Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

Arató, M.; Frecska, E.; MacCrimmon, Duncan J.; Guscott, Rick; Saxena, B.; Tekes, Kornélia; Tóthfalusi, László

doi:10.1016/0278-5846(91)90004-k

Cited by 55 publications

(22 citation statements)

References 13 publications

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“…Concerning the topographic distribution of action of serotonin-selective compounds, a large right centrotemporal region was involved in fluoxetine-induced changes. The fact that the right part of the scalp is involved is in line with post-mortem findings demonstrating, in both normal and suicidal subjects, a higher content of a serotonin metabolite (5-HIAA) as well as increased maximal density of imipramine binding sites in the right hemisphere [18]. In normal subjects, it has been reported that venlafaxine (inhibitor of monoamine uptake, mainly at noradrenergic and serotonergic synapses) induces more changes in P300 amplitude over the right hemisphere than over the left [19].…”

Section: Discussionsupporting

confidence: 61%

Effects of Serotonin-Selective and Classical Antidepressants on the Auditory P300 Cognitive Potential

et al. 1999

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The cognitive potential, P300, is a phenomenon frequently studied in relation to template matching of the brain. To understand the neurochemical mechanisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated application as well as after 1 week of withdrawal on the P300 and N200 waves in an auditory ‘odd-ball’ paradigm in three parallel groups of 10 healthy volunteers. Following single administration, both fluoxetine and clomipramine reduced (–39 ± 14%, p < 0.01) the peak amplitude of P300 at the Pz electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 ± 7% and 24 ± 11%, respectively, were found following 8 days of treatment, 2 h after administration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be significantly modified at the frontal scalp area 1 h after the tianeptine administration on day 8, whereas the postdosing changes induced by fluoxetine were localised in the midline and right centrotemporal scalp regions. Only minor reductions in peak latencies have been observed. It can be concluded that serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cholinergic systems. These results suggest that serotonin has a regulatory function in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.

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Section: Discussionsupporting

confidence: 61%

Effects of Serotonin-Selective and Classical Antidepressants on the Auditory P300 Cognitive Potential

et al. 1999

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“…In the few postmortem studies where male-female differences in the brain serotonin levels were examined, no significant differences were found (38,39). Moreover, no differences have been found between the number of serotonin re-uptake sites in the brains of male and female subjects (35,39). However, two CSF studies have suggested a higher rate of serotonin synthesis in female than male subjects (7,8), opposite to the results of the present study.…”

Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 96%

Differences between males and females in rates of serotonin synthesis in human brain

Nishizawa

Benkelfat²,

Young³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

825

587

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Rates of serotonin synthesis were measured in the human brain using positron emission tomography. The sensitivity of the method is indicated by the fact that measurements are possible even after a substantial lowering of synthesis induced by acute tryptophan depletion. Unlike serotonin levels in human brain, which vary greatly in different brain areas, rates of synthesis of the indolamine are rather uniform throughout the brain. The mean rate of synthesis in normal males was found to be 52% higher than in normal females; this marked difference may be a factor relevant to the lower incidence of major unipolar depression in males. Low brain serotonin (5-HT) levels or function have been implicated in various types of psychopathology, including depression, suicide, aggression, anxiety, and bulimia (for reviews see refs. 1-3). Until recently, the principal methods for studying serotonin metabolism in human brain were determination of the metabolite of serotonin 5-hydroxyindole-3-acetic acid (5-HIAA) in cerebrospinal fluid (CSF) and postmortem measurements of brain serotonin and 5-HIAA. Both methods have limitations. In particular, neither provides a direct measure of serotonin synthesis in the living brain. Recently, a method for measuring serotonin synthesis in the brain of living mammals has been developed (4-5) and tested successfully in dogs (6). The method uses positron emission tomography (PET) and ␣-[11 C]methyl-L-tryptophan as a tracer. The tracer is converted in part to ␣-[11 C]methylserotonin, which accumulates in serotonin neurons, because it is not a substrate for monoamine oxidase and does not cross the bloodbrain barrier.We report here in vivo measurements of serotonin synthesis in the brain of healthy volunteers. Both male and female subjects were studied because CSF studies suggest that the rate of brain serotonin metabolism is higher in females than in males (7-8), and because the incidence of major unipolar depression is higher in women (9). We measured rates of serotonin synthesis under two conditions: at baseline and after acute tryptophan depletion (ATD). For ATD, subjects ingest a tryptophan-free mixture of all the essential amino acids. This induces protein synthesis, which incorporates body stores of free tryptophan into protein, thus reducing the level of this amino acid in tissues, including brain (10). Because tryptophan is the precursor of serotonin, its reduction is thought to lower the rate of serotonin synthesis in brain (11-12). ATD was used in the present study for several reasons. First, low serotonin levels have been proposed to relate to various types of psychopathology (for reviews see refs. 1-3), so any useful method of in vivo measurements of the serotonin synthesis rate must have a demonstrated capability for measuring low rates of serotonin synthesis. Second, ATD induces a transient reappearance of depressive symptoms in patients under treatment with antidepressants (13). Moreover, ATD also produces a mild lowering of mood in normal subjects with a family history of de...

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“…One possible reason is that the serotonin neurotransmitter system implicated in depressive disorders and affected by SSRI antidepressants may have a lateralized distribution in the brain or may be asymmetrically disrupted in a subtype of depression that responds to an SSRI. Although it has been suggested that the serotonin neurotransmitter system is asymmetrically distributed in the brain (Mandell and Knapp, 1979;Tucker and Williamson, 1984), the findings of postmortem studies have been inconsistent (Arato et al, 1991a;Arora and Meltzer, 1991). Neuroimaging studies have provided evidence that individual differences among depressed patients in regional brain activity are related to subsequent response to an SSRI or other antidepressants (Buchsbaum et al, 1997;Mayberg et al, 1997;Brody et al, 1999;Hoehn-Saric et al, 2001;Saxena et al, 2003;Davidson et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Dichotic Listening Tests of Functional Brain Asymmetry Predict Response to Fluoxetine in Depressed Women and Men

Bruder

Stewart

McGrath

et al. 2004

Neuropsychopharmacol

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Patients having a depressive disorder vary widely in their therapeutic responsiveness to a selective serotonin reuptake inhibitor (SSRI), but there are no clinical predictors of treatment outcome. Studies using dichotic listening, electrophysiologic and neuroimaging measures suggest that pretreatment differences among depressed patients in functional brain asymmetry are related to responsiveness to antidepressants. Two new studies replicate differences in dichotic listening asymmetry between fluoxetine responders and nonresponders, and demonstrate the importance of gender in this context. Right-handed outpatients who met DSM-IV criteria for major depression, dysthymia, or depression not otherwise specified were tested on dichotic fused-words and complex tones tests before completing 12 weeks of fluoxetine treatment. Perceptual asymmetry (PA) scores were compared for 75 patients (38 women) who responded to treatment and 39 patients (14 women) who were nonresponders. Normative data were also obtained for 101 healthy adults (61 women). Patients who responded to fluoxetine differed from nonresponders and healthy adults in favoring left-over righthemisphere processing of dichotic stimuli, and this difference was dependent on gender and test. Heightened left-hemisphere advantage for dichotic words in responders was present among women but not men, whereas reduced right-hemisphere advantage for dichotic tones in responders was present among men but not women. Pretreatment PA was also predictive of change in depression severity following treatment. Responder vs nonresponder differences for verbal dichotic listening in women and nonverbal dichotic listening in men are discussed in terms of differences in cognitive function, hemispheric organization, and neurotransmitter function.

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Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

Cited by 55 publications

References 13 publications

Effects of Serotonin-Selective and Classical Antidepressants on the Auditory P300 Cognitive Potential

Effects of Serotonin-Selective and Classical Antidepressants on the Auditory P300 Cognitive Potential

Differences between males and females in rates of serotonin synthesis in human brain

Dichotic Listening Tests of Functional Brain Asymmetry Predict Response to Fluoxetine in Depressed Women and Men

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