{"id":1245,"date":"2023-03-31T17:38:02","date_gmt":"2023-03-31T17:38:02","guid":{"rendered":"https:\/\/content.one.lumenlearning.com\/introductiontopsychology\/chapter\/14-4-2-learn-it-causes-of-schizophrenia\/"},"modified":"2026-01-20T15:33:49","modified_gmt":"2026-01-20T15:33:49","slug":"14-4-2-learn-it-causes-of-schizophrenia","status":"publish","type":"chapter","link":"https:\/\/content.one.lumenlearning.com\/introductiontopsychology\/chapter\/14-4-2-learn-it-causes-of-schizophrenia\/","title":{"raw":"Schizophrenia and Related Disorders: Learn It 2\u2014Causes of Schizophrenia","rendered":"Schizophrenia and Related Disorders: Learn It 2\u2014Causes of Schizophrenia"},"content":{"raw":"
Causes of Schizophrenia<\/h2>\r\n
There is considerable evidence suggesting that schizophrenia has a genetic basis. The risk of developing schizophrenia is nearly 6 times greater if one has a parent with schizophrenia than if one does not (Goldstein, Buka, Seidman, & Tsuang, 2010). Additionally, one\u2019s risk of developing schizophrenia increases as genetic relatedness to family members diagnosed with schizophrenia increases (Gottesman, 2001).<\/p>\r\n
Genetic Contributions<\/h3>\r\n
Evidence from Family and Adoption Studies<\/h3>\r\n
When studying the genetics of any disorder, conclusions from family and twin studies face an important limitation: closely related family members typically share similar environments, making it difficult to separate genetic from environmental influences. Adoption studies help address this problem by examining children raised apart from their biological parents.<\/p>\r\n
One landmark adoption study by Heston (1966) followed 97 adoptees over 36 years, including 47 born to mothers with schizophrenia. Five of these 47 adoptees (11%) later developed schizophrenia, compared to none of the 50 control adoptees. Subsequent adoption studies consistently show that biological relatives of people with schizophrenia have higher schizophrenia rates than adoptive relatives (Shih, Belmonte, & Zandi, 2004).<\/p>\r\n\r\n
The Diathesis-Stress Model<\/h3>\r\n
Adoption studies demonstrate that schizophrenia arises from the interaction of genetic vulnerability and environmental factors\u2014not genes alone. A pivotal study by Tienari and colleagues (2004) examined 303 adoptees: 145 with biological mothers who had schizophrenia (high genetic risk) and 158 whose mothers had no psychiatric history (low genetic risk). Researchers also assessed whether adoptees were raised in healthy versus disturbed family environments.<\/p>\r\n
The findings were striking:<\/strong><\/p>\r\n
\r\n\t
High genetic risk + disturbed family environment: 36.8%<\/strong> developed schizophrenia or another psychotic disorder<\/li>\r\n\t
High genetic risk + healthy environment: 5.8%<\/strong> developed the disorder<\/li>\r\n\t
Low genetic risk + disturbed environment: 5.3%<\/strong> developed the disorder<\/li>\r\n\t
Low genetic risk + healthy environment: 4.8%<\/strong> developed the disorder<\/li>\r\n<\/ul>\r\n
These results support the diathesis-stress model<\/strong>: genetic vulnerability alone isn't sufficient\u2014environmental stress must also be present for schizophrenia to develop in most cases.<\/p>\r\n<\/section>\r\n
Modern Genetic Research<\/h3>\r\n
Today's large-scale genome studies have identified hundreds of genetic variants associated with schizophrenia risk. The largest genome-wide association study (GWAS) to date\u2014including over 76,000 patients\u2014identified 287 genetic variants linked to the disorder. Many of these implicate genes involved in synaptic organization, neurotransmitter signaling, and immune function (Trubetskoy et al., 2022).<\/p>\r\n
One of the most significant genetic findings involves complement component 4 (C4)<\/strong>, part of the immune system. Research published in Nature<\/em> demonstrated that genetic variants increasing C4A expression in the brain are associated with higher schizophrenia risk. The C4 protein localizes to synapses and plays a role in synaptic pruning<\/strong>\u2014the normal process of eliminating unnecessary neural connections during development. In schizophrenia, excessive C4 activity may lead to over-pruning of synapses, potentially explaining the reduced neural connectivity observed in the disorder (Sekar et al., 2016; Yilmaz et al., 2021).<\/p>\r\n
This finding provides a potential mechanism linking genetic risk to the structural brain changes observed in schizophrenia\u2014and may explain why the disorder typically emerges during adolescence and early adulthood, when synaptic pruning naturally peaks.<\/p>\r\n
Many schizophrenia risk genes also increase risk for bipolar disorder, autism, and other neurodevelopmental conditions, suggesting shared biological pathways across these disorders (Tandon et al., 2024).<\/p>\r\n
Neurotransmitter Systems<\/h2>\r\n
The Dopamine Hypothesis<\/h3>\r\n
Interest in dopamine's role in schizophrenia emerged from two key observations: drugs that increase dopamine can produce schizophrenia-like symptoms, and medications that block dopamine reduce symptoms (Howes & Kapur, 2009).<\/p>\r\n
The original dopamine hypothesis<\/strong> proposed that excess dopamine or too many dopamine receptors cause schizophrenia (Snyder, 1976). Modern research has refined this view, recognizing that dopamine abnormalities vary by brain region and contribute to different symptoms:<\/p>\r\n
\r\n\t
Mesolimbic pathway<\/strong> (from ventral tegmental area to limbic system): Excess dopamine activity may drive positive symptoms\u2014hallucinations and delusions<\/li>\r\n\t
Mesocortical pathway<\/strong> (from ventral tegmental area to prefrontal cortex): Reduced dopamine activity may contribute to negative symptoms and cognitive deficits<\/li>\r\n<\/ul>\r\n
This \"two-pathway\" model helps explain why dopamine-blocking medications effectively treat positive symptoms but often have limited impact on negative and cognitive symptoms (Davis et al., 1991; McCutcheon et al., 2020).<\/p>\r\n
Beyond Dopamine: The Glutamate Hypothesis<\/h3>\r\n
While dopamine dysfunction remains central to understanding schizophrenia, it cannot fully explain the disorder\u2014particularly negative symptoms and cognitive impairment. This led researchers to investigate glutamate, the brain's primary excitatory neurotransmitter.<\/p>\r\n
The glutamate hypothesis<\/strong> arose from observations that drugs blocking NMDA glutamate receptors (such as ketamine and PCP) produce symptoms remarkably similar to schizophrenia\u2014including positive, negative, and cognitive symptoms (Javitt & Zukin, 1991).<\/p>\r\n
Current understanding suggests both systems interact:<\/strong><\/p>\r\n
\r\n\t
Reduced NMDA receptor function on inhibitory neurons may lead to excess glutamate release<\/li>\r\n\t
This glutamate excess may then trigger downstream dopamine dysregulation<\/li>\r\n\t
Patients who don't respond to traditional dopamine-blocking medications may have predominantly glutamate-based dysfunction (Howes et al., 2015)<\/li>\r\n<\/ul>\r\n
The 2024 FDA approval of Cobenfy<\/strong> (xanomeline-trospium)\u2014which works through acetylcholine receptors rather than dopamine\u2014represents the first new medication mechanism in over 70 years and opens new treatment avenues beyond the dopamine system.<\/p>\r\n
Research also implicates that other neurotransmitters impact schizophrenia, including:<\/p>\r\n
\r\n\t
Serotonin<\/strong>: Many newer antipsychotic medications block serotonin receptors in addition to dopamine receptors (Baumeister & Hawkins, 2004)<\/li>\r\n\t
![\"Image](\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/855\/2017\/03\/30235926\/Schizophrenia_Brain.png\")
<\/a> Figure 1<\/strong>. Schizophrenia is associated with enlarged ventricles in the brain.[\/caption]\r\n<\/li>\r\n<\/ul>\r\n