Grant Proposal – Peer Reviews (WEEK 5)

SCHIZOPHRENIA: CAUSES & TREATMENTS

12

SCHIZOPHRENIA

Identifying the Causes of Schizophrenia and Discovering the Proper Treatment

PSY625: Biological Bases of Behavior

Professor Beharie

September 10, 2017

Identifying the Causes of Schizophrenia and Discovering the Proper Treatment

Specific Aims

The idea that Schizophrenia is a psychotic disorder that has not been fully understood by many psychologists is a common debate. Fernandez and Bliss (2016) define this disorder as “a mental disorder that involves disruptions in the areas of perception, thought, cognition, emotion, motivation and motor activity.” Schizophrenia is a disorder that still doesn’t have an explanation as to why it is caused but there are symptoms that psychologists have recognized to be a sign of the disorder. Some psychologist have the idea that the psychosis disorder is genetic and passed on from generation to generation, others think that it has to do with the formation of our cells, the way they are produced and transmitted.

“The mission of the Lieber Institute for Brain Development is to translate the understanding of basic genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that change the lives of affected individuals” (PR Newswire, 2015). Studying chromosomes and the transmission of them is important to understand whether schizophrenia can be passed along genetically or not. Klar (2010) suggests that genetics have nothing to do with the diagnosis of schizophrenia and in fact he claims it comes from the brain function and malfunctions of the brain system are what cause the disorder. Leonard, McClenon, Luck, Robinson, Kaiser, Hahn, Harvey, and Gold (2013) all suggest in their study that the brain function has a connection with schizophrenia, as they stated, “both the sensory threshold and the working memory capacity are impaired” due to schizophrenia. “Patients diagnosed with schizophrenia reliably exhibit deficits on episodic memory tasks, when compared to non-disordered control groups” (Poly, et. al., 2015). Many professionals believe that the brain function and memory system are highly important when diagnosing individuals with a psychotic disorder as dangerous as schizophrenia.

The specific goal and aim of this proposal is to assess studies on patients who have been diagnosed with schizophrenia, who are at-risk, and patients who are neither diagnosed nor at-risk to help determine the causes of the diagnosis. Comparing the results of these studies will allows us to better determine and identify the causes of schizophrenia. Also, performing studies with medication on individuals who are diagnosed so that we can learn what is the best proper treatment. Sometimes, antipsychotic medication is the best answer to help diminish the symptoms of those with the disorder but other times different treatments such as therapy and counseling for continuous evaluation to determine the best treatment is better than putting a patient on drugs immediately after being diagnosed. Lastly, running a study to determine how the brain is affected when individuals are diagnosed with this psychosis disorder. Is it that their brain is affected before being diagnosed which causes the disorder to activate or is it that the brain functions and developments are affected after the individual has been diagnosed with the disorder? The results to all these studies will help us determine the effects of schizophrenia, the cause of schizophrenia, the best treatment, the relation between the disorder and brain functions, and the relation between genetics and diagnosis. As Wolters (2016) states in his article, studying “schizophrenia as a cognitive illness will impact the way, we formulate the diagnosis, treatment guidelines, and risk phenotype in research and this perspective will radically influence the discourse on atrisk psychosis and also encourage the use of (and research into) early interventions such as cognitive and behavioral therapies.”

Background

Clinical diagnosis for patients with schizophrenia have depended on the individual’s symptoms, mental state examinations, and clinical reviews with psychologists. But some scientists have decided to focus on the relationship between the patient’s genes and their psychosis disorder diagnosis. According to Zhang, Xie, Yang, Zhao, Zhang, and Fang (2017), “blood is considered a valuable source of gene expression data and genome-wide blood transcriptome profiling coupled with network analyses provides a platform for identifying functionally relevant biological markers of disease; and with blood-based gene expression and transcriptome data, a model was able to be constructed for diagnosis of schizophrenia.” The connection between genes and disorders is strong, many scientists believe that disorders such as schizophrenia are passed on from generation to generation. O’Connell (2009) conducted a study analysis of nine million Swedish people which consisted of two million families. In his studies, he focused on biological and adoptive parents, full siblings and half siblings on both maternal and paternal sides of the family. O’Connell (2009) found that “first degree relatives are at increased risk of having schizophrenia than general population, full siblings were 9 times more likely, maternal half siblings were 3.6 times more likely to develop schizophrenia, while paternal half siblings were 2.7 times more likely to be diagnosed with schizophrenia.”

“The proportion of a trait that is inherited genetically rather than learned from the environment is sixty-four percent” (O’Connell, 2009). Although, some scientists suggest that the environment that an individual grows up in has a large effect on the outcome of whether they will develop schizophrenia or not. Schizophrenia is a psychotic disorder that is considered to be a label given to victims who experience a pattern of traumatic events, and these events result in the effect of mental damage that affect the individual’s behavior causing the disorders. Thom and O’Brien (2015) concentrated on “the relationship between personal experience of a trauma and later diagnosis of schizophrenia in their article that presented a legal case in New Zealand; In 2013, the decision of LS v. Accident Compensation Corporation decided that the appellant’s significant history of childhood sexual abuse was casually related to his diagnosis of schizophrenia granting he was unable to work due to his disorder and will now receive disability as compensation.” Ultimately, it is the psychiatrist’s duty to determine whether their patient’s mental disorder was caused because of the environmental risk factor, neglect, physical abuse, sexual abuse, emotional abuse and mental abuse, they are indicting lead them to being harmed and effected. “Schizophrenia is a neurodevelopmental disease caused by the interaction of genetic and environmental factors and childhood trauma is one of the non-hereditary factors intimately related to the development of schizophrenia in adulthood” (Alvarez, et. al., 2015).

Yung (2011) comments that there are risk factors associated with the development of schizophrenia, “factors such as family history of the illness, pre and perinatal brain insults, delayed developmental milestones and abuse during childhood placing the individual at increased risk.”

Approximately 10% to 30% of schizophrenic patients are treatment resistant, but for those whose symptoms are successfully controlled they go through therapy treatment and sometimes are prescribed antipsychotics (Fellner, 2017). Some antipsychotics prescribed to help control symptoms of schizophrenia are: Abilify, Clozril, Lurasidone, Olanzapine, Quetiapine, Risperidone, and Ziprasidone; and some of the therapeutic treatments they go through are family counseling, interventions, individual therapy, and group counseling. Eack’s (2012) central focus is on cognitive remediation when it comes to helping patients with schizophrenia because he suggests that antipsychotic medications help people with schizophrenia control some of their symptoms such as hallucination and delusion, but, unfortunately, antipsychotic medication doesn’t help with social, employment, functioning, and religious life. When a patient who has schizophrenia takes part in psychosocial interventions and combines it with pharmacotherapy it increases the chances of helping them minimize the psychotic symptoms and controlling their behaviors. On the other hand, Jingping, Hailong, and Xiaofeng (2012) believe that when symptoms are present and a patient being evaluated is at-risk the best option for them is to take antipsychotics to help lower their chances of later being diagnosed with schizophrenia or other mental disorders.

It is critical to understand what causes schizophrenia whether it is genetically passed on or if it is caused by environmental factors. But it’s also important to know what is the best treatment for each individual, some experience higher symptoms and experience more than others. Therapy trials, antipsychotic treatment trials and tests to study genes and blood-based generations is important to determine the best outcome for each individual who is experiencing schizophrenia whether they have been fully diagnosed with the disorder or simply described to be at-risk of developing the disorder.

Significance

The proposed research will use genetic examination to help determine which participants were diagnosed with schizophrenia based on heritable genes. While others will use mental state examinations, depression tests, anxiety tests, and conduct clinical interviews with psychiatrists to determine if their past experiences are linked to their diagnosis. Once the research has identified which participants suffer from schizophrenia due to genetics and which suffer from it due to environmental factors the psychosocial therapy and pharmacotherapy trials will begin. These therapy trials will be used separately and combined so that we can compare the results of those who only take therapy sessions to those who only take antipsychotics and lastly compare both those results to the participants who undergo both psychosocial therapy and pharmacotherapy. The results will help comprehend which therapeutic technique works best for those who are diagnosed with schizophrenia.

Some of the barriers that can interfere with the research is honesty of participants. As professionals, the psychologists should be able to distinguish when a patient is being untruthful and lying or over exaggerating but it isn’t always that way and sometimes patients can get away with it. The proposed study will help understand how to improve assessments when diagnosing and how to positively improve symptoms experienced by the participants. The study will allow the ability to distinguish positive effects and negative effects from both therapy and pharmacotherapy. Understanding the treatments that have the most effective outcome will help individuals diagnosed with schizophrenia succeed and manage to live their life with control.

Proposed Study

Participants:

There will be a total of one hundred participants between the ages of sixteen through thirty. All participants will be recruited from Lourdes Counseling Center. Gathering individuals who have been previously experienced signs and symptoms of schizophrenia and are seeking for professional assistance. The chosen participants will be assigned to two groups, Group A and Group B. They will be assigned based on the determination of their diagnosis; the focus is on two possible outcomes: diagnosis is due to genes or due to environmental factors and past trauma. Each group will undergo the same three trials at the same exact time. The groups will be checked into an inpatient facility for a duration of twelve months to complete this study. They will be receiving psychological assistance throughout the twelve months they are in the facility.

There are some risks to participants who take part in the experiment due to psychological distress and antipsychotics that have side effects. Any patient who has been previously diagnosed and has a mental health history will automatically be excluded from the research. For those participants under the age of eighteen will need parental written consent to participate. There will also be necessary written consent for those participants ages eighteen through thirty. Any participant is allowed to leave and exclude themselves from the research at any time. Although, there are benefits to taking part in the research study such as finding the proper treatment to help manage their symptoms and to determine the causes of the disorder.

Procedure:

Patients will be asked if they’d like to take part in the research as they come into Lourdes Counseling Center for an evaluation. They will be provided all the details of the research study and asked to sign a form of written consent once they’ve accepted to be a participant in the study. Once they are considered to be a participant, a professional psychologist will evaluate the individual for signs of schizophrenia. If the individual seems to be experiencing various signs of schizophrenia they will be asked more questions in depth to determine if their diagnosis is due to genetic heredity or environmental factors. Throughout this evaluation the participants will take mental state examinations and partake in clinical interviews. They will also speak about their past childhood experiences and anything they believe has caused trauma to them, and identify if other family members have experienced the same symptoms or if they’ve been diagnosed with schizophrenia. At this point the expert will determine whether the disorder is genetic or due to environmental factor. Once the decision is made the candidate will be placed in either Group A (due to genes) or Group B (due to environment). The participants will be enrolled in an inpatient facility with a total of fifty participants in each facility (two total).

At the facility both groups will undergo three trials within a period of twelve months, each trial taking approximately four months. The first trial will consist of the participants being involved in therapeutic interventions, to help control and manage their psychological, and social development and symptoms. The second trial will be focused on prescribing the correct antipsychotic and correct doses to each patient to help minimize their symptoms so that they can learn to have more of a ‘normal’ life. Lastly, the third trial is both previous trials combined. The participants will participate in therapy and pharmacotherapy. All participants will be expected to have clinical reviews every three days to help psychologists understand the effect of therapy and antipsychotics in each individual.

Hypotheses & Analysis:

There is no known factor that has been determined to cause schizophrenia but research study shows the suggestions of multiple psychologists. Schizophrenia is a mental disorder that can be genetically hereditable but also a disorder that can be triggered through traumatic events in life. If an individual is diagnosed with schizophrenia will psychosocial therapy improve and minimize their symptoms? If an individual is diagnosed with schizophrenia is pharmacotherapy necessary? Do antipsychotics worsen symptoms for those diagnosed with schizophrenia?

The reason in separating the groups based on the psychologist’s listed causes of the diagnosis is because since they are different symptoms and different causes they might need different assistance to cope and manage with schizophrenia. Some may be able to minimize symptoms with simply participating in therapy while others may need antipsychotics to help decrease symptoms and some may even need to partake in both therapeutic interventions and psychosocial therapy and pharmacotherapy.

The assessments and evaluations will show the results of whether the participant’s symptoms improved in all three trials (only therapeutic, only pharmacotherapy, and both combined). Evaluations will help determine the correct treatment for each individual. However, the assessments will also show if these treatments are negatively affecting the patient’s symptoms.

Budget Justification

Funding is requested for the facilities used to hold the one hundred participants. There is a total of two inpatient facilities being utilized. The cost of the facilities will include housing, electricity, food, professional therapy services and medication. There will also be a payment made to each participant at the end of the study for their participation.

See Appendix A: Budget for detailed budget figures.

References

Alvarez, M. A., Masramon, H., Pena, C., Pont, M., Gourdier, C., Roura-Poch, P., and Arrufat, F. (2015). Cummulative Effects of Childhood Trauma: Polytraumatization, Dissociation, and Schizophrenia. Community Mental Health Journal, 51, 54-62. 10.1007/s10597-014-9755-2

Eack, S. M. (2012). Cognitive Remediation: A New Generation of Psychosocial Interventions for People with Schizophrenia. Social Work, 57(3), 235-246. 10.1093/sw/sws008

Fellner, C. (2017). New Schizophrenia Treatments Address Unmet Clinical Needs. P&T, 42(2), 130-134.

Fernandez, J., and Bliss, S. (2016). Schizophrenia and the Estranged Self. Journal of Evaluation in Clinical Practice, 22(4), 615-621. 10.1111/jep.12583

Jingping, Z., Hailong, L., and Xiaofeng, G. (2012). Is Pharmacological Intervention Necessary in Prodromal Schizophrenia? Shanghai Archives of Psychiatry, (24)6, 347-349. 10.3969/j.issn.1002-0829.2012.06.006

Klar, A. S. (2010). A Proposal for Re-defining the way the Aetiology of Schizophrenia and Bipolar Human Psychiatric Diseases is Investigated. Journal of Biosciences, 35(1),11-15. 10.1007/s12038-010-0002-x

Leonard, C. J., Robinson, B. M., Kaiser, S. T., Hahn, B., McClenon, C., Harvey, A.N., Luck, S. J., and Gold, J. M. (2013). Testing Sensory and Cognitive Explanations of the Antisaccade Deficit in Schizophrenia. Journal of Abnormal Psychology, 122(4), 1111-1120. 10.1037/a0034956

O’Connell, N. (2009). Bipolar Disorder and Schizophrenia Share Common Genetic Causes. Nurse Prescribing, 7(2), 90.

Polyn, S. M., McCluey, J. D., Morton, N. W., Woolard, A. A., Luksik, A. S., and Heckers, S. (2015). Temporal Context and the Organisational Impairment of Memory Search in Schizophrenia. Cognitive Neuropsychiatry, 20(4), 296-310.10.1080/13546805.2015.1031372

PR Newswire. (2015). Lieber Institute for Brain Development Shares Large Collaborative Grant to Study Origins in Schizophrenia. http://www.prnewswire.com/news-releases/lieber-institute-for-brain-development-shares-large-collaborative-grant-to-study-origins-of-schizophrenia-3000.74199.html

Steele, D., Moore, R. L., Swan, N. A., Grant, J. S., and Keltner, N. L. (2012). Biological Perspectives: The Role of Glutamate in Schizophrenia and Its Treatment. Perspectives in Psychiatric Care, 48(3), 125-128. 10.1111/j.1744-6163.2012.00333.x

Thom, K., and O’Brien, A. (2015). Environmental Factors in the Development of Schizophrenia: Implications of a Recent New Zealand Legal Case. Psychiatry, Psychology, and Law, 22(6), 795-799. http://dx.doi.org/10.1080/13218719.2015.1112338

Tranulis, C., Lecomte, T., El-Khoury, B., Lavarenne, A., and Brodeur-Cote, D. (2013). Changing the Name of Schizophrenia: Patient Perspectives and Implications for DSM-V. PLoS ONE, 8(2), 1-5. 10.1371/journal.pone.0055998

Wolters, K. (2016). Time to Re-focus onto Cognitive Symptoms in Schizophrenia. Indian Journal of Psychological Medicine, 38(2), 93-96.10.4103/0253-7176.178765

Yung, A. R. (2011). Risk, Disorder, and Diagnosis. Australian and New Zeland Journal of Psychiatry, 45(11), 915-919. 10.3109/00048674.2011.614926

Zhang, H., Xie, Z., Yang, Y., Zhao, Y., Zhang, B., and Fang, J. (2017). The Correlation-Base-Selection Algorithm for Diagnostic Schizophrenia Based on Blood-Based Gene Expression Signatures. BioMed Research International, 7. http://doi.org/10.1155/2017/7860506

Appendix A: Budget

SUMMARY PROPOSAL BUDGET	FOR INSTITUTION USE ONLY
ORGANIZATION	PROPOSAL NO.	DURATION (MONTHS)
PRINCIPAL INVESTIGATOR (PI)/PROJECT DIRECTOR Student	AWARD NO.
A. PERSONNEL: PI/PD, Co-PIs, Faculty, Graduate Assistants, etc.	Funds
List each separately with name and title.	Requested By
	Proposer
1. Student	$0
2. Psychologist	$0
TOTAL SALARIES		$0
B. EQUIPMENT (LIST ITEM AND DOLLAR AMOUNT FOR EACH ITEM EXCEEDING $5,000.)
None
TOTAL EQUIPMENT	$0
C. TRAVEL	1. DOMESTIC - PI attendance at national meeting	$0
	2. OTHER - Travel for RA to participants home	$0
TOTALTRAVEL		$0
D. PARTICIPANT SUPPORT	$10,000
1. STIPENDS	$	100
2. TRAVEL
3. SUBSISTENCE
4. OTHER
TOTAL NUMBER OF PARTICIPANTS (40) TOTAL PARTICIPANT COSTS	$10,000
E. OTHER DIRECT COSTS
1. MATERIALS AND SUPPLIES- Computer for patient training, data collection and analysis	$2,500
2. FOOD	$3,000
3 OTHER Office supplies	$0
4. FACILITY: housing, electricity	$44,500
TOTAL OTHER DIRECT COSTS	$0
F. TOTAL DIRECT COSTS (A THROUGH E)	$60,000
G. TOTAL INDIRECT COSTS (F&A) (Rate = 37.5%)	$0
H. TOTAL DIRECT AND INDIRECT COSTS (F + G)	$60,000

PSY625: Biological Bases of Behavior Ashford University