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Data Support Kraepelinian Boundary Between Psychotic Disorders

October 9, 2013. Mood disorders with psychosis represent a distinct category from schizophrenia, according to a study published online October 2 in JAMA Psychiatry. Led by Roman Kotov at Stony Brook University, New York, the study re-examined the categories of psychotic illness using information about how symptoms changed over time and long-term outcome. Statistical modeling of these data showed a boundary between mood disorders with psychosis and schizophrenia, consistent with Emil Kraepelin’s original division of psychotic illnesses. The researchers also report that they found no evidence of a third intermediate category, which suggests that schizoaffective disorder, a blend of mood and psychotic symptoms categorized long after Kraepelin, should be lumped with schizophrenia.

The study contrasts with recent findings that place these disorders along a continuum. Though the Diagnostic and Statistical Manual of Mental Disorders (DSM) categorizes these as three separate entities, and Kraepelin’s distinction of schizophrenia as a thought disorder and bipolar disorder as an emotion disorder endures, genetic risk factors do not respect these boundaries, apparently (see SRF related news story). Similarly, the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) has identified points of convergence among bipolar disorder with psychosis, schizoaffective disorder, and schizophrenia: All three shared deficits in cognition and brain connectivity, with schizophrenia patients the most severely affected (see SRF related news story). Grouping these illnesses separately, some argue, may impede progress in finding their causes (see SRF Live Discussion).

But where diagnostic boundaries are drawn in the first place depends on the information used. In the new study, the researchers take into account how symptoms change over time rather than relying on a simple snapshot. The information comes from the Suffolk County Mental Health Project cohort, which has been followed over 10 years after an initial episode of psychosis (see SRF related news story). One measure, in particular—the percent of time a person was psychotic without any ongoing mood disturbance (called the NAP, for nonaffective psychosis)—allowed for the decisive split.

“[T]he authors have convincingly shown that with respect to one key psychopathologic dimension—the NAP ratio—and one key validator—outcome—the idea of a smooth continuum from psychotic mood disorders on one end to severe schizophrenia on the other can be rejected,” writes Kenneth Kendler of Virginia Commonwealth University in an editorial accompanying the study. “There is a difference here in kind and not just in degree.”

One boundary, two categories
Rather than looking at single features of these disorders and applying thresholds to define diagnostic boundaries, first author Kotov and colleagues plotted pairs of features—symptoms on one hand, and outcome measures on another—and looked for natural groupings. A similar method had been tried before but did not turn up evidence for categorical differences among psychotic disorders (Kendell et al., 1980). The new study applied more advanced statistical techniques to evaluate whether the data pointed to a single continuum or clear boundaries among the disorders.

Data on symptom course were obtained from 526 people in the Suffolk cohort over the first four years after initial hospitalization; of these, 413 people were contacted again six years later and evaluated with the Global Assessment of Functioning so the researchers could get a sense of 10-year outcome.

Among the symptoms followed, the NAP ratio was of special interest because the DSM relies on this feature to distinguish between mood disorders and schizophrenia: Someone with at least two weeks of psychosis without mood symptoms receives either a schizoaffective or schizophrenia diagnosis. When the researchers plotted NAP at four years against 10-year outcome scores for everyone, they found a non-linear relationship: As NAP ratios increased, outcome initially declined, but once the ratio hit 20 percent, the relationship bottomed out, with no further worsening in outcome as NAP ratios continued to climb.

The researchers then used curve-fitting techniques to evaluate how non-linear this relationship really was. This confirmed an abrupt transition in the relationship between NAP and outcome, suggesting a categorical boundary between those with little NAP and better outcomes, and those with more NAP and worse outcomes. The drop off occurred at 1.5 percent NAP, equivalent to 10 days of psychosis without ongoing mood disturbances. This two-step function fit the data significantly better than a linear function, arguing that there is a categorical difference between psychotic mood disorders and schizophrenia.

A three-step model with two abrupt transitions fit the data reasonably well, too—something consistent with the current DSM-5 situation that has three separate categories for mood disorders, schizoaffective disorder, and schizophrenia. But the researchers found that the two-step model was slightly better and suggest that, if replicated, schizoaffective disorder might be better grouped with schizophrenia.

Diagnostic agreement
The researchers then tested their 1.5 percent nonaffective psychosis boundary to see if this cleanly segregated people according to their diagnosis. Because diagnoses were given two years after an initial psychotic episode, the researchers relied on the symptom data taken at the two-year timepoint. They found high agreement, with 88.6 percent of the schizophrenia and schizoaffective disorder group in the category of people showing more than 1.5 percent nonaffective psychosis and 97.3 percent of the psychotic mood disorder group showing less than that.

Another symptom—percent of time manic—also showed a non-linear relationship with outcome and was best fit by a three-category model. These consisted of no mania (fewer than 11 days of mania), episodic mania (11 to 394 days), and chronic mania (>394 days). The mania-absent group included most people diagnosed with schizophrenia and nearly half of those diagnosed with schizoaffective disorder. The other two symptoms evaluated—percent of time psychotic and percent of time depressed—varied linearly with outcome and therefore did not demarcate boundaries between the disorders.

Based on their findings, the researchers suggest that schizoaffective disorder is, at its core, schizophrenia with a comorbid mood disorder layered on top. Whether the shared genetic factors turning up between schizophrenia and mood disorders reflect general vulnerability for psychiatric illness, or a twice-unlucky receipt of separate genetic factors will be challenging to sort out. But finding the core features of each disorder should help.—Michele Solis.

Reference:
Kotov R, Leong SH, Mojtabai R, Erlanger AC, Fochtmann LJ, Constantino E, Carlson GA, Bromet EJ. Boundaries of Schizoaffective Disorder: Revisiting Kraepelin. JAMA Psychiatry. 2013 Oct 2. Abstract

 
Comments on News and Primary Papers
Comment by:  Irving Gottesman, SRF AdvisorAksel Bertelsen
Submitted 23 October 2013 Posted 23 October 2013

Invigorating intellectual and heuristic debate in this Forum is kept alive by the challenging and informed summary of Kotov et al. by Michele Solis. The nagging problem of the status of schizoaffective disorder cannot be concluded by the evidence in hand from this study or others that are more biologically and genetically informed (e.g., B-SNIP data) because none are dispositive, to borrow a term from the lawyers. We applaud Kendler’s erudite and friendly dissection of Kotov et al. (Kendler, 2013) and concur with his conclusion that it would be premature to eliminate the Kraepelinian dichotomy. After all, the Alte Meister did not have access to GWAS or to DTI data from probands and their relatives, and ENCODE (Maurano et al., 2012) could not have been envisioned, either. We hope to supplement the SRF discussion with our twin (Cardno et al., 2012) and Scandinavian experiences (Bertelsen and...  Read more


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