A morphometric signature of depressive symptoms in unmedicated patients with mood disorders.

OBJECTIVE: A growing literature indicates that unipolar depression and bipolar depression are associated with alterations in grey matter volume. However, it is unclear to what degree these patterns of morphometric change reflect symptom dimensions. Here, we aimed to predict depressive symptoms and hypomanic symptoms based on patterns of grey matter volume using machine learning. METHOD: We used machine learning methods combined with voxel-based morphometry to predict depressive and self-reported hypomanic symptoms from grey matter volume in a sample of 47 individuals with unmedicated unipolar and bipolar depression. RESULTS: We were able to predict depressive severity from grey matter volume in the anteroventral bilateral insula in both unipolar depression and bipolar depression. Self-reported hypomanic symptoms did not predict grey matter loss with a significant degree of accuracy. DISCUSSION: The results of this study suggest that patterns of grey matter volume alteration in the insula are associated with depressive symptom severity across unipolar and bipolar depression. Studies using other modalities and exploring other brain regions with a larger sample are warranted to identify other systems that may be associated with depressive and hypomanic symptoms across affective disorders.

Instability of default mode network connectivity in major depression: a two-sample confirmation study.

Major depression is associated with altered static functional connectivity in various brain networks, particularly the default mode network (DMN). Dynamic functional connectivity is a novel tool with little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions. Functional connectivity stability between the mPFC and PCC over the course of a resting-state functional magnetic resonance imaging (fMRI) scan was compared between medication-free patients with major depression and healthy controls matched for age, sex and handedness. We tested replicability of the results in an independent sample using multi-echo resting-state fMRI. The primary sample included 20 patients and 19 controls, while the validation sample included 19 patients and 19 controls. Greater connectivity variability was detected in major depression between mPFC and PCC. This was demonstrated in both samples indicating that the results were reliable and were not influenced by the fMRI acquisition approach used. Our results demonstrate that alterations within the DMN in major depression go beyond changes in connectivity strength and extend to reduced connectivity stability within key DMN regions. Findings were robustly replicated across two independent samples. Further research is necessary to better understand the nature of these fluctuations in connectivity and their relationship to the aetiology of major depression.

Non-invasive measurement of brain temperature using radiometric thermometry: experimental validation and clinical observations in asphyxiated newborns.

BACKGROUND: Therapeutic hypothermia (HT) has been shown to decrease death and severe disability in infants with hypoxic-ischemic encephalopathy (HIE). Rectal temperature (RT) is used to determine the temperature set-points for treatment with HT, however experimental studies have shown significant differences between RT and brain temperature during HT. Knowledge of actual brain temperature during HT might allow better determination of optimal degree of cooling and improve outcomes. OBJECTIVES: To compare measurements of brain temperature obtained by non-invasive radiometric thermometry (RadT) to direct tissue measurements in an experimental model of HT, and to use RadT in newborn infants with HIE undergoing HT. STUDY DESIGN: RadT measurements of brain temperature were compared to fiber optic (Luxtron) thermometry measurements placed at a depth of 1.5 centimeters into the brain of cooled miniswine. Following validation studies, brain RadT and RT measurements were continuously recorded in thirty infants with HIE during HT and rewarming. RESULTS: RadT and Luxtron probe temperatures were comparable in miniswine throughout a temperature range similar to therapeutic HT. RadT measurements of brain temperature were higher than RT in 60% of infants with HIE undergoing HT. Higher RadT measurements compared to RT were associated with cerebral white matter abnormalities (p = 0.01). CONCLUSIONS: RadT provides a safe, passive and non-invasive way to measure brain temperature that can be used in the clinical setting. RadT may be helpful in determining the optimal degree of cooling and identifying infants at highest risk of brain injury.

Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type.

Clinically effective drugs against human anxiety and fear systematically alter the innate defensive behavior of rodents, suggesting that in humans these emotions reflect defensive adaptations. Compelling experimental human evidence for this theory is yet to be obtained. We report the clearest test to date by investigating the effects of 1 and 2 mg of the anti-anxiety drug lorazepam on the intensity of threat-avoidance behavior in 40 healthy adult volunteers (20 females). We found lorazepam modulated the intensity of participants' threat-avoidance behavior in a dose-dependent manner. However, the pattern of effects depended upon two factors: type of threat-avoidance behavior and theoretically relevant measures of personality. In the case of flight behavior (one-way active avoidance), lorazepam increased intensity in low scorers on the Fear Survey Schedule tissue-damage fear but reduced it in high scorers. Conversely, in the case of risk-assessment behavior (two-way active avoidance), lorazepam reduced intensity in low scorers on the Spielberger trait anxiety but increased it in high scorers. Anti-anxiety drugs do not systematically affect rodent flight behavior; therefore, we interpret this new finding as suggesting that lorazepam has a broader effect on defense in humans than in rodents, perhaps by modulating general perceptions of threat intensity. The different patterning of lorazepam effects on the two behaviors implies that human perceptions of threat intensity are nevertheless distributed across two different neural streams, which influence effects observed on one-way or two-way active avoidance demanded by the situation.

Human milk versus formula after gastroschisis repair: effects on time to full feeds and time to discharge.

OBJECTIVE: To determine if the choice of enteral feeds after gastroschisis repair relates to the time to achieve full feeds and time to discharge. STUDY DESIGN: A retrospective study of infants with gastroschisis from 2000 to 2010 examined demographics, days at closure, days at initiation of feeds, days to full feeds, time to discharge and length of stay. RESULT: Ninety infants were identified, 22 received (human milk) HM exclusively, 15 were fed >50% HM, 16 were fed <50% HM and 26 were fed only cow milk-based formulas. Infants fed exclusively HM had significantly shorter times to full enteral feedings (median 5 days versus 7 days, P=0.03). The time from initiation of feedings to hospital discharge, which accounts for initiation age, significantly favored the exclusively HM-fed infants (median 7 days versus 10 days, P=0.01). CONCLUSION: Exclusive HM feeding after gastroschisis repair decreases time to achieve full enteral feeds and time to discharge.

Clogging of feeding tubes.

This is a report of an in vitro study evaluating clotting ability of some formulas with intact protein and hydrolyzed protein sources in a series of buffers ranging from a pH of 1 thru 10. The following 10 products were tested: Ensure Plus, Ensure, Enrich, Osmolite, Pulmocare, Citrotein, Resource, Vivonex TEN, Vital, and Hepatic Acid II. Protein (10 and 20 g/liter) was added to Citrotein and Ensure Plus. All formulas were tested at full and some at half strength. Clotting occurred only in premixed intact protein formulas (Pulmocare, Ensure Plus, Osmolite, Enrich, Ensure) and in Resource. No clotting was observed for Citrotein (intact protein formula in powder form), Vital, Vivonex TEN, and Hepatic Aid II. Adding protein did not cause or increase clotting. In summary, clotting of some liquid formula diet appears to be an important factor causing possible gastric feeding tube occlusion. The following measures may help in preventing this problem: flushing before and after aspirating for gastric residuals to eliminate acid precipitation of formula in the feeding tube, advance the nasogastric feeding tube into the duodenum if possible, and avoid mixing these products with liquid medications having a pH value of 5.0 or less.