Could Magnetic Resonance Imaging create a paradigm shift in psychotic disorders in psychiatric practice?

Table of Contents

Acknowledgements

Abstract

Figures

Tables

Chapter One: Introduction
1.1 Introduction
1.2 Background
1.3 Aetiology
1.4 Current Diagnosis
1.5 Psychoradiology
1.6 Rationale
1.7 Project question
1.7.1 Hypothesis
1.7.2 Null Hypothesis
1.8 Aims
1.9 Objectives
1.10 Summary

Chapter Two: Methodology
2.1 Introduction
2.2 The Nature of a Literature Review
2.3 Research Design
2.3.1 Alternative Project Methods
2.4 Rationale for Systematic Literature Review
2.5 Sources of Information
2.6 Search Strategy
2.6.1 Search Technique
2.6.2 Search Terms
2.6.3 Search Criteria
2.7 Critical Evaluation of Literature
2.7.1 Bias
2.7.2 Validity and Reliability
2.8 Data Extraction and Analysis
2.9 Ethical Consideration
2.10 Summary

Chapter Three: Literature Review
3.1 Introduction
3.2 Structural Brain Changes
3.2.1 Falkenberg et al. (2017)
3.2.2 Schnack et al. (2014)
3.2.3 Rimol et al. (2012)
3.2.4 Sprooten et al. (2013)
3.2.5 Koutsouleris et al. (2015)
3.2.6 dePierrefeu et al. (2018)
3.2.7 Elfaki et al. (2013)
3.3 Functional Brain Changes
3.3.1 Collin et al. (2018)
3.3.2 Das et al. (2018)
3.3.3 Sarpal et al. (2016)
3.3.4 Cao et al. (2018)
3.4 Summary

Chapter Four: Discussion
4.1 Introduction
4.2 Variations in a Psychotic Brain
4.2.1 Functional Changes
4.2.2 Structural Changes
4.3 Explanation of Variabilities amongst Findings
4.3.1 Inclusion Criteria
4.3.2 Antipsychotic Medication
4.3.3 Machine-learning Algorithms
4.4 Differential Diagnosis
4.4.1 Organic Psychosis
4.4.2 Functional Psychosis
4.5 Project Limitations
4.6 Summary

Chapter Five: Conclusion
5.1 Introduction
5.2 Key Findings
5.2.1 Functional Changes
5.2.2 Structural Changes
5.2.3 Differential Diagnosis
5.3 Acceptance or Rejection of Hypothesis
5.4 Contribution of the Findings in Answering the Project Question
5.5 Meeting the Objectives
5.6 Summary

Chapter Six: Recommendations
6.1 Introduction
6.2 Study Design
6.3 Antipsychotic Medication
6.4 Summary

References

Appendix

Appendix A: Diagnostic Test Study CASP Tool

Appendix B: Data Extraction Table

Appendix C: Brain Abnormalities Table

Figures

Figure 1: The flow of information through the different phases used in this review. It organised the number of articles identified and eligible following the search criteria (adapted from Moher et al., 2009).

Figure 2: Top to bottom: axial, coronal and sagittal slices of the brain following separation patterns. Hot colours refer to the relative increase of GM density and vice versa for the cool colours. First column: separation of BP and schizophrenia; Second column: component shared with the separation of HC and schizophrenia; Third column: exclusive to schizophrenia and BP segregation; Fourth column: separation of BP and HC. 31

Tables

Table 1: Boolean logical operators and their role in search techniques.

Table 2: Key search terms and Boolean logic operators used in the literature search.

Table 3: Inclusion and exclusion search criteria used.

Acknowledgements

Throughout the writing of this project, I have received a great abundance of support and assistance. I would first like to acknowledge and express my gratitude to my dissertation supervisor, Tom Campbell-Adams, whose guidance was invaluable in the formulation of my research project. I want to thank my family, friends and partner for their patience and encouragement throughout this project. You all have supported me greatly and were always there for me and willing to help where possible. I would particularly like to thank my former co-workers at the Mater Private Hospital, who inspired me to do this course, as without them I would not be here today.

Abstract

Aim

This project aimed to ascertain whether MRI could create a paradigm shift in psychiatric practice for psychotic disorders.

Background

Psychotic disorders are mental illnesses that are characterised by hallucinations and delusions, with disturbances to the thinking process, insight, and judgement of the individual. A prompt and accurate diagnosis for psychoses is critical for effective patient management, treatment and subsequently, patient outcomes. Unlike most diseases, there are presently no reliable biomarkers that offer a definitive diagnosis for psychoses. The current symptom-based approach and is hindering the effectiveness of diagnosis due to validity and reliability issues. As psychoses are classified based upon clinical presentation, the diagnosis between brain disease, trauma and different psychotic disorders become blurred. Research from this project has suggested the potential use of structural and functional MRI techniques in determining a biomarker to overcome these issues.

Method

With this aim in mind, this paper will present a systematic literature review for remodelling the psychiatric disorder patient pathway. A critical appraisal skill programme tool was employed following a systematic search of relevant studies. There were eleven articles considered suitable following this criteria. Based upon their findings, these articles were divided into two key themes: structural and functional brain changes. Following these findings, conclusions were drawn, and recommendations were made based on the limitations presented as a whole.

Findings

Structural brain changes in psychoses were consistent with a reduction of grey matter volumes, particularly in the gyri, cingulate, pallidum, hippocampus, and within all four lobes of the cerebral cortex. A decrease in white matter volume was also noted. Additionally, findings have identified ventricle enlargements and asymmetry. Functional changes involved a displayed disorganised gyrification network and abnormal modular organisation connectome in high-risk individuals who later developed psychoses. In addition, the gyrus became more connected to the limbic region which is involved in processing emotions. This explains why individuals suffering psychoses experience auditory hallucinations. These findings suggest potential biomarkers for psychoses. Furthermore, on comparing bipolar disorder from schizophrenia; cortical thinning was not observed in bipolar disorder patients; subsequently, suggesting that this is unique to schizophrenia. This differentiation can be utilised to correctly diagnose and treat psychoses patients, which are often clinically confused.

Conclusion

Structural and functional MRI are nascent tools in psychoses research and currently, should only be used in conjunction with the current diagnosis of psychotic disorders. Although still at its early stages, it is a promising mechanism for clinical research and psychiatric practice for psychotic disorders. Despite studies consistently presenting potential biomarkers for detecting a psychosis, they have not yet been established to the level that could be solely utilised in practice until the variables involved, such as sample size and methodology are addressed and constant. The organic reflection and growth of impending imaging guidelines will ultimately lead to better patient care and help psychiatric practice strive towards achieving clinical excellence.

Recommendations

MRI has substantially advanced our understanding of the pathophysiology of psychosis. The current challenge facing the field of Psychoradiology is to translate the research findings into clinical practice. Larger sample sizes and standardised protocols should be implemented in future studies across various clinical sites. This ensures that research is replicable and therefore, more valid. The influence of antipsychotics additionally needs to be ascertained to determine the absolute effect of these medications on the structure and function of the brain. Only after overcoming these limitations, can MRI create a paradigm shift in psychiatric practice for psychotic disorders.

Glossary

Antipsychotics – medications believed to block dopamine nervous receptors to treat psychosis.

Biomarker – a biological or biologically derivative indicator of a condition.

Bipolar Disorder – a psychological disorder of mood which is characterised by alternating episodes of mania and depression.

Blood Oxygen Level Dependent Signal – the contrast of blood deoxyhemoglobin in MRI studies.

Computation Brain Analysis – develops theoretical models using mathematical and computer tools which test and expand the understanding of the brain and behavioural processes.

Diagnostic and Statistical Manual of Mental Disorders – produced by the American Psychiatry Association, a handbook used by healthcare professionals as a guide in diagnosing mental conditions. The handbook comprises of criteria such as descriptions and symptoms, for diagnosing mental disorders.

Evidence-based Practice – decisions about patients or populations are based on the best current evidence

First-episode Psychosis – refers to the initial period that an individual experiences a psychotic episode or symptom.

Functional Magnetic Resonance Imaging – a technique for examining brain activity.

Gyrification – the process by which the brain undergoes alterations in surface morphology to create gyral and sulcal regions.

International Statistical Classification of Diseases and Related Health Problems – produced by the World Health Organisation, it is the foundation for identifying health trends and statistics. It is also the international standard for reporting health disorders and diseases. It is the standard diagnostic classification for all research and clinical purposes.

Magnetic Resonance lmaging – utilises a strong magnetic field with radiofrequency waves to produce detailed images of the body’s tissues and organs.

Prodromal Phase – the first phase of psychosis. During this period the individual begins to experience changes but have not yet suffered psychotic symptoms.

Psychiatry – the medical speciality concerned with the prevention, diagnosis, and treatment of mental disorders.

Psychoradiology – a nascent medical imaging technology which is used to analysis neurophysiology and mental health.

Psychosis – a mental health condition which causes people to perceive or interpret reality differently, such as delusions and hallucinations.

Schizophrenia – a severe mental condition in which people interpret reality abnormally. This may be inclusive of delusions, hallucinations, and disordered behaviour and thinking. This can impair their functioning and be disabling to the individual.

Structural Magnetic Resonance Imaging – technique for examining the anatomy and pathology of the brain.

Support Vector Machines – classification technique that has been widely studied for classification, regression and density estimation. It was recently used in applications such as pattern recognition, bioinformatics and clinical diagnosis.

Voxel-based Morphometry – an automated quantitative analysis of the distribution of white and grey matter. This technique may be applied to individual or groups of patients.

Abbreviations

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Chapter One: Introduction

1.1 Introduction

Chapter one will introduce the research question and provide the rationale for conducting the project, with essential background knowledge. Additionally, the project question, aims, and objectives that will be used to later accept or reject the hypotheses will be identified.

1.2 Background

Psychotic disorders, also known as ‘psychoses’, is an umbrella term encompassing various mental illnesses manifested by severe symptoms including hallucinations, delusions, and disturbances in thinking, insight, and judgement. These defining symptoms can be extremely debilitating for the individual (Sims et al., 2018). The initial stage of these symptoms is the most critical as it is during this phase that determines the diseases chronicity (McGorry, Killackey & Yung, 2008); therefore, it is evident to accurately diagnose psychosis, and promptly. In actuality, this is not always the case. This inaccuracy is confirmed in a report by Levin (2006), who identified that 25% of 302 patients were misdiagnosed with a psychotic disorder but in fact, had substance-induced psychosis or were negative for psychosis. This is concerning considering that prolonged mistreatment and misdiagnosis is associated with poor patient outcomes (Soares-Weiser et al., 2015).

Psychoses are classified as either organic or functional. Organic psychoses are characterised by brain abnormalities that are induced by physical defects including brain trauma or illnesses, such as Alzheimer’s disease (Hager & Keshavan, 2015). Substance abuse can also generate psychosis. However, brain function that precipitates delusions and hallucinations are more frequently associated with specific psychiatric disorders, categorised as functional psychoses which incorporates schizophrenia and mood disorders, such as Bipolar Disorder (BD). The World Health Organisation (WHO) (2001) acknowledged schizophrenia as the most common of the psychoses, affecting 21 million people worldwide.

1.3 Aetiology

The nature of the brain is exceptionally complex leading to extreme difficulty in pathogenesis. Despite prolonged research, psychoses aetiology remains unknown. However, in recent decades, genetics, imaging, and post-mortem studies have significantly enhanced the biologic understanding of the brains dysfunction concerning psychoses (Beaumont, 2008). Inherited genetic predisposition is linked to psychosis. Thus, children of psychosis patients have a higher risk of developing the condition. While no causative link was identified in the investigation of psychosis patients, many neurological findings were noted. These patients manifested structural changes and abnormal electrical signalling in the brain (Sims, 2018).

1.4 Current Diagnosis

Unlike most diseases, there are presently no reliable biomarkers that offer a definitive diagnosis for psychoses. Current diagnosis is heavily reliant on psychiatric evaluation and by process of elimination. Psychiatric nosology remains exclusively syndromic, relying on symptom-based classification tools which require patients to conform to a checklist of symptoms to meet predefined criteria. The Diagnostic and Statistical Manual of MentaI Disorders (DSM) and the International Classification of Mental and Behavioural Disorders (ICD) are the most routinely used classifiers (Sims, 2018). Reliability is the greatest challenge in diagnosing psychoses, with current diagnostic methods questioning consistency. As psychoses are classified based upon clinical presentation, the diagnosis between schizophrenia and BD may become blurred. This leads to overarching issues pertaining to diagnosis as symptoms are not exclusive to a single psychotic disorder, with many psychoses having symptoms alike (Mullin, 2013). Consequently, this overlap presents a predicament for nosology and treatment between schizophrenia and BD.

1.5 Psychoradiology

Psychoradiology is an emerging field of intersection between radiology and psychiatry. The introduction of psychoradiology implemented a role in the diagnosis and treatment of psychosis to improve patients’ quality of life (Lui et al., 2016). Presently, MRI is the gold standard in gaining insight into the brains interior as it visualises anatomical structures, as well as function. MRI is a non-invasive approach that does not involve ionising radiation, making it a favourable intervention for research and routine scanning (Beaumont, 2008). Nevertheless, MRI is a specialised practice and is subject to availability (Nam, Barrack & Potter, 2014), this limitation significantly reduces the accessibility for psychosis patients.

1.6 Rationale

Despite imaging for psychoses not yet clinically justified (National Institute for Health and Care Excellence (NICE), 2008), growing evidence demonstrates its context to create a paradigm shift in psychiatric practice for psychotic disorders. Psychiatry is the only medical speciality that rarely looks at the organ that it treats (Amen, 2018), which could explain why psychosis is the third most disabling condition worldwide (WHO, 2001). Incorporating in-vivo imaging into practice could diagnose and treat psychosis promptly, limiting the disabling effects on patients. Currently, no biomarkers are known to diagnose psychotic disorders or to differentiate between them. Consequently, creating difficulty for diagnosis and treatment. Ergo, this project is of paramount importance to explore MRI in ultimately improving psychosis patient outcomes.

1.7 Project question

Could MRI create a paradigm shift in psychiatric practice for psychotic disorders?

1.7.1 Hypothesis

MRI could create a paradigm shift in psychiatric practice for psychotic disorders.

1.7.2 Null Hypothesis

MRI could not create a paradigm shift in psychiatric practice for psychotic disorders.

1.8 Aims

To illuminate this uncharted area, the author aimed to undertake a systematic literature review (SLR) to ascertain whether MRI could create a paradigm shift in psychiatric practice for psychotic disorders. This project considers the implications for both clinical and research purposes. This SLR aims to produce an unbiased, critical evaluation of both the abilities and restrictions of neuroimaging in psychoses; which will be assessed by appraising the literature which was found using a systematic search strategy. Additionally, this study will recommend further research needed to support the clinical implementation in the evolution of Psychoradiology and ways to overcome any limitations to facilitate this field in becoming evidence-based practice.

1.9 Objectives

- Construct a systematic search to investigate relevant literature using appropriate sources written within the last ten years.
- Choose and analyse the most relevant studies found using a Critical Appraisal Skills Programme (CASP) tool to discover scope, pertinence to the hypothesis and limitations.
- Evaluate and refine results.
- Discuss findings.
- Draw conclusions to agree with either the hypothesis or null hypothesis.
- Make recommendations for future research and clinical practice.

1.10 Summary

This chapter has introduced the research question and context for conducting the project, providing valuable background knowledge. Additionally, hypotheses, aims, and objectives were identified. Chapter two will further elaborate on these objectives and describe the approach used to accomplish the project.

Chapter Two: Methodology

2.1 Introduction

This section intends to outline the appropriateness of a SLR to answer the project question. This section incorporates an explicit discussion of the search strategy with different resources, critical evaluation of literature, data analysis, and ethical considerations.

2.2 The Nature of a Literature Review

A literature review presents a logically argued case supported by a comprehensive understanding of the extensive knowledge of the subject, to establish a convincing thesis to answer the study's question (Machi & McEvoy, 2016). A literature review can array from a quick search to a systematic review (Hart, 2004). This project is based on a systematic review approach. According to the Cochrane Handbook, the critical components of SLR’s are as follows:

- Objectives with pre-defined eligibility criteria for choosing studies;
- Reproducible methodology;
- Systematic search to identify eligible studies;
- Assessment of the validity of the selected studies, such as potential bias;
- Systematic presentation and synthesis of the findings (Higgins & Green, 2011).

2.3 Research Design

When undertaking a project, it is necessary to utilise the most appropriate research design to answer the project question. The diverse research strategies are outlined below, along with the reasoning behind choosing a SLR.

2.3.1 Alternative Project Methods

Clinical Audit

Starey (2001) defined clinical audit as

"A review of clinical performance, the refining of clinical practice as a result and the measurement of performance against agreed standards" (p.3).

There are currently no national standards for imaging psychoses; therefore, an audit would not be possible to answer this project question.

Research Project

A research project aims to answer questions through scientific procedures and primary research. Scientific methods can either be quantitative or qualitative research (Davies & Hughes, 2014). Bell and Waters (2014) describe quantitative research as collecting facts and studying the relationship between these facts. It utilises a conceptual framework using numerical data and predetermined research questions, which lead to a generalised conclusion. Whereas qualitative research is more interested in the author’s own findings. Typically, this study begins with general research questions using ‘non-numerical and unstructured data.' It was felt that the most effective way to undertake this project was not carrying out one study. Instead, it would be more beneficial to incorporate various aspects of previous research to execute this project.

2.4 Rationale for Systematic Literature Review

SLRs are becoming increasingly vital in healthcare, with clinicians use SLRs to stay updated within their field. Reviews are applied as a starting point for developing practice guidelines and are essential decision-making tools in primary healthcare. They unbiasedly analyse research, while recognising any gaps and distinguishing between beneficial or harmful interventions (Ganeshkumar & Gopalakrishnan, 2013). Within practice, there is a strong emphasis on evidence-based healthcare (Gray, 2009). Therefore, appropriate methods should be taken to ensure that an imaging-based nosology is the best approach for psychosis patients.

Undertaking a SLR achieves this project's objectives as it guarantees extensive, unbiased evidence to comprehensively evaluate all parts of the project question. Before conducting a SLR, it is crucial to develop a search strategy. To accomplish this, three tasks must be carried out;

1. Select literature
2. Search literature
3. Refine topic

Refining is crucial, and perhaps the most essential stage when conducting a search. Refining ascertains the relevant information from appropriate sources and utilises the best available evidence in that area (Machi & McEvoy, 2016).

2.5 Sources of Information

In ensuring that the SLR was as comprehensive as possible, the information gathered was from a multitude of sources.

Books

Books are a useful secondary resource. However, they quickly become outdated; therefore, they were not an appropriate source of evidence for this nascent topic.

Databases

The focus here was utilising online databases to find information to support clinical decision making. The University of Portsmouth database was searched as it incorporates various medical databases such as ScienceDirect and MEDLINE. Bergeron (2003) recommended valuable and user-friendly databases with academic references. With these recommendations, PubMed database was independently searched. These databases provided abstracts, allowing the relevance of the articles to be evaluated for inclusion.

Journals

A strong endeavor was made to incorporate peer-reviewed journals to ensure each article had been reviewed by experts prior to publication, producing evidence-based materials. The peer-reviewed journals used included The British Medical Journal and The Lancet.

2.6 Search Strategy

The following stage develops a refined list of search terms based on the project question, ensuring that sufficient information was researched using an appropriate, unbiased search strategy.

2.6.1 Search Technique

To identify the most relevant literature, the search was refined to the preliminary topic as best as possible. The most commonly used search refinement technique is Boolean Logic. A Boolean search was applied in this search as it uses keywords associated by logical operators to define the database search (displayed in Table 1).

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Table 1: Boolean logical operators and their role in search techniques.

A wildcard search was also utilised to find singular and plural forms of words and variant endings, for instance psychos#s found searches for both the singular (psychosis) and plural (psychoses) of the search term. Acronyms and synonyms were additionally used. These techniques frame the search to expand the research in question to include similar ideas that may provide valuable material to the project (Machi & McEvoy, 2016). Combining these methods ensures the inclusion of all relevant literature, reducing bias.

2.6.2 Search Terms

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Table 2: Key search terms and Boolean logic operators used in the literature search.

2.6.3 Search Criteria

Subsequently searching the preliminary topic, the literature was evaluated for pertinency using the inclusion and exclusion criteria shown in Table 3. An inclusion and exclusion criteria enable the author to identify literature that addresses the research question, thereby, focussing the search.

Due to the nascent field of Psychoradiology, literature published before 2008 was not included as it was considered outdated. Only research published in the English language was reviewed. The Cochrane Handbook does not recommend this as it may introduce bias (Higgins and Green, 2008); however, due to the financial and time limitations of this project, it was not feasible to translate articles. Furthermore, peer-reviewed articles were exclusively used. Peer-review is the process in which experts in the same field scrutinise the scientific work of an author. This review acts as a filter, ensuring that only high-quality research is published by determining the study’s’ significance, validity, and originality (Kelly, Sadeghieh & Adeli, 2014). Furthermore, reference lists of the studies found were screened to identify additional articles.

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Table 3: Inclusion and exclusion search criteria used.

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Figure 1: The flow of information through the different phases used in this review. It organised the number of articles identified and eligible following the search criteria (adapted from Moher et al., 2009).

2.7 Critical Evaluation of Literature

The CASP tool in Appendix A was deemed the most appropriate for the literature found as it critically evaluates diagnostic studies, which this project used.

2.7.1 Bias

Bias is any tendency that inhibits unprejudiced deliberation of a question (Pannucci & Wilkins (2010). SLR combine and synthesise studies that meet pre-specified eligibility criteria using methods that intend to minimise bias. Publication and selection bias are both common in SLR. It is easier to find studies with a positive outcome which could be eliminated by summarising the review findings in the author's point of view and form an overall opinion of the result, limiting publication bias (Ganeshkumar and Gopalakrishnan, 2013). Selection bias may also pose a challenge in SLR. The Cochrane Handbook advises that one database search is considered inadequate (Higgins and Green, 2011). Using multiple databases is pivotal for ensuring that as many relevant studies as possible are identified to minimise selection bias.

2.7.2 Validity and Reliability

Fundamentally, the quality of a SLR is based on the validity and reliability of the methods used to conduct the study. The inclusion of solely peer-reviewed literature ensured the author had more confidence in the validity and reliability of the articles used, as experts have evaluated them prior to publication.

Aveyard (2014) referred to validity as to whether an investigation is capable of measuring what it intends to. To ensure validity, clear objectives were defined at the beginning and were consistent throughout the project. Additionally, each article included underwent a critical appraisal which was applied using the criteria in Appendix A. Critical appraisal is the process by which individual studies are assessed for validity. Systematic review guidance puts a strong emphasis on critically appraising research studies (Bilotta et al. 2014).

Reliability is whether the study is replicable with the same measurements (Aveyard, 2014). The study’s reliability is whether the study appears to be representative of the population. If findings have been replicated using different studies, this indicates transferable and reliable results (McLeod, 2007).

2.8 Data Extraction and Analysis

This SLR collected information from the articles related to the project topic. Due to diverse methodologies in the chosen studies, a statistical analysis of the findings was not considered to be appropriate. The data was extracted from selected articles, and a summary of each article was presented in a data extraction table, which is displayed in Appendix B. The table was structured to collect information such as the aims, population samples, findings, and limitations. Following the completion of the extracted data, it was easier to analyse and compare each study. On interpreting the data analysis, it was determined that it would be categorised into appropriate themes, enabling the results to be analysed under similar topics. Following the systematic data extraction and analysis, the information was synthesised, and the hypothesis was put into test based on the interpretation of the included articles.

2.9 Ethical Consideration

As SLRs research literature that is already in the public domain, there was no need to obtain ethical approval for this project. Nonetheless, plagiarism is an ethical concern for SLRs. Wager and Wiffin (2011) defined plagiarism as using someone else's original work without permission or acknowledgement and claiming it as your own. As SLRs require evidence from previous research, the distinction between citation and plagiarism may become blurred. To avoid this, the author described the evidence applicable for this project in their own words, which was accomplished using appropriate citations, or quotation marks if using direct information from the research. All citations and direct quotes have been referenced using the requested American Psychological Association, Sixth Edition.

2.10 Summary

This chapter addressed the approach used to conduct the appropriate project search, and the rationale behind its selection. It details the methods used to gather and analyse the literature to ensure validity and reliability was maintained throughout. The following chapter will critically appraise the literature found. It aims to compare and contrast the relevant information found to answer the project question.

Chapter Three: Literature Review

3.1 Introduction

Chapter three will critically appraise the literature gathered and synthesised in chapter two. This will be accomplished by employing the previously mentioned CASP tool (in Appendix A). There were eleven articles considered following the inclusion criteria; one meta-analysis, one cohort study, two Randomised Control Studies (RCT), three longitudinal studies, and four cross-sectional studies. It became apparent during the critical review to divide these articles into two key themes: structural and functional brain changes.

3.2 Structural Brain Changes

The articles below consist of an array of structural abnormalities which could be employed as biomarkers for psychoses.

3.2.1 Falkenberg et al. (2017)

Falkenberg et al. (2017) assessed the clinical significance of using sMRI as part of the initial clinical assessment of patients with First-Episode Psychosis (FEP). This was assessed in a RCT comprised of participants without an organic aetiology, between the expansive age ranges of 16-64, yet, was limited to South London. This area restriction may inhibit the representation to a larger geographic. The study consisted of a clinical sample (n=241) with 66 Health Controls (HC), and a research sample (n=108) with 98 HC.

The most clinically relevant findings were cysts, lesions, and defects to the ventricles and white matter (WM), which were relatively common in FEP patients. 15% of the clinical sample and 6% of the research sample displayed these abnormalities. However, these abnormalities were also evident in 5.5% of HC; thus, it is unknown whether findings are indicative of psychosis. Patients in the clinical sample had a higher proportion of defects in comparison to the research sample. A possible explanation for these differences might be that the clinical samples were scanned using a 3-Tesla (T) MRI scanner, while the research samples were examined using a 1.5-T scanner. The higher-field strength scanner (3-T) may influence the detection of more subtle abnormalities. It is also plausible that the rates of abnormal findings were reduced by the exclusion of patients with organic aetiology, patients who were too unwell, or patients being treated without consent.

Although radiological abnormalities were a common discovery in both FEP samples, most were incidental findings and did not entail a change in clinical management. Despite these results not affecting patient management, Falkenberg (2017) emphasised that the consequences of neglecting to exclude such disorders when young may be so grave that it is beneficial to screen everyone, suggesting the inclusion of sMRI in the initial clinical assessment of FEP.

3.2.2 Schnack et al. (2014)

This cross-sectional study used a computation brain analysis produced by a Symptom Vector Machine (SVM). These algorithms were used to assort schizophrenia from BD patients, and additionally, differentiating both disorders from HC based on their Grey Matter (GM) densities. The first sample comprised of patients with schizophrenia (n=66), BD (n=66), and HC (n=66). The cohort was diagnosed against DSM criteria and later used to develop a classification model for each condition. These models generated vectors to distinguish schizophrenia from BD; schizophrenia from HC; and BD from HC. The second sample consisted of 47 schizophrenic patients, 46 BD patients, and 43 HC, likewise, diagnosed against the DSM criteria and scanned using the aforementioned vectors. In using a constant method, findings should be more consistent and reliable. The findings indicate that schizophrenia patients could be distinguished from HC with 90% accuracy. Schizophrenia patients could be separated from BD patients with 88% accuracy. The classification model delineating of BD patients from HC was less precise, only correctly classifying 67% of HC and 53% of BD patients.

This study is subjected to several limitations. Firstly, the modest sample size consequently means that findings may not be extrapolated to all psychoses patients. Secondly, all but one of the schizophrenic patients were receiving antipsychotic medication. The study excluded the striatum in the models as previous research found by the authors ratifies that antipsychotics influence the volume of this area.

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