Jürgen Hennig

Serotonin and dopamine as mediators of sensation seeking behavior

The purpose of the present paper was to investigate the relationship of the serotonergic and dopaminergic systems to subscales of sensation seeking (SS). Two of the subscales, Disinhibition (DIS) and Experience Seeking (ES), were chosen for analysis based on their representation of the two major factors obtained in a factor analysis: DIS represents a factor of lack of impulse control and ES a factor of novelty seeking. In studies 1 and 2 responsivity to a serotonergic (5-HT) challenge by a 5-HT1a receptor agonist (ipsapirone) was investigated by drug-induced prolactin (PRL) and cortisol responses, as well as by emotional states and behavioral measures. The dopaminergic (DA) response to a DA agonist (lisuride) and antagonist (fluphenazine) was analyzed in a condition of smoking deprivation (study 3) using PRL responses, emotional states, and behavioral measures of nicotine craving as dependent variables. In the studies of the serotonergic system, high ES subjects showed a blunted cortisol response in both studies and high DIS subjects demonstrated a blunted PRL response in study 2. A frequently observed side effect of serotonergic agonists, increase in emotional arousal, was not observable with ipsapirone in high ES and high DIS subjects as compared to low scorers. Behavioral aggression, which had been experimentally induced in study 2, was increased in high ES as well as in high DIS by the 5-HT1a agonist which exerted antiaggressive effects in low scorers. These findings were found compatible with the idea of a generally low responsivity of the serotonergic system in high ES as well as in high DIS types of sensation seekers of 5-HT1a subsensitivity in high DIS and subsensitivity of other postsynaptic 5-HT receptors in high ES. There was no association between SS subscales and DA-induced decrease of PRL, but high ES subjects seemed to tolerate nicotine deprivation better than low ES subjects indicating that they were less susceptible to deprivation of nicotine-induced DA. But craving for nicotine was increased in high ES subjects by the DA agonist lisuride as opposed to the antagonist, which was taken as evidence that DA stimulation may induce approach behavior in high ES. Although only two subscales had been selected for the investigation, this approach suggests both common and different relationships between SS subscales and neurotransmitter systems.

Identification of first candidate genes for creativity: a pilot study.

Studies from behavioral genetics have demonstrated the high heritability of intelligence. However, the endeavor to detect the genes forming the molecular basis of intelligence has been rather unsuccessful until now. Pharmacological studies have demonstrated the influence of the dopaminergic (DA) and the serotonergic (5-HT) system on subcomponents of cognitive functioning, and first studies from molecular genetics have demonstrated that genes related to the DA metabolism are associated with mental abilities. However, candidate genes for creativity have not been identified so far. Therefore, the influence of the catechol-O-methyltransferase (locus: COMT VAL158MET) gene and the dopamine D2 receptor gene (locus: DRD2 TAQ IA) on creativity was tested in addition to a serotonergic gene, TPH1 (locus: TPH-A779C), in a sample of N = 92 healthy Caucasian subjects while controlling for intelligence. Results showed that the DRD2 gene and the TPH gene were both associated with total creativity, explaining 9% of the variance, while COMT was not related to creativity at all. With respect to the subcomponents, the A1+ allele of DRD2 was related to higher verbal creativity as compared to the A1- allele, and carriers of the A allele of TPH1 showed significantly higher scores in figural and in numeric creativity, indicating that the two gene loci discriminate between higher cortical functions according to the organization of cognitive functions in the respective hemispheres.

Variation in the serotonin transporter gene modulates selective attention to threat.

The 5-HTTLPR is an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene. Prior research has revealed associations between the short-allele variant of this polymorphism, enhanced self-reported negative emotionality, and hypersensitivity of fear relevant neural circuits. In a sample of 50 healthy women we examined the role of 5-HTTLPR for cognitive-affective processing of phylogenetical fear-relevant stimuli (spiders) in a dot probe task. In contrast to homozygote long-allele carriers (ll), participants carrying at least 1 short allele (ss and sl) selectively shifted attention toward pictures of spiders, when these were presented for a duration of 2,000 ms. These results argue for an involvement of 5-HTTLPR in cognitive processing of threatening stimuli and thus, underpin its general role for individual differences in negative affect.

Imaging gene–substance interactions: The effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.

Impaired Executive Control Is Associated with a Variation in the Promoter Region of the Tryptophan Hydroxylase 2 Gene

Current models of attention describe attention not as a homogenous entity but as a set of neural networks whose measurement yields a set of three endophenotypesalerting, orienting, and executive control. Previous findings revealed different neuroanatomical regions for these subsystems, and data from twin studies indicate differences in their heritability. The present study investigated the molecular genetic basis of attention in a sample of 100 healthy subjects. Attention performance was assessed with the attention network test that distinguishes alerting, orienting, and executive control (conflict) using a simple reaction time paradigm with different cues and congruent and incongruent flankers. Two gene loci on candidate genes for cognitive functioning, the functional catechol-O-methyltransferase (COMT) VAL158MET and the tryptophan hydroxylase 2 (TPH2) 703 G/T promoter polymorphism, were tested for possible associations with attention. COMT is involved in the catabolism of dopamine, and TPH is the rate-limiting enzyme for serotonin synthesis. Results showed no effect of the COMT polymorphism on attention performance. However, the TT genotype of TPH2 03 G/T was significantly associated with more errors (a possible indicator of impaired impulse control; p = .001) and with decreased performance in executive control (p = .001). This single-nucleotide polymorphism on the TPH2 gene explained more than 10% of the variance in both indicators of attention stressing the role of the serotonergic system for cognitive functions.

Two types of aggression are differentially related to serotonergic activity and the A779C TPH polymorphism

The authors investigated whether different types of aggression relate to the A779C tryptophan hydroxylase (TPH) polymorphism and to serotonergic activity in volunteers. A factor analysis of the Buss-Durkee Hostility Inventory yielded 2 factors representing Neurotic Hostility (NH) and Aggressive Hostility (AH). The authors used a neuroendocrine challenge with Citalopram in 48 volunteers and increased cortisol concentrations only in those with high levels of AH. Finally, an association study with 58 volunteers revealed that the A779C TPH polymorphism significantly relates to AH, with the highest aggression levels for the genotype AA and the lowest aggression levels for the genotype CC, but not to NH. Results are discussed with respect to inconsistent findings in the literature, which may be explained by this distinction of types of aggression.

Auditory-Evoked Potentials and Selective Attention: Different Ways of Information Processing in Cannabis Users and Controls

The present study tested the hypothesis that chronic cannabis use leads to persistent attentional dysfunctions and that age of onset of cannabis use is a potential predictor of impaired test performance and information processing. Brain event-related potentials (ERPs) during a complex auditory selective attention task were recorded from 21 cannabis users divided into two groups according to age of onset and from 13 controls comparable with respect to age, IQ and educational background. Participants were instructed to detect target tones of a particular location, pitch and duration from a total sample of random frequencies. The study reveals that the latency of the greatest negative peak of ERPs (200 and 300 ms) to target tones was shorter in controls, while there was no clear difference between target and non-target within cannabis users. In addition, users displayed a reduced P3 to target tones. This was more pronounced in early-onset cannabis users. These data suggest that chronic cannabis use relates to different types of information processing under conditions of selective attention. There is some evidence that users employed different strategies of attention allocation. The results are discussed with respect to possible underlying mechanisms and clinical implications.

Inferring candidate genes for Attention Deficit Hyperactivity Disorder (ADHD) assessed by the World Health Organization Adult ADHD Self-Report Scale (ASRS)

Summary.The present study tests the psychometric properties and validity of the German version of the World Health Organization Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS), which is a short screening instrument for use in the general population. Furthermore, two candidate genes for ADHD, the COMT VAL158MET and the 5-HT2a T102C polymorphisms, were tested for associations with the ASRS subscales inattention and hyperactivity/impulsivity in N = 203 healthy subjects.The ordinal CFA yielded a two-factorial model corroborating the structure of the official English WHO version. Genetic analysis revealed an association between the VAL allele of COMT and the inattention scale (F(1, 201) = 7.20, p = 0.008), the hyperactivity/impulsivity scale (F1, 201 = 4.30, p = 0.039), and the total ASRS scale (F(2, 201) = 7.64, p = 0.006) with highest scores in carriers of the MET/MET genotype. The C-allele of 5-HT2a was significantly associated with the hyperactivity/impulsivity scale (F(1, 201) = 5.52, p = 0.020) and the total ASRS scale (F(1, 201) = 4.21, p = 0.042) with highest scores in carriers of the TT genotype.The data provide evidence for the structural as well as for the external validity of the ASRS.

Personality and emotion: test of Gray's personality theory by means of an fMRI study.

Although it is known that there are fundamental personality differences in the behavioral responses to emotional stimuli, traits have scarcely been investigated in this context by means of functional imaging studies. To maximize the variance with respect to personality, the authors tested 12 control subjects and 12 subjects who had sadomasochistic experiences with respect to the relationship between J. A. Grays (1970) personality dimensions, the behavioral approach system (BAS) and the behavioral inhibition system (BIS), and brain activity in regions of interest. The BIS was associated with activity in numerous brain areas in response to fear, disgust, and erotic visual stimuli, whereas few associations could he detected between the BAS and brain activity in response to disgust and erotic stimuli.

Personality and biological markers of creativity

The aim of the present study was to test (i) Eysencks theory that psychoticism (P) should be related to creativity, (ii) whether testosterone (T), due to its association with P claimed in the literature, can be identified as a biological marker of creativity, and (iii) whether the SEEK dimension of the Affective Neuroscience Personality Scales (ANPS) was also related to creativity and to testosterone due to its relationship to Sensation Seeking. In a sample of N = 48 male and female subjects, test scores on figural, verbal, and numeric creativity were compared between high and low P‐scorers as well as between high and low SEEK‐scorers. Effects were controlled for fluid intelligence as measured by Cattells CFT‐3 and crystallized intelligence as assessed by the Structure‐of‐Intelligence‐Test (Intelligenz‐Struktur‐Test, I‐S‐T 2000 R). Neither a main effect of P or T nor an interaction effect P×T on creativity could be obtained. Instead, SEEK was related to all components of creativity and explained more than 15% of the variance of total creativity. Moreover, significant differences in SEEK could be explained by differences in T, independently of gender. Furthermore, 39% of the variance of SEEK could be explained by the two uncorrelated indicators testosterone and creativity. Copyright