Pair-bonding has been suggested to be a critical factor in the evolutionary development of the social brain. The brain neuropeptide arginine vasopressin (AVP) exerts an important influence on pair-bonding behavior in voles. There is a strong association between a polymorphic repeat sequence in the 5 flanking region of the gene (avpr1a) encoding one of the AVP receptor subtypes (V1aR), and proneness for monogamous behavior in males of this species. It is not yet known whether similar mechanisms are important also for human pair-bonding. Here, we report an association between one of the human AVPR1A repeat polymorphisms (RS3) and traits reflecting pair-bonding behavior in men, including partner bonding, perceived marital problems, and marital status, and show that the RS3 genotype of the males also affects marital quality as perceived by their spouses. These results suggest an association between a single gene and pair-bonding behavior in humans, and indicate that the well characterized influence of AVP on pair-bonding in voles may be of relevance also for humans.monogamy ͉ neuropeptide ͉ polymorphism ͉ social behavior P rimate social organization is often characterized by bonded relationships, and recent analyses suggest that it may have been the particular demands for pair-bonding behavior that triggered the evolutionary development of the primate social brain (1). The brain neuropeptide arginine vasopressin (AVP), acting through the receptor subtype V1aR, plays a key role in the regulation of pairbonding behavior in male rodents, as revealed by a series of elegant studies on closely related vole species, i.e., montane voles (Microtus montanus), meadow voles (Microtus pennsylvanicus), and prairie voles (Microtus ochrogaster) (2). In prairie voles, which in contrast to montane and meadow voles are socially monogamous and highly social, pair-bond formation and related behaviors are facilitated by AVP and prevented by a V1aR antagonist (3). Supporting the theory that the striking difference in pair-bonding between monogamous and nonmonogamous voles is related to the influence of AVP on this behavior, the neuroanatomical distribution of V1aR differs considerably between these vole species (4) and is associated with sexual and social fidelity among prairie voles (5). Moreover, partner preference is enhanced in the nonmonogamous meadow vole when the V1aR density is increased in relevant brain areas by using viral vector gene transfer (6). Although there are no major differences in the coding sequence of the gene encoding V1aR (avpr1a) between prairie, montane or meadow voles, the former species displays a 428-base pair sequence in the 5Ј flanking region that is not found in the latter two species. When the avpr1a of the prairie vole, including the sequence in the 5Ј region, is transgenically inserted into the nonmonogamous species mouse (7), more pronounced social behavior, similar to that displayed by prairie voles, is generated. Furthermore, variation in the 5Ј flanking region of prairie vole avpr1a affects brain ex...

Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond to placebo are widely unknown. Here, we used functional neuroimaging to examine neural correlates of anxiety reduction resulting from sustained placebo treatment under randomized double-blind conditions, in patients with social anxiety disorder. Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period. Patients were genotyped with respect to the serotonin transporter-linked polymorphic region (5-HTTLPR) and the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene promoter. Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing. However, attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703T polymorphism, and not in carriers of short or T alleles. Moreover, the TPH2 polymorphism was a significant predictor of clinical placebo response, homozygosity for the G allele being associated with greater improvement in anxiety symptoms. Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity. Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.

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We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.