Post-script-Retail forecasting: Research and practice.

This note updates the 2019 review article "Retail forecasting: Research and practice" in the context of the COVID-19 pandemic and the substantial new research on machine-learning algorithms, when applied to retail. It offers new conclusions and challenges for both research and practice in retail demand forecasting.

Cognitive change is more positively associated with an active lifestyle than with training interventions in older adults at risk of dementia: a controlled interventional clinical trial.

BACKGROUND: While observational studies show that an active lifestyle including cognitive, physical, and social activities is associated with a reduced risk of cognitive decline and dementia, experimental evidence from corresponding training interventions is more inconsistent with less pronounced effects. The aim of this study was to evaluate and compare training- and lifestyle-related changes in cognition. This is the first study investigating these associations within the same time period and sample. METHODS: Fifty-four older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a matched wait-list control condition. Lifestyle was operationalized as the variety of self-reported cognitive, physical, and social activities before study participation. Cognitive performance was assessed with an extensive test battery prior to and after the intervention period as well as at a 3-month follow-up. Composite cognition measures were obtained by means of a principal component analysis. Training- and lifestyle-related changes in cognition were analyzed using linear mixed effects models. The strength of their association was compared with paired t-tests. RESULTS: Neither training intervention improved global cognition in comparison to the control group (p = .08). In contrast, self-reported lifestyle was positively associated with benefits in global cognition (p < .001) and specifically in memory (p < .001). Moreover, the association of an active lifestyle with cognitive change was significantly stronger than the benefits of the training interventions with respect to global cognition (ps < .001) and memory (ps < .001). CONCLUSIONS: The associations of an active lifestyle with cognitive change over time in a dementia risk group were stronger than the effects of short-term, specific training interventions. An active lifestyle may differ from training interventions in dosage and variety of activities as well as intrinsic motivation and enjoyment. These factors might be crucial for designing novel interventions, which are more efficient than currently available training interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01061489 . Registered February 2, 2010.

Effects of psychotherapy on DNA strand break accumulation originating from traumatic stress.

BACKGROUND: Previous research reveals an association between traumatic stress and an increased risk for numerous diseases, including cancer. At the molecular level, stress may increase carcinogenesis via increased DNA damage and impaired DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear cells from individuals with post-traumatic stress disorder (PTSD) and measured the cellular capacity to repair single-strand breaks after exposure to ionizing X-radiation. We also investigated the effect of psychotherapy on both DNA breakage and DNA repair. METHODS: In a first study we investigated DNA breakage and repair in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11 trauma-exposed subjects and 20 individuals without trauma exposure. In a second study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on DNA breakage and repair. Thirty-eight individuals with PTSD were randomly assigned to either a treatment or a waitlist control condition. Follow-up was performed 4 months and 1 year after therapy. RESULTS: In study 1 we found higher levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects than in controls, indicating that traumatic stress is associated with DNA breakage. However, single-strand break repair was unimpaired in individuals with PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms, but also DNA strand break accumulation. CONCLUSION: Our results show - for the first time in vivo - an association between traumatic stress and DNA breakage; they also demonstrate changes at the molecular level, i.e., the integrity of DNA, after psychotherapeutic interventions.

Telomere shortening in leukocyte subpopulations in depression.

BACKGROUND: Telomere shortening is a normal age-related process. However, premature shortening of telomeres in leukocytes--as has been reported in depression--may increase the risk for age-related diseases. While previous studies investigated telomere length in peripheral blood mononuclear cells (PBMCs) as a whole, this study investigated specific changes in the clonal composition of white blood cells of the adaptive immune system (CD4+ helper and CD8+ cytotoxic T lymphocytes, and CD20+ B lymphocytes). METHODS: Forty-four females with a history of unipolar depression were investigated and compared to fifty age-matched female controls. Telomere lengths were compared between three groups: 1) individuals with a history of depression but currently no clinically relevant depressive symptoms, 2) individuals with a history of depression with relevant symptoms of depression, and 3) healthy age-matched controls. Telomere length was assessed using quantitative fluorescence in situ hybridization (qFISH). RESULTS: Both groups with a history of unipolar depression (with and without current depressive symptoms) showed significantly shorter telomeres in all three lymphocyte subpopulations. The effect was stronger in CD8+ and CD20+ cells than in CD4+ cells. Individuals with a history of depression and with (without) current symptoms exhibited a CD8+ telomere length shortening corresponding to an age differential of 27.9 (25.3) years. CONCLUSIONS: A history of depression is associated with shortened telomeres in the main effector populations of the adaptive immune system. Shorter telomeres seem to persist in individuals with lifetime depression independently of the severity of depressive symptoms. CD8+ cytotoxic T cells and CD20+ B cells seem to be particularly affected in depression. The total number of depressive episodes did not influence telomere length in the investigated adaptive immune cell populations.

Posttraumatic stress disorder is associated with an enhanced spontaneous production of pro-inflammatory cytokines by peripheral blood mononuclear cells.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with an enhanced risk for cardiovascular and other inflammatory diseases. Chronic low-level inflammation has been suggested as a potential mechanism linking these conditions. METHODS: We investigated plasma cytokine levels as well as spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) in a group of 35 severely traumatized PTSD patients compared to 25 healthy controls. RESULTS: Spontaneous production of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α by isolated PBMCs was significantly higher in the PTSD compared to the control group and even correlated with PTSD symptom severity within the PTSD group. In contrast, circulating plasma levels of pro- and anti-inflammatory cytokines such as IL-6, IL-8, IL-10, TNF-α, or monocyte chemotactic protein (MCP)-1 were not significantly altered in PTSD patients compared to healthy controls. CONCLUSIONS: Our findings indicate that PBMCs of PTSD patients are already pre-activated in vivo, providing further evidence for low-grade inflammation in PTSD. This might possibly represent one psychobiological pathway from PTSD to poor physical health.

Sex differences in PTSD risk: evidence from post-conflict populations challenges the general assumption of increased vulnerability in females.

Background: Next to the dose-dependent effect of trauma load, female sex represents a well-established risk factor for PTSD. Exposure to particularly toxic traumatic event types, different coping styles, and biological risk factors are frequently listed as potential causes for the increased PTSD vulnerability in females. Nevertheless, sex differences have not been consistently observed in all study populations. Objective: To investigate sex differences in PTSD risk in post-conflict populations from different countries while considering trauma load. Method: In civilian post-conflict samples from Northern Uganda (N = 1665), Rwanda (N = 433), Syria (N = 974) and Sri Lanka (N = 165), we investigated sex differences in PTSD risk while taking trauma load into account. PTSD and trauma load were assessed using standardized diagnostic interviews. Potential sex differences in PTSD risk were analysed by logistic regression analyses considering trauma load. Results: Across all samples, males reported more traumatic events than females. Both sexes predominantly reported war-related traumatic events. Without considering trauma load, sex effects in PTSD risk were only detected in the Syrian sample. When taking trauma load into account, evidence for an increased PTSD vulnerability in females was found in the Syrian sample, and, to a much lesser extent, in the Northern Ugandan sample. Conclusion: In contrast to the literature, we did not find evidence for a general increased PTSD vulnerability in females. The dose-response effect of trauma load was a much stronger predictor of PTSD risk than sex across all samples.

Antecedentes: Junto al efecto dosis-dependiente de la carga traumática, el sexo femenino representa un factor de riesgo bien establecido para el desarrollo del trastorno de estrés postraumático (TEPT). La exposición a tipos de eventos particularmente tóxicos, diferentes estilos de afrontamiento y factores de riesgo biológicos se enumeran con frecuencia como causas potenciales del aumento de la vulnerabilidad al TEPT en las mujeres. Sin embargo, no se ha observado de manera consistente la diferencia según sexo en todas las poblaciones estudiadas.Objetivo: Investigar las diferencias según sexo para el desarrollo del TEPT en poblaciones post-conflicto de diferentes países teniendo en consideración la carga traumática.Métodos: Se investigaron diferencias en el TEPT según sexo tomando en consideración la carga traumática a partir de muestras post-conflicto de población civil en el norte de Uganda (N = 1665), Ruanda (N = 433), Siria (N = 947) y Sri Lanka (N = 165). El TEPT y la carga traumática se evaluaron empleando entrevistas diagnósticas. Se analizaron las potenciales diferencias según sexo para el riesgo de desarrollar el TEPT empleando un análisis de regresión logística y considerando la carga traumática.Resultados: En todas las muestras, los varones reportaron mayor número de eventos traumáticos que las mujeres. Ambos sexos reportaron predominantemente eventos traumáticos relacionados a la guerra. Dejando de lado la carga traumática, los efectos del sexo para el riesgo de desarrollar el TEPT solo se encontraron en la muestra siria. Cuando se toma en consideración la carga traumática, se encontró un incremento en la vulnerabilidad para el desarrollo del TEPT en mujeres dentro de la muestra siria y, en menor medida, en la del norte de Uganda.Conclusión: En contraste con la literatura, no se encontró evidencia de un incremento generalizado de la vulnerabilidad para el desarrollo del TEPT en mujeres. El efecto dosis-respuesta de la carga traumática fue un predictor mucho más fuerte para el riesgo del desarrollo del TEPT que el sexo en todas las muestras.

Hippocampal activity during the transverse patterning task declines with cognitive competence but not with age.

BACKGROUND: The hippocampus is a brain region that is particularly affected by age-related morphological changes. It is generally assumed that a loss in hippocampal volume results in functional deficits that contribute to age-related cognitive decline. In a combined cross-sectional behavioural and magnetoencephalography (MEG) study we investigated whether hippocampal-associated neural current flow during a transverse patterning task - which requires learning relational associations between stimuli - correlates with age and whether it is modulated by cognitive competence. RESULTS: Better performance in several tests of verbal memory, verbal fluency and executive function was indeed associated with higher hippocampal neural activity. Age, however, was not related to the strength of hippocampal neural activity: elderly participants responded slower than younger individuals but on average produced the same neural mass activity. CONCLUSIONS: Our results suggest that in non-pathological aging, hippocampal neural activity does not decrease with age but is rather related to cognitive competence.

Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts.

The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1-4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell-cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1-4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N1 = 924) and Rwanda (N2 = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (puncorrected = 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (puncorrected = 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (pcorrected = 0.003) and NOTCH receptor processing (pcorrected = 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.

No PTSD-related differences in diurnal cortisol profiles of genocide survivors.

Posttraumatic stress disorder (PTSD) has been associated with reduced cortisol levels. Opposing results have been interpreted as resulting from methodological differences between studies. We investigated the diurnal profile of salivary cortisol in a population of highly traumatized adult males from Rwanda with and without PTSD, who spent the whole day of examination together under a maximally standardized schedule. Besides the detection of PTSD-related alterations in cortisol release we aimed at determining physiologically relevant effects of cumulative trauma exposure on HPA functioning in interaction with or independent of diagnosis. There were no differences in the diurnal pattern of cortisol release between subjects with and without PTSD. We observed an increasing prevalence of PTSD with increasing number of different traumatic event types experienced, replicating earlier results on a "building-block effect" of multiple traumatization. However, size of cumulative exposure was not related to any of the cortisol measures. The results suggest that besides methodological constraints also confounding factors not previously controlled for, e.g., sex differences or current life stress, might contribute to the diverging results of lowered, unchanged or enhanced cortisol secretion in PTSD. Future research should therefore closely monitor these possible confounds to optimize models for cortisol in research on stress-dependent illnesses.

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia.

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100-250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer's dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (ß = 0.38, p = 0.003; ß = -0.27, p = 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (ß = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia.

Genetic variation is associated with PTSD risk and aversive memory: Evidence from two trauma-Exposed African samples and one healthy European sample.

The probability to develop posttraumatic stress disorder (PTSD), characterized by vivid, intrusive emotional memories of the encountered traumatic events, depends - among other factors - on the number of previous traumatic experiences (traumatic load) and individual genetic vulnerability. So far, our knowledge regarding the biological underpinnings of PTSD is relatively sparse. Genome-wide association studies (GWAS) followed by independent replication might help to discover novel, so far unknown biological mechanisms associated with the development of traumatic memories. Here, a GWAS was conducted in N = 924 Northern Ugandan rebel war survivors and identified seven suggestively significant single nucleotide polymorphisms (SNPs; p ≤ 1 × 10-5) for lifetime PTSD risk. Of these seven SNPs, the association of rs3852144 on chromosome 5 was replicated in an independent sample of Rwandan genocide survivors (N = 370, p < .01). While PTSD risk increased with accumulating traumatic experiences, the vulnerability was reduced in carriers of the minor G-allele in an additive manner. Correspondingly, memory for aversive pictures decreased with higher number of the minor G-allele in a sample of N = 2698 healthy Swiss individuals. Finally, investigations on N = 90 PTSD patients treated with Narrative Exposure Therapy indicated an additive effect of genotype on PTSD symptom change from pre-treatment to four months after treatment, but not between pre-treatment and the 10-months follow-up. In conclusion, emotional memory formation seems to decline with increasing number of rs3852144 G-alleles, rendering individuals more resilient to PTSD development. However, the impact on therapy outcome remains preliminary and further research is needed to determine how this intronic marker may affect memory processes in detail.

Spider phobics more easily see a spider in morphed schematic pictures.

BACKGROUND: Individuals with social phobia are more likely to misinterpret ambiguous social situations as more threatening, i.e. they show an interpretive bias. This study investigated whether such a bias also exists in specific phobia. METHODS: Individuals with spider phobia or social phobia, spider aficionados and non-phobic controls saw morphed stimuli that gradually transformed from a schematic picture of a flower into a schematic picture of a spider by shifting the outlines of the petals until they turned into spider legs. Participants' task was to decide whether each stimulus was more similar to a spider, a flower or to neither object while EEG was recorded. RESULTS: An interpretive bias was found in spider phobia on a behavioral level: with the first opening of the petals of the flower anchor, spider phobics rated the stimuli as more unpleasant and arousing than the control groups and showed an elevated latent trait to classify a stimulus as a spider and a response-time advantage for spider-like stimuli. No cortical correlates on the level of ERPs of this interpretive bias could be identified. However, consistent with previous studies, social and spider phobic persons exhibited generally enhanced visual P1 amplitudes indicative of hypervigilance in phobia. CONCLUSION: Results suggest an interpretive bias and generalization of phobia-specific responses in specific phobia. Similar effects have been observed in other anxiety disorders, such as social phobia and posttraumatic stress disorder.

Does trauma event type matter in the assessment of traumatic load?

Background: The likelihood of developing Posttraumatic Stress Disorder (PTSD) depends on the interaction of individual risk factors and cumulative traumatic experiences. Hence, the identification of individual susceptibility factors warrants precise quantification of trauma exposure. Previous research indicated that some traumatic events may have more severe influences on mental health than others; thus, the assessment of traumatic load may be improved by weighting event list items rather than calculating the simple sum score. Objective: We compared two statistical methods, Random Forests using Conditional Interference (RF-CI) and Least Absolute Shrinkage and Selection Operator (LASSO), based on their ability to rank traumatic experiences according to their importance for predicting lifetime PTSD. Methods: Statistical models were initially fitted in a sample of N1 = 441 survivors of the Northern Ugandan rebel war. The ability to correctly predict lifetime PTSD was then tested in an independent sample of N2 = 211, and subsequently compared with predictions by the simple sum score of different traumatic event types experienced. Results: Results indicate that RF-CI and LASSO allow for a ranking of traumatic events according to their predictive importance for lifetime PTSD. Moreover, RF-CI showed slightly better prediction accuracy than the simple sum score, followed by LASSO when comparing prediction results in the validation sample. Conclusion: Given the expense in time and calculation effort by RF-CI and LASSO, and the relatively low increase in prediction accuracy by RF-CI, we recommend using the simple sum score to measure the environmental factor traumatic load, e.g., in analyses of gene × environment interactions.

Event-related potentials when identifying or color-naming threatening schematic stimuli in spider phobic and non-phobic individuals.

BACKGROUND: Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. METHODS: Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. RESULTS: Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. CONCLUSION: Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.

How to quantify exposure to traumatic stress? Reliability and predictive validity of measures for cumulative trauma exposure in a post-conflict population.

BACKGROUND: While studies with survivors of single traumatic experiences highlight individual response variation following trauma, research from conflict regions shows that almost everyone develops posttraumatic stress disorder (PTSD) if trauma exposure reaches extreme levels. Therefore, evaluating the effects of cumulative trauma exposure is of utmost importance in studies investigating risk factors for PTSD. Yet, little research has been devoted to evaluate how this important environmental risk factor can be best quantified. METHODS: We investigated the retest reliability and predictive validity of different trauma measures in a sample of 227 Ugandan rebel war survivors. Trauma exposure was modeled as the number of traumatic event types experienced or as a score considering traumatic event frequencies. In addition, we investigated whether age at trauma exposure can be reliably measured and improves PTSD risk prediction. RESULTS: All trauma measures showed good reliability. While prediction of lifetime PTSD was most accurate from the number of different traumatic event types experienced, inclusion of event frequencies slightly improved the prediction of current PTSD. CONCLUSIONS: As assessing the number of traumatic events experienced is the least stressful and time-consuming assessment and leads to the best prediction of lifetime PTSD, we recommend this measure for research on PTSD etiology.

Metabolite profiling in posttraumatic stress disorder.

BACKGROUND: Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD. METHODS: Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA). RESULTS: Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%. CONCLUSIONS: This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology.

The effect of trauma-focused therapy on the altered T cell distribution in individuals with PTSD: evidence from a randomized controlled trial.

Posttraumatic stress disorder (PTSD) is associated with a reduced ratio of naïve cytotoxic T lymphocytes, an increased ratio of memory cytotoxic T lymphocytes, and a reduced proportion of FoxP3(+) regulatory T lymphocytes. This study investigated whether these immunological alterations are reversible through an evidence-based psychotherapeutic treatment. Therefore, 34 individuals with PTSD were randomly assigned to either a treatment condition of 12 sessions narrative exposure therapy (NET) or a waitlist control (WLC) group. PTSD symptoms were significantly reduced in the NET group, but not in the WLC group, four months post-therapy (effect size: Hedges' g = -1.61). One year after therapy, PTSD symptoms were improved even further in the NET group compared to baseline (Hedges' g = -1.96). This symptom improvement was mirrored in an increase in the originally reduced proportion of regulatory T cells (Tregs) in the NET group at the one-year follow-up, when comparing subgroups matched for baseline Treg numbers. However, no changes were found for the initially reduced proportion of CD45RA(+)CCR7(+) naïve T lymphocytes. In conclusion, NET was effective in reducing trauma-related PTSD symptoms and had a positive effect on the proportion of Tregs cells, thus demonstrating an effect of psychotherapy on an immunological level. Yet, the shift in the proportion of naïve and memory T lymphocytes in individuals with PTSD, discussed in the literature as a correlate of premature immunosenescence, was not reversible and thus might render these patients permanently more susceptible to infectious diseases.

Effects of aging and mild cognitive impairment on electrophysiological correlates of performance monitoring.

Performance monitoring tasks are suitable for investigating aging-related decline in executive functions. However, little is known about performance monitoring in premature pathological aging and mild cognitive impairment (MCI). This study recorded the error-related negativity (ERN) and the correct-related negativity (CRN) as indices of performance monitoring and compared these responses in older adults with MCI to the ones of younger and older adult controls. No differences in either ERN or CRN were found between younger and older adult controls. Compared to both control groups, we observed a more negatively pronounced CRN in MCI subjects. Only in this group did the amplitude of the CRN not differ from the one of the ERN. In general, larger differences between both components (i.e., ERN > CRN) were associated with better performances in cognitive tests requiring inhibition and executive control. These results indicate that electrophysiological correlates of performance monitoring (ERN and CRN) are differentially affected by aging and MCI.

The role of memory-related gene WWC1 (KIBRA) in lifetime posttraumatic stress disorder: evidence from two independent samples from African conflict regions.

BACKGROUND: Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD. METHODS: Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample. RESULTS: An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p = .007, odds ratio = .29 [95% confidence interval = .15-.54]). This effect was confirmed in the independent Ugandan sample. CONCLUSIONS: This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories.

Development of large-scale functional networks over the lifespan.

The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.