Innovative Research Views on Onset and Treatments
Schizophrenia:Innovative Research Views on Onset and Treatments
The term “schizophrenia” was coined by Swiss psychiatrist Eugen Bleuler to describe a splitting of psychic functions (Crespi, Sted & Elliot 2010, p. 1736). Schizophrenia is an extremely serious and devastating illness affecting 1% of the American population, causing symptoms that disrupt thought patterns, behavior, and emotions of individuals (Richard & Brahm 2012, p. 757; “Schizophrenia: What” 2012, p. 1). While some sources refer to schizophrenia as a “mental illness,” others refer to it as a “brain disorder” (“Schizophrenia: What” 2012, p. 1; “Schizophrenia” n.d.). Indeed, schizophrenia is a difficult disorder to characterize because its primary symptoms, such as hallucination, agitation, social withdrawal, delusions, thought disorder, flat affect, and memory issues, display as psychological problems; however, recent research has pointed to developmental, genetic, and immune problems leading to brain structure or even cellular-level differences in people with schizophrenia (“Schizophrenia” n.d.). In other words, schizophrenia is not wholly either a psychological or a physiological disorder, but a combination of both. It is a heterogeneous biopsychological disorder; researchers Richard and Brahm introduce this idea by writing, “schizophrenia is probably neither a single disease entity and nor is it a circumscribed syndrome—it is likely to be a conglomeration of phenotypically similar disease entities and syndromes” (2012, p. 757). Recent research seeks to pinpoint causes of schizophrenia in order to find ways to prevent it or to treat it; three prominent aspects studied are its possible association with immune dysfunction, the environmental factor of urbanicity, and specific genetic mechanisms such as those involved with the DISC1 gene.
The heterogeneous nature of schizophrenia underscores the complexity of diagnosing, treating, and understanding causes of the problem. Worldwide statistics show that both genders and all ethnic groups are affected equally, with the age of onset typically between the ages of 16 and 30 (“Schizophrenia” n.d.). People who have relatives with schizophrenia are at a much greater risk for developing it themselves; this aspect points toward the idea that it has a genetic component (Park et al. 2010, p. 17785). The current standard treatments for schizophrenia include antipsychotic medication in conjunction with psychosocial treatment such as cognitive-behavioral therapy, rehabilitation, family education, and illness management training (“Schizophrenia” n.d.). Like other illnesses with psychological components such as depression, medication that helps one patient may not help a different patient; therefore, close monitoring by a doctor or other medical staff is a necessity. The fact that different patients require different medications for successful treatment is another indicator of schizophrenia’s heterogeneous nature.
Research finds that patients with schizophrenia have decreased brain mass, most specifically a reduction in the size of the limbic system (Torres-Vega et al. 2012, p. 686). The limbic system of the brain includes the hypothalamus, thalamus, olfactory bulb, amygdala, and hippocampus; it supports functions such as motor coordination, emotions, memory, behavior, and olfaction (Boeree 2010; Torres-Vega et al. 2012, p. 686, Richard & Brahm 2012, p. 758). Torres-Vega et al. write, “During early development, especially the gestational period and the first year of life, the limbic system is more vulnerable to all types of disruptions than it is later in development” (2012, p. 686). While it is clear that the limbic system is affected in schizophrenic patients, it is unclear exactly when and how it is affected that leads to an outcome of schizophrenia.
Immunologic Dysfunction
Researchers Michelle D. Richard and Nancy C. Brahm conducted a review of recent research seeking to find a link between immune system dysfunction and schizophrenia. According to their analysis, “a growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia” (Richard & Brahm 2012, p. 757). Their conclusion was that immunologic dysfunction is likely to account for a subset of schizophrenic patients; in other words, some but not all cases of schizophrenia may be accounted for by immune system problems. Their analysis provides some valuable ideas not only for treatment, but also for prevention.
The immune system itself is complicated and can be compromised at many different points during a person’s lifetime, although Richard and Brahm place a lot of emphasis on genetics and gestational factors. Their survey of literature found that “having a history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia” (Richard & Brahm 2012, p. 758). Maternal infection during pregnancy increases the risk for the child to develop schizophrenia. For example, Richard and Brahm found that if mothers experience influenza in their first trimester, the risk for schizophrenia is increased by seven times, and mothers with reproductive or genital infections increases the risk by five times (2012, p. 759).
There are several ways that fetal development can be affected by infections that are possible causes of developmental differences leading to schizophrenia. For example, Richard and Brahm write, “one proposed mechanism for the increased risk of schizophrenia after maternal infection is that maternal antibodies cross the placenta and interact with fetal brain antigens, disrupting fetal brain development” (2012, p. 759). This problem can be caused by cytokines, proteins which are instrumental in cell communication. According to Richard and Brahm, an infection can cause maternal cytokines to be able to pass through the placenta, which then causes the mother’s immune system to attack or negatively affect the fetal immune system (2012, p. 759). The introduction of maternal cytokines can lead directly to the damage of or changes in the development of fetal white matter, which causes damage that “may lead to alterations in later development consistent with the findings in cases of schizophrenia” (2012, p. 759). In these cases, the infant is not experiencing the mother’s immune problem directly, but the indirect consequences still have an immense effect on the child’s future development. In other cases, a fetus may be directly infected, such as with venereal diseases, by contact with the mother’s cervix or vagina (2012, p. 759). Considering the heterogeneous nature of schizophrenia, Richard and Brahm suggest that “one or more of these maternal infections could play a role” in the development of schizophrenia (2012, p. 759).
Besides maternal infections, Richard and Brahm’s survey of literature relating immune system problems to schizophrenia found that schizophrenic patients showed decreased Th1 response; Th1 is a cytokine that helps cells create an immune response (2012, p. 760). Schizophrenic patients also may display deficiencies on T-cells, white blood cells that are an important part of immune response (2012, p. 760). This is significant, Richard and Brahm write, because “all components of the immune system must work together for proper immune function, [and] an imbalance of any kind has the potential to cause significant problems,” presumably to include development of and persistence of schizophrenia (2012, p. 760). It could be construed that if an immune deficiency, such as of Th1 response, is detected early, a child could be treated and development of schizophrenia could be prevented.
The survey of literature and research regarding the immune system’s association with schizophrenia can provide a valuable way to assess risk, practice preventative techniques, and to treat schizophrenia. A primary object of this type of study is to help identify at-risk groups. For instance, Richard and Brahm write, “According to the DSM-IV-TRM the first-degree relatives of a patient with schizophrenia have a 10-fold greater risk of developing the disorder than the general population” (2012, p. 762). Other prenatal and perinatal factors resulting in increased risk for schizophrenia include a pregnant mother having infections, severe stress, nutritional deficiencies, or obstetric complications, as well pregnancies associated with fathers of advanced age and births occurring in winter (Richard & Brahm 2012, pp. 758, 762). Therefore, a pregnant woman who has one or more of these risk factors could be considered part of the at-risk group. Once identified, at-risk groups should receive caregiver education, counseling, and special attention to women’s health (Richard & Brahm 2012, p. 762). This special attention to at-risk pregnancies may, in some cases, be able to prevent a future case of schizophrenia altogether.
Schizophrenic patients can benefit from increased awareness that immunologic dysfunction can be a contributing factor. Although immunologic dysfunction is not culpable in all cases of schizophrenia, treatment of the immune system should be considered in addition to standard treatment with antipsychotic medication. Studies involving immunotherapy with drugs such as celecoxib, azathioprine, atlizumab, anakinra, tumor necrosis factor- α blockers, funtolizumab, and polyunsaturated fatty acids have shown in some cases to provide “a significantly better response” when combined with traditional antipsychotic medication therapy in some cases (Richard & Brahm 2012, p. 763). Interestingly, Richard and Brahm’s survey discovered that some of the second-generation antipsychotics used in the treatment of schizophrenia, such as olanzapine, affect the function of the immune system in addition to their better-known affects on serotonin and dopamine receptors (2012, p. 763). However, in spite of these findings from their survey of the literature, Richard and Brahm emphasize the need for more research on autoimmune dysfunction and schizophrenia. While there appears to be excellent data showing an association between immunologic dysfunction and schizophrenia, further research must occur in order to help at-risk groups and current patients in order to prevent or better treat schizophrenia. Additionally, the researchers emphasize that immunologic dysfunction may only play a part in schizophrenia for a subset of and not for all patients.
Urbanicity
Childhood social stress related to urbanicity, or city living, is another risk factor for schizophrenia. According to researchers Lederbogen et al., “the incidence of schizophrenia is strongly increased in people born and raised in cities” (2011, p. 498). Although it has been common knowledge among psychiatrists for decades that city life is a risk factor for development of a variety of chronic mental disorders, Lederbogen et al.’s study sought to find the reasons behind it.
Lederbogen et al. utilized a stress-causing activity and functional magnetic resonance imaging (fMRI) with study participants. They discovered that the amygdala and perigenual ACC (pACC) portions of the brains of people who grew up in cities and people who lived in cities reacted differently to stressful situations than those who lived in or grew up in rural areas (Lederbogen et al. 2011, p. 498-499). The amygdala has many functions, but the important one noted in this study is its role in registering environmental threat and triggering the “fight or flight” response; it is “strongly implicated in anxiety disorders, depression, and other behaviours that are increased in cities, such as violence” (Lederbogen et al. 2011, p. 499). The pACC section of the brain helps process social stressors, and is also part of the regulation system for the adrenal “fight or flight” response (Lederbogen et al. 2011, p. 499). The fMRI scans during the experiment revealed that “no other brain regions” showed elevated levels of activity when associated with city living and upbringing besides the amygdala and pACC regions (Lederbogen et al. 2011, p. 499). As noted earlier, the limbic system is compromised in schizophrenic patients; Lederbogen et al. appear to have discovered an important association between how environmental factors can influence the development of this part of the brain, since the amygdala is a part of the limbic system.
If communication between the amygdala and pACC is impaired, it can lead to increased problems in handling social stress. The study discovered that “urban upbringing was associated with reduced connectivity” between the amygdala and pACC brain regions (Lederbogen et al. 2011, p. 500). This reduced connectivity can lead to problems in being able to deal with the stress of urban life because “the stress response doesn’t switch off,” leading to a variety of problems including high blood pressure, suppressed immune systems, and psychiatric illnesses (Abbott 2012, para. 6). A very important factor in their findings is that being raised in a city appears to be associated with a permanent change in the way these sections of the brain function.
Although schizophrenia is well known to be associated with genetic risk factors, Lederbogen et al.’s study highlights environmental risk factors associated with the disorder and pinpoints the areas of the brain associated with the social stress of city living. Considering the fact that more than half of the world’s population now lives within cities and that by 2050, approximately 69% of the world’s people will live in urban areas, Lederbogen et al.’s ideas should be of particular importance concerning the identification of risk and employing techniques to prevent schizophrenia (Lederbogen et al. 2011, p. 498). Lederbogen et al. suggest that the integration of public policy, social sciences, and neurosciences is essential in dealing with the risk factors causing increased mental health problems such as schizophrenia due to urbanicity (Lederbogen et al. 2011, p. 500).
Genetic Mechanisms
While the heterogeneous and heritable nature of schizophrenia makes it likely that more than one or multiple genes play roles in the onset of the disorder, researchers Park et al. discovered particular problems that the disrupted-in-schizophrenia 1 (DISC1) gene has in schizophrenia. While the previous examples examined physical differences in schizophrenic patients’ immune systems, brain capacity and function, and environmental factors, Park et. al’s research examines differences at the molecular level.
Research has shown that “mitochondrial dysfunction has been found to be associated with various psychiatric disorders, including schizophrenia” (Park et al. 2010, p. 17785). Park et al. point out that mitochondria play vital roles in basic cellular processes including monoamine metabolisim, programmed cell death, and energy production (2010, p. 17785). In schizophrenic patients, the DISC1 gene may be truncated, leading to deficiencies in Mitofilin, which helps maintain the functional integrity of mitochondria (Park et al. 2010, p. 17785). Additionally, DISC1 “can cause reductions in mitochondrial MAO-A activity;” compromised MAO-A activity can also affect the activity of dopamine, norepinephrine, and serotonin, all of which are chemicals leading to changes in behavior and brain function in schizophrenic patients (Park et al. 2010, p. 17790, “MAOA” 2013).
Park et al.’s research sheds some light on how problems with basic cellular cause chemical imbalances that affect the brain and can lead to schizophrenia. Though it establishes a link between DISC1 and mitochondrial dysfunction, their research does not explain exactly how DISC1 contributes to the onset of schizophrenia. For instance, their research does not establish whether DISC1 truncation is present in all schizophrenic patients or why some people with DISC1 truncation may develop schizophrenia and others may not. However, Park et al.’s discoveries provide a valuable basis for future research into causes and possible treatments for schizophrenia, especially considering that schizophrenia is considered to be highly heritable.
Conclusion
Considering the complexity of a heterogeneous disorder such as schizophrenia, it is unsurprising that multiple factors not only lead to the onset of the disorder, but also that a variety of preventative and treatment techniques is necessary. The variety of casual factors for schizophrenia, including immunologic dysfunction, environmental factors like urbanicity, and cellular-level dysfunction caused by genes such as DISC1, show that prevention and treatment of this disorder must occur on multiple levels. Research must continue and be integrated along many avenues, including public policy, social sciences, and neurosciences. For instance, Richard and Brahm’s research showed the association of schizophrenia with immunologic dysfunction, while Lederbogen et. al’s research showed an association of schizophrenia and growing up in a city. However, further research could seek to discover how urbanicity affects immunologic function and how this correlates with rates of schizophrenia. People who are under stress may be inclined to experience depressed immune function, and people living in cities may experience more stress than those who do not live in cities, another possible causal factor for schizophrenia. Utilizing the examples of these recent studies as well as the ever-increasing technology available to researchers of genetics, brain function, and other aspects of the human body, new studies can help people gain a better understanding of the biopsychological bases of schizophrenia. The accomplishments of these recent researchers show that for a disorder like schizophrenia, which once appeared to be mysterious, complex, and difficult to treat, the advent of new technology and methods of research bring forth new possibilities in gaining clarity concerning causes of and treatments for schizophrenia that could not have occurred even a decade ago.
References
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