Seasonal Affective Disorder (SAD), winter type, is a mood disorder characterized by the regular occurrence of depressive episodes during fall or winter followed by spontaneous remission or hypomanic episodes in spring or summer (Rosenthal et al., 1984). SAD patients fulfill the diagnostic criteria for major depressive disorder or bipolar II disorder, and their longitudinal course is described by the seasonal pattern specifier of the Diagnostic and Statistical Manual 4th Edition (DSM IV, American Psychiatric Association, 1994). Common symptoms in SAD include depressed mood and the so-called atypical or reverse vegetative symptoms such as hypersomnia, hyperphagia, fatigue, carbohydrate craving and subsequent weight gain (Rosenthal et al., 1984). There is strong evidence for a key role of serotonergic systems in the pathogenesis of SAD (Kasper et al., 1996 and Lam and Levitan, 2000). Controversy exists of whether serotonergic dysfunction may represent a trait marker in SAD (Schwartz et al., 1997; Neumeister et al., 1998 and Lam and Levitan, 2000).
When compared to non-seasonal depressives or controls, SAD has also been reported to be associated with an increased likelihood of personality disorder, reflecting a possible link between personality and seasonal mood changes (Schulz et al., 1988, Schuller et al., 1993 and Reichborn-Kjennerud et al., 1994). As proposed by Cloninger et al. (1993), temperament dimensions are believed to represent biologically based traits, while character traits may rather reflect sociocultural learning processes. This concept was realized in the Temperament and Character Inventory (TCI), a widespread instrument for the assessment of personality disorders (Cloninger, 1994).
The serotonin transporter (5-HTT) is a candidate locus for etiological involvement in affective disorders. A functional polymorphism in the serotonin promoter gene region (5-HTTLPR) has been found to influence serotonin transporter (5-HTT) expression in human cell lines (Heils et al., 1996 and Lesch et al., 1996). This polymorphism is a 44-bp insertion/deletion polymorphism located approximately 1 kb upstream from the 5-HTT coding sequence. The short variant (“s allele”) of the 5-HTT-linked polymorphic region (5-HTTLPR) restricts transcriptional activity of the 5-HTT promoter, leading to low functional expression of 5-HTT. The HTTLPR short allele (s) has been shown to be associated with reduced 5-HTT mRNA levels, lower 5-HTT densities on the cell surface, and reduced 5-HT uptake rates in cultured human lymphocytes ( Lesch et al., 1996). The s allele appears to be functionally dominant over the 5-HTTLPR long allele (l), since heterozygous cells behave like cells homozygous for the s allele ( Lesch et al., 1996).
It has been reported that the 5-HTTLPR-dependent variation in functional 5-HTT expression may confer a genetic susceptibility towards affective disorders (Collier et al., 1996). Moreover, the s allele has been associated with violent suicide behavior ( Bondy et al., 2000), alcoholism ( Sander et al., 1997), obsessive compulsive disorder ( McDougle et al., 1998), and schizophrenia ( Malhotra et al., 1998).
Controversy exists as to what extent the 5 HTTLPR polymorphism may contribute to personality dimensions. Several authors reported an effect of the 5-HTTLPR polymorphism on TCI scores such as Harm Avoidance (Cloninger et al., 1993, Allgulander et al., 1997, Peirson et al., 1998 and Osher et al., 2000), Novelty Seeking (Benjamin et al., 2000a), Persistence (Benjamin et al., 2000b) and Cooperativeness (Kumakiri et al., 1999). Other studies failed to find an association between 5-HTTLPR polymorphism and personality scores, suggesting that the factor structure of the TCI does not reveal the hypothesized phenotypic structure (Waller et al., 1993 and Herbst et al., 2000). There is considerable inconsistency in the association of Neuroticism with 5-HTTLPR from studies using different proportions of male and female subjects. As the effects of 5-HTTLPR are possibly gender related (Du et al., 2000), we conducted our study in females only.
With respect to SAD, Rosenthal et al. (1998) reported an association between the 5-HTTLPR s allele with SAD and high levels of seasonality. However, these data were not replicated in more recent studies ( Willeit et al., 2003 and Johansson et al., 2001). Jang et al., 1998 and Jang et al., 1997 found evidence for a hereditary component of seasonal changes in personality measures using the Dimensional Assessment of Personality Pathology ( Livesley and Jackson, 1992) in a sample of homozygotic and heterozygotic twin pairs.
In order to investigate whether 5-HTTLPR polymorphism may contribute to personality dimensions in SAD, we conducted a study on the potential interaction between 5-HTTLPR and personality in SAD patients and healthy controls using the TCI (Cloninger, 1994
