Depression and schizophrenia

KEY POINTS

• Comorbid depression is frequent, particularly in early stages of schizophrenia.

• Comorbid depression is a poor prognostic indicator for functional recovery, quality of life and suicide.

• Negative symptoms may be secondary to depression.

• SSRIs are generally safe to use for depression in the context of schizophrenia and are likely to be effective.

• Less evidence exists for CBTp and other psychosocial treatments, but those focused on hopelessness and reducing social isolation should be considered.

For many years the ‘Kraepelinian dichotomy’ that separated bipolar disorder and schizophrenia has been challenged. The presence of mood symptoms, and in particular depressive symptoms, is common in schizophrenia, as is the presence of first rank positive symptoms in bipolar disorder. Diagnostic fluidity is a key component in early stages of schizophrenia such as FEP, and depressive episodes are particularly common in this early phase of illness. Depression in the early stage may have long-term impacts in terms of suicidal behaviour and also functional outcome and relapse risk. However, existing treatments for depression do work in schizophrenia. Monitoring for significant mood symptoms in FEP and also later in the course of schizophrenia is essential in order to develop appropriate treatment plans.

Prevalence and importance of depression

Depression as a discrete syndrome is relatively common in schizophrenia, with a prevalence in cross-sectional studies of around 25–30% (Conley et al. 2007; Hafner et al. 2005); longitudinal studies show rates of over 50%. Prevalence figures for depressive features are higher still. In earlier phases of illnesses, such as the UHR phase, 40% of patients may meet criteria for a syndromal diagnosis of depression and this may be up to 80% of FEP patients in longitudinal studies. Depression in FEP thus occurs in prodromal, acute, and post-psychotic phases and classical post-psychotic depression rarely occurs unheralded by previous episodes (Upthegrove et al. 2010; Yung et al. 2006). See Box 10.1.

Box 10.1 Prevalence of depressive episodes and depressive symptoms in schizophrenia

• In cross-sectional studies up to 40% of patients with schizophrenia are depressed

• Highest rates are seen early in the course of illness

• Longitudinally, the majority of patients with schizophrenia experience a depressive episode of at least moderate severity

• Post-psychotic depression is often preceded by depression in the prodrome or acute phases, and rarely arises ‘de novo’

When depression is comorbid to any health disorder, there is a negative impact on the overall illness burden, and this is also the case in schizophrenia. Previously it has been proposed that depression in early psychosis may represent an individual patient’s trajectory leaning towards a more affective rather than non-affective psychosis, and hence a better outcome. However, it is now fairly clear that depression has largely negative consequences in schizophrenia. Depression in schizophrenia is associated with more frequent psychotic episodes (Buckley et al. 2009), longer duration of illness, substance abuse, poor quality of life, and suicide. Depression during and after FEP is the most significant risk factor for suicidal behaviour; 35 out of every 100 patients with FEP may have attempted suicide, and completed suicide is most common in these early years of illness (Dutta et al. 2011; Upthegrove et al. 2010). In a systematic review and meta-analysis, depression after FEP was shown to have a longer-term impact on the likelihood of suicidal behaviour, lasting up to 7 years (McGinty et al. 2017). Depression in schizophrenia also has impacts on systems outside of the individual and on the healthcare burden, with greater use of mental health services and the criminal justice system (Conley et al. 2007). See Box 10.2.

Box 10.2 Importance of depressive episodes and depressive symptoms in schizophrenia

• Despite previous considerations, depression comorbidity is now known to be a poor prognostic indicator in schizophrenia

• Depression is significantly associated with increased risk of suicidal behaviour

• Depression is related to poorer recovery and reduced quality of life

• Patients with schizophrenia and depression are more likely to experience coercive forms of treatment

Causation

That depression is common in schizophrenia should not come as a surprise, given the impact, stigma, and loss that may accompany any severe illness. There is also some limited biological evidence suggesting putative common aetiological pathways for symptoms of depression and positive psychotic symptoms, including systematic whole-genome linkage studies which have implicated chromosomal regions in common (International Schizophrenia Consortium 2009); brain imaging studies with similarities in both structural grey and white matter (Cui et al. 2011); and functional abnormalities in some key areas including the hippocampus, and prefrontal and frontal regions (Busatto 2013; Palaniyappan et al. 2019). Current biological models indicate commonality in pro-inflammatory cytokines and other innate immune markers; these are elevated in both depression and schizophrenia, and more so in those patients when both disorders occur together (Khandaker et al. 2014; Noto et al. 2015; Upthegrove et al. 2014). Furthermore, a number of studies have found that depression and anxiety tend to increase before the onset of a psychotic relapse, suggesting that affective dysfunction, rather than simply being a comorbidity, may be causally related to psychosis (Hall 2017).

There have been a number of quantitative and qualitative studies of depression in FEP and schizophrenia that have identified significant associations with the experience of positive symptoms, including powerful perceived persecutors, and commanding and authoritative hallucinations. Freeman and Garety have developed considerable evidence about powerfulness of persecutory beliefs and the adoption of safety behaviours (e.g. avoidance) that are important in emotional dysfunction in psychosis (Freeman and Garety 2003; Garety et al. 2001). It has also been demonstrated that depression emerging after psychosis is strongly associated with the loss of role and social status and internalized shame related to the experience and diagnosis of psychosis. Negative self-appraisals are common cognitive distortions also seen in non-psychotic depression, and intimately linked to past experience and the generation and perpetuation of depressive cognitions; similar psychological processes leading to depression in psychosis should be considered (Upthegrove et al. 2017).

In summary, models of depression in schizophrenia indicate that shared biological pathways, psychological response to the event of psychosis itself, and shared common factors, for example trauma, may all be indicated. Indeed, these are not mutually exclusive (see Chapter 3).

Recognition

The phenomenological symptoms of depression in schizophrenia are broadly similar to those found in major depressive disorder. However, some evidence suggests that negative cognitive appraisals of shame and loss are more prominent in post-psychotic depression as compared with major depressive disorder in other contexts (Häfner 2005; Sandhu et al. 2013). Also, acute phases of psychosis depression may be related to the experience of perceived threat from powerful persecutors and/or malevolent hallucinations (Birchwood et al. 2005; Garety et al. 2001).

There are a number of features common to both depression and negative symptoms of psychosis, such as social withdrawal, anhedonia and anergia (Krynicki et al. 2018). There may be some distinction between consummatory anhedonia and anticipatory anhedonia. Depression can be masked or misinterpreted as negative symptoms, with the distinction between primary negative symptoms and secondary (to depression, antipsychotic medication, enduring positive symptoms) needing careful examination. Hopelessness and suicidality may be significant distinctions.

The CDS (Addington et al. 1993) is a brief, useful assessment schedule specifically developed for use in people with schizophrenia. It encompasses nine items covering:

• depressed mood

• hopelessness

• self-depreciation

• guilty ideas of reference

• observed depression.

Box 10.3 Assessment of depression in schizophrenia