
Gottesman II, Bertelsen A. Confirming unexpressed genotypes for schizophrenia. Kringlen E, Cramer G. Offspring of monozygotic twins discordant for schizophrenia. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. The promise of epidemiologic studies: neuroimmune mechanisms in the etiologies of brain disorders. Adoption studies of schizophrenia.
Heston LL. Psychiatric disorders in foster home reared children of schizophrenic mothers. Higgins J. Effects of child rearing by schizophrenic mothers: a follow-up. J Psychiatr Res. A research strategy for clarifying the role of genetic and experiential factors in the etiology of schizophrenia.
Tienari P. Interaction between genetic vulnerability and family environment: the Finnish adoptive family study of schizophrenia. Acta Psychiatr Scand. The Finnish adoptive family study of schizophrenia. Yale J Biol Med. Implications for family research. Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia.
An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. The relationship between schizotypal personality disorder and schizophrenia. Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark. The types and prevalence of mental illness in the biological and adoptive families of adopted schizophrenics. The Transmission of Schizophrenia. Oxford, England: Pergamon Press; Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: a preliminary report based upon psychiatric interviews.
Genetic Research in Psychiatry. Kallmann FJ. The genetics of schizophrenia: A study of heredity and reproduction in the families of 1, schizophrenics. New York, NY: J. Augustin Publisher; Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective.
Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from to in Finland. Keller MC, Miller G. Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best? Behav Brain Sci. Fananas L, Bertranpetit J. Reproductive rates in families of schizophrenic patients in a case-control study.
Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings: the Uppsala — Birth Cohort Multigenerational Study. Psychol Med. Allison AC. Notes on sickle-cell polymorphism. Ann Hum Genet. The endophenotype concept in psychiatry: etymology and strategic intentions. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia.
Book JA. Schizophrenia as a gene mutation. Acta Genet Stat Med. Friedman JM. Genetic disease in the offspring of older fathers. Obstet Gynecol. Paternal age and schizophrenia: a population based cohort study. Crow JF. The origins, patterns and implications of human spontaneous mutation.
Nat Rev Genet. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet. No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Ioannidis JP. Why most discovered true associations are inflated. Genome-wide association studies for complex traits: consensus, uncertainty and challenges.
Environmental standardization: cure or cause of poor reproducibility in animal experiments? Nat Methods. Common variants on chromosome 6p Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genome-wide significance for dense SNP and resequencing data. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants.
Finding the missing heritability of complex diseases. Evaluation of coverage variation of SNP chips for genome-wide association studies. Halperin E, Stephan DA. SNP imputation in association studies. Nat Biotechnol. A comprehensive evaluation of SNP genotype imputation.
Hum Genet. Pritchard JK. Are rare variants responsible for susceptibility to complex diseases? On the allelic spectrum of human disease. Trends Genet. A polygenic theory of schizophrenia. Genetic linkage and complex diseases, with special reference to psychiatric disorders. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Common variants conferring risk of schizophrenia. Frontiers of psychiatric genetics.
Neurosci Res Program Bull. Leukemia-associated antigens in the mixed leukocyte culture test. Wei J, Hemmings GP. Traherne JA. Human MHC architecture and evolution: implications for disease association studies. Int J Immunogenet. High-resolution haplotype structure in the human genome. The structure of haplotype blocks in the human genome. Kleinjan DA, van Heyningen V.
Long-range control of gene expression: emerging mechanisms and disruption in disease. Reviewing the role of DNA cytosine-5 methyltransferase overexpression in the cortical GABAergic dysfunction associated with psychosis vulnerability.
Shi Y. Histone lysine demethylases: emerging roles in development, physiology and disease. Kawasaki H, Iwamuro S. Potential roles of histones in host defense as antimicrobial agents. Infect Disord Drug Targets. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers.
An update of the HLA genomic region, locus information and disease associations: Tissue Antigens. Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex. Genes Immun. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis.
Curr Biol. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat Neurosci. The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome.
Am J Med Genet A. Severe mental retardation with breathing abnormalities Pitt-Hopkins syndrome is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. Hum Mol Genet. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Neural mechanisms of a genome-wide supported psychosis variant. Prediction of individual genetic risk to disease from genome-wide association studies.
Genome Res. Whole-genome association study of bipolar disorder. Wellcome Trust Case Control Consortium: Genome-wide association study of 14, cases of seven common diseases and 3, shared controls. A multi-dimensional evidence-based candidate gene prioritization approach for complex diseases-schizophrenia as a case. Common variants at 30 loci contribute to polygenic dyslipidemia.
Twin studies in behavioral research: a skeptical view. Theor Popul Biol. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Strong association of de novo copy number mutations with sporadic schizophrenia. Large recurrent microdeletions associated with schizophrenia. Rare chromosomal deletions and duplications increase risk of schizophrenia.
Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. PLoS Genet. Late-onset psychosis in the velo-cardio-facial syndrome. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis. High rates of schizophrenia in adults with velo-cardio-facial syndrome.
Disruption of the neurexin 1 gene is associated with schizophrenia. Mackay TF. The genetic architecture of complex behaviors: lessons from Drosophila. Genome-wide association analysis identifies 20 loci that influence adult height. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Multiple loci identified in a genome-wide association study of prostate cancer.
What is familial about familial bipolar disorder? Resemblance among relatives across a broad spectrum of phenotypic characteristics. Diagnostic and Statistical Manual of Mental Disorders. Berrettini WH. Are schizophrenic and bipolar disorders related? A review of family and molecular studies.
Craddock N, Owen MJ. Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry. Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2pq14 and 13q Microduplications of 16p Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk.
Evaluation of the chromosome 2q Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Konstantareas MM, Hewitt T. Autistic disorder and schizophrenia: diagnostic overlaps.
Sandelowski M, Barroso J Handbook for synthesizing qualitative research. Springer, New York. Google Scholar. J Palliat Med 16 5 — Li JJ Top drugs: history, pharmacology, syntheses, 1st edn. Accessed 13 Jul Accessed 14 Jul Schizophr Bull 19 3 — Ryan KA Mothers of adult children with schizophrenia: an ethnographic study.
Schizophr Res 11 1 — Arch Psychiatr Nurs 11 3 — Howard PB The experience of fathers of adult children with schizophrenia. Issues Ment Health Nurs 19 4 — Arch Psychiatr Nurs 12 5 — Health Soc Care Community 9 4 — Nystrom M, Svensson H Lived experiences of being a father of an adult child with schizophrenia. Issues Ment Health Nurs 25 4 — Stalberg G, Ekerwald H, Hultman CM At issue: siblings of patients with schizophrenia: sibling bond, coping patterns, and fear of possible schizophrenia heredity.
Schizophr Bull 30 2 — Sethabouppha H, Kane C Caring for the seriously mentally ill in Thailand: buddhist family caregiving. Arch Psychiatr Nurs 19 2 — Res Theory Nurs Pract 20 3 — J Psychiatr Ment Health Nurs 16 10 — Afr J Nurs Midwifery 11 1 — Wiens SE, Daniluk JC Love, loss, and learning: the experiences of fathers who have children diagnosed with schizophrenia. J Couns Dev 87 3 — Arch Psychiatr Nurs 25 5 — Molefi S, Swartz L Caring for a relative with schizophrenia: Understandings, challenges and the interface with mental health professionals.
J Psychol Afr 21 2 — Arch Psychiatr Nurs 27 2 — Issues Ment Health Nurs 34 6 — Int J Ment Health Addict 14 4 — J Psychiatr Ment Health Nurs 21 2 — Int J Ment Health Nurs. Schizophr Bull 30 3 — Schizophr Res Treat Rungreangkulkij S, Chesla C Smooth a heart with water: Thai mothers care for a child with schizophrenia.
Arch Psychiatr Nurs 15 3 — Arch Psychiatr Nurs 16 5 — Ferriter M, Huband N Experiences of parents with a son or daughter suffering from schizophrenia. J Psychiatr Ment Health Nurs 10 5 — Part II: family perspective. Int J Soc Psychiatry 49 3 — Soc Work Health Care 52 2—3 — Hernandez M, Barrio C Perceptions of subjective burden among latino families caring for a loved one with schizophrenia.
Community Ment Health J 51 8 — Stein CH, Wemmerus VA Searching for a normal life: personal accounts of adults with schizophrenia, their parents and well-siblings. Am J Community Psychol 29 5 — Kung W Tangible needs and external stressors faced by Chinese American families with a member having schizophrenia. Soc Work Res 40 1 — Kung WW Culture- and immigration-related stress faced by Chinese American families with a patient having schizophrenia.
J Marital Fam Ther 42 3 — Nord J Psychiatry 70 4 — J Psychiatr Ment Health Nurs 5 4 — Negota AJ, Mashegoane S Mothering children with schizophrenia in a village setting: a multiple case study. J Psychol Afr 22 2 — Howard PB Lifelong maternal caregiving for children with schizophrenia.
Arch Psychiatr Nurs 8 2 — Wheeler C The diagnosis of schizophrenia and its impact on the primary caregiver. Nurs Prax N Z 9 3 — Jung M Lives of two Korean mothers of children with schizophrenia: an interpretive approach. J Am Psychiatr Nurses Assoc 6 3 — Jungbauer J, Angermeyer MC Living with a schizophrenic patient: a comparative study of burden as it affects parents and spouses.
Psychiatry 65 2 — Arch Psychiatr Nurs 17 3 — Arch Psychiatr Nurs 18 1 — J Clin Nurs 19 1—2 — Int J Soc Psychiatry 61 1 — Schizophr Res Treat. Yamashita M A study of how families care for mentally ill relatives in Japan. Int Nurs Rev 43 4 — Int J Psychiatry Clin Pract 13 4 — J Clin Psychiatry 68 5 — Arch Gen Psychiatry 56 3 — Psychol Psychother Theory Res Pract 87 3 — Schwartz C, Gidron R Parents of mentally ill adult children living at home: rewards of caregiving.
Health Soc Work 27 2 — Pilgrim RB The Buddhist mandala. Lit Med — Soc Psychiatry Psychiatr Epidemiol 48 2 — Tracing the genetic basis of the cerebral mechanisms that, might, express a particular genetic defect in psychosis or in a disease like schizophrenia will require specific information about, the human schizophrenic brain. Disease formulations will be testable as models for the genetic changes we will find in this illness. National Center for Biotechnology Information , U. Journal List Dialogues Clin Neurosci v.
Dialogues Clin Neurosci. Carol A. Deborah R. Medoff , PhD. Author information Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Schizophrenia is an illness where the clinical signs and symptoms, course, and cognitive characteristics are well described. Keywords: clinical presentation , dopamine , glutamate , pathophysiology , schizophrenia.
Schizophrenia: the clinical condition Psychosis The defining features of a schizophrenia diagnosis are hallucinations, delusions, paranoia, and thought disorder; these experiences are manifest in multiple sensory modalities and include abnormalities in all aspects of thought, cognition, and emotion Table I, see next, page. Positive symptoms Hallucinations, delusions, reality distortion Negative symptoms Anbedonia, asocial ity, alogia Cognitive deficits Attention, working memory, executive functions Neurophysiologic changes Eye movements, evoked potentials P50, P Open in a separate window.
Other disease features The advent of antipsychotic drugs that are effective in the treatment of psychosis has exposed aspects of schizophrenia that were often overlooked when the florid presentation was untreated. Course Schizophrenia characteristically begins in young adult years and lasts throughout life, with only occasional recovery. Risk factors for schizophrenia Genetics A risk for schizophrenia is inherited. Pre- or perinatal events Catastrophic pre- or perinatal events, like exposure to famine, radiation, or a maternal viral illness, especially during the second trimester, are significant risk factors for schizophrenia.
Factors during childhood and adolescence Environmental factors have also been suggested as risks for schizophrenia. Psychological and electrophysiologic characteristics of schizophrenia Cognitive dysfunction Patients with schizophrenia characteristically perform more poorly on neuropsychological tasks than normal subjects.
Neurophysiological dysfunction Measures of brain response to graded external stimuli have been characterized in schizophrenia and used to postulate its pathophysiology. Schizophrenia spectrum disorders There is an emerging formulation from several laboratories that schizophrenia is part of a larger set of disorders called schizophrenia spectrum disorders or schizotaxia; these disorders are related to each other in terms of genetics, symptom expression, cognitive characteristics, and, potentially, pathophysiology.
Figure 1. Schizophrenia spectrum disorders. Brain structure and function in schizophrenia Brain structure One of the first discoveries in schizophrenia using modern imaging technologies was structural, first with computerized axial tomography CAT scanning and later with magnetic resonance imaging MRI. Brain function When functional techniques for studying human brain became available, they were quickly applied to schizophrenia. Figure 2. Subtraction image at two different brain levels 40 mm and 50 mm above the anterior commissure-posterior commissure [AC-PC] line of schizophrenic volunteers SZ performing a task.
The regional cerebral blood flow rCBF of the schizophrenic volunteers who performed the task abnormally was subtracted from the rCBF of those who performed the task just like normals. All the schizophrenic volunteers differed from the normals only in the anterior cingulate cortex ACC. The schizophrenic volunteers who performed poorly also had abnormal flow in the right middle frontal cortex and in the ACC. Theories of schizophrenia Dopamine Hypotheses to explain the manifestations of schizophrenia have been posited for centuries.
Neural systems As knowledge of normal brain function has revealed intricate and complexly interacting neural systems, so these ideas have also been applied to schizophrenia. Neurodevelopmental factors The idea that schizophrenia is a neurodevelopmental illness, whose pathology is already set at birth and only expresses itself as psychosis later, has become popular.
Limbic cortex Experimental modalities beyond brain imaging have advanced our understanding of the pathophysiology of schizophrenia. Working hypothesis We would like to suggest a. Future The availability of the very new resource of the sequenced human genome is challenging our field to take advantage of this critical genetic information.
Carpenter WT. Schizophrenia [review] N Engl J Med. Tamminga CA. Neuropsychiatrie Aspects of Schizophrenia. Textbook of Neuropsychopharmacology. Cornblatt B. Cognitive and behavioral precursors of schizophrenia. Anclreasen NC. Symptoms, signs, and diagnosis of schizophrenia [review]. Domains of psychopathology relevant to the study of etiology and treatment in schizophrenia.
Schizophrenia: Scientific Progress. Andreasen NC. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch Gen Psychiatry. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Limbic system abnormalities identified in schizophrenia using positron emission tomography with f luorodeoxyglucose and neocortical alterations with deficit syndrome.
Liddle PF. The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. Br J Psychiatry. Sartorius N. The international pilot study of schizophrenia. Schizophr Bull. Ciompi L. Lifestyle and age of schizophrenics. A catamnestic long-term study into old age [in German].
Monographien aus demi Gesamtgebiete der Psychiatrie. Braff DL. The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results. Gruzelier J. Impairments on neuropsychologic tests of temporohippocampal and frontohippocampal functions and word fluency in remitting schizophrenia and affective disorders. Arndt S. The distinction of positive and negative symptoms.
The failure of a two-dimensional model. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. Bleuler M. Harding CM. The Vermont longitudinal study of persons with severe mental illness, II. The Vermont longitudinal study of persons with severe mental illness, I. Methodology, study sample, and overall status 32 years later. Ami J Psychiatry. Tsuang MT. Long-term outcome of major psychoses. Schizophrenia and affective disorders compared with psych iatrically symptom-free surgical conditions.
Friedman JI. Cognitive and functional changes with aging in schizophrenia. Biol Psychiatry. Kendler KS. Schizophrenia: genetics. Comprehensive Textbook of Psychiatry. Vol VI. Baltimore, Md: Williams andWilkins. Kety SS. The significance of genetic factors in the etiology of schizophrenia: results from the national study of adoptees in Denmark. J Psychiatr Res.
Gottesman II. Schizophrenia: The Epigenetic Puzzle. Kendell RE. Maternal influenza in the etiology of schizophrenia [see comments]. Barr CE. Exposure to influenza epidemics during gestation and adult schizophrenia. A year study. Mednick SA. Fetal development, birth and the syndromes of adult schizophrenia.
Fetal Neural Development and Adult Schizophrenia. O'Callaghan E. Schizophrenia after prenatal exposure to A2 influenza epidemic. McGrath J. Risk factors for schizophrenia: from conception to birth. Oxford, UK: Blackwell Science. Lewis SW. Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia [review].
Bradbury TN. Season of birth in schizophrenia: a review of evidence, methodology, and etiology. Psychol Bull. Chapman LJ. Problems in the measurement of cognitive deficit. Sullivan EV. A deficit profile of executive, memory, and motor functions in schizophrenia [published erratum appears in. Biol Psychiatry; Biol Psychiatry. Goldberg TE. Neuropsychological assessment of monozygotic twins discordant for schizophrenia.
Saykin AJ. Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Schizophrenic syndromes and frontal lobe performance. Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test [see comments]. Nuechterlein KH. Developmental processes in schizophrenic disorders: longitudinal studies of vulnerability and stress. Goldman-Rakic PS.
Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci. Cohen JD. Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia [review]. Psychol Rev. Frith C. Functional imaging and cognitive abnormalities [review]. Barnes GR. The mechanism of prediction in human smooth pursuit eye movements.
J Physiol. Lisberger SG. Visual motion processing and sensorymotor integration for smooth pursuit eye movements [review]. Annu Rev Neurosci. Holzman PS. Recent studies of psychophysiology in schizophrenia. Clementz BA. Is eye movement dysfunction a biological marker for schizophrenia? A methodological review [review]. Thaker GK. Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients. Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia.
Keefe RS. Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Chen Y. Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit. Sweeney JA. Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention. J Abnorm Psychol. Smooth pursuit eye movements to extra-retinal motion signals: deficits in patients with schizophrenia.
Psychiatry Res. Fukushima J. Disturbances of voluntary control of saccadic eye movements in schizophrenic patients. Crawford TJ. Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study. Berman RA. Cortical networks subserving pursuit and saccadic eye movements in humans: an FMRI study.
Hum Brain Mapp. Pfefferbaum A. Clinical application of the P3 component of event-related potentials. Dementia, depression and schizophrenia. Electroencephalogr Clin Neurophysiol. Blackwood DH. Auditory P and eye tracking dysfunction in schizophrenic pedigrees.
Freedman R. Neurobiological studies of sensory gating in schizophrenia. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 1 5 locus. Johnstone EC. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Shelton RC. Brain morphology in schizophrenia. In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress. Gur RE.
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