Chapter 3

Why are psychiatric comorbidities so common in schizophrenia and why are they so often missed in clinical practice?

The extent of psychiatric comorbidities in schizophrenia is well documented in Chapter 2 of this book. An excess risk is evident across the board, from early neurodevelopmental disorders such as autism and attention deficit disorder, through depression and all the anxiety disorders, as well as post-traumatic syndromes and OCD, and also encompassing substance use disorders. This chapter seeks to understand why these disorders are so common in people with schizophrenia, and also asks why they are so commonly missed in clinical practice. Subsequent chapters deal with each disorder in turn; hence this chapter provides an overview and conceptual working model. The reader is referred specifically to Chapter 1 for an overarching framework.

Why are comorbid psychiatric disorders so common in people with schizophrenia?

Semantic and nosological issues

Broadly, we can approach this question by addressing biological, psychological, and social determinants. But we also need to consider semantic issues. In hierarchical models of mental illness (see Figure 3.1) there is a tendency—mostly pragmatic and treatment-informed—to give schizophrenia status near the top of the pyramid. Only ‘organic’ factors ‘trump’ schizophrenia. Again, this is sensible in many ways but does beg questions about where ‘organic’ ends and ‘functional’ begins.

The exclusion from a diagnosis of schizophrenia of psychotic symptoms occurring in the context of a brain tumour makes perfect sense and has profound treatment implications. But an exclusion of the diagnosis in people who happen to be using a psychotomimetic drug is far more difficult to sustain. As outlined in Chapter 11, substance use and abuse are very common amongst people with schizophrenia, and some of these substances (e.g. cannabis) seem to raise the overall risk of the illness, bring forward the onset, and certainly make relapse more likely. Hence such drugs arguably act in concert with other factors, perturbing the dopamine system, acting as a cumulative causal factor, and triggering episodes of illness (Castle 2013). In such individuals a primary diagnosis of schizophrenia is applied and substance abuse is considered comorbid: as articulated in Chapter 11, we refer to this as ‘drug precipitated’. But the nosological status of those individuals who have repeated psychotic episodes in response to use of stimulant drugs such as methamphetamine remains uncertain, especially when after years of such exposure they develop a syndrome that looks to all intents and purposes like ‘schizophrenia’ (Voce et al. 2019).

Another conundrum is so-called schizoaffective disorder. This ‘nosological inconvenience’, as it has been described (Castle 2012), raises many questions about boundaries between disorders and the primacy of schizophrenia, on the one hand, and the mood disorders, on the other. Chapter 10 addresses the issue of depression in schizophrenia, essentially considering it as ‘comorbid’. But in some people it can be very difficult to parse schizophrenia-like and mood-like symptoms sets, and they might show risk factors (e.g. genetic) for both sets of symptoms (see Chapter 1). Again, we tend to be pragmatic about this and develop a formulation about the person that enables effective treatment across symptoms. But what the ‘truth’ is about the aetiology and nosology is as yet beyond our understanding, except at a very superficial level.

A further area of consideration is the role of trauma and the overlap between PTSD and psychosis. We know that traumatic life events are all too common in people with a mental illness, and schizophrenia is no exception. How trauma impacts people with schizophrenia is the subject of much recent research, as detailed in Chapter 9. But it is also the case that traumatic life events—notably childhood abuse—are associated with psychotic-like experiences in the general population, suggesting an impact of early trauma on the vulnerability to psychosis broadly (see Chapter 9). The obverse is that people with schizophrenia are differentially prone to various life traumas by the very nature of their illness—through experiencing terrifying delusions and hallucinations, for example, as well as through the trauma that is all too often part of treatment, notably forced treatment in hospitals, with restraint, seclusion, and forced medication. Hence there are complex interactions and causal pathways that eschew any simple binary PTSD vs. schizophrenia dichotomy.

Another problem is the overlap between autism spectrum disorders and schizophrenia (Chapter 4). One of the issues here is the fact that some features of schizophrenia itself are very much akin to those seen in autism: for example, the social awkwardness and lack of ‘theory of mind’ (being able to appreciate the emotions of others). Indeed, Bleuler included ‘autism’ as one of his primary symptoms of schizophrenia, part of what is now conceptualized as the negative symptom cluster (Castle and Buckley 2015). Hence, in a person presenting with schizophrenia—especially early onset, male preponderant ‘neurodevelopmental’ schizophrenia—autistic features would be considered a part of the illness itself, and a separate diagnosis of an autism spectrum disorder would seem superfluous. Yet some people with schizophrenia do have a seemingly comorbid set of symptoms warranting a discrete diagnosis of autism spectrum disorder. This is discussed in detail in Chapter 4.

Finally, the relationship of certain personality disorders to schizophrenia is confusing, as outlined in Chapter 5. Schizotypal personality disorder, for example, has many clinical features of schizophrenia itself; it tends to run in families of probands with schizophrenia; and shares a number of putative biomarkers with schizophrenia (for a full discussion and references see Chapter 5). Thus one could consider this ‘personality disorder’ part of the schizophrenia construct: this has been embraced by ICD-11 but not by DSM-5.

Genetic factors

Leaving aside the semantic issues raised above, there are a number of aetiological threads that tie schizophrenia to other psychiatric disorders. As discussed in Chapter 1, the genetics of schizophrenia are hugely complex and much remains to be elucidated about risk genes, gene expression, and gene–environment interaction effects. One matter that is now very clear is that there is a high degree of overlap in genetic risk across psychiatric disorders. For example, in a large-scale gene-wide association study of 33,332 people with a range of mental illnesses, there were shared risk genes across schizophrenia, autism spectrum disorder, attention deficit disorder, bipolar disorder and major depressive disorder (Cross-Disorder Group of the Psychiatric Genomics Consortium 2013). Which gene constellations predispose to which particular condition is not clear. Indeed, it is likely that no single gene is ‘required’ for any single psychiatric disorder, but that risk genes for some disorders are pertinent in others with similar or overlapping pathogenesis. For example, certain neurodevelopmental genes that impact neuronal migration and integration in schizophrenia would do likewise in other neurodevelopmental disorders such as autism.

The neurodevelopmental model of schizophrenia is now well accepted (Murray et al. 1992). In essence, it proposes that an early aberration of neural development leaves the individual vulnerable to the manifestation of schizophrenia as the brain develops in later teenage and early adult years. Whilst largely genetically determined, environmental factors such as in-utero stress and malnutrition, influenza type A, and toxoplasmosis, as well as pregnancy and birth complications can act in concert with genetic risk to increase the odds of schizophrenia developing in later life. A neurodevelopmental subtype of schizophrenia has been proposed, with the features listed in Box 3.1. It is obvious that the features show substantial overlap with other neurodevelopmental disorders such as autism, suggesting shared vulnerabilities (Chapter 4). What is not so obvious is that early-onset OCD also shows many of these features, as discussed in Chapter 8. Thus neurodevelopmental perturbations might predispose to a putative schizo-obsessive disorder, with shared features of both schizophrenia and OCD.

Related posts:

Generalized anxiety and panic disorder in schizophrenia Personality disorders and schizophrenia Social anxiety disorder and schizophrenia Post-traumatic stress disorder and schizophrenia Schizophrenia and obsessive compulsive disorder Understanding and assessing substance use in schizophrenia

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