Stress-reactivity in psychosis: Evidence for an affective pathway to psychosis

doi:10.1016/j.cpr.2006.09.005

Clinical Psychology Review

Volume 27, Issue 4, May 2007, Pages 409-424

https://doi.org/10.1016/j.cpr.2006.09.005 Get rights and content

Abstract

This paper will review a series of studies using the Experience Sampling Method that suggest that altered sensitivity to stress is an endophenotype for psychosis. The Experience Sampling Method is a structured diary technique allowing the assessment of emotional reactivity to stressors occurring in normal daily life. Elevated emotional reactivity to stress was found in subjects vulnerable to psychosis, suggesting that affective responses to stressors in the flow of daily life are an indicator of genetic and/or environmental liability to psychosis. Indeed, the small stressors in daily life associated with affective responses also predict more intense moment-to-moment variation of subtle positive psychotic experiences.

Increased emotional reactivity was found to be independent from cognitive impairments, and argued to constitute evidence of an affective pathway to psychosis that may underlie a more episodic, reactive, good-outcome type of psychosis. Evidence for this hypothesis was found in data suggesting that the experience of stressful life events and early trauma were associated with increased stress-sensitivity, and that women were more likely to display elevated stress-reactivity. These findings are discussed in the light of recent biological and psychological mechanisms.

Introduction

The search for causal mechanisms of psychotic disorders has led to an increased interest in the study of underlying vulnerability substrates, the so-called endophenotypes (Tsuang, 2001, Weinberger, 1999). Endophenotypes are more closely related to the genetic aetiology and its interaction with environmental risks, and thus may reveal underlying causal mechanisms that lead to the development of psychotic symptoms (Claridge, 1994). Since schizophrenia is characterized by a heterogeneous clinical expression and since multiple factors are argued to be on the causal pathway to psychosis, it is attractive to hypothesize that several endophenotypes contribute to the development of psychosis, possibly independent from each other. The current paper will focus on aberrations in sensitivity to stress that may be considered an endophenotype of psychosis, reflecting underlying gene-environment interactions associated with the impact of trauma and stressful life events in vulnerable individuals, and will give an overview of accumulating evidence for what we have called an “affective pathway to psychosis”.

Section snippets

Stress and psychosis

It has long been acknowledged that stress is an important factor in the development of psychosis. The vulnerability-stress model (Katschnig, 1991, Nuechterlein and Dawson, 1984, Zubin and Spring, 1977) has been widely accepted as a heuristically useful framework for the study of the etiology and clinical course of schizophrenia. According to this model, psychiatric symptoms emerge whenever a threshold of stressors exceeds the individual's vulnerability level, the latter being a stable

Emotional reactivity to stress in daily life

Sensitivity to stress can be assessed with questionnaires assessing the personality trait “Neuroticism”, a trait characterized by increased mood reactivity and sensitivity to stress. Patients with schizophrenia have been characterized by higher levels of neuroticism (Horan, Subotnik, Reise, Ventura, & Nuechterlein, 2005), and neuroticism may be associated with the severity of positive symptoms (Lysaker, Lancaster, Nees, & Davis, 2003). Neuroticism also increases the risk to develop both

How does emotional stress-reactivity relate to cognition?

A widely investigated psychosis endophenotype is cognitive impairment. Cognitive impairments have been extensively investigated as the possible substrate of schizophrenia vulnerability (Cosway et al., 2000, Harvey et al., 2004, Kraepelin, 1919, Weickert et al., 2000). Schizophrenia has been called a neurocognitive disorder (Green, 1998), the true phenotype of which may be “an impairment in the smooth coordination of mental processes” or “cognitive dysmetria” (Andreasen et al., 1999, Andreasen

Are the different pathways associated with different psychopathological expressions?

If altered stress-sensitivity and cognitive deficits truly are independent mechanisms to psychosis, it is attractive to speculate that they might represent the underlying mechanism contributing to the extensive clinical heterogeneity in schizophrenia, which many have suggested can be reduced to two main forms. The positive syndrome, good-outcome, non-deficit, type I schizophrenia (Andreasen, 1985, Carpenter et al., 1988, Crow, 1980, Murray et al., 1992, Robins and Guze, 1970, van Os and Selten,

Role of enduring environmental liabilities: association with life events

In order to further investigate the affective pathway to psychosis, it is important to understand how life events tie into these findings of stress-sensitivity to the small stresses of daily life. Life events have consistently been found to influence course and outcome of psychotic disorder (Bebbington et al., 1993, Lukoff et al., 1984). Increased numbers of life events have been associated with higher levels of symptomatology and increased relapse rates (Bebbington et al., 1993, Bebbington et

Vulnerability for psychosis or vulnerability for psychopathology in general?

So far, it has been argued that increased sensitivity to stress is a vulnerability marker for psychosis. However, vulnerability-stress models have been postulated to play a role in the aetiology and course of all major psychiatric disorders (Nuechterlein et al., 1994, Zubin and Spring, 1977, Zuckerman, 1999). Stressors such as life events and high expressed emotion have been found to precede the onset and recurrence of depression (Hooley et al., 1986, Kessler, 1997), bipolar disorder (Miklowitz

Is there a direct effect on psychosis?

So far, the effect of daily life stress on mood was investigated in patients with psychosis. If this truly constitutes a mechanism for positive psychotic experiences, one may hypothesize that stress also has a direct impact on the moment-to-moment fluctuation in intensity of psychotic experiences in daily life. Given the fact that delusions and hallucinations may vary in intensity from normality through to clinically relevant experiences, and given that this variability may occur over periods

Biological mechanisms

One obvious mechanism that may be involved in altered responses to stress in psychosis is the hypothalamic-pituitary–adrenal (HPA) axis, which is one of the major mediating systems involved in stress responses (Corcoran et al., 2003, Walker et al., 2004, Walker and Diforio, 1997). However, only a limited amount of research has been conducted investigating HPA axis activity associated with psychosis. Overall, the data suggest that patients with psychosis show evidence of overactivity of the HPA

Clinical implications

Although the results presented in this review are a long way from offering direct therapeutic insight, there are, if stress-sensitivity truly is a distinct area of vulnerability, some potentially important clinical implications, as the results suggest that specific therapies may be more useful for specific patients. For example, some patients may benefit more from cognitive remediation therapies while others would be more helped by focusing on coping techniques in dealing with the stresses of

Limitations

Most of the research presented in this review is based on data derived from one study including 42 patients with psychosis in a clinical state of remission, 47 first-degree relatives, and 49 healthy control participants. Since the pattern of results may reflect sample-specific characteristics of this small and highly researched data set, the generalizability of the findings could be questioned. However, the two central hypotheses have already been replicated. Stress-reactivity was found to be

Conclusion

This review showed cumulative evidence supporting the construct of an affective pathway to psychosis. ESM was used to demonstrate that aberrant emotional reactivity to daily stress may constitute part of the liability to psychosis, which is independent from cognitive impairments (Fig. 3). It was hypothesized that altered stress-sensitivity may be the underlying pathway leading to a more episodic, good-outcome type of psychosis characterized by a predominance of positive symptoms seen more

Acknowledgment

Dr. Inez Myin-Germeys was supported by a 2006 NARSAD Young Investigator Award and by the Dutch Medical Research Council (VENI and VIDI grant).

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Stress-reactivity in psychosis: Evidence for an affective pathway to psychosis

Abstract

Introduction

Section snippets

Stress and psychosis

Emotional reactivity to stress in daily life

How does emotional stress-reactivity relate to cognition?

Are the different pathways associated with different psychopathological expressions?

Role of enduring environmental liabilities: association with life events

Vulnerability for psychosis or vulnerability for psychopathology in general?

Is there a direct effect on psychosis?

Biological mechanisms

Clinical implications

Limitations

Conclusion

Acknowledgment

Positive versus negative schizophrenia: A critical evaluation

Schizophrenia Bulletin

Defining the phenotype of schizophrenia: Cognitive dysmetria and its neural mechanisms [see comments]

Biological Psychiatry

“Cognitive dysmetria” as an integrative theory of schizophrenia: A dysfunction in cortical–subcortical–cerebellar circuitry?

Schizophrenia Bulletin

Cognitive processes in auditory hallucinations: Attributional biases and metacognition

Psychological Medicine

The relationships among cognition, motivation, and emotion in schizophrenia: How much and how little we know

Schizophrenia Bulletin

Psychosis, victimisation and childhood disadvantage: Evidence from the Second British National Survey of Psychiatric Morbidity

British Journal of Psychiatry

The predictive utility of expressed emotion in schizophrenia: An aggregate analysis

Psychological Medicine

Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study

British Journal of Psychiatry

Life events before psychotic episodes: Do clinical and social variables affect the relationship?

Social Psychiatry and Psychiatric Epidemiology

Persecutory delusions: A review and theoretical integration

Clinical Psychology Review

Schizotypal symptoms in the relatives of schizophrenia patients: An empirical analysis of the factor structure [in process citation]

Schizophrenia Bulletin

Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume

Archives of General Psychiatry

Influence of family life on the course of schizophrenic disorders: A replication

British Journal of Psychiatry

Social origins of depression: A study of psychiatric disorder in women

Expressed emotion and psychiatric relapse: A meta-analysis

Archives of General Psychiatry

Deficit and nondeficit forms of schizophrenia: The concept

American Journal of Psychiatry

A risk factor screening and assessment protocol for schizophrenia and related psychosis

Australian and New Zealand Journal of Psychiatry

Gene-environment interactions in psychiatry: Joining forces with neuroscience

Nature Reviews Neuroscience

The subtyping of schizophrenia in men and women: A latent class analysis

Psychological Medicine

Single indicator of risk for schizophrenia: Probable fact or likely myth?

Schizophrenia Bulletin

Affective reactivity of speech and emotional experience in patients with schizophrenia

Schizophrenia Research

Self-reported stress and the deficit syndrome of schizophrenia

Psychiatry

The stress cascade and schizophrenia: Etiology and onset

Schizophrenia Bulletin

Neuropsychological change in young people at high risk for schizophrenia: Results from the first two neuropsychological assessments of the Edinburgh High Risk Study

Psychological Medicine

Stress and the progression of the developmental hypothesis of schizophrenia

British Journal of Psychiatry

Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology

Schizophrenia Bulletin

Molecular pathology of schizophrenia: More than one disease process?

British Medical Journal

Sexual selection, Machiavellian intelligence, and the origins of psychosis

Lancet

Validity and reliability of the Experience Sampling Method

Journal of Nervous and Mental Disease

Dopamine in schizophrenia: A review and reconceptualization

American Journal of Psychiatry

Assessing schizophrenia in daily life

Stress and arousability in schizophrenia

Schizophrenia Research

Affective reactivity of speech in schizophrenia patients and their nonschizophrenic relatives

Journal of Abnormal Psychology