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