Temperamental features can be predictors of later psychopathology [72,73], and a difficult temperament (irregular biological rhythms, irritability, inflexibility) has been suggested to be a premorbid feature in children with bipolar disorder [74,75].
One of the authors of this chapter [76,77] described three temperamental profiles potentially predisposing to adolescent or adult-onset bipolar disorder: the hyperthymic, cyclothymic and irritable types. These are characterized by excesses along the lines of exuberant, overconfident, over-energetic, impulsive, overtalkative, extraverted, meddlesome, uninhibited, stimulus seeking and mood labile traits. In an 11-year prospective study, high self-ratings of mood lability and energetic activity predicted bipolar II switching in depressed patients . Kochman et al. , using a new scale for cyclothymic-sensitive temperament, showed the same outcome in adolescent major depressions.
Studies of offspring at risk for bipolar disorder have found mood and behavioural difficulties suggestive of an affective dysregulation. A study considering seven 2-year-old sons of bipolar mothers found significant aggressive behaviours during laboratory observations, compared to control offspring of nonaffected mothers . Chang et al.  addressed this topic in a sample of 53 children and adolescents of bipolar parents, 27 of whom (52%) received a psychiatric diagnosis (28% ADHD, 15.1% anxiety disorder, 13.2% bipolar disorder and 11.3% depression), and were evaluated with a temperament measure . The bipolar offspring as a whole showed lower scores in the general activity scale and higher scores in the approach and rhythm-sleep scales. Bipolar offspring with psychiatric diagnoses showed higher activity levels than bipolar offspring without diagnoses, and lower scores on flexibility, positive mood and task orientation. Grigoroiu-Serbanescu et al.  found that bipolar offspring with psychopathology had less emotional stability, less frustration tolerance, and more anxiety and shallowness in relationships and schoolwork than bipolar offspring without psychopathology. All these findings may support the hypothesis that temperamental features such as less emotional stability, intolerance to frustration and irregular biological rhythms may predispose to a variety of psychopathologies.
The foregoing findings are consistent with the temperament construct of behavioural disinhibition [81,82]. This temperamental quality, evident in early childhood, is characterized by a tendency to seek out novelty, approach unfamiliar stimuli, and display disinhibition of speech or action. This temperament can often be associated with higher ratings of school behaviour problems, and may be linked with later disruptive behaviour and comorbid mood disorders, especially in high-risk populations such as bipolar offspring. These findings are also consistent with previous data from a study on a nonclinical cohort of high school students, which showed a correlation between decreased flexibility/increased distractibility and presence of depression, substance abuse and delinquency .
In an interactional model, a combination of genetic vulnerability with environmental stressors, deficient coping strategies and maladaptive patterns of behaviour may lead to development of full-blown bipolar disorder . We have formulated a pathogenetic model of bipolarity in which temperament plays a pivotal role in mediating between putative ''mood genes'' and clinical phenotypes .
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