Predicting Outcome in Schizophrenia

Predicting Outcome in Schizophrenia

Can sociodemographic and clinical variables predict outcome in cases of schizophrenia? Attempts to answer this question have been geared toward helping clinicians, patients, and family members have more informed expectations for the long-term prognosis. Results from studies related to prognostic variables for schizophrenia have yielded interesting yet inconsistent results.

In this article, we review the plethora of variables implicated as having prognostic significance in schizophrenia and briefly discuss possible reasons why the literature has not yielded consistent conclusions. Since presentation at intake may have important implications for treatment course, we also review findings from our recent prospective longitudinal study focusing on predicting outcome based on presentation at intake.1 The study addressed the effects of sex, education, and duration of illness; as well as positive, negative, affective, and cognitive symptoms on the level of long-term functioning.

Early reviews of prognosis in psychotic disorders from researchers such as Stephens2 and Vaillant3,4 suggested that positive long-term outcome was related to variables such as severity of the disorder at onset, prominent affective features, good premorbid functioning, being married, having a precipitating event, being confused, or having a family history of manic depressive disorder. Poor outcome was related to insidious onset, exhibiting an asocial premorbid personality, being withdrawn, never being married, or having a family history of schizophrenia. Surprisingly, Valliant's study results4 also led to suggestions that the course of psychosis is not reliably predictable at onset.

Similarly, there are several other inconsistencies in outcome studies investigating the role of sex, age, and symptoms, as well as various other clinical variables (Table). The reasons for such inconsistencies may have included sampling that mixed patients with new onset of schizophrenia and patients who had long-term psychosis, a lack of consideration of the stage of disorder (early course vs late course), and an inability to incorporate prospective randomized study design for the natural course of the illness.

Our recent investigation attempted to minimize some of these concerns in order to further clarify the relationship between clinical and demographic variables and functional outcome.1 We used a prospective design to examine the relationship between symptoms at intake and later functional outcome in first-episode (FE) patients and previously treated (PT) patients with schizophrenia. Patients were selected over a 20-year period; they were rigorously characterized using historical records, underwent physical and psychiatric evaluation by a research psychiatrist, were rated on clinical scales, and were interviewed by research associates using standardized diagnostic measures. These procedures were followed by consensus conferences that established a patient sample with no confounding diagnoses (eg, neurologic/medical illness or traumatic injury) or behaviors (eg, drug abuse). Patients were followed up for an average of 3 years. We also examined the contributions of the patients' sex, education, and duration of disorder to the functional outcome. The findings are discussed below, as well as the results of other investigations of prognostic variables in schizophrenia.



Some studies have found that illness course differs between men and women;5-7 some have found no differences between the sexes in this regard. 8-10 Our study found that male and female patients differed in the degree to which initial symptoms were correlated with later functioning.1 PT women were the only group in whom early levels of functioning did not determine quantity of work. Quantity of work reflects the number of hours or days per week of work as distinguished in the scale from quality of work, which reflects the competence of the individual at that job. There was a higher quantity of work among PT women, even with lower initial levels of functioning, leaving less capacity for incremental improvement relative to other groups.

The sex of the participant also influenced the relationship between depressive symptoms at intake and later quantity of work—higher levels of depression resulted in decreased quantity of work only in women.1 This may reflect a greater range of affective expression among women with schizophrenia, as well as a higher quantity of work relative to men, allowing greater variability in both dimensions.

We also found that men had lower levels of functioning than women at follow-up.1 Men were 3 times less likely to have meaningful social relationships than women were. This may be because men exhibit more socially unfavorable behaviors, which contribute to poorer social course, while women have a higher tendency towards cooperativeness and compliance, which may positively influence social course.11 In addition, estrogen may serve a functionally protective role by causing schizophrenia to manifest at a later age in women than in men, affording women greater opportunities to develop social and occupational skills.5,11 Thus, the sex of the patient appears to play an important role both in long-term social and occupational relationships.


Being married has been found to coincide with better outcome in patients with schizophrenia.12-14 Higher premorbid functioning may lead to the ability to enter into a long-term relationship. Alternatively, being married may be a surrogate marker for later onset, allowing greater social and support network development prior to illness. In addition, marriage may bode well for outcome because it is less socially acceptable to abandon a sick spouse than it is to avoid initiating a relationship with a psychotic individual.


Having obtained a higher level of education has also been correlated with better outcome in patients with schizophrenia.15 As noted above, this may be related to higher premorbid functioning. Furthermore, higher education may yield greater employment possibilities after illness onset, as it does in the general population. Our study found that the impact of education was influenced by treatment status. Although FE patients showed a positive association between level of education and future quantity of work, this was not apparent for PT patients.1 This suggests that the increased employability benefit of education among FE patients is lost as the illness progresses.

Age at onset

Better prognosis has been associated with older age at onset and possibly greater life experience or development prior to illness.16 Yet, some have found no relationship between age at onset and outcome,14 while others have suggested that the older the person is at onset, the poorer the outcome.

Prognostic variables
Variables Prognosis

  Higher level of education 
  Later age at onset 

Mixed findings1,5-10
Predicts more positive outcome12-14
Predicts more positive outcome1,15
Mixed findings6,12,14

  Better premorbid functioning 
  Previous treatment status 
  Shorter length of untreated 
  Symptom severity 
    Positive symptoms 
    Negative symptoms 
    Depressive symptoms 

Predicts more positive outcome1,17
Predicts more positive outcome1,18-20
Predicts more positive outcome1,6,12,14,21,22
Mixed findings1,23,25
Mixed findings1,23,26
Mixed findings1,18,23
Mixed findings1,30,31


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