Longitudinal hair cortisol in bipolar disorder and a mechanism based on HPA dynamics.

Bipolar disorder (BD) is marked by fluctuating mood states over months to years, often with elevated cortisol levels. Elevated cortisol can also trigger mood episodes. Here, we combine longitudinal hair cortisol and mood measurements with mathematical modeling to provide a potential mechanistic link between cortisol and mood timescales in BD. Using 12 cm hair samples, representing a year of growth, we found enhanced year-scale cortisol fluctuations whose amplitude averaged 4-fold higher in BD (n = 26) participants than controls (n = 59). The proximal 2 cm of hair correlated with recent mood scores. Depression (n = 266) and mania (n = 273) scores from a longitudinal study of BD showed similar frequency spectra. These results suggest a mechanism for BD in which high emotional reactivity excites the slow timescales in the hypothalamic-pituitary-adrenal (HPA) axis to generate elevated months-scale cortisol fluctuations, triggering cortisol-induced mood episodes.

Major depressive disorder and bistability in an HPA-CNS toggle switch.

Major depressive disorder (MDD) is the most common psychiatric disorder. It has a complex and heterogeneous etiology. Most treatments take weeks to show effects and work well only for a fraction of the patients. Thus, new concepts are needed to understand MDD and its dynamics. One of the strong correlates of MDD is increased activity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which produces the stress hormone cortisol. Existing mathematical models of the HPA axis describe its operation on the scale of hours, and thus are unable to explore the dynamic on the scale of weeks that characterizes many aspects of MDD. Here, we propose a mathematical model of MDD on the scale of weeks, a timescale provided by the growth of the HPA hormone glands under control of HPA hormones. We add to this the mutual inhibition of the HPA axis and the hippocampus and other regions of the central nervous system (CNS) that forms a toggle switch. The model shows bistability between euthymic and depressed states, with a slow timescale of weeks in its dynamics. It explains why prolonged but not acute stress can trigger a self-sustaining depressive episode that persists even after the stress is removed. The model explains the weeks timescale for drugs to take effect, as well as the dysregulation of the HPA axis in MDD, based on gland mass changes. This understanding of MDD dynamics may help to guide strategies for treatment.

Negating in order to be negative: the relationship between depressive rumination, message content and negation processing.

The current research explored the interaction between brooding, a maladaptive subtype of depressive rumination, and content valence, in a basic cognitive process of negation. Following presentation of positive and negative trait descriptions, phrased affirmatively or negatively (e.g., "Liz is/is not a smart person"), participants' associations were examined for congruency with the schema (e.g., "smart") or with its negation (e.g., "stupid"). We predicted that brooders' processing of negations would enhance the accessibility of negative content. Consistent with our prediction, brooders generated schema-congruent associations for negatively valenced schemas, but negation-congruent associations for positively valenced schemas, thus, maintaining negative content in both cases. In contrast, nonbrooders generated associations congruent with the negation regardless of schema valence. This processing pattern is suggestive of a possible pathway for negative content perseveration in rumination, and it attests to the context and person sensitivity of the negation process.

Cognitive-behavioral therapy for depression.

Major Depressive Disorder is one of the most common and debilitating mental disorders. Cognitive behavioral therapy (CBT) for depression has received ample empirical support and is considered one of the most effective modes of treatment for depression. In this article, we review the theoretical underpinnings of this approach, whereby biased cognition and maladaptive behavioral patterns are thought to be core factors contributing to the development and maintenance of depression. We describe cognitive and behavioral strategies and techniques used in the treatment of depression. We conclude with an updated review of outcome research comparing the effectiveness of CBT as a whole and its specific cognitive and behavioral components with a standard treatment of anti-depressant medication.