What Is the Core of Schizophrenia

Most clinicians agree that schizophrenia is a useful diagnosis, but fewagreeonwhat it is.Wehaveembraced schizophrenia toclassify somepeculiarmental statesand tomanagesome unusual,bizarre, and,at times, frighteningbehaviors.But there is little agreement on the mechanismofdisease. In this issue of JAMA Psychiatry, Kahn and Keefe1 claim that we have gotten it all wrong: “schizophrenia is not primarily a psychoticdisorder, it isacognitive illness.”Theyforcefullystate that the focus on psychosis has held us back from finding better treatments for schizophrenia. Ironically, they list Emil Kraepelin and Eugen Bleuler as their witnesses to allege that dementia praecox and schizophrenia were defined as cognitive disorders and that psychosis is a “secondary or associated part of the illness.” They list 5 arguments to make their case. Cognitive underperformance, oftenmeasured as low IQ, is a risk factor for schizophrenia, presents before the onset of psychosis, continues after the onset of psychosis, distinguishes schizophrenia from bipolar disorder, and predicts functional outcome. Their reviewof the evidence is compelling, but there are some concerns. First, not all persons who underperform cognitively will go on to develop schizophrenia. In fact, most will not. It will be important to find the right balance between early detection of true risk and avoiding harmwith overzealous diagnosis. In addition, some persons with low IQ who develop psychosis have a preexisting neurodevelopmental disorder. Kraepelindistinguishedthesepatients fromschizophreniawith the term pfropfschizophrenie (pfropfmeaning graft; ie, tissue from one plant inserted into another) and this is recognized with the diagnostic criterion F for schizophrenia in the DSM. Second, their claim that cognitive underperformancedistinguishes schizophrenia from bipolar disorder is open to debate. There is mounting evidence that patients with psychotic bipolar disorder and schizophrenia do share many clinical features including impaired cognition. Rather than a simple categorical distinctionof schizophrenia (impaired cognition) vs other psychotic disorders (normal cognition), it is much more likely that there is a gradient of cognitive underperformance from schizophrenia > schizoaffective disorder > psychotic bipolar disorder > nonpsychotic bipolar disorder.2 They do not mention schizoaffective disorder—are theyproposing that their redefinitionof schizophreniaasacognitive disorder will solve this nosological nuisance3 as well? Third, they fail tomention thepossibility of recovery from schizophrenia. Their focus on cognitive decline is out of balancewith a growing emphasis on recovery. Kraepelin’s thinking was influenced by the reactionary mindset of imperialist Germany,making it easy for him to think about degeneration and irreversible brain damage as the cause ofmental illness.4 We do not want to go back there. Aftermaking their case,KahnandKeefegive5 recommendations: (1) cognitivedeclineprior toonsetofpsychosis should be part of the diagnosis and (2) central in treatment guidelines, (3) schizophrenia shouldbe reclassifiedasacognitivedisorder, (4) early recognitionand interventionhave tobemoved to an earlier age at onset, and (5) cognitive underperformance rather thanpsychosis proneness is theproper riskphenotype. Are we ready tomake cognitive decline prior to the onset of psychosis a diagnostic criterion and reclassify schizophrenia as a cognitive disorder? Did we just miss this opportunity with DSM-5, where schizophrenia remains in the chapter on psychotic disorders?5 Cognitive decline is not defined easily. Decline requires at least 2 assessments. What is the interval between the 2 measurements? Does such an interval vary between different age groups (ie, is there a nonlinear change over time)? Furthermore, the decline has to be outside of a normal range for each age group. What normative data set can a clinician refer to? Kahn andKeefe rightly ask for the development of “cognitive growth curves”—but what is a clinician to do now? It is premature to call for cognitive decline as a necessary diagnostic criterion for schizophrenia. Crucial normativedata are simplynot available. Schizophrenia is currently defined as a disorder of perception, inference testing, thought process, psychomotor behavior, and volition. Making cognitive decline a gatekeeper for the schizophrenia diagnosis is clinically not feasible at this time and will affect caseness. But let us look into the future. KahnandKeefedefine cognition as “memory, attention, acquisition of knowledge, processing speed, reasoning, and executive function.” Which of these cognitive domains will become the core of schizophrenia?Theyacknowledge that “the core cognitivedifficulties are more subtle than canbemeasuredwith traditional neuropsychological tests.” Did Kraepelin know this already? Having trainedwithWilhelmWundt,hewasapioneerofcognitiveneuroscienceandactivelypursuedthepsychological testingofpsychotic patients, but he did not recommend it for clinical practice. In fact, the laboratory and the clinic were separate. Kahn and Keefe are correct that this needs to change and that cognitive underperformance deserves greater attention in the diagnosis of schizophrenia. It also rings true that cognitive underperformance needs to become a target for the development of new treatments, pharmacological as well as nonpharmacological.6 But Kahn and Keefe go much further: Related article page 1107 Opinion