Psychotic Disorders and Schizophrenic Disorders

Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 8 Schizophrenia Spectrum and Other Psychoses I have always taught my students that the DSM system makes the most sense for categorizing severe mental disorders but has problems in classifying milder ones. Psychoses, marked by dramatic symptoms and severe dysfunction, are much like medical illnesses. One might therefore expect them to present easier diagnostic challenges than common mental disorders. Yet uncertainty about boundaries also afflicts psychoses.

he core problem, once again, is that diagnosis based on phenomenology alone can never be more than approximate. Defining the Schizophrenia Spectrum The overall definition of schizophrenia in DSM-5 has not greatly changed from that of previous manuals, although some details have changed (Tandon et al., 2013). A patient must have at least two characteristic symptoms for at least 1 month: delusions, hallucinations, disorganized speech, abnormal psychomotor activity, negative symptoms (including at least one from the first three), social/occupational dysfunction, and a 6-month duration of illness. Previous criteria giving particular weight to bizarre delusions or Schneiderian hallucinations have been removed because there is no evidence these symptoms are pathognomonic. The traditional subtypes of schizophrenia have also been dropped because they are rarely used (Braff et al., 2013). Although some of the older literature 111 EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 112 | Part II Specific D i ag n ose s suggested that the paranoid type may be distinct, recent studies have not confirmed that conclusion (Tandon et al., 2013). Disorders assumed to lie in the schizophrenia spectrum are also listed: schizotypal personality disorder (which is also under personality disorders), schizophreniform disorder, brief psychotic disorder, and delusional disorder. Differential Diagnosis of Schizophrenia and Bipolar Disorder Emil Kraepelin (1921) introduced a dichotomy between schizophrenia and bipolar disorder based on course of illness. This idea shaped psychiatry for almost a century. Kraepelin proposed that schizophrenia (then called “dementia praecox”) is usually a chronic illness with a slow declining course, whereas bipolar disorder (then called manic-depression) is usually an intermittent illness with periods of good functioning between episodes. (He acknowledged that some cases are difficult to put in one or the other category.) The Kraepelinian dichotomy became even more influential after the introduction of lithium, when differential diagnosis became of practical importance for choosing pharmacological treatment. But this distinction has been recently undermined by research findings. Only some cases of bipolar disorder show remission between episodes, whereas others, particularly those with prominent psychotic symptoms, tend to develop severe and chronic psychosocial dysfunction (Goodwin & Jamison, 2007).

Moreover, neither schizophrenia nor bipolar disorder “breed true”—patients in the same families can have one or the other condition (Craddock & Owen, 2005). Do these discrepancies reflect inaccuracy of diagnosis or a common diathesis for psychosis? The latter possibility is supported by twin studies showing an overlap in heritability (Cardno et al., 2002). A large-scale molecular genetic study found that patients with both diagnoses have similar alleles, suggesting that what is EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 8 Schi zophreni a S pec trum a nd O t h e r P sy c h o se s | 1 1 3 inherited could be a vulnerability to psychosis rather than to a particular diagnosis (International Schizophrenia Consortium, 2009). Nonetheless, many experts maintain that differences between these two conditions are real. The British psychiatrist Robin Murray and his colleagues (2004) argued as follows: Individuals with schizophrenia have more obvious brain structural and neuropsychological abnormalities than those with bipolar disorder; and pre-schizophrenic children are characterized by cognitive and neuromotor impairments, which are not shared by children who later develop bipolar disorder. Furthermore, the risk-increasing effect of obstetric complications has been demonstrated for schizophrenia but not for bipolar disorder. (p. 405) Lawrie et al. (2010) concluded the following: We acknowledge that there is overlap in genetic susceptibility, symptoms, treatments and prognoses between schizophrenia and bipolar disorder. Indeed, perhaps the most striking finding of recent genetic association and genome-wide association studies has been the degree of shared genetic susceptibility to schizophrenia and bipolar disorder. However, shared polygenic vulnerability does not necessarily imply that the resultant conditions lie on one continuum or even several continua. Indeed, there is considerable evidence for differences between the disorders in terms of risk factors, pathology, and treatment response. Thus urban birth, abnormal neurodevelopment, and premorbid cognitive impairment are strongly associated with schizophrenia but not with bipolar disorder. Schizophrenia is associated with an increased burden of large and rare chromosomal abnormalities (copy number variants) not seen in bipolar disorder. In addition there are replicated differences in brain structure and function between the disorders, which although primarily quantitative allow for EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 114 | Part II Specific D i ag n ose s considerable separation of the disorders. Most importantly, there are clearly established differences in responsiveness to lithium and other treatments (p. 424). These controversies might be resolved if schizophrenia and bipolar disorder are rooted in multiple rather than single diatheses. Psychotic Disorders and Schizophrenic Disorders

They could have genes in common and still be different diseases. In any case, genetic overlap reflects only one aspect of either illness, and other features could depend on different mechanisms. At the beginning of the genomic era, it was hoped that molecular genetics would be a key to unlock psychoses and that specific disorders would be associated with a few specific alleles. These days, the consensus is that such a simple solution is unlikely. McClellan et al. (2007) concluded that schizophrenia is highly heterogeneous genetically and that many predisposing mutations are highly penetrant and individually rare, even specific to single cases or families. This “common disease–rare alleles” hypothesis is supported by recent findings in human genomics and by allelic and locus heterogeneity for other complex traits. (p. 194) But genetic studies are not the only way to explore biological mechanisms. Although we all worship at the shrine of DNA, epigenetic mechanisms may be just as important. Finally, although biological markers could eventually be used for differential diagnosis (Benes, 2010), there is no sign that they are coming any time soon. Differentiating schizophrenia and bipolar disorder would be an academic matter if it were not for the fact that diagnosis makes a real difference for choice of treatment. Psychotic Disorders and Schizophrenic Disorders

Both patient groups respond to antipsychotics, but these drugs have more consistent preventive effects against recurrence in schizophrenia, whereas lithium is much more specific to bipolar disorder, both for acute treatment and for EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 8 Schi zophreni a S pec trum a nd O t h e r P sy c h o se s | 1 1 5 the prevention of relapse (Healy, 2009). Psychotic Disorders and Schizophrenic Disorders

For that reason, DSM-5 was correct to maintain the distinction. Schizophrenia—One Disorder or Many? Schizophrenia may not be a disease but, rather, a syndrome. Its heterogeneity may be the reason why no biological markers have yet been found to be associated with the diagnosis. The classical subtypes used in DSM-IV (paranoid, disorganized, catatonic, undifferentiated, or residual) did not do a good job of dissecting schizophrenia, and all have been eliminated in DSM-5. These subcategories were taught to students for years, but research has never confirmed their validity (Linscott et al., 2009). In any case, subtypes were not commonly used in practice. Paranoid symptoms are associated with a later onset of disease, a less severe course, and fewer negative symptoms (Gottesman et al., 1982). But there is nothing specific about paranoid delusions, which can also be seen in mania, psychotic depression, delusional disorder, and dementia (Bentall et al., 2009). Catatonia, a term with a long history in psychiatry, may also not be specific to schizophrenia (Fink et al., 2009). In DSM-5, it is treated as a specifier rather than a subtype. We do not understand why schizophrenia presents so differently in different patients. Why do some patients have striking negative symptoms, whereas others suffer from more florid positive symptoms? Kraepelinian theory, now 100 years old, walks on slippery ground. Renaming would not solve the problem. Van Os (2009), concerned as much about stigma as about validity, suggested the disorder be renamed as a “salience syndrome”—but this unfamiliar term is very unlikely to catch on. Few would be prepared to discard a concept so basic to psychiatry as schizophrenia, even if the name fails to describe the fundamental features of the illness. We will have to wait for a better understanding of the illness before we are in a position to give it a better name. EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved.

May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 116 | Part II Specific D i ag n ose s Attenuated Psychosis Syndrome One of the most controversial proposals for DSM-5 was for a category of risk psychosis—or, in its renamed version, attenuated psychosis syndrome. Psychotic Disorders and Schizophrenic Disorders

The diagnosis would be based on the presence of milder symptoms (but still including delusions, hallucinations, and disorganized speech) that are present at least once a week, progress over time, and cause disability, while leaving reality testing intact. Early psychosis—that is, prodromal cases of schizophrenia— has been a major subject of research in recent years. Researchers have suggested that the treatment of first-episode psychosis might prevent sequelae (Addington et al., 2008; McGlashan & Johanessen, 1996), but the evidence is not there to support that idea. Research has not shown that early treatment in patients at risk actually prevents the development of the illness. A clinical trial of olanzapine failed to yield any benefits over placebo (McGlashan et al., 2006). One recent report (highlighted in the media) suggested that omega-3 fatty acids can slow or even prevent the onset of psychosis in high-risk groups (Amminger et al., 2010). But that is only one study—practice should not change until these findings are firmly replicated. Finally, cognitive therapy is of little preventive value in early onset cases (Morrison et al., 2012). Thus, despite some promising recent research (Hegelstad et al., 2012), we lack convincing evidence that early treatment of risk psychosis makes a difference in prognosis (McGorry et al., 2010). It is difficult to give up hope of preventing such a serious illness.

William Carpenter was the chair of the DSM-5 workgroup and is a senior schizophrenia researcher (he testified at the trial of John Hinckley in 1982). Citing data from a follow-up study of high-risk cases by Woods et al. (2009), Carpenter (2009) proposed that patients with early psychosis can be identified, diagnosed, and successfully treated. In Australia, under the influence of a prominent psychiatrist, Patrick McGorry, a national program was put in place for early identification and treatment. But attenuated psychosis is not necessarily early psychosis, and it can have a very different outcome. EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 8 Schi zophreni a S pec trum a nd O t h e r P sy c h o se s | 1 1 7 Patients meeting the criteria for attenuated psychosis do have an increased risk for conversion to schizophrenia. The problem is the very large number of false positives. Psychotic Disorders and Schizophrenic Disorders

One large-scale study (Cannon et al., 2008) found that the conversion rate after 30 months was only 35%. That number leaves two-thirds who would be treated unnecessarily. In practice, identification of attenuated psychosis could be become higher if, as shown by previous diagnostic epidemics, clinicians—who are trained not to “miss anything”—are less cautious than researchers in identifying cases. Thus, diagnosing people who are not ill would lead to treatment for those who will never develop schizophrenia, not to speak of stigmatization. This would be another example of DSM’s “mission creep,” in which a category spreads from clear-cut disease to near-normal problems. And once a diagnosis is accepted, it is almost assured that physicians will use it frequently, concerned families will insist on treatment, and a larger number of people will receive antipsychotic medication. The problem with adding risk categories to a diagnostic manual is that nearly everyone is vulnerable to some form of mental illness. If we were to follow this precedent, the entire population would almost certainly merit a psychiatric diagnosis. To justify making diagnoses in preclinical cases, one has to be sure that the risk is very high and/or to make use of objective measures (as physicians do for pre-diabetes). In schizophrenia, we lack the science to predict who will go on to develop psychosis and who will not.

That is why there is little basis for intervening in putative prodromal cases. In May 2012, DSM chose not to adopt this diagnosis but relegated it to Section III. This was the correct decision. Changes in DSM-5 There are a few changes in the new manual. In diagnosing schizophrenia, delusions no longer need to be bizarre. This may be a mistake because this is a fundamental characteristic of thought in EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 118 | Part II Specific D i ag n ose s schizophrenia. Also, no special notice is taken of auditory hallucinations with two or more voices conversing. This goes along with a long-standing trend to reject “Schneiderian first-order symptoms” as in any way pathognomic. At least two Criterion A symptoms must be present, one of which needs to be delusions, hallucinations, or disorganized speech. As noted previously, the subtypes of schizophrenia have been dropped. To diagnose schizoaffective disorder, a major mood episode must be met for most of the disorder’s duration. This will help differentiate that diagnosis from schizophrenia with depression. To diagnose delusional disorder, it is no longer required that delusions be non-bizarre. However, the delusions still do not interfere with functioning in the same way as in schizophrenia. Some Unresolved Problems The other categories of psychosis are more poorly understood than schizophrenia, and it is not even clear whether they belong in the same spectrum. The most clinically important example is delusional disorder, a condition one sees with some frequency in the clinic but about which research is thin. This poorly understood diagnosis is marked by delusions without thought disorder. It could be a form of schizophrenia or a unique form of psychopathology. Psychotic Disorders and Schizophrenic Disorders

A family study conducted in a community population (Kendler & Walsh, 2007) found delusional disorder not related to schizophrenia but, rather, to alcoholism. This surprising observation reminds us that patients outside the schizophrenia spectrum can also suffer from delusions. No changes in this category have been proposed for DSM-5. The definition describes delusions of at least 1 month duration that are not bizarre and that do not markedly impair functioning.

Another problem child is schizophreniform disorder, first introduced in DSM-III to account for cases that recover rapidly and do not progress to chronicity. The diagnosis is not often made because briefer psychotic episodes resolve rapidly, whereas those of first-episode schizophrenic patients, who usually have a long EBSCO : eBook Collection (EBSCOhost) – printed on 7/10/2018 4:09 PM via WALDEN UNIV AN: 939818 ; Paris, Joel.; The Intelligent Clinician’s Guide to the DSM-5? Account: s6527200.main.ehost Copyright @ 2015. Oxford University Press. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. 8 Schi zophreni a S pec trum a nd O t h e r P sy c h o se s | 1 1 9 duration of untreated psychosis, do not (McGlashan, 1999). In a family study, Kendler and Walsh (2007) found schizophreniform cases to be related to mood disorders and not to schizophrenia, supporting Kraepelin’s concept of schizophrenia as a chronic disease. In DSM-5, clinicians are asked to rate whether good prognostic features are present, but we do not know whether doing so is clinically useful. Finally, brief psychotic disorder (less than 1 month of symptoms, not accounted for by substance use) remains in DSM without revised criteria. It may or may not belong in the schizophrenia spectrum. There is little research on the outcome of such cases, and one cannot assume that they necessarily represent a first episode of schizophrenia. Future Directions in the Schizophrenia Spectrum Schizophrenia remains a central concern for psychiatrists. We usually manage positive symptoms successfully, … Psychotic Disorders and Schizophrenic Disorders