Several theorists have hypothesized a heritable trait vulnerability factor common to most, if not all, emotional disorders. This trait has been defined slightly differently and given various labels by different theorists, including harm avoidance (Cloninger, 1987), neuroticism (Eysenck, 1947), trait anxiety (Gray, 1982), behavioral inhibition (Kagan, Reznick, & Snidman, 1987), and negative affectivity (Watson & Tellegen, 1985), although the conceptual and empirical overlap among these constructs far outweighs the differences. Each implies a trait disposition to experience negative affect. The term neuroticism is often used to refer to this trait, and is consistent with the emergence of the Big Five model of personality as the dominant model of personality structure in children (e.g., Digman & Inouye, 1986; Digman & Shmelyov, 1996), adolescents (e.g., Digman, 1989; Graziano & Ward, 1992), and adults (e.g., Goldberg, 1992; McCrae & Costa, 1987).

Longitudinal studies have shown that neuroticism predicts later negative affect and symptoms of emotional distress (Costa & McCrae, 1980; Larson, 1992; Levenson, Aldwin, Bosse, & Spiro, 1988), even after controlling for initial symptom levels (Gershuny & Sher, 1998; Jorm, Christensen, Henderson, & Jacomb, 2000). Clark, Watson, and Mineka (1994) reviewed sev eral longitudinal studies showing that neuroticism predicts both subsequent diagnoses and chronicity of major depression. Since this review, studies reported by Hayward, Killen, Kraemer, and Taylor (2000), Kendler and colleagues (Kendler, Kessler, Neale, Heath, & Eaves, 1993; Kendler et al., 2002; Roberts & Kendler, 1999), and Krueger et al. (1996) have each obtained results consistent with the conclusions of Clark et al. (1994). For example, in a large adult female twin sample, Kendler et al. (1993) found that neuroticism predicted the onset of MDD over a 1-year period, and recently, Kendler et al. (2002; Kendler, Kuhn, & Prescott, 2004) tested a multifactorial model and showed that, after stressful life events, neuroticism was the strongest predictor of the onset of major depression.

The relation between neuroticism and depression may vary somewhat by age. Hirschfeld et al. (1989) found that whereas among 31-to 41-year-old individuals neurotic-like characteristics of decreased emotional strength, increased interpersonal dependency, and increased thoughtfulness predicted the first onset of depression, this was not the case for younger 17-to 30-year-old individuals. Similarly, Rohde, Lewinsohn, and Seeley (1990) found that adult participants who experienced a first episode of MDD had exhibited elevated levels of dependent traits 2 to 3 years earlier. Rohde, Lewinsohn, and Seeley (1994), however, found no differences with regard to prior levels of dependency between adolescents who later developed a first MDD and adolescents who were depression-free during a 1-year follow-up period.

In contrast, studies using other measures of neurotic-like traits in children have found evidence of a link with vulnerability for depression. Elevated levels of behavioral inhibition have been observed in laboratory tasks with young offspring of depressed parents (Kochanska & Kuczynski, 1991; Rosenbaum et al., 2000). Caspi, Moffit, Newman, and Silva (1996) reported that children who had been rated as inhibited, socially reticent, and easily upset at age 3 had elevated rates of depressive disorders at age 21. Similarly, van Os, Jones, Lewis, Wadsworth, and Murray (1997) found that physicians' ratings of behavioral apathy at ages 6, 7, and 11 predicted both adolescent mood disorders and chronic de

pression in middle adulthood. Finally, Gjerde (1995) reported that gender may moderate the relation between temperament and mood disorders. Whereas females with higher levels of chronic depression during young adulthood had been described as shy and withdrawn at 3 to 4 years of age, males with chronic depression exhibited higher levels of undercontrolled behaviors as young children. Thus, there is some evidence of an association between neurotic-like traits during childhood and subsequent depression, though it may depend on gender as well as how these traits are measured.

Neuroticism also has been found to be a risk factor for other forms of psychopathology, however, and thus it is not specific to mood disorders. For example, neuroticism has been shown to be a risk factor in the development of posttraumatic stress disorder (PTSD) following trauma (Breslau & Davis, 1992; Breslau, Davis, & Andreski, 1995; Helzer, Robins, & McEvoy, 1987). Behaviorally inhibited children are at greater risk for the development of multiple phobias and various anxiety disorders in later childhood (Biederman et al., 1990; Hirshfeld et al., 1992) and social phobias in adolescence. Hayward et al. (2000) also found that neuroticism predicted the development of panic attacks in a 4-year prospective study in adolescents. Thus, neuroticism appears to be a significant predictor of depression, though it might not be a specific vulnerability marker. Moreover, it is still difficult to distinguish among common cause, precursor, and predisposition models of the relation between neuroticism and depression (Klein, Durbin, Shankman, & Santiago, 2002).

According to cognitive theories of depression (Abramson, Metalsky, & Alloy, 1989; Abramson, Seligman, & Teasdale, 1978; Beck, 1967), depressed individuals have more negative beliefs about themselves, the world, and their future, and tend to make global, stable, and internal attributions for negative events. These negative cognitions are expected to be both concurrently associated with depression and to contribute to the onset and exacerbation of depressive symptoms. Cognitive theories of depression are in herently concordant with diathesis-stress theories. When confronted with stressful life events, individuals who have such negative cognitive tendencies will appraise the stressors and their consequences negatively, and hence are more likely to become depressed than are individuals who do not have such cognitive styles.

Several types of cognitions have been proposed to be related to depression, including low self-esteem, negative automatic thoughts, dysfunctional attitudes, and cognitive distortions (Beck, 1967); self-control (Rehm, 1977); control-related beliefs and self-efficacy (Bandura, 1977); depressive attributional style (Abramson et al., 1978); hopelessness (Abramson et al., 1989); and a ruminative response style (Nolen-Hoeksema, 2000). Cross-sectional studies with clinic and community samples of children have consistently shown a significant relation between negative cognitions, particularly low self-esteem and a pessimistic attributional style, and depression (Garber & Hilsman, 1992). Meta-analyses of studies reporting on attributional style and depression have demonstrated moderate to large effect sizes in cross-sectional studies suggesting a strong concurrent association between negative attributional style and higher levels of depressive symptoms in children and adolescents (Gladstone & Kaslow, 1995; Joiner & Wagner, 1995).

Longitudinal investigations of the role of cognitions in the prediction of childhood depression have yielded varying results. Global self-worth (Allgood-Merton, Lewinsohn, & Hops, 1990; Garber, Martin, & Keiley, 2002; Vitaro, Pelletier, Gagnon, & Baron, 1995) and perceived self-competence in specific domains (Hoffman, Cole, Martin, Tram, & Seroczynski, 2001; Vitaro et al., 1995) have predicted child and adolescent depressive symptoms (e.g., Allgood-Merton et al., 1990; Vitaro et al., 1995) and diagnoses (Garber, Martin, & Keiley, 2002), controlling for prior levels of depression. However, these same cognitive constructs also failed to predict depressive symptoms (Dubois, Felner, Brand, & George, 1999) and onset of new episodes. However, in one of these null studies, participants were selected from a drug and alcohol treatment clinic. The mean depression score in this sample was lower at the second assessment. Treatment procedures may have reduced depression levels dur

ing the assessment interval, making it difficult to predict maintenance or exacerbation of depression.

Attributional style generally has been investigated in the context of stress, though several studies have tested main-effects models or reported main effects in the absence of interactions. Significant prospective relations have been observed between attributional style and later depressive symptoms in children and young adolescents (Nolen-Hoeksema, Girgus, & Seligman, 1986; 1992; Panak & Garber, 1992), though a few studies have failed to find this relationship. In a longitudinal study of the developmental trajectories of negative attributions and depressive symptoms, Garber, Keiley, and Martin (2002) showed that attributional styles that were increasingly negative across time were associated with significantly higher initial levels and increasing growth of depressive symptoms during adolescence.

Prospective studies in children and adolescents have also found support for the cognitive diathesis–stress model of depression (Dixon & Ahrens, 1992; Hilsman & Garber, 1995; Lewinsohn, Joiner, & Rohde, 2001; Nolen-Hoeksema et al., 1992; Panak & Garber, 1992). Using different stressors (grades, peer rejection, and school transition) and different time periods, Garber and colleagues showed in three (Dixon & Ahrens, 1992; Panak & Garber, 1992; Robinson, Garber, & Hilsman, 1995) different short-term longitudinal studies that cognitions (attributions, self-worth) measured before the stressors occurred moderated the effect of the stressors on depressive symptoms in children. Among children who experienced high levels of stress, the relation between negative cognitions about the self or causes of events and depressive symptoms was stronger than in those without such negative cognitions. Lewinsohn et al. (2001) found that among adolescents who had experienced negative life events, intermediate levels of dysfunctional attitudes predicted the onset of depressive disorders a year later.

Developmental theorists (Nolen-Hoeksema et al., 1992; Weisz, Southam-Gero, & McCarty, 2001) have suggested that negative cognitions emerge over time and that their relation with depression becomes stronger with development. For example, in a longitudinal study of children in grades 3 through 8, Nolen-Hoeksema et al. (1992) showed that attributional style alone and in conjunction with stress significantly predicted depressive symptoms in the older but not in the younger children. Similarly, in a cross-sectional comparison of children in grades 4, 6, and 8, Turner and Cole (1994) found that negative cognitions contributed to the prediction of depressive symptoms for the oldest children, but not for the two younger groups. Thus, the relation between the cognition–stress interaction and depressive symptoms appears to be increasing from middle childhood to early adolescence.

If negative cognitions contribute to the development of mood disorders, then “high-risk” offspring of depressed parents should be more likely to exhibit a cognitive vulnerability than children whose parents have not experienced mood disorders. Indeed, children of depressed mothers report significantly lower perceived self-worth and a more depressive attributional style than do children of well mothers (Garber & Robinson, 1997). Thus, children who are at risk for depression, but who have not yet experienced depression themselves, have been found to report a more negative cognitive style that likely represents a vulnerability to later depression.

In summary, correlational, predictive, and offspring studies have provided evidence that there is a cognitive style that represents a vulnerability to depression in children. This cognitive style involves beliefs about the self and explanations about the causes of negative events. Future studies need to examine the development of this cognitive vulnerability over time, and whether it needs to be primed in children (Ingram, Miranda, & Segal, 1998).

Common to all definitions of stress is a focus on environmental conditions that threaten to harm the biological or psychological well-being of the individual (Grant et al., 2003). Stress may occur either as an acute event or as chronic adversity, and as a major life event or as minor events with accumulated effects (either additive or multiplicative) (Grant et al, 2003). Stressful events may be normative (e.g., school transition) or patho

logical (e.g., abuse) and may be independent of, or directly related to and thus dependent on, an individual's actions. Objective environmental consequences of a stressor (i.e., can be reliably rated by objective observers) are hypothesized to have a direct effect on the development of depression. The subjective threat of a stressor involves individuals' appraisals of an event as stressful, which then may impact their psychological well-being (Lazarus, Delongis, Folkman, & Gruen, 1985). Finally, there may be specificity in the relation between stress and psychopathology such that certain subdomains of stressors may be more highly related to depression than others (Beck, 1967; Grant et al., 2003).

Stress plays a prominent role in most theories of depression, and a clear empirical link exists between stressful life events and depression in children and adolescents (Compas, Grant, & Ey, 1994). In infants, depressive symptoms have been associated with stressful life circumstances and often are responsive to changes in the environment (Moreau, 1996). One stressor particularly linked with depression in infants is separation. Spitz and Wolf (1946) noted that a common feature in depressed infants ages 6 to 8 months is separation from the mother. Separation in young children has been found to be associated with grief responses characterized by negative changes in sleep patterns, activity, heart rate, temperature, monoamine systems, immune function, and endocrine function (Kalin & Carnes, 1984). Spitz noted the phenomenon of hospitalism, referring to evidence that infants subjected to long hospital stays experienced a number of psychological difficulties. Longer and more frequent hospital stays and earlier age of entering the hospital were associated with more depressive symptoms in infants (Moreau, 1996).

In school-aged children, cross-sectional studies using either life events checklists or interview methods consistently have shown that depressive symptoms and disorders are significantly associated with both minor and major undesirable life events in children, particularly cumulative or chronic stressors, and negative life events are more prevalent among depressed than nondepressed children (Goodyer, Wright, & Altham, 1988). Cross-sectional studies, however, are not informative about the direction of the relation between stress and depression. Given the association between dependent stressors and depression (Garber, Martin, & Keiley, 2002), it is possible that depression contributes to the occurrence of stressors. Depressed individuals have been found to generate many of the stressors they encounter, and these stressors then serve to exacerbate and maintain the depressive symptoms (Bennett, Pendley, & Bates, 1995).

Laboratory animal studies have shown that antenatal stress impacts the developing physiology of the fetus and later physiological and behavioral outcomes in the offspring of stressed rat and primate mothers. These studies are reviewed in part in this section and in further detail later in this chapter. Henry, Kabbaj, Simon, Le Moal, and Maccari (1994) showed that prenatally stressed rat pups had an elevated corticosterone response to novel environments and reduced hippocampal corticosteroid receptor density, suggesting that prenatal stress may affect the neurobiological development of systems associated with depression. Behaviorally, rat pups stressed in utero had greater distress and defensive behavior (Takahashi, Baker, & Kalin, 1990) and reduced environmental exploration when exposed to aversive or stressful conditions (Poltyrev, Keshet, Kay, & Weinstock, 1996).

Prepartum exposure to stress also may result in hyperresponsiveness to later stressors. Clarke and associates (Clarke & Schneider, 1993; Clarke, Wittwer, Abbott, & Schneider, 1994) randomly assigned pregnant rhesus monkeys to stress and control conditions. The prenatally stressed offspring were less likely than control offspring to play and explore the environment and were more likely to engage in clinging, which is associated with distress in primates. Clarke and Schneider suggested that hypothalamic–pituitary–adrenal (HPA) axis activity was implicated in the hyperresponsiveness to later environmental stressors of prenatally stressed rhesus monkeys.

Thus, these data from animal models and additional data (see below) indicate that stress that occurs as early as at conception likely contributes to an increased vulnerability to depression. In human infants, stress during pregnancy is associated with negative outcomes for offspring (Lou et al., 1994). Although the mechanisms by

which stress impacts the developing fetus are still unknown, it is hypothesized that fetal neurophysiological development may be sensitive to the intrauterine hormonal environment, and neurophysiological vulnerability (e.g., HPA axis dysregulation) may make these offspring more sensitive to stress and thereby predispose them to depression as they mature. Recently, Stowe and colleagues (unpublished observations) noted that infants of women depressed during pregnancy or postpartum had significantly greater salivary cortisol responses to a standardized stressor than offspring of normal control women or women with a past history of depression who were not depressed during the index pregnancy/postpartum period.

Longitudinal studies in which stressors are assessed prior to the onset of symptoms can be informative about the temporal relation between stress and depression. Prospective studies have found that stress predicts depressive symptoms, controlling for prior symptom levels in children (Goodyer, Herbert, & Altham, 1998) and adolescents (Allgood-Merten et al., 1990). The relationship is stronger when children's self-reports are used than when parents' reports of children's depressive symptoms are used (Stanger, McConaughy, & Achenbach, 1992).

Fewer studies have examined the contribution of negative life events to the onset of depressive disorders in children. Stress has predicted the onset of depressive symptoms in previously asymptomatic children (Aseltine, Gore, & Colten, 1994) and the onset of clinically significant depressive episodes, controlling for prior symptom levels in samples comprised of both children and adolescents (Hammen, 1991) and adolescents alone (Garber, Keiley, et al., 2002). Only three of these studies (Aseltine et al., 1994; Garber & Kaminski, 2000; Monroe, Rohde, Seeley & Lewinsohn, 1999) controlled for lifetime history of MDD to rule out the possibility that earlier depressive disorder contributed to onset.

Reports of stressful life events have been shown to increase for both boys and girls from childhood through adolescence, with increases being greater for girls (Ge, Longer, Lorenz, & Simons, 1994), paralleling increases in rates of depression for boys and girls (Hankin et al., 1998). However, few studies have found that gender moderates the relationship between stress and depression. Cohen (1987) reported that negative events predicted depressive symptoms in girls who had experienced minimal positive events in the same time interval, and Ge et al. (1994) showed that growth of stressful life events over time predicted growth in depressive symptoms for girls but not boys.

Although no one specific type of stressful event invariably leads to depression in children and adolescents, certain stressors consistently have been found to be associated with depression. Childhood abuse or maltreatment is an especially robust predictor of depression (Andrews, 1995; Bifulco, Brown, & Adler, 1991; Trad, 1994), and this is particularly true for women (Weiss, Longhurst, & Mazure, 1999). Sexual assault during childhood or adulthood has been found to increase the risk of depression by 2.4 in women (Burnam, Stein, Golding, Siegel, Sorenson, Forsythe, et al., 1988). Poverty also has been shown to contribute to vulnerability to depression (Bruce, Takeuchi, & Leaf, 1991; Grant et al., 2003; McLoyd, 1998). For example, the rates of depression among low-income mothers are about twice as high as in the general population (Bassuk, Buckner, Perloff, & Bassuk, 1998). Recently, Caspi et al. (2003) elegantly demonstrated the relationship between a genetic variable, polymorphism of the serotonin transporter (SERT), and the development of depression after exposure to child abuse. Individuals with the l/l form of the SERT were immune to the depressogenic affects of child abuse, whereas those with s/s allele were highly likely to develop depression after child abuse.

Events such as disappointments, loss, separation, and interpersonal conflict or rejection are also linked with depression (Aseltine et al., 1994; Goodyer, Herbert, Tamplin, & Altham, 2000; Panak & Garber, 1992). This is especially probable for individuals who tend to be more socially dependent or sociotropic. According to the specific vulnerability hypothesis (Beck, 1983, Blatt, Quinlan, Chevron, McDonald, & Zuroff, 1982), individuals whose self-esteem is derived from interpersonal relationships (sociotropy) are at increased risk for depression when they experience stressors within the social domain; in contrast, those who derive their self-worth from