Schizophrenia as a systemic disorder : studies of peripheral and central biological functions

Psychiatric disturbances with an onset in adulthood may show subtle signs in childhood and school age. This is particularly applicable to patients with schizophrenia. A plasma membrane disturbance has been proposed as a common denominator responsible for both the central nervous system abnormalities and the changes in peripheral organs in patients with schizophrenia. The aim of the present thesis was to investigate central (neuropsychological, neurological and psychomotor) and peripheral (neuromuscular, tyrosine transport across the cell membrane) functions in schizophrenia with tyrosine kinetics as an indicator of membrane function. Another aim was to study possible familial transmission(s) of central and peripheral biological changes by investigating the occurrences of such abnormalities in unaffected first-degree relatives to the patients.

Patients with schizophrenia (n = 39) their first degree- relatives (n = 44) and healthy controls (n = 55) were investigated according to the below listed studies.

I. Clinical neurological investigation of neurological signs were performed. Psychomotor functions were investigated using the finger tapping, Purdue pegboard and pronation-supination tests, hand grasp strength, and gait.

II. Histopathological examination of the skeletal muscle fibre was performed. The electrophysiological properties of the motor unit was studied in patients with schizophrenia and controls using the macro electromyographical (EMG) technique.

III. Investigation of the muscle fibre histology and electrophysiology was performed as in study II in unaffected first-degree relatives to patients with schizophrenia.

IV. Tyrosine transport (Km and Vmax) across the cell membrane was investigated in vitro using cultivated fibroblasts from patient with schizophrenia and healthy controls.

V. Cognitive functions in patients with schizophrenia, their first-degree relatives and controls were assessed using an extensive battery of neuropsychological tests.

Patients with schizophrenia exhibited neurological abnormalities and aberrant psychomotor performance to a significantly greater extent than healthy controls. Neuromuscular changes were found significantly more often in patients with schizophrenia and their unaffected first-degree relatives compared to controls. The most frequent histopathological finding in patients was muscle fibre atrophies, affecting both type I and type II fibres. Increased amplitude and area of the motor unit action potentials were found in the macro EMG recordings from patients and relatives but not in that from controls. The patients exhibited aberrant tyrosine transport kinetics with significantly lower Vmax (indicating lower tyrosine transport) and Km (indicating higher affinity) compared to controls. Finally, the patients performed significantly worse than their first-degree relatives and the controls in most of the neuropsychological tests and this significantly correlated with a lower level of functioning.

Biological and clinical changes have been demonstrated deriving both from the central nervous system and peripheral organs indicating that schizophrenia is a systemic disease. Furthermore, the type of macro EMG findings and tyrosine transport aberrations indicate a membrane dysfunction. These results entail a different perspective on the ethiology of schizophrenia.

List of scientific papers

I. Flyckt L, Sydow O, Bjerkenstedt L, Edman G, Rydin E, Wiesel FA (1999). "Neurological signs and psychomotor performance in patients with schizophrenia, their relatives and healthy controls" Psychiatry Res 86(2): 113-29
https://pubmed.ncbi.nlm.nih.gov/10397414

II. Flyckt L, Borg J, Borg K, Ansved T, Edman G, Bjerkenstedt L, Wiesel FA (2000). "Muscle biopsy, macro EMG, and clinical characteristics in patients with schizophrenia" Biol Psychiatry 47(11): 991-9
https://pubmed.ncbi.nlm.nih.gov/10838067

III. Flyckt L, Wiesel FA, Borg J, Edman G, Ansved T, Sydow O, Borg K (2000). "Neuromuscular and psychomotor abnormalities in patients with schizophrenia and their first-degree relatives" J Psychiatr Res 34(4-5): 355-64
https://pubmed.ncbi.nlm.nih.gov/11104850

IV. Flyckt L, Venizelos N, Edman G, Bjerkenstedt L, Hagenfeldt L, Wiesel FA (2000). "Aberrant tyrosine transport across the cell membrane in patients with schizophrenia." (Submitted)

V. Eriksson A, Nyman H, Flyckt L, Edman G, Bjerkenstedt L, Wiesel FA (2000). "Neuropsychological function in patients with schiziphrenia, their relatives, and normals." (Submitted)