A Low Brain Serotonergic Neurotransmission in Children With Type 1 Diabetes Detected Through the Intensity Dependence of Auditory-Evoked Potentials

Abstract

The decrease of the FFT in plasma and increase in the N1/P2 component amplitude may reflect a functional relationship between the brain serotonergic activity with the N1/P2 changes. The increase of the ASF slope in children with type 1 diabetes suggests that the response of the auditory cortex to sound intensity stimulus may be regulated by the serotonergic tone and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in children with type 1 diabetes. These changes may be related to psychoemotional manifestations observed in diabetic children such as anxiety and depression.

Functional change of the auditory cortex related to brain serotonergic neurotransmission in type 1 diabetic adolescents with and without depression

“…These tests were undertaken as noninvasive clinical indicators of brain serotonin biosynthesis and activity. The present results confirm that FFT and FFT/total L-Trp ratio are significantly decreased in only diabetic patients (Herrera et al 2003;Manjarrez et al 2006Manjarrez et al , 2007. Interestingly, diabetic subjects who were depressed showed a similar decrease of these biochemical markers.…”

“…These findings support a lowered activity of serotonergic neurotransmission in the brain during the diabetic state, particularly in the auditory cortex (Manjarrez et al 2006(Manjarrez et al , 2007, which may be detected through a change in the amplitude of the N1/P2 component of the intensity-dependent auditory-evoked potentials (IDAEPs) (Hegerl and Juckel 1993;Manjarrez et al 2001Manjarrez et al , 2005aManjarrez et al ,b, 2006Manjarrez et al , 2007. We also recently observed in patients with type 1 and 2 diabetes a significant increase in the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component, obtained at various intensities of auditory stimuli (Manjarrez et al 2006(Manjarrez et al , 2007. More specifically, a strong increase in auditory-evoked cortical responses with increasing stimuli intensities does reflect a low serotonergic activity, whereas low-intensity dependence is assumed to result from high serotonergic function, as we have observed in infants and rats with intrauterine growth restriction (Manjarrez et al 2001(Manjarrez et al , 2005a.…”

“…In the diabetic state and during depression there is also an increase in catabolism of L-Trp due to stimulation of liver tryptophan oxygenase activity (Salder et al 1983). Diabetic patients also present an increase of neutral amino acids (NAA) that compete with L-Trp for its transport to the brain, decreasing even more its availability (Herrera et al 2003;Manjarrez et al 2006Manjarrez et al , 2007. This finding, together with an altered activity of tryptophan-5-hydroxylase, also supports a low serotonin biosynthesis (Herrera et al 2005).…”

“…Interestingly, diabetic patients without depression showed similar biochemical changes compared with patients who were only depressed, suggesting a propensity of diabetic subjects to develop depressive biochemical and electrophysiological traits. Alterations of the N1/P2 component of the IDAEP reflect an impaired cortical activity associated with anomalies of brain serotonergic neurotransmission (Hegerl and Juckel 1993;Juckel et al 1997; Manjarrez et al 2001Manjarrez et al , 2005Manjarrez et al , 2006Manjarrez et al , 2007. Diabetic subjects with depression showed a significantly higher ASF than the other groups, which translates to a more intense cortical reactivity in the presence of a low brain serotonergic tone.…”

“…This suggests that co-morbidity of both pathologies implies a deeper modification of the brain serotonergic system, altering auditory cortex responses. The N1/P2 segment has been proposed as an indicator of serotonergic neuronal activity in the primary auditory cortex where a low serotonergic tone leads to higher N1/P2 amplitudes (Hegerl and Juckel 1993;Manjarrez et al 2006Manjarrez et al , 2007. A low intensity dependence is assumed to result from a high serotonergic function.…”