The development of psychiatric nosology after Kendell and in subsequent iterations of the Diagnostic and Statistical Manuel (DSM) and International Classification of Diseases (ICD) has sought to refine and characterize the essence of this enigmatic condition termed schizophrenia (Tandon 2012). Conceptualizations have variously highlighted positive symptoms, negative symptoms, cognitive deficits, and illness course. Additionally, the boundaries of schizophrenia have been blurred by substantial overlap of the clinical manifestations between psychotic disorders and mood (neurotic) disorders (Waddington and Buckley 2013), between psychotic (paranoid and delusional) states, and between even broader developmental spectrum disorders (Tandon 2012). Many have asserted that DSM-5 rather than clarifying these issues has added further complexity, including the recognition of attenuated psychosis syndrome (“schizophrenia lite,” just like a “head cold” might resemble and presage a “flu”) (Tandon 2012; Frances and Nardo 2013; Regier et al. 2013). Zink and colleagues (2014) observed more similarities than differences [although higher positive symptoms overall] in individuals with at-risk mental states who had OC symptoms compared to those individuals who did not.

It was hoped that DSM-5 would afford, based upon fundamental advances in the neurobiology of psychiatric conditions, the opportunity to advance beyond approaches that are overly reliant on aggregations of symptoms and move to a higher understanding based on the basic neurobiological constructs that may underlie the protean expressions of specific symptom or group of psychiatric conditions (“spectrum disorder”) (Regier et al. 2013). The Research Domain Criteria (RDOC) represents the latest effort – firmly at a research rather than clinical level – to understand the neurobiology of mental illnesses (Cuthbert and Insel 2013).

Given such sustained and uncertain technetronic shifts in nosology, it is hardly surprising that psychiatric comorbidities in schizophrenia remain a nosological conundrum and are inadequately studied to date. There is, of course, still the hope that by further exploration of comorbid psychiatric conditions may provide better insight whether they are intricate to the illness, define some distinct subgroup, or speak to some other etiological process or vulnerability that results in the high co-occurrence of distinct psychiatric comorbidities in patients with schizophrenia (Kim et al. 2013; Opler et al. 2013; Buckley et al. 2009).

There is now emergent evidence that people with schizophrenia are at greater risk of childhood physical and psychological trauma, effects that might also lead to comorbidities like anxiety and substance abuse as a result of shared epidemiological risk factors (Clarke et al. 2013). Another plausible explanation for co-occurrence is that there is some shared genetic vulnerability. There is now ample evidence of substantial overlap of genetic aberrancies between schizophrenia and other psychiatric and neurodevelopmental disorders (Cross-Disorder Group 2013). There may also be fundamental biological perturbations that represented a shared “final common pathway” for psychosis and for a specific psychiatric comorbidity. As just one example, extant neuroscience literature now points to a similar neurobiological end point of dopamine receptor “supersensitivity” both in psychosis and in craving among addiction disorders (Wang et al. 2010). Reynolds, Mehta, and Nasrallah point to the overlap between depression and schizophrenia with respect to perturbations in brain-derived neurotrophic factor (BDNF). Another, often-cited reason for comorbidities is the effects of stress. As one example, it is proposed that people with schizophrenia will self-medicate their stress and symptoms like hallucinations by using alcohol or drugs like marijuana (Buckley et al. 2009). At the other end of this range of multiple plausible explanations for psychiatric comorbidities, there is also evidence that our medications may also be contributory. For example, the expression of OC symptoms as a side effect of clozapine (and, to a lesser extent, also with other second-generation antipsychotic medications) is now well appreciated (Table 1.2) (Doyle et al. 2014).