Schizophrenia Spectrum and Other Psychotic Disorders PDF

Chapter 12 Schizophrenia Spectrum and Other Psychotic Disorders Matilda Azis, Ivanka Ristanovic, Andrea Pelletier-­Baldelli, Hanan Trotman, Lisa Kestler,...

Chapter 12 Schizophrenia Spectrum and Other Psychotic Disorders Matilda Azis, Ivanka Ristanovic, Andrea Pelletier-­Baldelli, Hanan Trotman, Lisa Kestler, Annie Bollini, and Vijay A. Mittal Chapter contents History and Phenomenology 248 Conceptions and Classification of Psychosis 249 The Origins of Schizophrenia 255 Onset, Course, and Prognosis 259 Evidence-­Based Interventions 264 Summary268 References269 Copyright © 2019. Taylor & Francis Group. All rights reserved. Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  248 | Matilda Azis et al. Schizophrenia is among the most debilitating of mental illnesses. It is typically diagnosed between 20 and 25 years of age, a stage of life when most people gain independence from parents, develop relationships, plan educational pursuits, and begin work or career endeavors (De Lisi, 1992). Because the clinical onset usually occurs during this pivotal time, the illness can have a profound negative impact on the individual’s opportunities for attaining social and occupational success, and the consequences can be devas- tating for the patient’s life course, as well as for family members (Addington & Addington, 2005). Further, the illness knows no national boundaries. Across cultures, estimates of the lifetime prevalence of schizophrenia range around 1% (Arajarvi et al., 2005; Jongsma et al., 2018; Keith, Regier, & Rae, 1991; Kulhara & Chakrabarti, 2001; Torrey, 1987), although there is some research indi- cating that the rate may be as low as 0.4% with more stringent measurement criteria (Saha, Chant, Welham, & McGrath, 2005). Studies also suggest that the prognosis may differ among countries, with better outcomes in developing nations (Kulhara & Chakra- barti, 2001), and there is strong evidence to suggest a link between migration and increased risk (Cantor-­Graae & Selten, 2005). However, more recent evidence suggests that variation in prognosis may not be that straightforward as there appear to be differences within individual developing nations in course of illness, as well as discrepancies in measurement and access to care (Snowden & Yamada, 2005). Access to treatment may be associated with better outcome across countries (Cohen, Patel, Thara, & Gureje, 2008; Jorm, Patten, Brugha, & Mojtabai, 2017). The origins of schizophrenia have continued to elude researchers, despite many decades of scientific research. To date, no single factor has been found to characterize all patients with the illness. This holds for potential etiological factors, as well as clinical phe- nomena. Patients with schizophrenia vary in symptom profiles, developmental histories, family backgrounds, cognitive function, and even brain morphology and neurochemistry. Although this has led some to express dismay at the chances of ever finding the cause of schizophrenia, research efforts have succeeded in revealing numerous pieces of what is now recognized as a complex puzzle of etiological processes. Based on findings from various lines of research, the consensus in the field is that: 1. Schizophrenia is a brain disease 2. Its etiology involves the interplay between genetic and environmental factors 3. Multiple developmental pathways eventually lead to disease onset 4. Brain maturational processes play a role in the etiological process. In this chapter, we provide an overview of the current state of our knowledge about schizophrenia. We begin with a discussion of history and phenomenology of the disorder, and then proceed to a description of some of the key findings which have shed light on the risk factors, the development and the progression of this illness, and finally to a discussion of evidence-­ based interventions. History and Phenomenology Written descriptions of patients experiencing psychotic symptoms (i.e., symptoms indicative of an inability to discern what is reality), similar to those of what we now call schizophrenia, have been recorded since antiquity. However, because psychotic symp- toms can be a manifestation of a variety of disorders, it is unclear whether schizophrenia, as we view it today, is an ancient or a relatively new phenomenon. In the mid-­to late-­19th century, European psychiatrists were investigating the etiology, classification, and prognoses of various types of psychosis. The term psychosis refers broadly to the presence of psychotic symptoms and may include various diagnoses such as schizophrenia-­related diagnoses, together with mood disorders with psychotic features. At that time, the most common cause of psychosis was tertiary syphilis, although researchers were unaware that there was any link between psycho- sis and syphilis (Kohler & Johnson, 2005). The psychological symptoms of tertiary syphilis frequently overlap with symptoms of what we now call schizophrenia. The cause of syphilis was eventually traced to an infection with the spirochete, Treponema pal- lidum, and antibiotics were found to be effective for prevention and treatment of the disorder. This important discovery served to Copyright © 2019. Taylor & Francis Group. All rights reserved. illustrate how a psychological syndrome can be produced by an infectious agent. It also sensitized researchers to the fact that similar syndromes might be the result of different causes. Emil Kraepelin (1856–1926), the medical director of the famous Heidelberg Clinic, was the first to differentiate schizophrenia, which he referred to as dementia praecox (or dementia of the young) from manic-­depressive psychosis (Kraepelin, 1913). He also lumped together “hebephrenia,” “paranoia,” and “catatonia” (previously thought to be distinct disorders) and classified all of them as variants of dementia praecox. He based this classification on their similarities in age of onset and the clinical feature of poor prognosis. Kraepelin did not believe that any one symptom was diagnostic of dementia praecox, but instead focused on the total clinical picture and changes in symptoms over time. If a psychotic patient deteriorated over an extended period of time (months/­ years), the condition was assumed to be dementia praecox. Many contemporary mental health professionals continue to expect negative outcomes in those afflicted with schizophrenia, and this expectation infuses the mental health profession with an unfortunate sense of therapeutic nihilism. Yet, while it is true that the majority of patients manifest a chronic course that entails lifelong disability, this bleak scenario is not inevitable (Carpenter & Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  Schizophrenia Spectrum and Other Psychotic Disorders | 249 Buchanan, 1994). The story of Dr. John Nash, professor and mathematician at Princeton, as told in the movie A Beautiful Mind, illus- trates this point: Dr. Nash was able to function at a very high level in his academic field, despite his struggle with schizophrenia. Conceptions and Classification of Psychosis Early Conceptions of Schizophrenia The term schizophrenia was introduced at the beginning of the 20th century by Eugen Bleuler (1857–1939), a Swiss psychiatrist and the medical director of a mental hospital in Zurich (Howells, 1991, pp. xii, 95). The word is derived from two Greek words: schizo, which means to tear or to split, and phren, which has several meanings: in ancient times, the word phren, meant “the intellect” or “the mind”; phren also referred to the lungs and the diaphragm, which were believed to be the seat of emotions. Thus, the word schizo- phrenia literally means the splitting or tearing of the mind and emotional stability of the patient. Bleuler classified the symptoms of schizophrenia into fundamental and accessory symptoms. The fundamental symptoms of schizophrenia are often reported in textbooks as the four As, although, in fact, there are five As and one D (Bleuler, 1950). These fundamental symptoms are listed in Box 12.1. According to Bleuler, these symptoms are present in all patients, at all stages of the illness and are diagnostic of schizophrenia. Box 12.1 Bleuler’s Fundamental Symptoms of Schizophrenia Disturbances of association (loose, illogical thought processes). Disturbances of affect (indifference, apathy, or inappropriateness). Ambivalence (conflicting thoughts, emotions, or impulses which are present simultaneously or in rapid succession). Autism (detachment from social life with inner preoccupation). Abulia (lack of drive or motivation). Dementia (irreversible change in personality). Bleuler’s “accessory symptoms” of schizophrenia included delusions, hallucinations, movement disturbances, somatic symp- toms, and manic and melancholic states. In contrast to fundamental symptoms, he believed that these accessory symptoms were not present in all patients with schizophrenia and often occurred in other illnesses. For these reasons, he assumed that the accessory symptoms were not as diagnostic of schizophrenia. Further refinements in the diagnostic criteria for schizophrenia were proposed by Kurt Schneider (1959) in the mid-­1900s. Like Bleuler, Kurt Schneider thought that certain “key” symptoms were diagnostic of schizophrenia. In his classification, he referred to these diagnostic symptoms as “first rank symptoms” (see Box 12.2). He believed that, after medical causes of psychosis were ruled out, one could make the diagnosis of schizophrenia if one or more first rank symptoms were present. Schneider’s descriptions of the symptoms were more detailed and specific than were Bleuler’s fundamental symptoms. Subsequent diagnostic criteria for schizophrenia have been heavily influenced by Schneider’s approach (Nordgaard, Arnfred, Handest, & Parnas, 2008). Box 12.2 The Schneiderian “First Rank Symptoms” Thought echoing or audible thoughts (the patient hears his thoughts out loud). Copyright © 2019. Taylor & Francis Group. All rights reserved. Thought broadcasting (patient believes that others can hear his thoughts out loud). Thought intrusion (patient feels that some of his thoughts are from outside; that is, not originating in his own mind). Thought withdrawal (patient believes that the cause of having lost track of a thought is that someone is taking his thoughts away). Somatic hallucinations (unusual, unexplained sensations in one’s body). Passivity feelings (patient believes that his thoughts, feelings, or actions are controlled by another or others). Delusional perception (a sudden, fixed, false belief about a particular everyday occurrence or perception. Following longitudinal research in the 1960s, German researcher Gerd Huber laid out a list of symptoms that were evident (through retrospective study) in the early course of illness as well as in the later stages of psychosis (Huber, Gross, Shuttler, & Linz, 1980). These symptoms are termed “basic symptoms” and generally refer to symptoms reported by the patient himself and include impairment in cognition, perception, motor function, will, initiative, level of energy, and tolerance of stress (Olson & Rosenbaum, 2006). Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  250 | Matilda Azis et al. Moving Towards a Modern Conception of Schizophrenia During the middle of the 20th century, different diagnostic criteria for schizophrenia became popular in different parts of the world. The “Kraepelinian” tradition, with its longitudinal requirements for diagnosis, identified patients with poorer long-­term prognosis. In contrast, the Bleulerian and Schneiderian diagnostic systems allowed for a wider range of psychotic patients to be diagnosed with schizophrenia. Thus, the patients diagnosed with these two systems tended to have a better prognosis than those diagnosed in the more stringent Kraepelinian tradition. Because of these discrepancies, the use of multiple diagnostic systems had a detrimental effect on research progress; research findings from countries using different diagnostic criteria were not comparable, thus limiting the generalizability of the results. The next generation of diagnostic systems evolved with the intent of achieving uniformity in diagnostic criteria and improving diagnostic reliability. Among these were the “Feighner” or “St. Louis” diagnostic criteria (Feighner, Robins, & Guze, 1972), and the Research Diagnostic Criteria developed by Robert Spitzer and his colleagues (Spitzer, Endicott, & Robins, 1978). These two approaches to the diagnosis of schizophrenia strongly influenced modern-­day diagnostic systems. Updating Our Conceptions of Schizophrenia While investigators have continued to focus on positive symptoms (excess of ideas, sensory experiences or behavior) such as hal- lucinations, delusions, and bizarre behaviors, recently there has also been a renewed Bleulerian approach to core phenomenology, including negative symptomatology, social processing dysfunction, and cognitive deficits. Negative Symptoms While most of the first-­rank symptoms described by Schneider are also considered to be positive symptoms, negative symptoms, in contrast, involve a decrease in behavior, such as blunted or flat affect and lack of motivation. A wide range of negative symptoms such as anhedonia (lack of enjoyment), avolition (lack of volition), emotional withdrawal, social isolation, apathy (lack of interest), and deterioration in role functioning are frequently reported in patients with schizophrenia (Bobes, Arango, Garcia-­Garcia, & Rejas, 2010). Negative symptoms typically emerge several years prior to the onset of a psychotic disorder – in the prodromal phase. This phase is characterized by attenuated symptoms: mild, less severe, or less frequent psychotic-­like symptoms. Negative symptoms typ- ically emerge before positive symptoms in this phase (Schmidt et al., 2017), they are associated with poor functional outcome (Milev, Ho, Arndt, & Andreasen, 2005), they are highly debilitating to the patient, and they pose a substantial burden on the carers and families of patients with schizophrenia and health-­care systems. (Milev et al., 2005; Sicras-­Mainar, Maurino, Ruiz-­Beato, & Navarro-­Artieda, 2014). Compounding the importance of these symptoms, several studies have found that they are persistent (Haro et al., 2018), associated with relapse (Bowtell, Ratheesh, McGorry, Killackey, & O’Donoghue, 2017), and associated with cognitive decline (Sum, Tay, Sengupta, & Sim, 2018). Due to these factors there has been a recent focus on the assessment and treatment of negative symptoms in schizophrenia. A recent meta-­analysis found few interventions focused on these symptoms, and most treatments were not clinically meaningful (Fusar-­Poli et al., 2015). Therefore, such symptoms can result in a dramatic reduction in quality of life. A further route of exploration in this area has been to examine the concept of negative symptoms, how they can be defined, and whether all symptoms fall under one category, or whether there are several different distinct constructs included under the umbrella term of negative symptoms. A consensus has been reached to incorporate five domains of negative symptoms: blunted affect, alogia, asociality, anhedonia, and avolition (Kirkpatrick, Fenton, Carpenter Jr., & Marder, 2006), and several studies have confirmed the presence of two distinct dimensions within the five domains of negative symptoms: avolition–apathy and expressive deficit (Blanchard & Cohen, 2005; Strauss et al., 2013). This distinction may contribute to our understanding of the pathophysio- logical mechanisms underlying these symptoms and lead to new treatments for this debilitating facet of schizophrenia. Copyright © 2019. Taylor & Francis Group. All rights reserved. Social Processing Deficits Among the core features of schizophrenia are social processing deficits (Savla, Vella, Armstrong, Penn, & Twamley, 2013). Studies of social-­cognitive abilities in schizophrenia patients have consistently shown that they are impaired in their ability to comprehend and solve social problems, processing of emotions, social perception, attribution of events, and theory of mind (the ability to per- ceive the judgments, beliefs, intentions, and emotions of others; Green & Horan, 2010; Hooley, 2010; Meherwan Mehta et al., 2013; Penn, Corrigan, Bentall, Racenstein, & Newman, 1997; Tseng et al., 2015). These deficits also adversely affect functional outcome in patients (Javed & Charles, 2018). Social-­cognitive imaging studies consistently point to abnormalities in brain regions and circuitry associated with social processing, adding to the evidence that social-­cognitive impairment is a hallmark feature of schizophrenia (Fujiwara, Yassin, & Murai, 2015; Modinos et al., 2015). Deficits in social cognition may be partially due to limitations in more basic cognitive processes, such as memory and reasoning (Kring & Elis, 2013). However, basic cognitive impairments do not account completely for the more pervasive and persistent social-­ cognitive dysfunction observed in schizophrenia, and there is increasing evidence to support the idea that social cognition is a separate construct (Meherwan Mehta et al., 2013). For example, imaging studies show that there is something unique in brain Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  Schizophrenia Spectrum and Other Psychotic Disorders | 251 activation when an individual is involved in a social versus strictly cognitive task (Viviano et al., 2018), and other research finds that social cognitive and cognitive tasks often load on different domains when evaluated together using a statistical technique called factor analysis (Billeke & Aboitiz, 2013). One of the diagnostic criteria for schizophrenia is blunted or inappropriate affect. It is not surprising therefore, that patients show abnormalities in the expression of emotion in both their faces and verbal communications (Zou et al., 2018). These abnor- malities include less positive and more negative emotion, as well as emotional expressions that seem inconsistent with the social context (termed inappropriate affect; Brozgold et al., 1998; Tremeau et al., 2005). Further, patients with schizophrenia are less accurate than unaffected comparison subjects in their ability to label facial expressions of emotion, with a particular difficulty in labeling fear and sadness (Amminger et al., 2012; Bigelow et al., 2006; Penn et al., 2000, Martin, Baudouin, Tiberghien, & Franck, 2005, Walker, 1981). Numerous studies have examined the link between social-­cognitive impairments, such as emotional process- ing and social functioning, indicating a strong relationship between poor social-­cognitive ability and social difficulties (Moran, Culbreth, & Barch, 2018; Salva et al., 2013). Specifically, research indicates that social cognition may be more closely tied to func- tioning than other cognitive domains, suggesting that social cognition may be especially informative for understanding etiology and developing treatment (Fett et al., 2011; Silberstein, Pinkham, Penn, & Harvey, 2018). Patients with schizophrenia demonstrate deficits in motivation, decision-­making, and learning that suggest impairments in aspects of the reward system, the system responsible for generating a response to rewarding stimuli (Gold, Waltz, Prentice, Morris, & Heerey, 2008). This is strongly related to negative symptoms such as anhedonia and apathy (Simon et al., 2010); however, several studies have found no difference in self-­reported anhedonia and apathy between patients with schizophrenia and healthy controls (Taylor et al., 2012), and a review of the research found that motivational impairments may be associated with difficulty translating reward information into motivated behavior rather than a deficit in hedonic experience (Strauss, Waltz, & Gold, 2014). Cognitive Deficits Among the most well-­established aspects of schizophrenia are the cognitive impairments that accompany the illness (Nuechterlein, Ventura, Subotnik, & Bartzokis, 2014). Neurocognitive deficits are found in the premorbid phase (the phase before the emergence of symptoms, prior to the prodromal phase), in a substantial minority of youth who later develop schizophrenia, and these deficits typically worsen over disease course. The degree of cognitive impairment has also been found to be strongly related to social and role functioning in the illness (Seidman & Mirsky, 2017). Furthermore, research has shown that cognitive deficits persist during symptomatic remission (Hoff et al., 1999). In fact, some experts argued that cognitive impairment should have been added as a characteristic symptom in the DSM-­5 (Keefe & Fenton, 2007). The DSM-­5 Task Force decided against making this recommendation because of its lack of diagnostic specificity. Similar to negative symptoms, a consensus was reached by the National Institute of Mental Health’s (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, defining seven cognitive domains affected in schizophrenia: processing speed, attention/­vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition (Nuechterlein et al., 2008). Patients with schizophrenia manifest performance deficits on a broad range of cognitive tasks, from simple to complex (Elvevag & Goldberg, 2000; Keefe & Harvey, 2012), and a recent meta-­analysis examining the longitudinal prevalence of cognitive deficits over the disease course of schizophrenia found that deficits were present before the prodromal phase, supporting a neurodevelopmental model of cognitive decline (Bora & Murray, 2014). One of the most basic cognitive deficits present in the very earliest stages of the disease course is an impairment in visual information-­processing. Using a laboratory procedure called backward masking, researchers have shown that compared with both healthy individuals and psychiatric controls, patients with schizophrenia are slower in the initial processing of stimuli (Green, Nuech- terlein, Breitmeyer, & Mintz, 1999, 2006). Deficits also have been found in perceptual functioning. Individuals with schizophrenia tend not to be susceptible to optical illusions such as perceiving two-­dimensional objects in three-­dimensional form. This type of perceptual impairment can actually produce superior performance on certain tasks such as depth inversion illusions, in which concave faces appear as convex (Keane, Silverstein, Wang, & Papathomas, 2013). Of note, there is some evidence that nicotine is beneficial to Copyright © 2019. Taylor & Francis Group. All rights reserved. such cognitive impairments, and there is ongoing work evaluating its effectiveness in clinical trials (Gee et al., 2017; Kem et al., 2018). There is current debate as to whether the cognitive deficits present in schizophrenia are part of a single broad impairment (Dickinson, Goldberg, Gold, Elvevag, & Weinberger, 2011; Dickinson, Iannone, Wilk, & Gold, 2004), or whether the deficits are present in specific domains (Repovs, Csernansky, & Barch, 2011). Growing evidence supports the theory that both general and specific cognitive deficits are present (Fornito, Yoon, Zalesky, Bullmore, & Carter, 2011; Sheffield et al., 2014). Current Approaches to Classification The two diagnostic systems currently in use for schizophrenia and other mental disorders are the Diagnostic and Statistical Manual of Mental Disorders (DSM), used predominantly in the United States (American Psychiatric Association, 2013) and the International Statistical Clas- sification of Diseases and Related Health Problems (ICD) used predominantly in Europe (World Health Organization, 1992). Dimensional approaches such as the NIMH’s Research Domain Criteria (RDoC) are not diagnostic systems, but provide a framework for the integration of basic behavioral and neuroscience research with our current understanding of mental disorders (Insel et al., 2010). Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  252 | Matilda Azis et al. Diagnostic and Statistical Manual of Mental Disorders (DSM) The fifth edition of DSM was published in 2013. Schizophrenia is included with a group of disorders under the category of “Schiz- ophrenia Spectrum and Other Psychotic Disorders,” reflecting a dimensional understanding of psychosis (Johns & van Os, 2001; Barch et al., 2013); there are six criteria needed to meet the threshold for diagnosis (Table 12.1). DSM-­5 criterion A states that there must be two characteristic symptoms present from: 1. Hallucinations 2. Delusions 3. Disorganized speech (e.g., frequent derailment or incoherence) 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (i.e., affective flattening, alogia, or avolition). This is different from previous versions of the DSM, owing to the elimination of allowing for only one of these symptoms to be sufficient if it is bizarre in nature or if it is a Schneiderian first-­rank auditory hallucination (e.g., multiple voices conversing with Table 12.1 DSM-­5 Criteria for Schizophrenia Criterion Category Description A Characteristic Two (or more) of the following, each present for a significant portion of time during a 1-­month period symptoms (or less if successfully treated). At least one of these should include 1, 2, or 3. 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (i.e., diminished emotion expression or avolition) B Social/­occupational For a significant portion of the time since the onset of the disturbance, level of functioning in one dysfunction or more major areas, such as work, interpersonal relations, or self-­care, are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement). C Duration Continuous signs of the disturbance persist for at least 6 months. This 6-­month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-­phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or by two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences). D Schizoaffective Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out and mood disorder because either (1) no major depressive or manic episodes have occurred concurrently with the active exclusion phase symptoms; or (2) if mood episodes have occurred during active-­phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness. E Substance/­general The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medical condition medication) or another medical condition. exclusion Copyright © 2019. Taylor & Francis Group. All rights reserved. F Relationship to Global If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the Developmental Delay additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition or Autism Spectrum to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if Disorder successfully treated). Course specifiers 1. First episode, currently in acute episode 2. First episode, currently in partial remission 3. First episode, currently in full remission 4. Multiple episodes, currently in acute episode 5. Multiple episodes, currently in partial remission 6. Multiple episodes, currently in full remission 7. Continuous 8. Unspecified Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  Schizophrenia Spectrum and Other Psychotic Disorders | 253 each other) (Tandon et al., 2013). The reason for the change relates to a general consensus in the field that there was poor empirical evidence to support the prior stipulation. Criterion B emphasizes that, in addition to the presence of characteristic symptoms, there must be significant social/­occupational dysfunction. Schizophrenia can be diagnosed with DSM-­5 when these signs and symptoms of the disorder are present for six months (including prodromal and residual phases – the phases preceding and following the psychotic disorder) (Criterion C). Further, significant mood disorders, such as depression or mania, along with schizoaffective disorder must be ruled out to ensure that the symptoms present are not better accounted for by one of these diagnoses (Criterion D). Also, general medical conditions or sub- stance use that might lead to psychotic symptoms must be ruled out (Criterion E). Finally, Criterion F stipulates that if a pervasive developmental disorder (PDD) or autistic disorder or other communication disorder of childhood onset is present, schizophrenia could only be diagnosed if prominent delusions or hallucinations were present for at least one month or less if successfully treated (Dyck, Piek, & Patrick, 2011; Tandon et al., 2013). A dimensional rating of severity of core symptoms is included in Section III, a section of the manual that includes tools to enhance diagnosis. The schizophrenia workgroup had strongly recommended including this dimensional approach in the primary text section but this decision was overturned at the last minute because the American Psychiatric Association (APA) was concerned that this would hamper communication between providers and insurance companies (Barch et al., 2013). Despite this, the inclusion of this new dimensional approach in DSM-­5 highlights the heterogeneous presentation of schizophrenia and, in theory, negates the necessity of subtypes while providing the possibility for increased diagnostic description for more effective communication between providers (Pagsberg, 2013). There are eight course specifiers for schizophrenia in DSM-­5 that define the acute and longitudinal nature of the illness. These specifiers indicate whether the episode being assessed is the first episode or one of multiple episodes, along with coding whether the episode is active (currently in acute episode) or in full or partial remission. Finally, there are two course specifiers that allow for some ambiguity through labeling the episodes as continuous (i.e., the episodes are too continuous to determine a specific course of symptoms) and unspecified (i.e., the information needed to clarify course of symptoms is lacking). The main purpose of these changes was to reduce comorbidity and the incidence of the “not otherwise specified” diagnoses as well as to improve diagnostic communication between healthcare providers. It remains to be seen whether comorbidity and diagnostic ambiguity will lessen and communication improve through these changes; however, the specifiers do appear to add some specificity to course of illness description that was absent in previous diagnostic manuals (Tandon et al., 2013). In Section III of DSM-­5, “Emerging Measures and Models,” attenuated psychosis syndrome (APS) has been included, which was not included in previous editions. This category identifies individuals who do not meet full criteria for schizophrenia, but who exhibit attenuated (less intense or severe) characteristic symptoms and intact reality testing. These individuals are at heightened risk of developing a psychosis spectrum disorder. The decision to include the new diagnosis accompanied a fierce debate in the period leading up to publication. Although expert consensus for the diagnosis is still evolving, the impetus for including APS in DSM-­5 arose from accumulating evidence that high-­r isk patients are currently ill and at elevated risk for more serious mental illness (Cannon et al., 2008), the criteria for a risk state can be made with reliability and validity (in a research setting), and no DSM-­IV diagnosis accurately captured the current illness/­future risk (Addington et al., 2007; Yung et al., 2007). The proponents argued that providing a DSM-­5 diagnosis could minimize potential harm to patients and families and could improve general provider education (Woods et al., 2010). Those who argued against the new label suggested that inclusion was premature because of a lack of information from community-­based trials and significant concern about stigma (Shrivastava et al., 2011). Opponents also questioned the clinical validity of the syndrome because APS is predictive of a number of disorders outside schizophrenia (e.g., affective psychoses) and therefore, the label is in a non-­specific initial stage. These critics also noted that because a primary focus relates to risk for future illness, a high rate of false positives (i.e., those who do not transition to psy- chosis) is ethically problematic as it exposes a disproportionate number of youth to unnecessary medications and stigma (Cor- coran, First, & Cornblatt, 2010). The ultimate decision to place APS in the research section of DSM-­5 speaks to the valid points on both sides of this debate, and to the complex and delicate issues accompanying the diagnosis. A recent study exploring the stigma of using terms such as APS and Clinical High Risk for Psychosis (CHR) found that patients at risk of psychosis may expe- Copyright © 2019. Taylor & Francis Group. All rights reserved. rience less stigma related to labels than expected by professionals, and those more likely to experience stigma were those who have had previous stigmatizing experiences such as a family history of psychosis and those who had transitioned to psychosis (Kim et al., 2017). However, there is still ongoing debate as to the use of this label with previous proponents van Os and Gulok- suz arguing that in using such terms we may be applying “misleadingly simple, unnecessary and inefficient binary concepts of ‘risk’ ” (van Os & Guloksuz, 2017). Several other diagnoses under the ‘schizophrenia spectrum and other psychotic disorders’ group are worth noting. The first is schizotypal personality disorder (SPD), which now falls both under this grouping, as well as under personality disorders. The diagnostic criteria for SPD includes social anxiety or withdrawal, affective abnormalities, eccentric behavior, unusual ideas (e.g., persistent belief in extrasensory perception/­phenomena, aliens), and unusual sensory experiences (e.g., repeated experiences with confusing noises with peoples’ voices, or seeing objects move). Although the individual’s unusual ideas and perceptions are not severe or persistent enough to meet criteria for delusions or hallucinations, they are recurring and atypical of the person’s cultural context. An extensive body of research demonstrates genetic and developmental links between schizophrenia and SPD. The genetic link between SPD and schizophrenia has been documented in twin and family history studies (Barrantes-­Vidal Grant & Kwapil, 2015; Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  254 | Matilda Azis et al. Ettinger et al., 2014; Kendler, Neale, & Walsh, 1995; Raine & Mednick, 1995). The developmental transition from schizotypal signs to schizophrenia in young adulthood has been followed in several more recent longitudinal studies, with researchers reporting that 20–40% of schizotypal youth eventually develop a schizophrenia spectrum disorder (Cannon et al., 2008; Miller et al., 2002; Yung et al., 1998). The inclusion of schizotypal personality disorder in this grouping again illustrates the shift towards conceptualization of psychosis on a dimensional continuum. An additional category, schizophreniform disorder, is for individuals whose symptoms do not meet the six-­month criterion. This diagnosis is frequently made as a prelude to the diagnosis of schizophrenia when the patient presents for treatment early in the course of the disorder. Some individuals who fall into this category, however, will recover completely and not suffer further episodes of psychosis. It is important to emphasize that, despite advances in diagnosis, the diagnostic boundaries of schizophrenia are still quite unclear (Wolff, 1991). Moreover, the boundaries between schizophrenia and mood disorders are sometimes obscure. Many indi- viduals who meet criteria for schizophrenia show marked signs of depression or manic tendencies. These symptoms are sometimes present before the onset of schizophrenia, and frequently occur in combination with marked psychotic symptoms. As a result, the DSM-­5 includes a diagnostic category called schizoaffective disorder. This disorder can be conceived of as a hybrid between the mood disorders (bipolar disorder or major depression with psychotic features) and schizophrenia. The two subtypes of schizoaffective disorder are the depressive subtype (i.e., if the mood disturbance includes only depressive episodes) and the bipolar subtype (i.e., where the symptoms of the disorder have included either a manic or a mixed episode). The prognosis for patients with schizoaffective disorder is, on average, somewhere between that of schizophrenia and the mood disorders. International Statistical Classification of Diseases and Related Health Problems (ICD) The ICD, currently undergoing revision for its 11th edition (released in 2019) is a second diagnostic system used alongside DSM. The ICD classification system is focused on clinical use and is therefore designed to be practical, clear, and concise for clinical decision-­making. In order to ensure the simple practical implementation of the system, two phases of field-­testing were used for ICD-­11, firstly in case-­controlled field studies, mental health professionals were presented with cases for diagnosis (Keeley et al., 2016) to determine reliability; and secondly in a naturalistic setting to determine usability (Keeley & Gaebel, 2018). Previously (in ICD-­10, World Health Organization [WHO], 1992) individuals with schizophrenia were categorized into one of a set of discrete subtypes. The subtypes each represented a prototypic combination of schizophrenia symptoms, however critics have argued that these subtypes are not of diagnostic value. The list is not exhaustive and some individuals may not fit in to a specific subtype, while individuals’ symptomatic presentation may change over time therefore changing the subtype for which they meet criteria, and furthermore the subtypes have not been found to have distinct course and prognosis (Braff, Ryan, Rissling, & Carpenter, 2013). Similarly to DSM-­5, ICD-­11 has moved away from a categorical approach to a more dimensional approach, describing the pres- ence or absence of clinical symptoms and the relative severity of specific symptoms (Gaebel, 2012; Gaebel, Zielasek, & Cleveland, 2012). The scale includes six domains: Positive Symptoms, Negative Symptoms, Depressive Symptoms, Manic Symptoms, Psycho- motor Symptoms, and Cognitive Symptoms. A course specifier, similar to DSM-­5, is also included. Again, similarly to DSM, APS will not be included in the main diagnostic categories, but in the “Mental Health States Requiring Further Study” section. The organizers behind DSM and ICD (APA and WHO, respectively) have worked together to create harmonious systems in more recent editions; however, there are differences between the two publications. Whereas the ICD is aimed at practical implementation by a wide range of professionals, DSM is mainly targeted at mental health specialists, and includes more detailed descriptions, rec- ommendations, and assessments. This is evident in schizoaffective disorder: there is no longitudinal criteria in ICD-­11 so as to simplify the diagnostic process, whereas DSM-­5 maintains the longitudinal approach, making a time-­consuming history taking necessary (Biedermann & Fleischhacker, 2016). Dimensional Approaches Copyright © 2019. Taylor & Francis Group. All rights reserved. A dimensional approach argues that a categorical approach such as that used in the DSM and ICD, where diagnosis is determined on the basis of symptoms and characteristics typical of a disorder into discrete and distinct disorders, does not accurately represent clinical presentation. Such a categorical approach does not take into account that significant overlap may exist between different diagnostic categories, while imposing categories on dimensional phenomena may lead to a simplistic picture, missing valuable clinical information due to the need to achieve diagnostic reliability (Brown & Barlow, 2009). Several dimensional approaches have been proposed: 1. Research Domain Criteria (RDoC): In 2009, the NIMH (one of the primary funding sources for research on schizophrenia) created a working group to set in motion efforts to develop new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures. This allows for a new approach to research aimed at cutting across diagnostic labels to create improved classification of mental disorders through understanding underlying dimensions of functioning. This approach, views schizophrenia not as a specific disease, but rather as a syndrome that is composed of several symptom dimensions and represents one segment of a broad spectrum of serious mental illness (Morris, Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  Schizophrenia Spectrum and Other Psychotic Disorders | 255 Vaidyanathan, & Cuthbert, 2016). Further, a focus of this initiative is to integrate multiple levels of analysis including genes, behavior, and neurobiology with the hope of translating basic research into improved understanding of psychopathology and better targeted treatment (Insel et al., 2010). 2. The Hierarchical Taxonomy Of Psychopathology (HiTOP): This is another empirically driven classification system based on advances in quantitative research on the organization of psychopathology. Mental health is defined as a spectrum from normal- ity to pathology with no arbitrary cut off for diagnosis. In accordance with recent empirical evidence, HiTOP also does not categorize risk factors for diagnosis, but rather identifies risk profiles for certain symptomatic presentations. HiTOP posits that psychopathology is hierarchically structured: level 1 – symptoms/­signs; nested within level 2 – syndromes/­traits; nested within level 3 – factors; nested within level 4 – broad spectra (Kotov et al., 2017). While RDoC is aimed at examining genetic and neurobiological factors contributing to symptomatology, HiTOP focuses on the structure of the symptoms themselves, to provide an empirical organization of psychopathology (Hengartner & Lehmann, 2017). Similarly to RDoC, this allows us to think of schizophrenia as several symptom dimensions graded on a continuum. 3. Systems Neuroscience of Psychosis (SyNoPsis): This is a conceptual framework specifically for schizophrenia and defining it as a disorder of interindividual communication. This is done in order to disentangle the clinical manifestations of schizophrenia into behavioral domains and the underlying neurobiological systems. It includes an operational clinical rating scale and defines psychotic symptoms according to three dimensions: language, affectivity, and motor behavior (Strik, 2017). It includes an assessment scale strongly rooted in theory (the Bern Psychopathology Scale) and aims to guide theoretically informed research while directly informing intervention development (Mittal, 2017). While DSM-­5 and ICD-­10 are purely diagnostic tools, the dimensional approaches described above provide an alternate framework for research and have the potential to redefine mental disorders in future versions of the DSM and ICD. This approach is already being adopted, as has been evidenced by the shift towards incorporating a dimensional approach in both DSM-­5 and ICD-­11. The Origins of Schizophrenia Kraepelin, Bleuler, and other early writers on schizophrenia did not offer specific theories about the origins of schizophrenia. They did suggest, however, that there might be a biological basis for at least some cases of the illness. Likewise, contemporary ideas about the origins of schizophrenia focus on biological vulnerabilities that are assumed to be present in early development. Researchers have identified two sources of constitutional vulnerability: genetic factors and environmental factors (e.g., prenatal or obstetric complications, traumatic brain injury). Both appear to have implications for prenatal and postnatal brain development, which is a focus of our understanding of the development of schizophrenia. The Genetics of Schizophrenia One of the most well-­established findings in schizophrenia research is that a vulnerability to the illness can be inherited (Gottesman, 1991). Behavior genetic studies utilizing twin, adoption, and family history methods have all yielded evidence that the risk for schizophrenia is elevated in individuals who have a biological relative with the disorder; the closer the level of genetic relatedness, the greater the likelihood the relative will also suffer from schizophrenia (Hilker et al., 2018). In a review of family, twin, and adoption studies conducted from 1916 to 1989, Irving Gottesman (1991) outlined the com- pelling evidence for the role of genetic factors in schizophrenia. Monozygotic twins, who essentially share 100% of their genes, have the highest concordance rate for schizophrenia. Among monozygotic co-­twins of patients with schizophrenia, 25–50% will develop the illness. Dizygotic twins and other siblings share, on average, only about half of their genes. About 10–15% of the dizy- gotic co-­twins of patients are also diagnosed with the illness (Sullivan, Kendler, & Neale, 2003). Further, as genetic relatedness of the relative to the patient becomes more distant, such as from first-­degree (parents and siblings) to second-­degree relatives (grand- Copyright © 2019. Taylor & Francis Group. All rights reserved. parents, half siblings, aunts, and uncles), the relative’s lifetime risk for schizophrenia is reduced. However, the presence of schizo- phrenia in a first degree relative does not only increase the risk of schizophrenia, but also many other psychiatric disorders (Cheng et al., 2017; Shah et al., 2017) Adoption studies have provided evidence that the tendency for schizophrenia to run in families is primarily due to genetic factors, rather than the environmental stressors related to growing up in close proximity to a mentally ill family member. In a seminal adoption study, Heston (1966) examined the rates of schizophrenia in adoptees with and without a biological parent who was diagnosed with the illness. He found higher rates of schizophrenia, and other mental illnesses, in the biological offspring of parents with schizophrenia, when compared with adoptees with no mental illness in biological parents. Similarly, in a Danish sample, Kety (1988) examined the rates of mental illness in the relatives of adoptees with and without schizophrenia. He found that the biolog- ical relatives of adoptees who suffered from schizophrenia had a significantly higher rate of the disorder than the adoptive relatives who reared them. Also, the rate of schizophrenia in the biological relatives of adoptees with schizophrenia was higher than in the relatives (biological or adoptive) of healthy adoptees. These adoption studies provide ample evidence for a significant genetic com- ponent in the etiology of schizophrenia. Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  256 | Matilda Azis et al. Findings from an adoption study in Finland indicate that genetic influences often act in concert with environmental factors. Tienari, Wynne, Moring, and Lahti (1994) found that the rate of psychosis and other severe disorders was significantly higher in adoptees who had biological mothers with schizophrenia than in the matched control adoptees who had no history of having a first-­degree relative with psychosis. However, the difference between the groups was only detected in adoptive families that were rated as dysfunctional. The genetic vulnerability was mainly expressed in association with a disruptive adoptive environ- ment and was not detected in adoptees reared in a healthy, possibly protective, family environment. A meta-­analysis of twin studies found a high heritability along with significant environmental effects (Sullivan et al., 2003). These findings, which highlight a genetic vulnerability interacting with environmental events, are consistent with the prevailing diathesis stress models of etiology. Taken together, the findings from behavioral genetic studies of schizophrenia lead to the conclusion that the disorder involves multiple genes, rather than a single gene (Gottesman, 1991; Van Winkel et al., 2010; Wimberley et al., 2017). Consistent with this assumption, attempts to identify a genetic locus that accounts for a significant proportion of cases of schizophrenia have not met with success. Instead, researchers using molecular genetic techniques have identified numerous genes that may account for a small proportion of cases. In the past decade, linkage studies using genome-­wide association scans have evaluated over 1,000 genes for schizophrenia (Gejman, Sanders, & Kendler, 2011, Ruderfer et al., 2018). Association studies compare variations in specific gene sequences between individuals with and without schizophrenia. Variants found with significantly different frequency among those with schizophrenia are considered to confer susceptibility to the disease. Results from association studies generally have very small effect sizes, owing to the large number of gene variants that can potentially be evaluated; thus, while replication is critical, efforts to do so have met with limited success (Gejman et al., 2011). However, through combining data from multiple studies, results have uncovered a number of notable common polymorphisms (variations in DNA sequence, such as single nucleotide polymorphisms involving the alteration in a single nucleotide of the DNA sequence) and copy number variants (variations in DNA structure involv- ing the number of copies of a section of DNA within an individual’s genotype; Gejman et al., 2011; Insel, 2010; Van Winkel et al., 2010). Over 100 loci have been shown to be associated with schizophrenia risk as identified by single nucleotide polymorphisms (SNPs) in genome-­wide association studies (Harrison, 2015), however the cumulative effect of common variants found cannot explain the high heritability of schizophrenia. More recently, Compliment Component 4 (C4), a small protein found in the blood as part of the immune system, has been the first specific gene to shown to be associated with schizophrenia risk (Sekar et al., 2016). Although finding only a small effect on schizophrenia, this was the first study to link genetic variants to biologically meaningful changes in function. A study of copy num- ber variants (sections of the genome that are repeated) previously found to be associated with schizophrenia demonstrated that although they had a substantial effect on risk of schizophrenia they were in fact more likely to result in other phenotypes, such as developmental disorder, autism spectrum disorder, and congenital malformations (Coelewij & Curtis, 2018; Kirov et al., 2014). Findings from genome-­wide association studies (a study of the whole sequence of DNA or genome, to find variations across indi- viduals) have allowed for the discovery of many risk variants, which has led to the formulation of the Polygenic Risk Score (PRS), a score based on variation in multiple genetic loci and their associated impact on (Wray et al., 2014), which has been shown to be associated with increased risk of psychotic disorder (Agerbo et al., 2015) as well as several different psychopathologies within schizophrenia (Mistry, Harrison, Smith, Escott-­Price, & Zammit, 2017). Despite the large number of genetic variants involved, research postulates that approximately 32% of the underlying contribu- tion to schizophrenia may be explained by such common polymorphisms (a discontinuous genetic variation dividing individuals into distinct groups; Purcell et al., 2009; Ripke et al., 2013). However, the genetic basis of schizophrenia has proven to be highly complex, heterogeneous, and polygenic. Despite advances in molecular genetics, our knowledge of the etiology of schizophrenia and our understanding of the gene-­environment interaction remain limited (Henriksen, Nordgaard, & Jansson, 2017). Using quantitative genetic techniques with large twin samples, researchers have shown that there is significant overlap in the genes that contribute to schizophrenia, schizoaffective disorder, bipolar disorder, and other neurodevelopmental disorders such as autism (Cardno, Rijsdijk, Sham, Murray, & McGuffin, 2002; Fanous & Kendler, 2005; van Winkel et al., 2010). Based on these and other findings, many experts have concluded that genetic vulnerability does not conform to the diagnostic boundaries listed in DSM Copyright © 2019. Taylor & Francis Group. All rights reserved. and other taxonomies (Boks, Leask, Vermunt, & Kahn, 2007; Pelletier & Mittal, 2012). Rather, it appears that there is a genetic vul- nerability to psychosis in general, and that the expression of this vulnerability can take the form of schizophrenia or an affective psychosis, depending on other genetic and acquired risk factors. Clearly, more research is needed to understand the specificity for genetic liability for schizophrenia and mood disorders. As already mentioned, we now know that the environment begins to have an impact before birth; prenatal events are linked with risk for schizophrenia, and some of these events are discussed below. Thus, in order to index environmental events that con- tribute to non-­genetic constitutional vulnerability, we must include both the prenatal and postnatal periods. There has been inves- tigation in to epigenetic (heritable changes in gene function that do not involve changes in the DNA sequence) changes that can be passed on to future generations, suggesting that environmental factors encountered by the parents can possibly affect the child’s genetic code (Roth et al., 2009). At this point, however, researchers are not in a position to estimate the relative magnitude of the inherited and environmental contributors to the etiology of schizophrenia. Moreover, we do not yet know whether genetic vulner- ability is present in all cases of schizophrenia or if some cases of the illness may be solely attributable to environmental risk factors. Maddux, J. E., & Winstead, B. A. (Eds.). (2019). Psychopathology : Foundations for a contemporary understanding. Taylor & Francis Group. Created from vuw on 2024-10-05 06:45:10.  Schizophrenia Spectrum and Other Psychotic Disorders | 257 Neurotransmitter Alterations The idea that schizophrenia involves an abnormality in the brain first began with a focus on neurotransmission. Initial neurotrans- mitter theories focused on epinephrine and norepinephrine. Subsequent approaches have hypothesized that serotonin, glutamate, and/­or gamma-­aminobutyric acid (GABA) abnormalities are involved in schizophrenia. But, compared with other neurotransmit- ters, dopamine (DA) has played a more enduring role in theorizing about the biochemical basis of schizophrenia. In this section, we review the major neurotransmitter theories of schizophrenia, with an emphasis on dopamine. In the early 1950s, investigators began to suspect that dopamine might be playing a central role in schizophrenia. Dopamine is widely distributed in the brain and is one of the neurotransmitters that enables communication in the circuits that link subcortical with cortical brain regions (Jentsch, Roth, & Taylor, 2000). Since the 1950s, support for this idea has waxed and waned. In the past decade, however, there has been a resurgence of interest in dopamine, largely because research findings have offered a new perspective. The initial support for the role of dopamine in schizophrenia was based on two indirect pieces of evidence (Carlsson, 1988): 1. Drugs that reduce dopamine activity also serve to diminish psychotic symptoms. 2. Drugs that heighten dopamine activity exacerbate or trigger psychotic episodes. It was eventually shown that standard antipsychotic drugs had their effect by blocking dopamine receptors, especially the “D2” subtype that is prevalent in subcortical regions of the brain. The newer antipsychotic drugs, or “atypical” antipsychotics, have the advantage of causing fewer motor side effects. Nonetheless, they also act on the dopamine system by blocking various subtypes of dopamine receptors. The relationship between dopamine activity and psychotic symptoms can be demonstrated by studies examining compounds, such as levodopa, that are used to treat Parkinson’s disease by increasing dopamine transmission. For example, motor abnormalities associated with Parkinson’s disease (i.e., hypokinesias – loss of muscle movement, slow jerking movements, and rigidity) are related to low levels of dopamine characteristic of the disease. However, patients with Parkinson’s disease, who are being treated with