Followup Studies

Prospective follow-up studies are rare in the literature on juvenile bi-polarity. One of the major problems in detecting bipolar disorder in children is the extent to which depressive states, temperamental moodiness, ''atypical'' mood swings with explosive moods and behaviour, and/or ultra-rapid cycling represent variants and/or precursors of clinically more recognizable bipolar disorder. This question cannot be resolved by cross-sectional observation. A family history of bipolar disorder may reinforce the bipolar nature of the presenting mood instability, but, in the absence of genetic markers, prospective follow-up is the ultimate clinical ''test'' available today for supporting a bipolar diagnosis in a child presenting with such instability. This is what one of the authors of this chapter attempted to accomplish in his mood clinic, where adult manic-depressive patients brought their children or younger siblings with what they deemed to be early signs of bipolarity, similar to what they had experienced as children before the illness fully declared itself at a later age.

In this prospective follow-up over 3-4 years [25], carried out in 68 offspring or siblings (age range 6 to 24 years) of adult bipolar patients, 79% of those with a provisional diagnosis of depression had a depressive recurrence, and 37.5% developed a bipolar disorder (type I or II). Eleven subjects with polysubstance abuse without a clinical affective disorder were re-diagnosed as having either a dysthymic or a cyclothymic disorder during the follow-up. Anxiety disorders, substance abuse and/or disruptive behaviour disorder appeared as antecedents to the full-blown mood disorder rather than coexisting as independent comorbid conditions.

Indeed, the Zahn-Waxler et al. study [9], which found that offspring of a bipolar parent showed a range of adjustment problems as infants and toddlers, which continued four years later - including some that could be classified as DSM-III psychiatric disorders - represents a further extension of the same perspective, according to which relatively amorphous mood instability in the children of bipolar mothers crystallizes over time into more recognizable affective disorder.

In a Canadian study, LaRoche et al. [15] reported that 24% of 37 school-aged offspring from 21 families with a manic-depressive parent received a positive DSM-III diagnosis, largely in the affective illness spectrum. When the presence of affective traits was considered, a lack of evidence for continuity of psychopathology over a 3-7-year follow-up period resulted in most cases. These data support the notion of a broad bipolar spectrum. Along these lines, Hammen et al. [17] observed diagnoses from both past lifetime and prospective follow-up assessments in the offspring of unipolar, bipolar and chronically medically ill mothers, and found that the highest psychopathological risk (including that for bipolar disorder) during all evaluations was in the offspring of unipolar women. Indeed, school-aged children of bipolar mothers experienced fewer chronic, recurrent or new-onset psychiatric disorders over 1-3 years, including both affective disorders alone or in combination with behaviour or anxiety disorders. It would appear to us that some of the so-called ''unipolar'' offspring of mothers may have been bipolar II cases, whose hypomanic episodes were missed in the clinical evaluation procedure with diagnostic interviews in which 4 days of hypomania are needed for such a diagnosis [59].

Duffy et al. [23], in their prospective, longitudinal follow-up study described earlier, reported that offspring of lithium responders tended to have an episodic affective disorder, with an abrupt onset, often preceded by sleep and anxiety disorders, and good recovery. On the contrary, offspring of lithium nonresponders showed early-onset academic and behavioural problems, which continued alongside the mood disorder, which showed chronic course and poor remission. This study supports the characterization of two bipolar phenotypes: a classical, narrow form, and a broad form, with subcontinuous course, incomplete remissions and predominately irritable mood and unstable course. These two phenotypes run in the family and may partly be predicted by lithium response.

Further longitudinal research is needed to follow up children with different psychopathologies, in order to describe putative different pathways to bipolarity. The high frequency of anxiety disorders preceding the onset of bipolar disorder, mainly in the classical form, is considered an antecedent of the full-blown mood disorder rather than ''true comorbidity'', in the context of variable phenotypic expression during development. The high incidence of current and past anxiety disorders in bipolar offspring

(including separation anxiety, panic and social phobic disorders) may in part stem from the chaotic environment and attachment difficulties related to the presence of one or two bipolar parents [35], and in part represent an alternative pathway to bipolarity [60,61]. The latter is suggested by current studies in adults whereby panic and related disorders appear to characterize the bipolar II subtype and its unstable course [62-66].

Follow-up studies are warranted to ascertain the possibility that children with subsyndromal features of bipolar disorder (including temperamental disinhibition, high levels of activity and mood dysregulation) may develop a fully expressed bipolar disorder during childhood, adolescence and early adulthood, in order to describe possible vulnerability factors. It would finally be relevant to study temperamental, genetic and environmental characteristics of children of bipolar parents who never develop psycho-pathology, in order to define possible factors of resilience.

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