Reduced Melatonin Secretion Research Articles

The Relationship Between Ect Nonresponsiveness and Calcification of the Pineal Gland in Bipolar Patients

It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5-methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients.

The Relationship of Pineal Calcification to Subtypes of Tardive Dyskinesia in Bipolar Patients

Recent studies have suggested that bipolar patients may be at high risk for developing tardive dyskinesia (TD) if exposed to chronic neuroleptic therapy. It has been suggested that reduced melatonin secretion may favor the development of TD in bipolar and schizoaffective patients. Since pinealectomized rats have been reported to develop increased incidence and severity of abnormal chewing movements, and as depression is associated with reduced melatonin secretion, the increased risk of TD in bipolar patients may be associated with diminished melatonin secretion. Evidence suggestive of an inverse correlation between pineal calcification and reduced melatonin secretion, led me to study the relationship between pineal calcification on CT scan and the severity of axial (truncal) and limb and orofacial dyskinesias in bipolar patients with TD. The incidence of pathologically enlarged pineal calcifications (i.e., greater than 1 cm in diameter) in the bipolar patients was 25 times greater than the reported incidence in the literature among nonpsychiatric patients. In addition, there was a significant difference in scores of axial dyskinesias between patients with pineal calcification of less than 1 cm in diameter compared to those with pineal calcification of greater than 1 cm in diameter (F = 3.24; p = .04, one-way ANOVA). There was no significant association between scores of limb and orofacial dyskinesias and pineal calcification. These findings suggest a meaningful association between the presence of enlarged pineal calcification, and axial dyskinesias in bipolar patients. Further studies using direct plasma melatonin measurements are required to more precisely define the association between TD and melatonin secretion in bipolar patients.

Pineal calcification and subtypes of tardive dyskinesia

There is evidence that reduced melatonin secretion is associated with the pathophysiology of tardive dyskinesia (TD). To investigate the relationship between melatonin secretion and TD, I evaluated scores of subtypes of TD with CT scan measurements of pineal calcification (PC) size in 77 chronic institutionalized schizophrenic and bipolar patients. There was a significantly greater incidence of pathologically enlarged calcified pineal glands (greater than 1 cm in diameter) in the patients (18.1%) compared to the reported incidence in the literature in nonpsychiatric subjects (1%). In addition, there was a significant association between scores of limb-axial (but not orofacial) dyskinesias and the presence of pathologically enlarged PC (p less than 0.05). These findings support the notion that the pathophysiology of orofacial dyskinesias may be distinct from limb-axial dyskinesias. In addition, since it is possible that a pathologically enlarged calcified pineal gland is associated with reduced melatonin secretion, these findings add further support to implicate decreased melatonin secretion in the pathophysiology of TD. Further studies using direct measurements of plasma melatonin levels are required to define more precisely the relationship between TD and melatonin secretion.

The association of pineal calcification with drug-induced dystonic movements

There is evidence that reduced melatonin secretion is associated with the pathophysiology of neuroleptic-induced movement disorders including tardive dyskinesia and Parkinsonism. It has been recently reported that pinealectomized rats developed increased incidence and severity of spontaneous chewing movements compared to normal controls. Increased chewing movements in rats has been suggested to reflect acute drug-induced dystonias in humans. To investigate the relationship between melatonin secretion and the pathophysiology of neuroleptic-induced dystonic movements, the presence and size of pineal calcification (PC) on CT scan was studied in relation to the severity of dystonic movements in 34 neuroleptic-treated chronic schizophrenic patients. The incidence of pathologically enlarged PC (greater than 1 cm in diameter) in the schizophrenic patients was 8-9 times greater than the incidence reported in the literature among nonpsychiatric patients. In addition, there were significant differences (p less than .0001) between the severity of dystonic movements in patients with no PC and those with pathologically enlarged PC, and between the severity of the dystonic movements in patients with PC of less than 1 cm and those with PC of greater than 1 cm diameter. These findings indicate an association between the pathophysiology of neuroleptic-induced dystonic movements and the presence of enlarged PCs and suggest that disturbances of melatonin secretion is associated with the emergence of neuroleptic-induced dystonic movements in schizophrenic patients. Further studies using direct measurements of plasma melatonin levels are required more precisely to confirm the association between pineal melatonin secretion and the pathophysiology of drug-induced dystonic movement disorders.