Affective disorders in a stress-vulnerability perspective : a clinical, biological and psycho-social study

Affective illness is a common, recurrent and often severe illness, which causes severe suffering to the patients and their families, friends and co-workers. Furthermore the costs for society are substantial. The aims of this thesis were to study affective disorder from a stress-vulnerability perspective, investigating how genetic, biological and psychosocial factors influence the aetiology and the course and outcome of the illness.

First, we explored the genetic influence on the aetiology of affective illness, comparing monozygotic and dizygotic twins. The results showed that genetic factors play a major role in the aetiology of affective illness and that heritable factors appear to be equally important in affective illness as ascertained in clinical and epidemiological samples.

The aim of the second study was to investigate the presence of cognitive impairment in a group of patients with affective illness. The findings indicate that a subgroup of patients are defined by more episodes of hospitalization and cognitive impairment even when euthymic.

The third study analyzed if the age of onset in affective illness relates to family history, early parental separation and life events. A five-year lower onset was found in bipolar patients with a positive family history of affective illness, compared to those without a family history. Furthermore, bipolar patients with heredity, had less life events at onset. Bipolar patients with preceding life events had a 4.8-year higher onset, compared to those without life events. For bipolar as well as unipolar patients, life stressors more frequently preceded the first episode than the subsequent episodes.

In the fourth paper, the purpose was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Despite a 80 % reduction of tryptophan (precursor to serotonin), no clinically relevant mood changes were observed, suggesting that a transient reduction in serotonergic function does not seem to affect mood in patients, stabilized on lithium treatment.

The influence of social support on bipolar illness was investigated in the fifth study. Patients without full interepisode recovery and patients with a higher risk of relapse during a one-year follow-up were found to perceive a significantly lower level of social support.

Finally, in the sixth study, the influence of personality on the course and outcome of bipolar I illness was explored. Patients in partial interepisode recovery and with a higher risk of hospitalization during a three-year follow-up had a significantly higher level of harm avoidance, a higher level of interpersonal problems, and a lower level of sense of coherence.

In summary, the results of this thesis suggest that: (1) genetic factors play a major aetiological role in affective illness and influence the age of onset in bipolar illness; (2) life events are of greater importance early in the course of affective illness; and (3) bipolar patients with cognitive impairment, a low level of perceived social support, and abnormal levels of certain personality characteristics are at higher risk of poor outcome.

List of scientific papers

I. Kendler KS, Pedersen N, Johnson L, Neale MC, Mathe AA (1993). A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples. Arch Gen Psychiatry. 50(9): 699-700.
https://pubmed.ncbi.nlm.nih.gov/8357295

II. Tham A, Engelbrektson K, Mathe AA, Johnson L, Olsson E, Aberg-Wistedt A (1997). Impaired neuropsychological performance in euthymic patients with recurring mood disorders. J Clin Psychiatry. 58(1): 26-9.
https://pubmed.ncbi.nlm.nih.gov/9055834

III. Johnson L, Andersson-Lundman G, Aberg-Wistedt A, Mathe AA (2000). Age of onset in affective disorder: its correlation with hereditary and psychosocial factors. J Affect Disord. 59(2): 139-48.
https://pubmed.ncbi.nlm.nih.gov/10837882

IV. Johnson L, El-Khoury A, Aberg-Wistedt A, Stain-Malmgren R, Mathe AA (2001). Tryptophan depletion in lithium-stabilized patients with affective disorder. Int J Neuropsychopharmacol. 4(4): 329-36.
https://pubmed.ncbi.nlm.nih.gov/11806858

V. Johnson L, Lundstrom O, Aberg-Wistedt A, Mathe AA (2002). Social support in bipolar disorder: its relevance to remission and relapse. [Submitted]

VI. Johnson L, Carlsson AM, Aberg-Wistedt A, Mathe AA (2002). Personality traits in bipolar I disorder: its relevance to recovery and relapse. [Manuscript]