One consistent observation concerning schizophrenia is the relationship between stress and psychotic exacerbation. This observation has led to a stress-diathesis model1,2 that postulates that vulnerability to the schizophrenic psychosis occurs on a continuum in the human population, with a small percentage of people having a high vulnerability and most people having a very low vulnerability. In between, there is a sliding progression of decreasing vulnerability with increasing percentage of the population.
THE STRESS-DIATHESIS MODEL
Evidence of this vulnerability continuum derives from the clinical observation that stress in any domain - social, psychological, or biological - can be detrimental to patients with schizophrenia, predisposing them to exacerbations of psychotic symptomatology and other unfortunate outcomes. For example, life events have been associated with psychotic exacerbations in schizophrenia,3 and individuals with schizophrenia often manifest a pattern of social and vocational withdrawal that may be attributable to an attempt to avoid such stress. Indeed, one of the main reasons for social skill training is to help patients avoid the hazards of stress in this domain. High expressed emotion, and the beneficial possibilities of reducing this form of familial stress by modulating highly charged critical comments within families, focuses on one kind of social stress vulnerability.4
Intrapsychic psychological stress is also recognized as being counterproductive for individuals with schizophrenia, and an older, elegant literature details the difficulties that individuals with schizophrenia may encounter in dealing with intrapsychic conflicts and the ways in which this can contribute to psychosis.5,6
Biological stressors are also relevant triggers of psychosis in schizophrenia. Nonspecific biological stressors such as physical exhaustion, sleep deprivation, pain, and hunger may exacerbate psychosis. Substance use is widely recognized as being associated with the onset of psychosis in vulnerable individuals, and, more selectively, biochemical challenge studies have been pivotal strategies for advancing our understanding of the mechanisms of psychosis.7
In each stressful situation, there is a relationship between the seventy of the stress and the level of vulnerability such that if a threshold is exceeded, psychotic symptoms will occur. The greater the vulnerability, the less stress required to exceed the threshold. Adaptive resources counterbalance against adverse events, mitigating (or failing to mitigate) the resulting degree of stress. For example, the degree of stress entailed in having an argument with a close friend may be mitigated by having other friends, having the social skills to be able to make up, or having the psychological flexibility to be able to decathect the relationship. An analogous repertoire of mechanisms on a biological level could be invoked for biological stressors.
POSSIBILITY OF A CO-OCCURRING PSYCHIATRIC DIATHESIS AS A STRESSOR
One potential form of biopsychosocial stressor that can be considered in this model is the independent existence of the diathesis for another psychiatric disorder.8,9 This type of stressor would be interactive with the individual's psychosis vulnerability threshold in the same manner as other stressors and with the same results. Certainly, enough psychiatric diatheses exist with serious stress values in the social, psychological, and, presumably, biological domains to make this a possibility worth considering. With such a "built-in" stressor, a lower vulnerability would be required for the expression of psychosis in individuals with an associated psychiatric syndrome. With more moderate vulnerabilities to the schizophrenic psychosis being more common in the population than extreme vulnerabilities, a higher proportion of individuals who have phenotypical schizophrenia with the co-occurrence of a second associated psychiatric diathesis would be expected than would be predicted by simply multiplying the likelihood of schizophrenia in the population by the likelihood of each of the other psychiatric diatheses involved.
Currently, the interaction of diatheses for which such a relationship is best established is schizophrenia and affective disorder. Mania and depression can he highly stressful events, and psychotic features are sometimes known to occur at the height of severe affective symptoms. When this happens, perhaps it represents a crossing of the psychotic threshold for individuals with a low but non-zero vulnerability to psychosis. Other individuals, perhaps those with somewhat higher vulnerabilities to psychosis, demonstrate psychotic symptoms at the height of their affective disorders, and psychotic symptoms then continue. This may bring us into the domain of the still controversial category of schizoaffective disorder.10
The model described here suggests an additional group of patients, with yet a higher vulnerability, whose threshold for psychosis would be exceeded by less severe affective stressors. In this regard, it is of interest that affective-like symptoms (eg, irritability, sleeplessness, and disinhibition representing mania; or dysphoria, withdrawal, anergia, and hypersomnia representing depression) are frequently noted during the process of decompensation in at least some cases of schizophrenia.11'12 Moreover, when specifically inquired about, affective symptoms are often found at the height of psychotic episodes in schizophrenia.13 It is further relevant that lithium has been found to be a useful adjunct to antipsychotic medication among patients with schizophrenia who have patterns of episodic excitement, overactivity, euphoria, and for depression accompanying their psychotic episodes,9 and that maintenance prophylactic treatment of "post-psychotic depression" in schizophrenia with Imipramine, among responders, resulted not only in fewer depressive relapses, but also in a lower incidence of psychotic exacerbation among responders.14
Panic is another psychiatric diathesis that represents a state of extreme stress. Although panic is currently less studied in the context of schizophrenia, it is possible that it could also activate a triggering stress mechanism for psychosis in vulnerable individuals.15 Many individuals with panic disorder manifest fixed untrue and irrefutable beliefs at the height of their panic episodes (eg, they are having a heart attack or are otherwise in danger of dying), although it is not standard practice to label such beliefs delusions. These might represent what happens when panic attacks occur in individuals with low but nonzero vulnerability to psychosis.
Episodes of panic associated with psychotic exacerbations in schizophrenia have been described,15 and a relationship has been postulated between panic and specifically paranoid symptomatology.16 These phenomena may represent panic attacks occurring in individuals with somewhat higher vulnerabilities (ie, lower thresholds) for psychosis, and may contribute to a variety of strongly held beliefs regarding personal danger.
Obsessive-compulsive disorder also occurs in a substantial proportion of individuals with schizophrenia.17"20 It too is stressful and could have the described triggering relationship with psychosis. The psychotic features occurring with certain severe cases of obsessive-compulsive disorder21 may represent individuals with low but non-zero vulnerabilities to psychosis, whereas patients described as having schizophrenia with obsessive-compulsive features may represent individuals with higher psychotic vulnerabilities.
One of the provocative areas concerning the interaction between psychosis and obsessive-compulsive symptomatology involves delusions: to what extent do the delusions simply represent fixed false beliefs, and to what extent do they represent unwanted thoughts that the patient is unable to get rid of? Stated another way, how much of the problem derives from the belief's being factually false, and how much of the problem comes from the patient's inability to stop thinking about it?
The above list of associated syndromes is not exclusive. Other associated syndromes in schizophrenia may act as triggers to psychotic vulnerability, although less data have been gathered regarding these and the details are therefore more sketchy. One example is posttraumatic stress disorder, another highly stressful psychiatric syndrome that has also been described as occurring in the context of schizophrenia.22 One concern involving posttraumatic stress disorder is whether the experience of a psychotic episode itself or, alternatively, the hospitalization for such an episode could be a sufficiently traumatic event to evoke a posttraumatic stress disorder syndrome. Obviously, in the case of posttraumatic stress disorder, flashbacks of traumatic events associated with psychotic episodes would be difficult to disentangle from reemerging psychotic symptoms themselves. Nevertheless, despite technical difficulties in evaluation, the principles of vulnerability interacting with stress in posttraumatic stress disorder would be the same.
In all cases, the detection of an associated psychiatric syndrome acting as an endogenous stressor triggering psychosis in schizophrenia is complicated by the florid nature of most psychotic symptomatology. Once psychotic symptoms have begun, the associated triggering symptomatology may be less obvious. Awareness of the possibility of an associated psychiatric syndrome, and careful, relevant observation and questioning, is crucial to the determination of its existence.
THE ISSUE OF HETEROGENEITY IN SCHIZOPHRENIA
It is widely recognized that schizophrenia is a disorder involving substantial heterogeneity. Beyond this broad generalization, however, much remains to be accomplished regarding creating a truly useful subcategorization scheme, particularly in terms of devising an informative nosology for treatment. Recognition of "positive" and "negative" syndromes has been helpful, but the current DSM-IV2* subclassification system of paranoid, disorganized, catatonic, and undifferentiated types has little to offer in terms of guiding interventions, whether they be pharmacologic, psychotherapeutic, rehabilitative, or related to the selection of ancillary support systems such as housing.24,25 Moreover, little evidence exists that the DSM-TV subdiagnostic scheme relates to substantive pathophysiologic issues in schizophrenia.
Many types of stress are known to initiate or exacerbate psychosis in schizophrenia. This article suggests that associated psychiatric syndromes may act as endogenous stressors in the context of the stress-diathesis model of psychosis, and that this model offers a rich heuristic approach worthy of consideration as a component of a diagnostic subclassification scheme for schizophrenia. In future studies, aspects of what is known about the biology of these associated syndromes in nonschizophrenic populations could be assessed among individuals with schizophrenia, providing a powerful test of their existence. Crucially, treatment hypotheses could also be tested not only for the reduction of the morbidity of the associated syndromes themselves, but also for the possibility of these syndromes serving to exacerbate psychosis.
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