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Updated: Aug 9, 2026
Preparation of Quality Inositol Pyrophosphates
Published on: September 3, 2011
Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia
J R Atack1, J Levine, R H Belmaker
1Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
Insights
Cerebrospinal fluid (CSF) inositol monophosphatase (IMPase) activity is elevated in depression and schizophrenia. Lithium treatment further increases IMPase activity in some schizophrenia patients, suggesting it may be a biomarker for these neurological disorders.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Inositol monophosphatase (IMPase) regulates the phosphatidyl inositol (PI) signaling pathway.
- IMPase in cerebrospinal fluid (CSF) may indicate PI signal transduction dysfunction.
Purpose of the Study:
- To measure CSF IMPase activity in depressed and schizophrenic patients.
- To investigate the effects of lithium and inositol on CSF IMPase levels.
Main Methods:
- Assayed IMPase activity in lumbar CSF from depressed and schizophrenic patients.
- Measured IMPase activity in subgroups of schizophrenic patients after lithium or inositol treatment.
Main Results:
- CSF IMPase activity was significantly higher in depressed (88%) and schizophrenic (172%) patients compared to controls.
- Lithium markedly increased CSF IMPase activity, particularly in a subgroup of schizophrenic patients (>300% increase).
- Inositol administration did not affect CSF IMPase activity.
Conclusions:
- Elevated CSF IMPase activity in depression and schizophrenia could serve as a biomarker for underlying pathophysiological processes.
- Differential regulation of CSF IMPase activity is suggested by lithium's effect in a subgroup of schizophrenic patients.
- The direct correlation between CSF IMPase activity and neuronal PI signaling requires further investigation.
Background:
Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinal fluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction.
Methods:
IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and to gain an insight into the factors that influence the levels of CSF IMPase, enzyme activity was measured in subgroups of schizophrenic patients treated for 3-7 days with lithium or 7 days with inositol.
Results:
CSF IMPase activity was significantly increased by 88% in depressed and by 172% in schizophrenic patients relative to control subjects. Lithium produced a marked increase in CSF IMPase activity in the group as a whole, and this group effect could be more specifically attributed to 3 of the 8 individuals in whom enzyme activity increased by over 300%. On the other hand, inositol had no effect on CSF IMPase activity.
Conclusions:
In the absence of a clear relationship between CSF IMPase activity and neuronal PI signaling pathways it is not possible to correlate these changes with altered neuronal function. Nevertheless, increased CSF IMPase activity in depression and schizophrenia may be a marker of the pathophysiological processes underlying these disorders. Moreover, the large lithium-induced increase in IMPase activity seen in a subgroup of schizophrenic subjects suggests a differential regulation of CSF enzyme activity in these patients.
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