Elsevier

Psychiatry Research

Volume 129, Issue 1, 30 November 2004, Pages 11-19
Psychiatry Research

Serotonergic function in the central nervous system is associated with daily ratings of positive mood

https://doi.org/10.1016/j.psychres.2004.06.010Get rights and content

Abstract

Serotonin constrains a broad array of animal and human behavior and may also inhibit the expression of mood or affective states among humans. For the most part, this research has focused on the association of central serotonergic function with negative affectivity (i.e., anxiety, depression, hostility), with less attention on the relationship between serotonergic function and positive affect or mood. The current study was conducted to examine the relationship between a measure of central serotonergic activity and daily ratings of positive and negative mood in a nonpatient sample. Two hundred and fifty-four adults, aged 24–60, completed end-of-day ratings of positive and negative mood items over 7 consecutive days. A neuropharmacological challenge was administered to index central serotonergic function, i.e., the maximal prolactin (PRL) response to fenfluramine, a serotonin releasing agent. Hierarchical linear regression analyses indicated that the peak PRL response to fenfluramine was positively associated with positive mood, averaged over 7 days, after controlling for known predictors of the PRL response. This relationship remained significant after controlling for average negative mood, for the presence of a current DSM-III-R diagnosis, and for trait measures of Neuroticism and Extraversion. In contrast, the PRL response to fenfluramine was not associated with average negative mood, although it was inversely correlated with trait negative affectivity (i.e., Neuroticism). These results suggest that deficiencies in serotonergic function may reflect the relative absence of positive mood.

Introduction

Serotonin largely modulates behavioral responses activated by other neurotransmitter systems, serving to constrain or inhibit a broad range of animal and human behavior (e.g., locomotor activity, exploratory behavior, aggression; for reviews, see Soubrié, 1986, Spoont, 1992). In humans, deficiencies in central nervous system (CNS) serotonergic function are associated with diverse psychiatric conditions and symptoms, including negative affect Depue, 1995, Depue and Collins, 1999. For example, acute depletion of tryptophan, the essential amino acid precursor of serotonin, promotes relapse in some depressive patients Moore et al., 2000, Bell et al., 2001 and increases negative mood in nonpatient volunteers with a family history of affective disorder (Benkelfat et al., 1994; although see Ellenbogen et al., 1999). Administration of the selective serotonin reuptake inhibitors (SSRIs) is associated with decreases in negative mood states in both patients and non-depressed volunteers (e.g. Barge-Schaapveld et al., 1995, Salzman et al., 1995, Steiner et al., 1995, Knutson et al., 1998).

In contrast, less is known about the association of positive mood with serotonergic activity. When administered chronically, tryptophan can enhance mood, but the effect is seen most clearly in patients who are mildly depressed (reviewed in Young and Leyton, 2002). Moore et al. (1998) reported that acute tryptophan depletion causes a decline in positive mood states (e.g., vigor, elation; Moore et al., 1998), and Barge-Schaapveld et al. (1995) observed increases in positive mood ratings in non-patients (e.g., happy, calm, energetic) following administration of an SSRI. In contrast, Knutson et al. (1998) did not observe changes in positive affect as measured with the Positive and Negative Affect Scale (PANAS: Watson et al., 1988) in euthymic adults in a placebo-controlled trial of an SSRI.

A recent study more directly addressed the association of CNS serotonergic function with positive and negative affect in a sample of 32 nonpatient men (Zald and Depue, 2001). Participants completed the PANAS three times per day for a period of 2 work weeks. To index central serotonergic activity, a fenfluramine challenge protocol was administered. Fenfluramine enhances serotonergic activity acutely through pre- and post-synaptic mechanisms and by subsequent activation of hypothalamic serotonin receptors, and it causes proportional release of pituitary-derived hormones, such as prolactin, into the circulation. The consequent rise in prolactin concentration reflects relative CNS serotonergic responsivity and has been found to be attenuated among people with a current or lifetime diagnosis of a mood disorder, when compared with nondepressed controls Flory et al., 1998a, Flory et al., 1998b, Bhagwagar et al., 2002.

Zald and Depue (2001) reported that the maximal prolactin (PRL) response to fenfluramine was inversely associated with both negative and positive affect, as averaged over multiple assessments, and concluded that serotonergic function constrains the experience of affect generally. However, the association of higher positive affect (i.e., enthusiasm, interest, alertness) with a lower PRL response to fenfluramine, a marker of diminished serotonergic function, appears inconsistent with at least some of the clinical literature cited above. Further, in this study, the aggregate ratings of positive and negative affect ratings were positively correlated, which suggests an anomalous response set in this sample. The association was modest, but positive and negative affect ratings have been reported to be generally independent (or modestly inversely correlated) across varying intervals of time (Watson and Clark, 1997). Finally, this study was conducted with only male participants, and the sample size was relatively small (n=31). Accordingly, the current analysis was conducted to further examine the relationship of mood to central serotonergic responsivity as assessed in a larger sample of 254 nonpatient men and women. Participants completed ratings of negative and positive moods at the end of the day for 7 consecutive days. Approximately 6 weeks later, a fenfluramine challenge was administered.

Section snippets

Participants

Participants were derived from a study examining the association of serum cholesterol with mood and neurobehavioral functioning and were recruited through media advertisements and local distribution of brochures. Exclusion criteria included (1) medical diagnoses of cancer, stroke, diabetes requiring pharmacological treatment, chronic kidney or liver disease, or lifetime history of psychotic symptoms; (2) untreated hypertension; or (3) use of psychotropic, glucocorticoid, or hypolipidemic

Results

Slightly under half of the sample were women (n=119) and, as shown in Table 1, participants averaged 45 years of age and nearly 16 years of education. T-tests and χ2 analyses indicated that men and women were comparable across race and employment status variables (P's>0.10), but men reported more years of education [t(252)=2.31, P=0.02] and were more likely to be married [χ2(1)=4.33, P=0.04]. Owing to their lower weight [t(252)=9.6, P<0.0001], women received a significantly lower dose of

Discussion

In the current study, lower positive mood ratings were associated with a blunted PRL response to fenfluramine in a large sample of men and women. Positive mood, averaged over 7 consecutive days, accounted for nearly 2% of the variation in the maximal PRL response to fenfluramine after controlling for known predictors of this response, including baseline PRL concentrations, age, sex, and fenfluramine and norfenfluramine levels assessed during the challenge. In addition, the association of

Acknowledgements

This research was supported by National Institutes of Health grants HL46328, HL40962, and HL65137.

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