Schizophrenia

The clinical symptoms and course of prototypical schizophrenia are described in the next two chapters. In this section, I merely want to note that psychiatrists have long tried to delineate distinct subgroups of patients within the syndrome of schizophrenia. Eugen Bleuler basically recognized that schizophrenia was a heterogeneous syndrome when he called his influential textbook, Dementia Praecox or the Group of Schizophrenias [3]. Reducing presumed biological heterogeneity and introducing more homogeneous subgroups based on different etiologies and particularly pathophysiologies are seen as a prerequisite for better treatments.

Traditionally, patients were assigned to clinical subtypes, based on the predominant clinical picture (paranoid, disorganized (hebephrenic), catatonic). Given overlap between subtypes (and resulting in an “undifferentiated subtype”), longitudinal instability, and lack of prognostic relevance clinical subtypes have been abandoned in recent revisions of the major classification systems. You could say that clinicians and researchers voted with their feet when they simply stopped using classic subtypes [4]. There is one exception: the catatonic subtype of schizophrenia. It is critical to identify catatonic symptoms in your patients with psychosis since this group of patients requires a different treatment approach (see below).

There is on the other hand great interest in delineating biological subgroups of schizophrenia using biomarkers as such subtypes may lead to different and targeted treatments. The work on gluten sensitivity in schizophrenia patients represents one such an effort as the gut may need to be target if this line of inquiry proves to be relevant [5]. Patients with insulin resistance are less responsive to antipsychotics and may require treatment of the inflammatory status for an optimal response [6]. Another example separates schizophrenia into two molecular subtypes based on the dorsolateral prefrontal cortex (DLPFC) transcriptome [7]. However, at this point none of those genetic-biological subtypes have found their way into the clinic to help clinicians with their day-to-day clinical management of schizophrenia.

Schizoaffective Disorder

Some patients experience the symptoms of schizophrenia and bipolar disorder simultaneously and equally prominently, leading to a diagnosis of schizoaffective disorder. The necessity for this residual diagnostic category is a challenge for nosology and has led to the idea of a “unitary psychosis,” in which any patient can be located on a continuum between schizophrenia-like illness and bipolar-like illness, with varying admixtures of mood and psychotic symptoms [8]. According to DSM-5, schizoaffective disorder can be diagnosed if a manic or depressive episode has been present concurrent with characteristic psychotic symptoms of schizophrenia and if psychotic symptoms have persisted for at least 2 weeks when there were no prominent mood symptoms. In addition, mood symptoms need to be present “for the majority of the total duration of the active and residual portions of the illness” [9]. It should be obvious that these complex rules are open to interpretation (and require knowledge of longitudinal symptoms that is often impossible to ascertain). Moreover, we rarely see patients completely untreated, the effect of treatment obscuring the true longitudinal symptom picture. Consequently, the inter-rated reliability of schizoaffective disorder is low [10]. Combined with its questionable validity, one may ask if we should use this term at all [11].

Atypical Psychoses

Some patients experience brief psychotic episodes with return to good baseline function between episodes and no significant residual impairment. Clinically, the onset tends to be rather acute, and confusion and bewilderment are prominent; patients are described as “perplexed” [13]. Those patients with such atypical psychoses present a diagnostic dilemma. Although it is certainly conceivable that they represent a forme fruste of schizophrenia, they might also be very different illnesses [14], a third group of psychoses other than schizophrenia and bipolar disorder. The clinical point here is that narrowly defined schizophrenia assumes a particular disease course, marked by some form of deterioration and often a typical prodrome. Those atypical (non-affective) psychoses in contrast are acute onset and remitting [15]. Until we better understand the pathophysiology of schizophrenia, we should be conservative in diagnosing it and consider somebody undiagnosed when face with atypical psychosis.

Older psychiatrists have spent much energy to better delineate these atypical psychoses. Cycloid psychoses or the Kleist-Leonhard classification [16] are examples of such nosologies [17]. These elaborate systems while interesting offer insights into the clinical richness of psychotic disorders but have limited practical value. In DSM-5 terminology, atypical patients are classified as having a brief psychotic disorder if symptoms of psychosis last for more than 1 day but for less than 30 days and schizophreniform disorder if symptoms last for less than 6 months. Schizophreniform disorder is a heterogeneous category. About 50% of patients diagnosed with schizophreniform cases will in fact have schizophrenia [18] in which case a diagnosis of provisional schizophrenia would have been correct. It is only for technical reasons that a different diagnostic term is assigned for the first 6 months, until the DSM-5 duration criterion for schizophrenia is fulfilled. Some cases of schizophreniform disorder fully remit within a few weeks, and patient may never have again another episode or only many years later. Acute and transient psychotic disorders (ATPD) and bouffée délirante (in French-speaking countries like Haiti) are other terms applied to this good-prognosis patient group. Interestingly, atypical cases of psychosis are more common in non-Western cultures than in the United States or Europe, with many societies having their own term for these acute-onset, good-prognosis illnesses. “Psychogenic” psychosis is a form of psychosis induced by severe stress which has been proffered as a possible mechanism to explain this phenomenon although some cases may be “organic” and caused by infections [19].