1. Diagnostic Criteria for Schizophrenia: Clinical Implications and Challenges

“You take in information from all 5 senses properly, but you interpret it wrong. I thought communists sprayed gas under my apartment door at night and performed brain surgery on me while I was sleeping” - Former Air Canada Employee (Diagnosed with Schizophrenia)

Diagnostic and Statistical Manual of Mental Disorders
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The most recent edition of the Diagnostic and Statistical Manual
of Mental Disorders (DSM) was published in May 2013.
Source: Autism Consortium. 2013. Retrieved March 29, 2014, from:
http://www.autismconsortium.org/attachments/dsm-5.jpg.


Despite substantial research initiatives, the biological mechanisms and cellular processes that underlie the pathophysiology of schizophrenia remain elusive. As a result, the Diagnostic and Statistical Manual of Mental Disorders is the primary source of schizophrenia diagnoses in North America. Since it’s inception in 1952, the DSM has evolved through 5 subsequent versions to the DSM-5, the most current manual to date[1]. The aim of each revision is to progress towards an increasingly valid diagnostic manual that will aid in the development and application of successful treatment regimes[2]. The publication of DSM 5 in May 2013 has profound implications on the diagnoses and classification of schizophrenia. In prior editions, schizophrenia was diagnosed according to 5 subtypes: paranoid, disorganized, catatonic, residual and undifferentiated. Due to the heterogeneity between schizophrenia subtypes and inconsistent diagnostic practises, the DSM 5 has introduced the abolition of the subtypes that were previously used to characterize the disorder. Consistent with the notion of moving away from the subtype approach, the DSM 5 employs a dimensional approach that focuses instead on the severity of varying symptom clusters[3]. Although the incorporation of the DSM 5 into clinical practise has promising potential, its implementation into the clinical setting is not without challenge. These diagnostic adjustments may not be widely accepted by clinicians or they may have devastating effects on the prevalence of a given mental disorder in a population. As research on the etiology of schizophrenia continues, diagnostic practises aimed at earlier identification and intervention will emerge. The comprehensive result of this process is a continually improved diagnostic system that will better serve mental health professionals in the effective, accurate diagnosis of schizophrenia.

1. What is Schizophrenia?

Schizophrenia is best described as a psychotic disorder that is characterized by major disturbances in cognitive functioning, emotion and behaviour. According to the Canadian Mental Health Association, it is estimated that 1% of the Canadian population is affected by schizophrenia[4]. It is a chronic and debilitating disease that most often diagnosed in teenage or early adult years. As a result, the Canadian Mental Health Association reports that schizophrenia is the greatest disabler of youth aged individuals in the country. That being said, the possibility of both childhood and old age onset should not be excluded from the diagnostic criteria.

a) Symptomatology

Schizophrenia presents with a wide variety of symptoms that include: flat affect, bizarre motor activity, delusions, hallucinations, and difficulty identifying reality[5]. These symptoms have been divided into two categories, positive and negative symptoms[5]:

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Positive Symptoms Negative Symptoms
Description Symptoms of excess that include: Symptoms of deficit that include:
Examples Delusions: beliefs that are contrary to reality
Hallucinations: sensory experiences without a prompting environmental stimulus
Disorganized Speech: inability to organize ideas, thoughts and speech
Avolition: apathy, lack of interest in routine activities
Alogia: decreased quality and content of speech
Anhedonia: inability to experience pleasure
Flat Affect: lack of emotional response to any stimulus
Asociality: impaired social relationships
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Left Fusiform Gyrus Activation in Patients with Schizophrenia
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Figure 1: An inverse correlation between the severity of negative symptoms
and activation of the left fusiform gyrus is observed when the patient
is exposed to (a) neutral (b) fearful and (c) happy faces
Source: Do-Won Kim et. al. (2013)[6]
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b) Neurobiological Correlates of Schizophrenia Symptoms

This categorical division is reinforced by differential brain region activation that is mediated by positive and negative symptom severity. Facial emotion processing is a fundamental skill required for effective social interaction and many schizophrenia sufferers show deficits in evaluating the intentions and emotions of others. The Positive and Negative Syndrome Scale that evaluates the presence and magnitude of both types of symptoms in schizophrenia was administered to 23 participants[6]. PANSS positive scores were found to be negatively related to right middle frontal lobule activation, implicating that positive symptoms influence early facial emotion processing. Contrarily, negative symptom scores were negatively associated with fusiform gyrus activation, indicating that negative symptoms influence regions independent of those implicated by PANSS positive scores. These results pose a scientific foundation for the division of symptoms outlined above, showing that they affect differential brain regions during facial emotion processing.

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2. DSM-IV-TR Diagnosis of Schizophrenia

Interviewing a Patient with Paranoid Schizophrenia
The individual in the video discusses his daily experiences of
hallucinations, a hallmark symptom of Paranoid Schizophrenia.

a) DSM-IV-TR: Schizophrenia Subtypes

The Diagnostic and Statistical Manual of Mental Disorders IV-TR (DSM-IV-TR) outlines the following schizophrenia subtypes[7]. Until the most recent publication of DSM-5 in May 2013, this manual was the primary diagnostic tool used to identify clinical cases of schizophrenia. Upon observation of the dominant symptoms at the time of evaluation, a clinician may categorize a patient into one of the 5 following subcategories:

i. Paranoid Type: The paranoid subtype is best described by a dominant presence of delusions and auditory hallucinations. It is marked by the limited presence of disorganized speech and catatonic behaviour and the sufferer typically does not exhibit inappropriate or flat affect.

ii. Disorganized Type: Unlike paranoid type schizophrenia, the diagnosis of disorganized type schizophrenia requires the presence of disorganized speech, behaviour and flat affect in absence of catatonic type symptoms. 


iii. Catatonic Type: catatonic type schizophrenia is uniquely identified by the presence of atypical motor behaviour. Patients diagnosed under this subcategory experience immobility, excessive motor activity, rigid posture (extreme negativism) and peculiarities of voluntary movement.
 


iv. Residual Type: Residual type schizophrenia is best described as an attenuated form of schizophrenia. Patients under this diagnosis do not experience prominent delusions, hallucinations, disorganized speech or behaviour. However, the diagnosis requires evidence of psychological disturbances indicated by odd beliefs or unusual perceptual experiences. 


v. Undifferentiated Type: The individual experiences some of the following symptoms, but does not meet the criteria for either of the remaining subtypes: delusions, hallucinations, disorganized speech, disorganized behaviour, negative symptoms. 

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b) Using DSM-IV-TR to Diagnose Schizophrenia

The DSM-IV-TR outlines the diagnostic criteria for schizophrenia[7]. The diagnostic criteria is divided into six sub-sections ranging from Criteria A to Criteria F.
Note: The publication of DSM-5 included revisions of this diagnostic criteria [8]. The most important, influential revisions are listed in section 3a.

DSM-5
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Published by the American Psychiatric Association.
Scientific American. 2013. Retrieved March 29, 2014, from:
http://blogs.scientificamerican.com/mind-guest-blog/files/2013/05/DSM5.jpg.

c) DSM-IV-TR: Highlighting the Need for a Reliable and Predictive Diagnostic Criteria

The publication of DSM-5 in May 2013 was preceded by many studies that attempted to investigate the validity, reliability and predictive diagnostic value of the DSM-IV-TR subcategories of schizophrenia. The results of these investigations did not support the taxonomical categorization of schizophrenia included in the DSM-IV-TR and indicated the requirement for an updated, revised diagnostic criteria in the newest edition of the DSM.

i. Subtype Heterogeneity

__In order to validate the use of a categorical diagnostic criteria, patients diagnosed under each criteria should exhibit significant differences in symptomatology in terms of cognitive functioning, severity of psychopathology. This would indicate that patients suffering from schizophrenia exhibit a marked heterogeneity that justifies a taxonomical separation of schizophrenia based on symptom clusters. Using a large sample size of 1064 patients diagnosed with a psychotic disorder, Korver et. al employed statistical analyses to examine the validity of schizophrenia subtypes[9]. The results indicated that patients classified under varying subtypes did not differ significantly with respect to: demographic or clinical characteristics, severity of psychopathology, current social functioning or indicators of quality of life. In terms of cognitive functioning, individuals diagnosed under differing subtypes did not differ significantly in: IQ scores, problem solving speed, or working memory. Accordingly, this demonstrates that there is no support for the division of schizophrenia diagnoses into subtypes.
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__To further the discussion on subtype heterogeneity, researchers turn to the study of sibling pairs in which both were diagnosed with schizophrenia. The identification of genetic or environmental factors that contribute to a schizophrenia diagnosis would pose as scientific evidence in support of the subtype classification model[10]. These investigations indicate that none of the subtypes of schizophrenia were significantly associated in sibling pairs, constituting mounting evidence that subtypes are not influenced by genetic or environmental factors. In the study of first-degree relatives of schizophrenia sufferers, researchers failed to identify a relationship between subtype of the individual and familial liability [11]. In other words, family members were not more likely to be diagnosed with the same subtype of schizophrenia as their diagnosed relative. The results of these studies indicate that the clear-cut heterogeneous categorization of schizophrenia does not have a basis in either genetic or environmental contributions.

ii. Predictive Value

Predictive value indicates that the diagnosis will remain stable over time. If a diagnosis does not have significant predictive value, this can implly that symptomatology changes along a temporal scale as the illness progresses or, alternatively, it can indicate that the original diagnostic measure is not reliable. Upon further examination, Helmes et. al discovered that subtypes have limited clinical utility when symptoms are considered over a longitudinal time course; in a 10 year period, subtype diagnoses were unstable[12]. Additional studies demonstrate that the course of illness is not, in any way, affected by the subtype diagnoses[9]. That is, all subtypes display varying courses of illness that are not more similar between individuals diagnosed under the same subcategory.

3. Battle of the DSM's: DSM-IV vs. DSM-5

The growing body of research that contributes to an increasingly accurate understanding of mental disorders continually prompts revisions in the DSM. In light of the shortcomings of DSM-IV-TR, the American Psychiatric Association initiated the formation of a workgroup comprised of 12 accredited, world-renowned medical professionals to re-assess the Psychotic Disorder subsection. The overarching goal of this initiative is to create a diagnostic guide that will accurately characterize the symptomatology of schizophrenia, ultimately facilitating better access to increasingly effective treatment options and improved patient care.

a) DSM-5: Moving Towards a Valid Diagnostic Criteria

The publication of the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) includes the following key modifications in the schizophrenia category[8]:

i. Subtype Abolition

Consistent with the research findings mentioned in section 2c(i), the DSM-5 no longer includes the categorical classification system previously used to diagnose schizophrenia. This decision was premised on the fact that subtypes were not useful to clinicians because patients’ symptoms varied considerably over the course of the illness, ultimately resulting in re-classification under a new subtype [13]. Additionally, patients often presented with multiple subtype symptoms, making classification difficult and extraneous. That being said, the subtypes have not been rendered completely useless for DSM-5; rather, they are now used as specifiers for schizophrenia to distinguish it from other psychotic conditions. For example, catatonia (which previously presented in the catatonic schizophrenia subtype) is now used to distinguish schizophrenia from schizoaffective disorder. Ultimately, the discontinuation of subtype differentiation is supported by the following: they do not characterize the heterogeneity of schizophrenia, have low longitudinal diagnostic stability and they do not show any patterns of heritability [1]. Together, these pieces of evidence facilitated subtype removal in DSM-5.

ii. Symptom Threshold Increase

Criteria A Symptoms Required for Diagnosis
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Figure 2: In two studies performed at Vanderbilt University and McLean Hospital,
researchers show that a majority of schizophrenia diagnoses are
made in patients that exhibit 2-3 Criteria A symptoms.
Source: Shinn et. al. (2013) [15]

DSM-5 raises the symptom threshold: to be diagnosed with schizophrenia, an individual must display two of the specified Criterion A Characteristic Symptoms, irrespective of the presence of bizarre delusions (BD) or first-rank auditory hallucinations (FRAH). The Criterion A symptoms include: delusions, hallucinations, disorganized speech, disorganized/catatonic behaviour, and negative symptoms. In previous editions of the DSM, only one of these symptoms was required for diagnosis if the patient presented with bizarre delusions or Schneiderian first-rank hallucinations[14].This change requires that an individual exhibit two Criteria A symptoms, given that Schneiderian symptoms will be treated equally in their diagnostic implication, relative to other symptoms [1]. This modification included in the DSM-5 is founded on the notion that although first-rank auditory hallucinations (FRAH) and bizarre delusions (BD) are rather common in patients with schizophrenia, the diagnosis on the basis of either of these symptoms alone is very rare [15]. Most often, diagnosis of schizophrenia involves 2 to 3 Criteria A symptoms (Figure 2). The fact that so few cases are diagnosed on the basis of the presence of FRAH and BD alone indicates that their special consideration in DSM-IV-TR is inappropriate. Thus, this modification results in a diagnostic manual that encompasses a more accurate characterization of schizophrenia that readily facilitates more accurate diagnoses.

iii. Symptom Severity Scale

To replace the categorical diagnosis of schizophrenia, the American Psychiatric Association introduced a dimensional classification system in DSM-5 (SS-DSM-5). This categorical system classifies the Criteria A symptoms along a continuous severity rating scale [3]. The distribution of SS-DSM-5 symptoms in paranoid schizophrenia, schizoaffective disorder and mood disorders are pictured in Figure 3. The severity of each is assessed using a 0-4 weighting scale for the following dimensions: hallucinations, delusions, depression/mania, cognition, motor symptoms, disorganized speech and negative symptoms[16]. The five points of the rating scale are defined as: 0= not present; 1= severity or duration is not enough to qualify for psychosis; 2= psychotic symptoms are present, but they are rather mild; 3= symptoms are moderate; 4= symptoms are severe [16]. If a patient scores two or higher, the symptom is considered an indicator of a psychotic disorder. The aim of this approach is to better orient physicians towards the most effective treatment for a patient, depending on the symptom profile that is generated.

Distribution of Criteria A Symptoms
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Figure 3: This graph displays the frequency and distribution of SS-DSM-5
symptoms across 3 disorders: paranoid schizophrenia,
schizoaffective disorder and mood disorders.
Source: Ritsner et. al. (2013) [3]

Just as research was required to demonstrate that the previous taxonomical criteria was inappropriate for schizophrenia diagnoses, research must also illustrate increases in diagnostic reliability and validity of this new dimensional approach. The evaluation of the psychometric properties of the symptom severity scale includes the consideration of the following: reliability, internal consistency and diagnostic ability. The first study of this kind was completed by Ritsner et. al at the Israel Institute of Technology in 2011 [13]. This study involved an unselected convenience sample of 314 patients diagnosed with schizophrenia, other psychotic disorders and mood disorders. To determine the similarity between the symptom severity scale and PANSS diagnostic decisions, the researchers used the kappa reliability test. Convergent validity and inter-rater reliability were measured using Pearson’s correlation coefficients and intraclass correlation coefficients (ICC), respectively. Finally, diagnostic validity of SS-DSM-5 was assessed via comparison to the PANSS scale. The results of the study are as follows:

  1. Reliability and Internal Consistency: Internal consistency is used to measure the correlations between different items on the same scale, both aimed at measuring the same variable. When internal consistency is high, the scale is said to be reliable. Total scores were very strong, indicated by a Cronbach’s alpha score of >0.70 for the entire sample.

  2. Inter-Rater Reliability: Inter-rater reliably is used to assess the consistency of diagnoses made when different clinicians use a given rating scale. ICC scores were between 0.79 - 0.97, indicating that inter-rater reliability is high and resembled that of other rating scales. Thus, multiple clinicians can use this scale and arrive at the same diagnosis for a given patient.

  3. Clinical Feasibility: Regardless of the validity and reliability of a rating scale, it is of fundamental importance that it is applicable and appropriate in a clinician setting. SS-DSM-5 is easier to understand and administer, resulting in a seamless incorporation into clinical practise.

These results strongly support that the new symptom severity scale incorporated in DSM-5 is a reliable and valid diagnostic tool that will be easily translatable into clinical practise.

b) Does the DSM-5 Really Have More to Offer than Previous Versions?

In spite of the mounting evidence that clarifies the validity and reliability of DSM-5 for the diagnosis of schizophrenia, the potential shortcomings of these new revisions must be considered.

i. Effects of Diagnostic Changes on the Prevalence of Schizophrenia

As indicated in section 3a.ii, DSM-5 no longer includes special consideration of bizarre delusions or auditory hallucinations. To account for this change, DSM-5 introduces the requirement that an individual must experience at least one of the following for a schizophrenia diagnosis: delusions, hallucinations or disorganized speech. These diagnostic changes have the potential to impact the overall presence of schizophrenia. In order to assess whether or not the diagnostic criteria will result in an increase in schizophrenia diagnoses, Tandon et. al sampled 221 patients that were previously diagnosed with schizophrenia under DSM-IV-TR [17]. The results of the analysis indicated that only 2% of individuals who met DSM-IV-TR requirements for diagnosis did not meet DSM-5 requirements, as a result of the aforementioned changes. Overall schizophrenia caseness is not affected by the changes made to Criteria A symptom consideration in DSM-5.

ii. Clinical Translation

A useful diagnostic manual is one that is easily integrated into clinical practise. The value of an incredibly reliable and valid diagnostic manual is significantly reduced if it experiences great difficulty when attempts are made to translate it into the clinical setting. Although the revision of a diagnostic manual is premised on a multitude of research initiatives and guided by highly accredited individuals involved in DSM workgroups, there are many disadvantages associated with this process. During the assessment phase of a diagnosis, a clinician employs the use of standardized diagnostic interviews (later evaluated using algorithmic techniques) that are developed in close relation to the most current DSM available [18]. When the DSM undergoes editing and revising, the costly and time consuming process of re-calibrating these interviews to maintain compatibility with a new DSM is unavoidable. This circumstance poses as a barrier for clinical application of a new diagnostic manual. Clinicians may, for some time, continue to diagnose mental disorders with the preferential use of DSM-IV-TR instead of DSM-5.

c) DSM-5.1 and Beyond

The American Psychiatric Association has eliminated the use of the roman numeral numbering system in order to make incremental updates to the DSM easier to characterize (e.g. DSM 5.1, 5.2, 5.3) [19]. Research on some disorders progresses faster than others, making the production of an entirely new edition to incorporate relatively small changes unnecessary and costly. Updates will be numbered accordingly until a new edition of the DSM is required. As increasing genetic and environmental contributing factors of schizophrenia are identified, it is likely that the American Psychiatric Association will continue to revise previous editions of the DSM to accommodate this information. In the more immediate future, continuing studies on the validity, reliability, potential negative effects and oversights of DSM-5 will lead to subsequent modifications. All of these initiatives will be directed towards creating an increasingly holistic and accurate diagnostic manual that is readily able to diagnose patients suffering from schizophrenia. Beyond this, an accurate diagnosis is imperative in determining the course of treatment (e.g. pharmacological treatment or psycho-social treatment). Researchers, clinicians and other medical professionals remain united in the pursuit of improved patient care for schizophrenia patients: this improved patient care begins at the level of the Diagnostic and Statistical Manual for Mental Disorders.

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