精神疾患における血清中クレアチンキナーゼ活性上昇とカルシウム値の変動について

Increased creative kinase (CK) activity in serum is frequenently observed in many pathological conditions, such as cardiac infarction, muscular, neuromuscular, neurological and malignant diseases, etc. In these diseases, appearance of CK-BB and CK-MB type isoenzymes are observed. On the other hand, in 40-50% of acute “functional” psychotic patients without any somatic diseases mentioned above, increases in CK activity are frequently noticed. The increases in CK activity occur in various psychotic diseases, such as acute schizophrenia, manic-depressive disease, periodic psychosis, etc. Though the increased CK activity cannot differentiate these functional psychosis, it clearly corresponds to the symptoms of excitement, agitation or psychiatric stress. The isoenzyme type of the increased CK in psychotic patients is always MM type. Skeletal muscle abnormalities are found in psychotic patients with high CK serum activity. Subterminal branching of the terminal motor neuron is significantly increased in the patients. Electron microscopy revealed some changes in morphology of Z band in the patients. These findings altogether suggest that the high CK activity in the psychotic patients sera results from leakage of the enzyme from the muscle cells due to higher permeability or other kind of damage to the muscle cell membrane.<br>There is a myth how the pathologic condition in the brain influences the muscle cell to cause leakage of the enzyme molecule. The link between these two apparantly unrelated phenomena are discussed and the role of calcium ion is proposed in the psychotic patient.<br>Serum Ca level is delicately regulated by many factors, such as hormones and neural activity, etc. In psychotic patients, the fluctuations of serum Ca level is frequently observed. In an excitement phase or an acute psychotic phase, the serum Ca level is high, while in a non-psychotic period or a depressive stage, the serum Ca level is normal or even lower than the normal Ca level. The CSF Ca level control is more intriguing.<br>The CSF Ca level is low when the patient is in an excitement phase with high serum Ca level. The increase in serum Ca level is only temporary, and it seems Ca surge in serum may trigger the psychotic excitement, resulting in the “switch-on” of the excitement phase. Experimental infusion of Ca into the ventricle of cat causes drowsiness, inactivity and mimicking the symptom of depression or catatonic stupor. On the other hand, infusion of EDTA or dihydrotachysterol, both of which decrease Ca, into CNS causes excitement and agitation in the animal.<br>The decrease in CSF Ca level causes neural excitation resulting in behavioral excitement and agitation. In physiological situation, the fine homeostatic mechanism is functioning to regulate CSF Ca level compensating the fluctuations of serum Ca level. Actually, the healthy people shows little fluctuations of CSF Ca level after experimental or pathological modification of serum Ca level. In psychotic patients, however, the change in serum Ca level is excessively compensated by CSF Ca controlling mechanism, resulting in the reverse shift of CSF Ca level. This unstable regulation of CSF Ca could be the mechanism underlying the onset of psychotic symptoms. We speculate the homeostatic regulation of Ca in CSF is essential for CNS activity and the function of thyroid may play the most important role in this homeostasis of Ca.