Ms.

Geller Biology

Zara Hoffman March 22, 2011

SCHIZOPHRENIA
Etiology of Schizophrenia Schizophrenia is a psychotic disorder in which a person generally withdraws from external surroundings and both psychological and physical perceptions deteriorate.1 Schizophrenia was originally called "dementia praecox" in the late 19th Century by the German psychiatrist Emil Kraepelin and was renamed "schizophrenia" in 1911 by a Swiss psychiatrist named Eugen Bleuler.2 Scientists are still unsure of what exactly causes the disorder, but it is now known that there are multiple genes that can increase a person's risk for developing the mental disorder. The general consensus is that a combination of external factors, paired with a genetic predisposition, trigger the onset of schizophrenia.3 There are multiple subtypes of schizophrenia: Paranoid, Disorganized, Catatonic, among less common ones. The onset most often manifests in young adults between the ages of nineteen and thirty; it is more common in males during this interval, but more so in females between the ages of thirty and sixty-five. 4 Schizophrenia affects about 0.5%-1% of all populations

worldwide.5 However, it is difficult to be precise in comparing the rates due to the different
1 "Schizophrenia, n.". OED Online. December 2011. Oxford University Press. http://www.oed.com/view/Entry/172410?redirectedFrom=schizophrenia (accessed March 05, 2012). 2 VandenBos, Gary, R. "Schizophrenia." In The APA Dictionary of Psychology. Washington, DC: American Psychological Association, 2006. 815. 3 Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support. http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012) 4 The Internet Mental Health Initiative. "Schizophrenia Facts and Statistics." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/szfacts.htm (accessed January 9, 2012). 5 The Internet Mental Health Initiative. "Schizophrenia Facts and Statistics." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/szfacts.htm (accessed January 9, 2012).

"measuring standards in many countries." 6 As of 2007, approximately 2.2 million people (7.2 per 1000) were diagnosed as schizophrenics in the United States; twice the number of people diagnosed with Alzheimer's. "Schizophrenia runs in families... [and] occurs in 10% of people who have a first-degree relative with the disorder... The highest chance of developing schizophrenia is if one has a identical twin he or she has 40%-60% chance of developing the disorder." 7 People with other schizophrenic relatives have a smaller chance of developing the onset, but their chances are still higher than the regular 1% of the population. Within schizophrenia, there are three categories of symptoms: Positive, Negative, and Cognitive. Positive symptoms are only seen in psychotic people and often cause patients to "lose touch with reality."8 Positive symptoms include hallucinations (the most prevalent in

schizophrenia is hearing voices), delusions or false beliefs (a common delusion, being persecuted, is diagnosed with Paranoid Schizophrenia), thought disorders such as disorganized thinking (a key symptom for the diagnosis of Disorganized Schizophrenia), and movement disorders such as repetition of movements (observed in multiple types of schizophrenia) or catatonia (Catatonic Schizophrenia). In the DSM-IV, there are certain criteria required for an accurate diagnosis. There are six different criteria (A-F) in addition to specific symptoms associated with each type of schizophrenia.9 Of the numerous types of schizophrenia, Paranoid

6 The Internet Mental Health Initiative. "Schizophrenia Facts and Statistics." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/szfacts.htm (accessed January 9, 2012). 7 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 8 Ibid. 9 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSM-IVCriteria-for-Schizophrenia.html (accessed February 6, 2012).

Type A, Disorganized Type A, and Catatonic Type A are the most common.10 Criterion A of schizophrenia is defined in the DSM-IV as follows: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): (1) delusions (2) hallucinations (3) disorganized speech (e.g., frequent derailment or incoherence (4) grossly disorganized or catatonic behavior (5) negative symptoms, i.e., affective flattening, alogia (poverty of speech), or avolition (lack of motion). Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping a running commentary on the person's behavior or thoughts, or two or more voices conversing with each other. 11 These are the general symptoms associated with Type A schizophrenia subtypes, but there are unique criteria for each specific individual type of schizophrenia. Paranoid Type A satisfies this criteria, but falls under the category prescribed in the note and therefore, the only prominent symptoms from the above list that are met are: "delusions or frequent auditory hallucinations,"12 often involving irrational fears of persecution.13 Disorganized Type A meets Criterion A and is characterized by disorganized speech and thinking,14 and a "flat or inappropriate affect."15 Catatonic Type A fulfills Criterion A and is generally "dominated by at least two of the following [symptoms]:" 16 immobility, "catalepsy (waxy flexibility), excessive [irregular and repetitive]
10 University of Washington Faculty. "Neuroscience for Kids - Schizophrenia." UW Faculty Web Server. http://faculty.washington.edu/chudler/schiz.html (accessed March 19, 2012). 11 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSMIV-Criteria-for-Schizophrenia.html (accessed February 6, 2012). 12 Ibid. 13 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 14 University of Washington Faculty. "Neuroscience for Kids - Schizophrenia." UW Faculty Web Server. http://faculty.washington.edu/chudler/schiz.html (accessed March 19, 2012). 15 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSMIV-Criteria-for-Schizophrenia.html (accessed February 6, 2012). 16 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSMIV-Criteria-for-Schizophrenia.html (accessed February 6, 2012).

movement," 17 negative emotions or mutism, rigid or abnormal postures,18 "echolalia (word repetition) or echopraxia (repetitive imitation)."19 The causes of schizophrenia are still relatively unknown, but it is now believed that a genetic predisposition and certain external stimuli can trigger the onset of schizophrenia.20 "Interactions between genes and the environment are necessary for schizophrenia to develop." Some of these external factors may be stress, "inflammation, nutrient deprivation, and oxygen deficiency"21 in addition to "exposure to viruses... [and] problems during birth."22 Scientists are also finding genes and chromosomes which can potentially increase a person's risk of developing schizophrenia. It has been the prevailing view in psychiatric genetics that there are probably dozens, if not hundreds, of genetic variations that could lead to schizophrenia, but each gene has a small effect. It is the wrong mix of many genes, plus environmental stressors, that trigger the onset of symptoms."23 Ongoing research has revealed that schizophrenics have different brain structure than those unaffected by the disorder. They are discovering that "an imbalance in the...chemical reactions of
17 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSMIV-Criteria-for-Schizophrenia.html (accessed February 6, 2012). 18 University of Washington Faculty. "Neuroscience for Kids - Schizophrenia." UW Faculty Web Server. http://faculty.washington.edu/chudler/schiz.html (accessed March 19, 2012). 19 American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSMIV-Criteria-for-Schizophrenia.html (accessed February 6, 2012). 20 The Internet Mental Health Initiative. "Schizophrenia Facts and Statistics." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/szfacts.htm (accessed January 9, 2012). 21 The American Journal of Human Genetics. "New Schizophrenia Risk Gene Identified - Chitinase." Schizophrenia.com, In-depth Schizophrenia Information and Support. http://www.schizophrenia.com/sznews/archives/004546.html (accessed February 4, 2012). 22 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 23 Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012).

the brain involving neurotransmitters dopamine and glutamate, and possibly others, plays a role in schizophrenia."24 The brain's chemical reactions form special "links" that change the brain's shape. One of the reasons that schizophrenia is prominent in people during late adolescence is because during puberty the brain goes through many changes while developing into an adult brain; this process is called "pruning."25 Some schizophrenic brains have larger "fluid-filled cavities at the center of the brain, called ventricles,[and] also tend to have less gray matter."26 In addition, there can be a change in activity levels in certain regions of the brain. On November 17, 2005, scientists reported the discovery of a new gene associated with schizophrenia, which was named "phosphodiesterase 4B (PDE4B)."27 PDE4B has a vital role in the brain's cognitive functions involving thinking and building memories. It was the second individual gene discovered that had a link to schizophrenia; the first was called "Disrupted in Schizophrenia 1 (DISC1),"28 which also increases the probability of a person developing schizophrenia. In the 2005 study, scientists learned that when PDE4B was damaged, the risk of developing a mental illness increased. The most interesting discovery they made was that the two genes were connected: "DISC1 acts as a regulator for PDE4B."29 In 2007, another study identified "nine

24 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 25 Dvir, M.D., Yael, and Jean A. Frazier, MD. "Autism and Schizophrenia - Psychiatric Times." Psychiatric Times. http://www.psychiatrictimes.com/ schizophrenia/content/article/10168/1822823 (accessed January 6, 2012). 26 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 27 BBC News. "Schizophrenia Daily News Blog: Another Gene linked to Schizophrenia (PDE4B)." Schizophrenia.com, In-depth Schizophrenia Information and Support. http://www.schizophrenia.com/sznews/archives/002669.html (accessed February 4, 2012). 28 Ibid. 29 Ibid.

genetic markers that can increase a person's risk for schizophrenia."30 All of these "genetic markers" were recessive genes, requiring offspring to inherit a homozygous pair of the recessive allele in order to increase their risk. In this 2007 study, Todd Lencz, PhD, discovered that the "markers" in these nine chromosome regions potentially "play a large role in triggering the disease when two identical variants are inherited... Many of the genes located in these regions are involved with the structure and survival of neurons."31 Another 2007 research program identified Chitinase 3-like 1 (CHI3L1) as a schizophrenia-linked gene in Chinese people. CHI3L1 "acts as a survival factor in response to adverse environments, countering various types of physiological stress...which may induce high expression of CHI3L1."32 The overactivity of CHI3L1 can cause the body to always "fight," even when in reality there is no threat. At present, there is no single treatment or solution for schizophrenia. However, the goal at the moment is to "eliminate the symptoms of the disease. Treatments include antipsychotic medications and various psychosocial treatments."33 There are now two types of antipsychotic drugs: older ones, dating back to the mid-1950's are called "typical;" and the newer medications, used since the 1990's are called "atypical."34 Today, many patients take atypical antipsychotics,35

30 Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012). 31 Ibid. 32 The American Journal of Human Genetics. "New Schizophrenia Risk Gene Identified - Chitinase." Schizophrenia.com, In-depth Schizophrenia Information and Support. http://www.schizophrenia.com/sznews/archives/004546.html (accessed February 4, 2012). 33 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 34 Ibid. 35 Dvir, M.D., Yael, and Jean A. Frazier, MD. "Autism and Schizophrenia - Psychiatric Times." Psychiatric Times. http://www.psychiatrictimes.com/ schizophrenia/content/article/10168/1822823 (accessed January 6, 2012).

because the typical medications can cause agranulocytosis (white blood cell deficiency),36 making a person more vulnerable to infections. In addition to medications, rehabilitation programs are often prescribed. They often include psychosocial treatments that help improve schizophrenics' abilities to interact with the outside world.37 Because some side effects are considered unbearable, patients sometimes quit their medications once they are released from rehab. Scientists are continuing to study the schizophrenia-linked genes in hopes that the genetics will help them develop new, more efficient antipsychotics that do not only treat the symptoms, but also the actual disorder. 38 Finding a universally effective treatment is complicated due to the diverse genetics and symptoms associated with the disease. In Benedict Carey's article "From the Elusiveness of Schizophrenia, Clues to Treatment" in the New York Times, he remarks that maybe schizophrenia is in fact multiple disorders that need to be treated individually. He also discusses the shift in focus from the neurotransmitter dopamine, which was thought to be elevated in schizophrenics, to the neurotransmitter called glutamate, "the brain's primary stimulating agent."39 Although the glutamate hypothesis is still being tested, it has been "reported that a compound acting on the brain's glutamate system reduced symptoms of schizophrenia without major side effects."40 At the end of the article, Carey mentions retreats where schizophrenics take
36 US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http://www.nimh.nih.gov/health/publications/schizophrenia/completeindex.shtml (accessed January 6, 2012). 37 Ibid. 38 Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012). 39 Carey, Benedict. "From the Elusiveness of Schizophrenia, New Clues to Treatment - NYTimes.com." The New York Times- Breaking News, World News & Multimedia. http://www.nytimes.com/ref/health/healthguide/esn-schizophrenia-ess.html (accessed February 4, 2012). 40 Ibid.

medication only when necessary. This approach has resulted in 33%-50% of the patients being able to operate well for years without being drug-dependent; researchers are still unsure why.41 Although significant research is still needed to fully understand the causes and treatment of schizophrenia, progress has been made in isolating genetic factors that may contribute to the onset of schizophrenia. The presence of specific genes (e.g. DISC1, PDE4B, CHI3L1 and "nine genetic markers"42) can impact the manifestation of the disease. Scientists are now targeting the neurotransmitter glutamate instead of dopamine to help them develop more effective antipsychotic drugs. The most current medications prescribed (atypical antipsychotics) cause fewer side effects than their predecessors (typical antipsychotics). However, patients often still experience enough discomfort with atypical antipsychotic drugs so that they eventually abandon treatment. Schizophrenia is a complex disorder that needs to be more fully understood with regards to its etiology, the impact of genetic and environmental factors, and the development of effective treatments that are tolerable enough for patients to continue using as long as needed.

41 Carey, Benedict. "From the Elusiveness of Schizophrenia, New Clues to Treatment - NYTimes.com." The New York Times- Breaking News, World News & Multimedia. http://www.nytimes.com/ref/health/healthguide/esn-schizophrenia-ess.html (accessed February 4, 2012). 42 Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012).

WORK CITED
1. American Psychiatric Association. "DSM-IV Criteria for Schizophrenia :: DNA Learning Center." DNA Learning Center. http://dnalc.org/view/899-DSM-IV-Criteria-forSchizophrenia.html (accessed February 6, 2012). 2. BBC News. "Schizophrenia Daily News Blog: Another Gene linked to Schizophrenia (PDE4B)." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/sznews/archives/002669.html (accessed February 4, 2012). 3. Carey, Benedict. "From the Elusiveness of Schizophrenia, New Clues to Treatment NYTimes.com." The New York Times - Breaking News, World News & Multimedia. http://www.nytimes.com/ref/health/healthguide/esn-schizophrenia-ess.html (accessed February 4, 2012). 4. Dvir, M.D., Yael, and Jean A. Frazier, M.D. "Autism and Schizophrenia - Psychiatric Times." Psychiatric Times. http://www.psychiatrictimes.com/schizophrenia/content/article/ 10168/1822823 (accessed January 6, 2012). 5. US Department of Health and Human Services. "NIMH Schizophrenia." NIMH. http:// www.nimh.nih.gov/health/publications/schizophrenia/complete-index.shtml (accessed January 6, 2012). 7. Proceedings of the National Academy of Sciences. "Nine Genetic Markers Identified that can Increase a Person's Risk for Schizophrenia." Schizophrenia.com, In-depth Schizophrenia Information and Support. http://www.schizophrenia.com/sznews/archives/005810.html (accessed February 4, 2012). 8. "Schizophrenia, n.". OED Online. December 2011. Oxford University Press. http:// www.oed.com/view/Entry/172410?redirectedFrom=schizophrenia (accessed March 05, 2012). 9. The Internet Mental Health Initiative. "Schizophrenia Facts and Statistics." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/szfacts.htm (accessed January 9, 2012). 10. The American Journal of Human Genetics. "New Schizophrenia Risk Gene Identified Chitinase." Schizophrenia.com, In-depth Schizophrenia Information and Support. http:// www.schizophrenia.com/sznews/archives/004546.html (accessed February 4, 2012). 11. University of Washington Faculty. "Neuroscience for Kids - Schizophrenia." UW Faculty Web Server. http://faculty.washington.edu/chudler/schiz.html (accessed March 19, 2012). 12. VandenBos, Gary R. "Paranoid Schizophrenia," "Schizophrenia," and "Psychosis." The APA Dictionary of Psychology. Washington, DC: American Psychological Association, 2006. 256, 815, 670.