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Lena Flyckt, MD; Nikolaos Venizelos, MD, PhD; Gunnar Edman, MD, PhD; Lars Bjerkenstedt, MD, PhD; Lars Hagenfeldt, MD, PhD; Frits-Axel Wiesel, MD, PhD

Arch Gen Psychiatry. 2001;58:953-958.

Background  There is evidence that patients with schizophrenia exhibit abnormalities, not only in the brain but also in peripheral organs. An abnormal cell membrane composition has been suggested to be a common denominator, supported by findings of alterations in membrane phospholipid levels. In a previous study, the transport of amino acids across the plasma membrane was investigated with fibroblasts from patients with schizophrenia and controls. An isolated decrease in the maximal transport capacity (V_max) of tyrosine was observed in the cells from patients. In this context, tyrosine transport across the fibroblast membrane was investigated in patients with schizophrenia and healthy control subjects.

Methods  Skin fibroblasts were obtained from 36 patients with schizophrenia (15 first episode and 21 chronic) and 10 healthy controls. Tyrosine transport across the cell membrane was studied in cultivated fibroblasts. The V_max and the affinity of the tyrosine binding sites (K_m) were determined.

Results  Significantly lower V_max (F_1,41 = 12.80; P = .001; effect size = 1.36) and K_m (F_1,41 = 24.85; P<.001; effect size = 1.00) were observed in fibroblasts from the patients. The findings were present in both neuroleptic-naive patients with their first episode and patients with chronic schizophrenia.

Conclusions  The lower V_max and K_m are compatible with a cell membrane disturbance and support the view of schizophrenia as a systemic disorder. The decreased V_max and K_m observed in cells from schizophrenic patients probably reflect a genetic trait, as the changes were transmitted through several cell generations of cultured fibroblast.

From the Division of Psychiatry, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden (Drs Flyckt, Edman, and Bjerkenstedt); Center for Inherited Metabolic Diseases, Karolinska Institutet, Huddinge University Hospital, Stockholm (Drs Venizelos and Hagenfeldt); and Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala, Sweden (Dr Wiesel).

Corresponding author and reprints: Lena Flyckt, MD, FoUU, Department of Psychiatry, Danderyds Hospital, S-18288 Danderyd, Sweden (e-mail: lena.flyckt{at}kids.ki.se).

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