Relationships between changes in sustained fronto-striatal connectivity and positive affect with antidepressant treatment in major depression

Objective: Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. Method: Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during per- formance of an emotion regulation para- digm in 21 depressed patients before and after 2 months of antidepressant treat- ment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. Results: After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when control- ling for negative affect. None of these associations were observed in healthy comparison subjects. Conclusions: Treatment-induced change in the sustained engagement of fronto- striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a va- riety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to under- stand changes in daily positive affect.

Prehistoric activity in Peterstone Great Wharf Palaeochannels: field survey 2005-6

This is an interim report on research carried out at the intertidal site of Peterstone Great Wharf, located on the Wentlooge Levels, c. 7 km east of Cardiff. The project is the first detailed survey and excavation of a site originally recorded in 1996-7 as part of a larger survey of the intertidal zone from Cardiff to the Second Severn Crossing. The 1997 survey produced important evidence for prehistoric human activity preserved within four palaeochannels. Significant erosion has taken place since then. A new survey of the foreshore has identified additional palaeochannels not seen in 1997 which form part of a more complex system of inter-cutting channels, many containing wood structures including short lines of timbers on the channel edge. Artefacts include a wooden axe handle, antler artefacts, an animal bone assemblage and some pottery of Beaker and Bronze Age date. The finds are thought to derive from a nearby, possibly eroded, settlement. The channels have trapped artefacts and preserved evidence of a range of activities, including what are interpreted as possible boat landings and fishing structures.

Increases in prefrontal cortex activity when regulating negative emotion predicts symptom severity trajectory over six months in depression

Context: Emotion regulation is critically disrupted in depression and use of paradigms tapping these processes may uncover essential changes in neurobiology during treatment. In addition, as neuroimaging outcome studies of depression commonly utilize solely baseline and endpoint data – which is more prone to week-to week noise in symptomatology – we sought to use all data points over the course of a six month trial. Objective: To examine changes in neurobiology resulting from successful treatment. Design: Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from one of two antidepressant treatments over a six month trial. Participants were scanned pretreatment, at 2 months and 6 months posttreatment. Setting: University functional magnetic resonance imaging facility. Participants: 21 patients with Major Depressive Disorder and without other Axis I or Axis II diagnoses and 14 healthy controls. Interventions: Venlafaxine XR (doses up to 300mg) or Fluoxetine (doses up to 80mg). Main Outcome Measure: Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm as well as regular assessments of symptom severity by the Hamilton Rating Scale for Depression. To utilize all data points, slope trajectories were calculated for rate of change in depression severity as well as rate of change of neural engagement. Results: Those depressed individuals showing the steepest decrease in depression severity over the six months were those individuals showing the most rapid increases in BA10 and right DLPFC activity when regulating negative affect over the same time frame. This relationship was more robust than when using solely the baseline and endpoint data. Conclusions: Changes in PFC engagement when regulating negative affect correlate with changes in depression severity over six months. These results are buttressed by calculating these statistics which are more reliable and robust to week-to-week variation than difference scores.

Neural processing of reward and punishment in young people at increased familial risk of depression

Background Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. Methods We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16–21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. Results We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Conclusions Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior.

The sources of phosphorus in the waters of Great Britain

Total phosphorus (TP) and soluble reactive phosphorus (SRP) loads to watercourses of the River Basin Districts (RBDs) of Great Britain (GB) were estimated using inventories of industrial P loads and estimates of P loads from sewage treatment works and diffuse P loads calculated using region-specific export coefficients for particular land cover classes combined with census data for agricultural stocking densities and human populations. The TP load to GB waters was estimated to be 60 kt yr(-1), of which households contributed 73, agriculture contributed 20, industry contributed 3, and 4 came from background sources. The SRP load to GB waters was estimated to be 47 kt yr(-1), of which households contributed 78, agriculture contributed 13, industry contributed 4, and 6 came from background Sources. The 'average' area-normalized TP and SRP loads to GB waters approximated 2.4 kg ha(-1) yr(-1) and 1.8 kg ha(-1) yr(-1), respectively. A consideration of uncertainties in the data contributing to these estimates suggested that the TP load to GB waters might lie between 33 and 68 kt yr(-1), with agriculture contributing between 10 and 28 of the TP load. These estimates are consistent with recent appraisals of annual TP and SRP loads to GB coastal waters and area-normalized TP loads from their catchments. Estimates of the contributions of RBDs to these P loads were consistent with the geographical distribution of P concentrations in GB rivers and recent assessments of surface waters at risk from P Pollution.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

The depression of tropical snow lines at the Last Glacial Maximum: what can we learn from climate and model experiments?

Analyses of simulations of the last glacial maximum (LGM) made with 17 atmospheric general circulation models (AGCMs) participating in the Paleoclimate Modelling Intercomparison Project, and a high-resolution (T106) version of one of the models (CCSR1), show that changes in the elevation of tropical snowlines (as estimated by the depression of the maximum altitude of the 0 °C isotherm) are primarily controlled by changes in sea-surface temperatures (SSTs). The correlation between the two variables, averaged for the tropics as a whole, is 95%, and remains >80% even at a regional scale. The reduction of tropical SSTs at the LGM results in a drier atmosphere and hence steeper lapse rates. Changes in atmospheric circulation patterns, particularly the weakening of the Asian monsoon system and related atmospheric humidity changes, amplify the reduction in snowline elevation in the northern tropics. Colder conditions over the tropical oceans combined with a weakened Asian monsoon could produce snowline lowering of up to 1000 m in certain regions, comparable to the changes shown by observations. Nevertheless, such large changes are not typical of all regions of the tropics. Analysis of the higher resolution CCSR1 simulation shows that differences between the free atmospheric and along-slope lapse rate can be large, and may provide an additional factor to explain regional variations in observed snowline changes.