No abstract

In sum, our results show that a functional polymorphism of the 5-HTT genotype, family relations, and interactions between these variables predict adolescent alcohol consumption in a randomized sample of adolescents.

Transcription factor AP-2␤ is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia. 1,2 The gene encoding AP-2␤ contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612. 3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2␤ genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2␤ genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2␤ genotype, albeit with significant difference between genders. Based on this result the human AP-2␤ gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2␤ gene is one factor that contributes to development of the constitutional component of specific personality traits. Molecular Psychiatry (2000) 5, 220-224.

Major changes in psychiatric phenotypes due to genetic factors are seldom the result of single gene polymorphisms, but more often the result of several genetic mechanisms. In this millennium article we discuss the notion that the expression of numerous candidate genes could be regulated by the same transcription factors, and that polymorphisms in transcription factor genes might explain some phenotypes. We describe recent results of studies on the biological marker thrombocyte monoamine oxidase (trbc MAO) and the transcription factor AP-2␤. Low levels of trbc MAO is associated with temperamental characteristics such as sensation seeking and impulsiveness, and the enzyme is genetically regulated by specific transcriptional mechanisms. Transcription factor AP-2␤ is important for the development of midbrain structures and AP-2␤ has several binding sites in the regulatory regions of genes encoding key proteins in the monoamine transmitter systems. We have recently shown AP-2␤ to be linked to personality, binge-eating disorder, treatment with antidepressant drugs, and also to trbc MAO. Regardless of whether transcriptions factors, such as AP-2␤, regulate the expression of eg, the number of monoamine neurons or a variety of candidate genes within the monoamine systems, or both, we would like to emphasize the role of transcription factors, besides polymorphisms in monoaminergic candidate genes, when explaining inter-individual differences in temperament and psychiatric vulnerability. Molecular Psychiatry (2001) 6, 503-510.

The importance of an interaction between environment and biological factors for the expression for a particular behaviour is illustrated by results from a series of adolescents in which effects of platelet MAO activity and psychosocial environment on criminality was investigated. In a favourable environment platelet MAO-B activity was not associated with criminality, while a very strong association was found in adolescents from a bad psychosocial environment. Essentially similar findings were obtained when a MAO-A promoter polymorphism was analysed instead of platelet MAO-B activity. In boys, presence of the low functioning allele seemed to be protective against criminal activity in combination with a good environment, while it predisposed for criminality in a bad psycho-social environment. In girls, instead, homozygosity for the high activity MAO-A allele interacted with environment to predict criminality. Possible mechanisms underlying the role of monoamine oxidases for behaviour are discussed.