Depression is associated with hyperconnectivity of an introspective socio-affective network during the recall of formative relationship episodes.

BACKGROUND: Depression and the experience of early adversity are associated with impairments in interpersonal and social cognitive functioning. The neural mechanisms involved in these impairments remain insufficiently understood. METHODS: In a sample of 48 depressed and 50 healthy participants, we explored seed-to-voxel functional connectivity (FC) during the recall of formative relationship episodes using functional magnetic resonance imaging. RESULTS: While depressive symptoms were associated with increased FC of brain regions that form an introspective socio-affective network, such as the precuneus, bilateral anterior insula, dorsal anterior cingulate cortex, left amygdala, and medial prefrontal cortex, early adversity linked to decreased FC of brain regions mediating emotion processing such as the bilateral anterior insula and increased FC of the bilateral parahippocampal gyrus. LIMITATIONS: We report both results that are corrected for the number of seeds tested in FC analyses using strict Bonferroni adjustments and unadjusted results as part of an exploratory analysis. DISCUSSION: Our findings suggest that depression and early adversity are associated with differential FC patterns in the brain during the recall of formative relationship episodes. Hyperconnectivity of an introspective socio-affective network associated with depressive symptoms may link to enhanced self-focus and emotional reactivity. Patterns of neural activation associated with early adversity may underpin numbed affective states or enhanced affective memory regulation. Overall, these findings inform about the neural underpinnings of a reflective ability that is predictive of the adaptation to depression and to early adversity and relevant for psychotherapy outcomes.

Thinking about the past to shape the present: neural activation during the recall of relationship episodes.

Reflecting on oneself and others in relationships is an ability that is central to our social existence. Specifically, considering formative autobiographical experiences in relationships may contribute to more flexibility in perceiving, as well as in shaping present relationships. Reflecting on such experiences mobilizes different social cognitive and affective processes. We aim to explore the neural basis of these processes. With a newly developed functional magnetic imaging (fMRI) task, we investigated brain activation in 35 healthy individuals during recall of relationship episodes involving themselves or others. We found that recalling formative episodes involving themselves modulated brain activity in the right parahippocampus, left precuneus, bilateral fusiform gyrus, bilateral insula, and left presupplementary motor area. These areas are involved in memory processes, self-generated thought, and affective experience. The recall of relationship episodes involving others led to similar activation patterns. Our results underscore the close link between self-reflection, understanding others, and memory processes and emphasize the role of affective dimensions for self-relevant experiences. They contribute to a growing body of research on neural mechanisms involved in complex social cognitive processes decisive for our capacity to navigate our social environment.

Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder.

There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD. However, until now, no study investigated in vivo PACC glucose and lactate levels in MDD. Proton magnetic resonance spectroscopy was therefore used to test the hypothesis that patients with MDD have increased PACC glucose and lactate levels. In 40 healthy and depressed participants, spectra were acquired from the PACC using a maximum echo J-resolved spectroscopy protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate. Targeting these metabolic disturbances might affect the balance of metabolic pathways regulating neuronal energetics and result in an attenuation of the elevated basal activity of brain regions within the neural circuitry of depression.

Neural correlates of 'pessimistic' attitude in depression.

BACKGROUND: Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that 'pessimism'-related emotion processing would characterize brain activity in major depression.MethodDuring functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences--pleasant, unpleasant and neutral--and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the 'unknown' expectation was compared with the 'known' expectation conditions. RESULTS: While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. CONCLUSIONS: Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a 'pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

Determinants of voluntary vs. involuntary admission in bipolar disorder and the impact of adherence.

INTRODUCTION: Treatment adherence plays a pivotal role in hospitalisation in bipolar disorder (BD). We examined the impact of adherence and pharmacological variables on involuntary vs. voluntary admission on a sample of inpatients from the European Mania in Bipolar Longitudinal Evaluation of Medication study (EMBLEM). METHODS: 1374 inpatients with an acute manic or mixed episode of BD participated in this observational study on clinical, functional and economic outcomes of pharmacological treatment. We analysed data at the time of study inclusion, and the primary outcome measure was admission status (voluntary vs. involuntary admission). RESULTS: The strongest baseline factor of admission status was adherence whereby patients' adherence was significantly associated with admission when treated with atypical antipsychotics or lithium as monotherapy. Adherence with typical antipsychotics was not significantly associated with admission status. DISCUSSION: These results emphasise the crucial role of treatment adherence for admission status and, within the context of a naturalistic study, some advantage of atypical over typical antipsychotics on admission in acute mania of BD.

[Subjective experience and neuronal integration in the brain: do we need a first-person neuroscience?]. / Subjektives Erleben und neuronale Integration im Gehirn: Benötigen wir eine Erste-Person-Neurowissenschaft?

Unlike other medical disciplines psychiatry can be characterized by the special importance of subjective experience. Since subjective experience is tied to First-Person-Perspective and investigation of the brain is possible only in Third-Person-Perspective, the question how subjective experience can be linked to neuronal processes is raised in psychiatry. We suggest a novel methodological approach, First-Person-Neuroscience where subjective experience can be linked directly and systematically to neuronal processes. Due to complexity of the structures and contents of subjective experience, localization in specific brain regions seems inappropriate. Instead, the interplay and coordination of neuronal activity across several brain regions, so-called neuronal integration, should be considered in First-Person-Neuroscience. This is illustrated by two principles of neuronal integration, top-down modulation and reciprocal modulation, whose abnormal function can be related to subjective experience of patients with catatonia and depression. It is concluded that First-Person-Neuroscience can contribute to reveal abnormal brain function in psychiatric disorders and ultimately to development of diagnostic and therapeutic markers.