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Cyclic nucleotides in mental disorder.

R H Belmaker, J Zohar, R P Ebstein

    Advances in Cyclic Nucleotide Research
    |January 1, 1980
    PubMed
    Summary
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    Cerebrospinal fluid cyclic nucleotides do not reliably differentiate psychiatric disorders. However, lithium treatment inhibits epinephrine-stimulated plasma cyclic AMP, suggesting a role in mood stabilization.

    Area of Science:

    • Neuroscience
    • Psychiatry
    • Biochemistry

    Background:

    • Cyclic nucleotides in human cerebrospinal fluid (CSF) have been investigated for their potential to distinguish between patients with manic-depressive illness, schizophrenia, and healthy controls.
    • Previous research suggests neuroleptic therapy can alter CSF cyclic nucleotide levels, potentially reflecting dopamine neurotransmission blockade.
    • Lithium is a common treatment for bipolar disorder, but its precise mechanism of action, particularly at the cellular level, remains under investigation.

    Purpose of the Study:

    • To investigate the utility of CSF cyclic nucleotides in differentiating psychiatric patient groups.
    • To examine the effects of neuroleptic and lithium treatments on cyclic nucleotide levels in patients.
    • To explore the potential of plasma cyclic AMP responses to predict lithium responsiveness.

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    Main Methods:

    • Measurement of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in human cerebrospinal fluid (CSF).
    • Analysis of cyclic AMP levels in plasma following epinephrine and glucagon stimulation in patients undergoing lithium treatment.
    • Correlation of biochemical findings with clinical status and treatment response in psychiatric patients.

    Main Results:

    • CSF cyclic nucleotides did not effectively distinguish between manic-depressive patients, schizophrenic patients, and controls, although a subgroup of schizophrenics with poor prognosis and high CSF cyclic AMP was noted.
    • Neuroleptic treatment increased CSF cyclic GMP and decreased CSF cyclic AMP in responder subgroups, consistent with dopamine blockade.
    • Lithium treatment did not alter CSF cyclic AMP levels but inhibited the plasma cAMP response to epinephrine in vivo after chronic administration, while the glucagon response remained unaffected.

    Conclusions:

    • CSF cyclic nucleotides are not reliable biomarkers for differentiating major psychiatric disorders.
    • Neuroleptic effects on CSF cyclic nucleotides support their role in modulating dopamine neurotransmission.
    • Lithium's inhibition of epinephrine-stimulated plasma cAMP suggests a potential role for norepinephrine-sensitive adenylate cyclase in lithium's therapeutic action, offering a possible method for distinguishing lithium-responsive patients.