The core feature of separation anxiety is excessive distress when faced with actual or perceived separation from people to whom the individual has a strong emotional attachment. So far little is known about the neurobiological underpinnings of separation anxiety. Therefore, we investigated functional (amygdala responsiveness and functional connectivity during threat-related emotion processing) and structural (grey matter volume) imaging markers associated with separation anxiety as measured with the Relationship Scale Questionnaire in a large sample of healthy adults from the Münster Neuroimaging Cohort (N = 320). We used a robust emotional face-matching task and acquired high-resolution structural images for morphometric analyses using voxel-based morphometry. The main results were positive associations of separation anxiety scores with amygdala reactivity to emotional faces as well as increased amygdala grey matter volumes. A functional connectivity analysis revealed positive associations between separation anxiety and functional coupling of the amygdala with areas involved in visual processes and attention, including several occipital and somatosensory areas. Taken together, the results suggest a higher emotional involvement in subjects with separation anxiety while watching negative facial expressions, and potentially secondary neuro-structural adaptive processes. These results could help to understand and treat (adult) separation anxiety.
The fear of negative evaluation is one of the hallmark features of social anxiety. Behavioral evidence thus far largely supports cognitive models which postulate that information processing biases in the face of socially relevant information are a key factor underlying this widespread phobia. So far only one neuroimaging study has explicitly focused on the fear of negative evaluation in social anxiety where the brain responses of social phobics were compared to healthy participants during the processing of self-referential relative to other-referential criticism, praise or neutral information. Only self-referential criticism led to stronger activations in emotion-relevant regions of the brain, such as the amygdala and medial prefrontal cortices (mPFC), in the social phobics. The objective of the current study was to determine whether these findings could be extended to subclinical social anxiety. In doing so, the specificity of this self-referential bias was also examined by including both social and non-social (physical illness-related) threat information as well as a highly health anxious control group in the experimental paradigm. The fMRI findings indicated that the processing of emotional stimuli was accompanied by activations in the amygdala and the ventral mPFC, while self-referential processing was associated with activity in regions such as the mPFC, posterior cingulate and temporal poles. Despite the validation of the paradigm, the results revealed that the previously reported behavioral and brain biases associated with social phobia could not be unequivocally extended to subclinical social anxiety. The divergence between the findings is explored in detail with reference to paradigm differences and conceptual issues.
Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.
Vor kurzer Zeit hat der eine von uns (K.) eine umfassende Obersicht uber die Methoden der quantitativen Papier-Chromatographie auf dem Fettgebiet gegeben, wobei im besonderen iiber die Anwendung der Planimetrie, Retentiometrie, Radiometrie, Kolorimetrie, Spektralphotometrie und Photometrie berichtet wurde Die Genauigkeit dieser Methoden kann durch Verunreinigungen, aus dem Papier und den verwendeten Losungsmitteln (die meist nicht optisch leer sind) stammend, beeintrachtigt werden. Dies trifft vor allem fur die kolorimetrischen und spektralphotometrischen Verfahren zu. Bei einer direkten photometrischen Auswertung des Chromatogramms entstehen andererseits mitunter Schwierigkeiten durch die ungleichmai3ige Beschaff enheit des Papiers und eine schwache Untergrund-Farbung, wodurch die Festlegung der Null-Linie erschwert wird. Auch erlaubt letztere Methode, die sich durch ihre schnelle und einfache Durchfiihrbarkeit auszeichnet, nur die Bestimmung der relativen Mischungsverhaltnisse, jedoch nicht die Absolutmessung von Einzelkomponenten.Unter diesen Gesichtspunkten wurde im Rahmen des hier gestellten Problems die Moglichkeit einer quantitativen papierchromatographischen Analyse mit Hilfe der P o 1 a r o g r a p h i e gepruft. Erste Ergebnisse wurden bereits in der eingangs erwahnten Veroff entlichung mitgeteilt Der wesentliche Vorteil dieser Mikromethode liegt neben ihrer groi3en Empfindlichkeit vor allem in der Tatsache, dai3 hier Fremdstoffe, z. B. andere Metall-Ionen als die zu bestimmenden, die polarographische Bestimmung nicht storen und dariiber hinaus Absolutbestimmungen moglich sind. Hier vereinen sich also die Spezifitat der papierchromatographischen Trennung mit der spezifischen quantitativen Erfassung.
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