Central Serotonin Activity Research Articles

Prevalence and Correlates of Serotonin Syndrome in Real-World Inpatients.

Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction due to an increased central and peripheral serotonin activity, which usually presents as a triad of behavioral changes, neuromuscular excitability, and autonomic instability. Probably SS is often misdiagnosed, and its symptoms are mistaken for psychiatric symptoms or general medical issues: the true incidence of SS is not clear, and literature concerning potential risk factors is scarce. Our aims were to examine the prevalence of SS in a naturalistic sample of hospitalized patients and to evaluate potential factors related to the risk of developing the condition. The sample included 133 patients being treated with serotonergic medications admitted to the psychiatric inpatient unit of the San Luigi Gonzaga Hospital. All patients received a medical examination (including a neurological examination) within 24 hours of admission. Serotonin syndrome was diagnosed according to Hunter Criteria. Sixteen patients (12%) were diagnosed with SS. In the subgroup of subjects with SS, we found a higher rate of male patients when compared with subjects with no SS (62.5% vs 33.3%, P = 0.023). SS probably is an underestimated condition, which should be carefully assessed in patients on serotonergic medications. Male gender was the only factor found to be significantly related to a higher risk of developing SS. Further studies on larger samples are needed, to gain more information on possible risk factors and to identify subjects more prone to developing SS, given the potential risk for patients' health.

Mutuality of thyroid hormones and psychiatric disorders

Abnormalities in thyroid function may induce affective, anxious, psychotic, and cognitive disorders and are a potential marker for assessing suicidal risk in patients suffering from psychiatric disorders. This retrospective, cross-sectional, electronic, and data-based study, comprising 118 adult psychiatric patients, aimed to establish differences in the concentrations of total T3, T4, and thyroid-stimulating hormone among patients diagnosed with common psychiatric disorders. The analysis encompassed the levels of these hormones in patients who had attempted suicide and those who had not. Lower values of total T3 were observed in patients with depressive disorder compared to patients with psychotic and bipolar disorder, as well as the control group. Furthermore, lower total T3 values were observed in patients who had reported a suicide attempt in their lives compared to participants who had not attempted suicide. These findings suggest a potential link between thyroid hormones and the regulation of central serotonin activity. The study underscores the importance of routinely assessing thyroid function in clinical practice to facilitate early detection of suicidality and the prevention of suicide.

Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract.

The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function and cognitive capacities as diverse as reward processing, exploration, and the psychedelic experience, over 95% of the serotonin in the body is released in the gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural serotonin as a rostral extension of the gastrointestinal serotonergic system dissolves much of the mystery associated with the central serotonergic system. Specifically, we outline that central serotonin activity mimics the effects of a digestion/satiety circuit mediated by hypothalamic control over descending serotonergic nuclei in the brainstem. We review commonalities and differences between these two circuits, with a focus on the heterogeneous expression of different classes of serotonin receptors in the brain. Much in the way that serotonin-induced peristalsis facilitates the work of digestion, serotonergic influences over cognition can be reframed as performing the work of cognition. Extending this analogy, we argue that the central serotonergic system allows the brain to arbitrate between different cognitive modes as a function of serotonergic tone: low activity facilitates cognitive automaticity, whereas higher activity helps to identify flexible solutions to problems, particularly if and when the initial responses fail. This perspective sheds light on otherwise disparate capacities mediated by serotonin, and also helps to understand why there are such pervasive links between serotonergic pathology and the symptoms of psychiatric disorders.

Serotonin syndrome: a clinical review of current controversies.

Serotonin syndrome is a state of increased central and peripheral serotonin (5-hydroxytryptamine) activity. Unless recognized and treated early, serotonin syndrome can lead to seizures, shock and death. Both substances with direct and indirect serotonergic activity can precipitate the syndrome. Serotonin syndrome can occur not only in psychiatric but also in non-psychiatric settings. Yet, clinicians may not be familiar with the condition. We explore some of the current controversies regarding serotonin syndrome. Specifically, we tested the following assumptions: (i) Despite being rare, serotonin syndrome is still clinically relevant; (ii) The Hunter criteria are the gold standard for diagnosing serotonin syndrome; (iii) Hyperthermia is common in cases of serotonin syndrome; (iv) Serotonin syndrome usually develops fast; (v) Severe serotonin syndrome usually or almost exclusively involves monoamine oxidase inhibitors. We found that (i) despite being rare, serotonin syndrome was clinically relevant, (ii) the Hunter criteria could not be regarded as the gold standard for the diagnosis of serotonin syndrome since they missed more cases than the other two diagnostic criteria systems (Sternbach and Radomski criteria), (iii) Serotonin syndrome could occur in the absence of an elevated temperature, (iv) fast onset could not be regarded as a reliable clinical sign of serotonin syndrome, and (v) absence of monoamine oxidase inhibitors treatment did not exclude a diagnosis of serotonin syndrome. Clinicians should bear in mind that in the context of relevant drug history, serotonin syndrome may still be possible in these circumstances.

Serum Levels of Tumor Necrosis Factor-α and Loudness Dependence of Auditory Evoked Potentials at Pretreatment and Posttreatment in Patients with Major Depressive Disorder.

Background: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), are associated with the pathophysiology of major depressive disorder (MDD). Several studies have reported that increased TNF-α might be associated with tryptophan depletion, which eventually could result in MDD. However, other studies revealed that TNF-α increased serotonin firing in raphe. Therefore, whether TNF-α increases or decreases serotonin activity remains unclear. Here, we aimed to determine the relationship between serum TNF-α level and central serotonergic activity using the loudness dependence of auditory evoked potentials (LDAEP) and standardized low-resolution brain electromagnetic tomography (sLORETA), as well as to evaluate the effects of antidepressants on TNF-α levels. Methods: LDAEP, serum TNF-α level, and depression severity were measured in 64 MDD outpatients pre and post 3 months of treatment. Results: Pretreatment TNF-α levels were negatively correlated with the pretreatment N1 sLORETA-LDAEP, P2 sLORETA-LDAEP, and N1/P2 sLORETA-LDAEP (p < 0.05). In multiple regression analysis for N1/P2 sLORETA-LDAEP, lower N1/P2 sLORETA-LDAEP was significantly related to higher TNF-α (CE = −0.047, p = 0.017) when all subjects were dichotomized based on the median TNF-α level (7.16 pg/mL) into pretreatment low- and high-TNF-α groups. In addition, the pretreatment Beck Depression Inventory, P2 LDAEP, and N1/P2 sLORETA-LDAEP were greater in the high-TNF-α groups than in the low-TNF-α groups (p < 0.05). Moreover, the posttreatment TNF-α level was significantly decreased compared to the pretreatment TNF-α level (z = −2.581, p = 0.01). However, the posttreatment TNF-α levels were not associated with posttreatment LDAEP. Conclusions: Higher TNF-α level is associated with decreased LDAEP, which could indicate compensatory elevation of central serotonin activity in outpatients with MDD, although this effect disappeared and TNF-α level was reduced after three months of antidepressant treatment.

Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU) patients

IntroductionPhenylketonuria (PKU) is an inborn error of metabolism associated with an increased risk of behavioural and mood disorders. There are currently no reliable markers for monitoring mood in PKU. The purpose of this study was to evaluate salivary serotonin as a possible non-invasive marker of long-term mood symptoms and central serotonin activity in patients with PKU. Methods20 patients were recruited from our Adult Metabolic Diseases Clinic. Age, sex, plasma phenylalanine (Phe) level, DASS (Depression Anxiety Stress Scales) depression score, DASS anxiety score, BMI, salivary serotonin, salivary cortisol, 2-year average Phe, 2-year average tyrosine (Tyr), and 2-year average Phe:Tyr ratio were collected for each patient. Spearman's ρ correlation analysis was used to determine if there was any relationship between any of the parameters. ResultsThere were positive correlations between DASS anxiety and DASS depression scores (Spearman's ρ = 0.8708, p-value < 0.0001), BMI and plasma Phe level (Spearman's ρ = 0.6228, p-value = .0034), and 2-year average Phe and BMI (Spearman's ρ = 0.5448, p-value = .0130). There was also a negative correlation between salivary cortisol and plasma Phe level (Spearman's ρ = −0.5018, p-value = .0338). All other correlations were not statistically significant. ConclusionSalivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, implying that salivary serotonin does not reflect central serotonin turnover. Additionally, this study suggests that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU. SynopsisSalivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, suggesting that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU.

Low Inherent Sensitivity to the Intoxicating Effects of Ethanol in Rhesus Monkeys with Low CSF Concentrations of the Serotonin Metabolite 5-Hydroxyindoleacetic Acid.

Type 2 alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol (EtOH), which is thought to be marker for future alcohol use disorders (AUDs). As such, an important aim of studies investigating the origins of AUDs is to understand the relationship between serotonin system functioning and level of intoxication. A nonhuman primate model was used to evaluate observational ratings of sensitivity to EtOH and to further investigate the relationship between central serotonin activity and behavioral response to EtOH. Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were obtained from 4 cohorts of alcohol-naïve, adolescent rhesus macaques (N=82, 45 females, 37 males). One to 3months after the CSF sample, subjects were administered a standardized intravenous EtOH bolus (males: 2.1g/kg body weight, females: 2.0g/kg body weight), placed into an open-top, clear plexiglass chamber suspended from the ceiling, and their latency to escape was recorded as a measure of the degree of intoxication. Thereafter, subjects were rated using a Likert scale for the degree of intoxication during a 30-minute observation period. Our results indicate that latency to escape from the chamber was associated with intoxication ratings (p=0.0009) following the standardized intravenous administration of EtOH. Low CSF 5-HIAA concentrations predicted short escape latency (p=0.007) and were associated with low intoxication ratings (p=0.02), indicating that low central nervous system (CNS) serotonin functioning is related to relative insensitivity to the intoxicating effects of alcohol. Our study shows that, in monkeys exposed to alcohol for the first time, objective measures of intoxication are associated with subjective ratings for intoxication, and both were associated with CSF 5-HIAA concentrations. Our data confirm and extend the finding that low CNS serotonin functioning is predictive of intrinsic low sensitivity to the intoxicating effects of EtOH.

The role of serotonin in personality inference: tryptophan depletion impairs the identification of neuroticism in the face

Serotonergic mechanisms mediate the expression of personality traits (such as impulsivity, aggression and anxiety) that are linked to vulnerability to psychological illnesses, and modulate the identification of emotional expressions in the face as well as learning about broader classes of appetitive and aversive signals. Faces with neutral expressions signal a variety of socially relevant information, such that inferences about the big five personality traits, including Neuroticism, Extraversion and Agreeableness, can be accurately made on the basis of emotionally neutral facial photographs. Given the close link between Neuroticism and psychological distress, we investigated the effects of diminished central serotonin activity (achieved by tryptophan depletion) upon the accuracy of 52 healthy (non-clinical) adults’ discriminations of personality from facial characteristics. All participants were able to discriminate reliably four of the big five traits. However, the tryptophan-depleted participants were specifically less accurate in discriminating Neuroticism than the matched non-depleted participants. These data suggest that central serotonin activity modulates the identification of not only negative facial emotional expression but also a broader class of signals about personality characteristics linked to psychological distress.

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity.

BackgroundGene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP) is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs) in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.MethodsA total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ) and hospital anxiety and depression scale (HADS). Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT) were analyzed in healthy subjects.ResultsThere was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.ConclusionsOur findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.

Differences in central serotoninergic transmission among patients with recent onset, sub-chronic, and chronic schizophrenia as assessed by the loudness dependence of auditory evoked potentials

Previous research has shown that abnormalities in serotonin systems are associated with schizophrenia. The loudness dependence of auditory evoked potentials (LDAEP) has been used as a metric of central serotonin activity. The present study aimed to evaluate LDAEP in patients with schizophrenia of differing chronicity. Sixty-four patients with schizophrenia and 50 healthy controls were enrolled in this study. LDAEP and psychometric ratings, such as the positive and negative syndrome scale (PANSS), were measured. The cohort was stratified into three subgroups according to the duration of illness: recent onset (<2years, n=21), sub-chronic (2–9years, n=28), and chronic (≥10years, n=15) groups. The LDAEP differed significantly among the three groups. A post-hoc analysis (Bonferroni) demonstrated that the LDAEP differed significantly between the recent onset and chronic groups (p=0.029), and between the healthy control and chronic groups (p=0.008). Age, sex, dosage of antipsychotics, and smoking did not significantly affect the group differences. In the correlation analysis, there was a significant correlation of LDAEP values with illness duration (r=−0.259, p=0.045). The present study verifies that the LDAEP is related to the duration of illness in patients with schizophrenia. This suggests that central serotonin neurotransmission is changeable, and it may depend on the chronicity of schizophrenia pathology.

David vs. Goliath: Serotonin modulates opponent perception between smaller and larger rivals

During agonistic encounters, the perception of a larger opponent through morphological signaling typically suppresses aggression in the smaller individual, preventing contest intensity escalation. However, non-morphological factors such as central serotonin (5-HT) activity can influence individual aggression, potentially altering contest intensity despite initial size discrepancies. When male stalk-eyed flies (Teleopsis dalmanni) fight, contest escalation is directly proportional to similarity in body size, with escalation being lower in size-mismatched contests. We have shown that both high-intensity aggression and the probability of winning are increased in males with pharmacologically elevated 5-HT relative to size-matched non-treated opponents. Here, we hypothesized that, in size-mismatched contests, increasing brain 5-HT in the smaller opponent could similarly increase aggression and counteract the low contest intensity normally driven by size discrepancy. Size-mismatched male pairs (greater than 5% difference in eyestalk length) engaged in a forced fight paradigm, with the smaller fly either untreated or with pharmacologically elevated 5-HT levels. The expression of high-intensity aggressive behaviors was significantly increased in smaller treated opponents, but the probability of winning was not altered. This suggests that while elevated serotonergic activity can increase aggression and intensity despite perception of a larger opponent, this is not sufficient to overcome size biases with respect to contest outcome. However, the fact that larger opponents continued to win against smaller treated flies was not simply a function of size. Instead, untreated larger males adjusted their fighting strategy to match the increased aggression of their smaller treated opponent, suggesting contextual flexibility in behavior based on individual opponent assessment.

Serum BDNF Levels in Relation to Illness Severity, Suicide Attempts, and Central Serotonin Activity in Patients with Major Depressive Disorder: A Pilot Study

The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders – text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that conflicts with previous results.

Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients

The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008–December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F1;379=9.29; P=0.002), suicidal status (F1;379=4.49; P=0.04) and the interaction between sex and suicidal status (F1;379=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk.

Exercise Increases Tryptophan Availability to the Brain in Older Men Age 57–70 Years

Many aspects of serotonergic activity, both central and peripheral in origin, undergo significant changes with human aging. These alterations might predispose elderly people to develop mood disorders. Because previous work showed that increasing the peripheral availability of tryptophan (TRP) to the brain holds antidepressant properties, this study evaluated whether TRP availability to the brain is increased during prolonged exercise in older men. Nineteen males age 64 ± 3 yr completed a treadmill exercise bout at an HR eliciting ∼68% V˙O(2peak) for 60 min. Fasting blood was collected at rest, after 30 and 60 min of exercise, and at 90 min (after exercise). Branched-chain amino acids (BCAA), total and free TRP, prolactin, ammonia, nonesterified fatty acids, glucose, and lactate were measured. Changes in free TRP/BCAA ratio and prolactin were used as peripheral proxies of central serotonin synthesis rate and activity. The free TRP/BCAA ratio observed at baseline was increased by 102% after 1 h of exercise (P < 0.0001) and remained elevated after exercise (78% above baseline, P < 0.001). The free TRP portion in serum increased from 2.8 ± 0.7 to 5.7 ± 1.8 μmol·L⁻¹ after 1 h of exercise (P < 0.001) and was strongly correlated with plasma nonesterified fatty acid contents (r₁₇ = 0.887, P < 0.0001, all time points). Serum prolactin was significantly elevated after 1 h of exercise (8.6 ± 2.4 μg·L⁻¹, P < 0.001) and was positively correlated with free TRP/BCAA ratio (r₁₆ = 0.48, P < 0.05, all time points). These results concur with previous observations in younger men and unveil that significant elevations in TRP availability to the brain are encountered during sustained exercise in older men. These results provide support to the hypothesis that increases in serotonin synthesis and activity might be involved in the antidepressant effect of exercise in the elderly.

Complex Regional Pain Syndrome Type 1 in a Child With Migraine

Complex regional pain syndrome type 1 is a rare painful syndrome in children involving an extremity which consists of pain out of proportion to the cause, loss of function, and significant evidence of autonomic dysfunction. We report a child, a known case of migraine who presented with spontaneous onset pain and sudomotor changes in an extremity not preceded by any trauma. A good clinical eye is required for the identification and diagnosis of this underreported condition to prevent doing extensive investigations. The coexistence of migraine and complex regional pain syndrome type 1 in a patient is interesting and is probably due to the common underlying pathophysiological abnormalities involving central serotonin activity and neurogenic inflammatory mechanisms.

Serotonergic Activity Influences the Cognitive Appraisal of Close Intimate Relationships in Healthy Adults

Close supportive relationships protect against psychological disorders and also facilitate recovery. However, little is known about the neurochemical mechanisms that mediate these effects. Variation in serotonin function influences affiliative behavior in humans and nonhuman primates. Here, we used tryptophan depletion in healthy adults to investigate the role of serotonin in the cognitive appraisal of close personal relationships. Twenty-two healthy adults drank an amino acid drink without tryptophan, and 19 healthy adults drank an amino acid drink containing tryptophan. Participants were presented with color photographs of heterosexual "couples" standing apart or making affiliative touch gestures and rated the couples for descriptors that capture qualities of close personal relationships. Trait attachment style and state affect of participants were also measured. Tryptophan depletion reduced the judged intimacy and romance of photographed couples. Tryptophan-depleted women rated men as more dominant in relationships and touching couples as more able to resolve their conflicts, when compared with nondepleted women. These effects were not due to changes in mood and remained statistically reliable when the marked impact of attachment style upon relationship judgments was statistically controlled. Our results suggest that central serotonin activity influences the appraisal of close intimate partnerships, raising the possibility that serotonergic dysfunction contributes to altered cognitions about relationships in psychiatric illnesses.

In Search of Endophenotypes for Suicidal Behavior

In Search of Endophenotypes for Suicidal Behavior

Serotonin Augmentation Reduces Response to Attack in Aggressive Individuals

We tested the theory that central serotonin (5-hydroxytryptamine, or 5-HT) activity regulates aggression by modulating response to provocation. Eighty men and women (40 with and 40 without a history of aggression) were randomly assigned to receive either 40 mg of paroxetine (to acutely augment serotonergic activity) or a placebo, administered using double-blind procedures. Aggression was assessed during a competitive reaction time game with a fictitious opponent. Shocks were selected by the participant and opponent before each trial, with the loser on each trial receiving the shock set by the other player. Provocation was manipulated by having the opponent select increasingly intense shocks for the participant and eventually an ostensibly severe shock toward the end of the trials. Aggression was measured by the number of severe shocks set by the participant for the opponent. As predicted, aggressive responding after provocation was attenuated by augmentation of serotonin in individuals with a pronounced history of aggression.

The role of serotonin in risky choice and the acquisition of reciprocal cooperative behaviour: 2 investigations using tryptophan depletion

Abstract. Making decisions between risky actions involves weighing the pros and cons of each, and considering the relative probabilities with which good and bad outcomes will occur. In this paper, I review 2 recent studies suggesting that serotonin modulates the cognitive and emotional processes involved in such decision-making in both non-social and social contexts. First, we have found that tryptophan depletion – leading to diminishes central serotonin activity – alters attention towards the gains associated with risky options. Second, we have found that tryptophan depletion alters the acquisition of socially cooperative behaviour in an iterated Prisoner's Dilemma game. These findings highlight the significance of serotonin in altered non-social and social risky choice in psychiatric illnesses.

Is the loudness dependence of auditory evoked potentials modulated by the selective serotonin reuptake inhibitor citalopram in healthy subjects?

The loudness dependence of auditory evoked potentials (LDAEP) has been discussed as a non-invasive in vivo marker of central serotonergic function. Evidence for this has been found in animal studies, but studies in humans provide less consistent results. In this study, the relationship between LDAEP and directly modulated central serotonergic activity in healthy subjects was investigated. In a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/- 2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo. LDAEP was measured at five different time points before, during and up to 60 min after drug/placebo administration and dipole source analysis was performed. The increase of the central serotonin activity in response to citalopram was not accompanied by a significant change of the LDAEP compared to the placebo condition. The result underlines that the acceptance of LDAEP as a marker of central serotonergic function still needs further discussion.