Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [¹²³I] nor-β-CIT in DD patients (n = 8) and compared it to that in MD patients (n = 11) and healthy controls (n = 19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [¹²³I] nor-β-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t = 3.55, p = 0.009; MD: t = 5.86, p < 0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [¹²³I] nor-β-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [¹²³I] nor-β-CIT binding correlated inversely with the duration of both dysthymia (rho = −0.76, p = 0.03) and MD (rho = −0.83, p = 0.01) in the DD group. No such finding was observed in the MD group (rho = 0.26, p = 0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [¹²³I] nor-β-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [¹²³I] nor-β-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [¹²³I] nor-β-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.     

RGS4 polymorphism and response to electroconvulsive therapy in major depressive disorder

We studied the association between RGS4 (rs951436) polymorphism and treatment response in electroconvulsive therapy (ECT) as well as risk of treatment-resistant depression. The study sample consisted of 119 patients with major depressive disorder (MDD) and 384 healthy control subjects. RGS4 polymorphism was not associated with treatment response in ECT or risk of MDD. According to the present data, the impact of RGS4 genotype is not decisive in major depressive disorder. The results provide preliminary data on the impact of RGS4 polymorphism in treatment response in ECT.     

Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction

Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [¹⁸F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = −0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival.     

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets

OBJECTIVE

We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.

RESEARCH DESIGN AND METHODS

Whole pancreata from untreated (n = 3), MnCl₂ and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl₂ and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.

RESULTS

In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of β-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.

CONCLUSIONS

Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo.Despite the high incidence of diabetes, the precise molecular and cellular mechanisms that cause the decrease in the mass and function of the insulin-producing β-cells, observed in both the type 1 and type 2 forms of the disease, remain to be elucidated (1). At present, the only, although somewhat indirect, way to monitor the onset and the evolution of the diseases in a given individual is by using sensitive immunological and functional tests, which require injections and repeated blood sampling. However, we still lack a method that could visualize and quantitate pancreatic β-cells in vivo, in a fully noninvasive way. As a result, we also lack a solid biological basis to target new therapeutic approaches that could promote the regeneration (type 1 diabetes) or the function (type 2 diabetes) of β-cells. The difficulty in imaging these cells stems from their deep abdominal location, their distribution in small (50–600 μm in diameter) islets of Langerhans, their modest volume density (∼1%) in a control pancreas, and their close relationships to different cell types of both endocrine and exocrine nature.Several of these issues have been partially solved using optical methods, which can now investigate laboratory rodents (2–4), but which cannot be adapted to human studies, given the limited tissue penetration of light (2,4–6). Penetration is not an issue in magnetic resonance (MR) imaging (MRI) and positron-emitting tomography (PET) imaging, which are convenient for human applications, specifically if combined with computed tomography. Because islets are structurally and functionally heterogeneous, and are not all simultaneously altered to the same degree during diabetes development, their individual visualization is important. The choice of an imaging modality is then restricted to MRI, given that the lateral resolution of PET is, at best, in the millimeter range (7). MRI has already been used to visualize transplanted islets (8–11), but has not yet been shown to detect native islets in situ, mostly because of an insufficient spatial resolution, which is only provided by the use of a high magnetic field (8,12–14).The aim of the current study was to investigate whether imaging of individual islets could be achieved using a 14.1 Tesla (T) MR scanner. In the absence of a validated probe for the specific staining of β-cells, we have also tested whether the MRI contrast of these islets could be enhanced by an in vivo infusion of manganese (12). Our data document that the combination of these conditions, in manganese-enhanced high-field magnetic resonance imaging (MEHFMRI), allows for the easy differentiation of multiple tissues within the whole murine pancreas, including individual islets of Langerhans. The approach quantitatively detects the loss of pancreatic islets in an animal model of type 1 diabetes, and with this approach pancreatic islets in the living animal can be investigated.     

Effects of the Preschool-Based Family-Involving DAGIS Intervention on Family Environment: A Cluster Randomised Trial

Interventions promoting young children’s healthy energy balance-related behaviours (EBRBs) should also examine changes in the family environment as this is an important determinant that may affect the effectiveness of the intervention. This study examines family environmental effects of the Increased Health and Wellbeing in Preschools (DAGIS) intervention study, and whether these effects differed when considering three parental educational level (PEL) groups. The DAGIS intervention was conducted in preschools and involving parents in Southern Finland from September 2017 to May 2018. It was designed as a randomised trial, clustered at preschool-level. Parents of 3–6-year-olds answered questionnaires recording PEL, parental role modelling for EBRBs, and the family environment measured as EBRBs availability and accessibility. Linear Mixed Models with Repeated Measures were used in order to detect intervention effects. Models included group by time interactions. When examining intervention effects separated by PEL groups, models with three-level interactions (group × time-points × PEL) were evaluated. There was an interaction effect for the availability of sugary everyday foods and drinks (p = 0.002). The analyses showed that the control group increased availability (p = 0.003), whereas in the intervention group no changes were detected (p = 0.150). In the analysis separated by PEL groups, changes were found only for the accessibility of sugary treats at home; the high PEL control group increased the accessibility of sugary treats (p = 0.022) (interaction effect: p = 0.027). Hence, results suggest that the DAGIS multicomponent intervention had a limited impact on determinants for children’s healthy EBRBs, and no impact was found in the low PEL group.