Assessing in-session rumination and its effects on CBT for depression.

The study evaluated if rumination of patients during therapy (i.e., in-session rumination) relates to whether or not they do less well in CBT treatment. We developed a reliably assessed in-session rumination observational measure and evaluated its relationship to depression over the course of CBT. Rated sessions came from 63 treatment-naïve patients with major depressive disorder who participated in CBT in the PReDICT study (Dunlop et al., 2017). In-session rumination was operationalized as repetitive, negative, and passive talking about depressive topics. Trained undergraduates rated the intensity and duration of in-session rumination occurring during 57 initial therapy sessions (i.e., session one) and 45 sessions in the middle of treatment (i.e., session eight). The observational ratings were sufficiently reliable (all ICCs > 0.69). Mixed model results indicated that greater intensity of in-session rumination during the initial treatment session predicted higher levels of subsequent clinician-rated depressive symptoms (p < .023). Regression results indicated that greater intensity and duration of in-session rumination at session 8 significantly predicted higher clinician-rated symptoms at end of treatment (p's < 0.02). In-session rumination intensity and duration were not, however, related to subsequent self-reported depressive symptoms. The results support efforts to identify which patients might benefit from rumination-specific interventions.

Hyper-responsivity to losses in the anterior insula during economic choice scales with depression severity.

BACKGROUND: Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain. METHODS: Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex). RESULTS: Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies. CONCLUSIONS: Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

BDNF function as a potential mediator of bipolar disorder and post-traumatic stress disorder comorbidity.

Bipolar disorder (BD) and post-traumatic stress disorder (PTSD) frequently co-occur among psychiatric patients, leading to increased morbidity and mortality. Brain-derived neurotrophic factor (BDNF) function is associated with core characteristics of both BD and PTSD. We propose a neurobiological model that underscores the role of reduced BDNF function resulting from several contributing sources, including the met variant of the BDNF val66met (rs6265) single-nucleotide polymorphism, trauma-induced epigenetic regulation and current stress, as a contributor to the onset of both illnesses within the same person. Further studies are needed to evaluate the genetic association between the val66met allele and the BD-PTSD population, along with central/peripheral BDNF levels and epigenetic patterns of BDNF gene regulation within these patients.

A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders.

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, "best proven diagnostic and therapeutic method" that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls.