Life-charting patients with treatment-refractory affective disorder

Sammanfattning: Introduction:In treatment-refractory affective illness there are several hypothesis to suggest alterations in the neurobiological systems in relation to illness course. The underlying mechanisms have been scantily investigated. The sensitisation hypothesis suggests a sensitisation process over time for affective disorder the affective illness course shows a tendency towards more frequent, deeper, and less stress related episodes over time. There are reasons to believe that these alterations in biological systems are a result of the wear-and-tear of the affective illness itself, a change from homeostasis to allostasis. By means of the Life-charting method, a graphical method to visualise the illness course in relation to stress and treatments over a lifetime, these hypothesis can be further analysed. Earlier Life-charting research has exclusively focussed on illness course per se, or in relation to stressing life events and treatment. Childhood experiences and its impact on later vulnerability for psychopathology have been emphasized earlier. The Life-charting method can help shed light on this vulnerability in relation to illness course. Aims:The current study was undertaken to explore the Life charting method in measuring illness course in 38 treatment refractory affective disorder patients in relation to the Sensitisation hypothesis, the HPA axis, monoamine metabolites in cerebrospinal fluid as well as experience of parental rearing. Subjects:The patients were consecutively admitted over a three-year period, to a Treatment Refractory Affective Disorder Program at the Sahlgrenska University Hospital at Mölndal, Sweden.Results: Our results partially support the sensitisation hypothesis of affective disorders in demonstrating this phenomenon in more than half of our affectively recurring patients. However, a substantial minority clearly were non-sensitisers showing a stable but more malignant illness course.We found cerebrospinal fluid (CSF) concentrations of the noradrenalin metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), to be positively related to the accumulated burden of mood swings (defined as time spent in illness  depth of episodes) over a lifetime, irrespective of age, gender, uni- or bipolarity, and current severity of depression. Thus, the involvement of noradrenalin turnover in the long-term burden of affective illness is a likely reality. These results point towards a shift in the biological set-points from homeostasis to allostasis.Also, the HPA axis, determined by the CRH challenge test, seemed to shift to a new biological set-point, an allostatic shift, as the individual experienced three or more illness episodes.We found that a patient with severe treatment refractory affective illness who perceived himself/herself as not wanted by his/her parents in childhood can be expected to have a more malignant illness course, as compared to a similar patient who instead perceived himself or herself as wanted during childhood.Conclusions: In conclusion, the life-charting method is useful in investigating psychological and biological variables in relation to illness course. Our findings support the hypothesis of altered neurobiological systems in relation to illness course in patients suffering from treatment refractory affective disorders. Furthermore, our findings also point towards a more malignant illness course in individuals with a more negative perception of parental rearing.