Leukocyte differentials predict short-term clinical outcome following antipsychotic treatment in schizophrenia

The majority of patients with schizophrenia and many of their unaffected siblings exhibit a relative granulocytosis and lymphopenia. To characterize these abnormalities better, we examined leukocyte differentials and organ nonspecific autoantibodies in relationship to intake phenomenology and short-term clinical outcome.

We studied patients with schizophrenia (n = 81) and their siblings (n = 18). At intake assessment, about one-half of the probands (n = 38) were neurolepticnaive first-episode patients; the remainder were medication-free for at least 2 weeks. Hematologic indices were obtained at intake assessment, and psychiatric symptomatology was assessed at baseline and following 6 months of clinically determined treatment.

A relative granulocytosis and lymphopenia prospectively predicted poorer recovery in positive, but not negative, symptoms after 6 months of antipsychotic treatment. Abnormal leukocyte proportions were specific to patients who presented with clinically significant positive symptomatology at intake. In contrast, clinically significant negative symptoms were only evident in a small subgroup of patients who were positive for antinuclear autoantibodies and/or rheumatoid factor.

Future research should further test the hypothesis that a relative granulocytosis and lymphopenia reflect genetic loading for the pathophysiologic determinants of positive symptoms. Future research also should determine the etiologic significance of organ nonspecific autoimmunity in predominantly negative symptom schizophrenia.