[Diagnostic Performance and Validity of the German Version of the BDI-II - A Secondary Analysis with Data from Clinical and Nonclinical Samples]. / Diagnostische Performanz und Validität des deutschsprachigen BDI-II ­ Eine Sekundäranalyse mit Daten aus klinischen und nichtklinischen Stichproben.

OBJECTIVES: Study of the diagnostic performance and validity of the German Beck Depression Inventory (BDI-II) in a large data set from multiple adult samples. METHODS: The BDI-II was assessed together with the SCID-I as external criterion in 638 individuals (385 currently or remitted depressed individuals, 253 controls). The screening performance of the BDI-II was calculated for suggested cut-offs from the BDI-II manual and for optimal cut-offs derived from ROC-analyses. RESULTS: The internal consistency of the BDI-II was high (> 0,90) and it showed plausible associations with construct-related scales. Optimal cut-off scores of 16+ resulted for MDE (Youden's J = 0.838) and of 14+ for DD (J = 0.814). CONCLUSIONS: The German BDI-II is a reliable und valid screening tool for detecting depressive episodes and depressive disorders in the adult population. Depending on prioritized goals different cut-off-values can be used.

Stability of Attention Performance of Adults with ADHD over Time: Evidence from Repeated Neuropsychological Assessments in One-Month Intervals.

Neuropsychological assessments of attention are valuable sources of information in the clinical evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the attention performance of adults with ADHD is stable or fluctuates over time, which is of great importance in the interpretation of clinical assessments. This study aimed to explore the stability of attention performance of adults with ADHD in repeated assessments at one-month intervals. Twenty-one adults diagnosed with ADHD took part in this study by completing selective attention and vigilance tests three times, each one month apart. Test scores of participants were compared with and interpreted based on test norms. A considerable proportion of 'below average' performance scores were observed in most of the variables of selective attention and vigilance in all three assessments. Further, selective attention and vigilance performance scores did not differ significantly between the three repeated assessments. Finally, the majority of participants received consistent test score interpretations across the three repeated assessments. This study confirms previous research and highlights abnormal selective attention and vigilance performance in adults with ADHD. Further, this study preliminarily demonstrates relatively stable attention performance across repeated assessments, which has the potential to support clinical assessment, treatment planning, and evaluation.

Family-centered music therapy-Empowering premature infants and their primary caregivers through music: Results of a pilot study.

BACKGROUND: In Neonatal Intensive Care Units (NICUs) premature infants are exposed to various acoustic, environmental and emotional stressors which have a negative impact on their development and the mental health of their parents. Family-centred music therapy bears the potential to positively influence these stressors. The few existing studies indicate that interactive live-improvised music therapy interventions both reduce parental stress factors and support preterm infants' development. METHODS: The present randomized controlled longitudinal study (RCT) with very low and extremely low birth weight infants (born <30+0 weeks of gestation) and their parents analyzed the influence of music therapy on both the physiological development of premature infants and parental stress factors. In addition, possible interrelations between infant development and parental stress were explored. 65 parent-infant-pairs were enrolled in the study. The treatment group received music therapy twice a week from the 21st day of life till discharge from hospital. The control group received treatment as usual. RESULTS: Compared to the control group, infants in the treatment group showed a 11.1 days shortening of caffeine therapy, 12.1 days shortening of nasogastric/ orogastric tube feed and 15.5 days shortening of hospitalization, on average. While these differences were not statistically significant, a factor-analytical compound measure of all three therapy durations was. From pre-to-post-intervention, parents showed a significant reduction in stress factors. However, there were no differences between control and treatment group. A regression analysis showed links between parental stress factors and physiological development of the infants. CONCLUSION: This pilot study suggests that a live-improvised interactive music therapy intervention for extremely and very preterm infants and their parents may have a beneficial effect on the therapy duration needed for premature infants before discharge from hospital is possible. The study identified components of the original physiological variables of the infants as appropriate endpoints and suggested a slight change in study design to capture possible effects of music therapy on infants' development as well. Further studies should assess both short-term and long-term effects on premature infants as well as on maternal and paternal health outcomes, to determine whether a family-centered music therapy, actually experienced as an added value to developmental care, should be part of routine care at the NICU.

Scary symptoms? Functional magnetic resonance imaging evidence for symptom interpretation bias in pathological health anxiety.

Patients with pathological health anxiety (PHA) tend to automatically interpret bodily sensations as sign of a severe illness. To elucidate the neural correlates of this cognitive bias, we applied an functional magnetic resonance imaging adaption of a body-symptom implicit association test with symptom words in patients with PHA (n = 32) in comparison to patients with depression (n = 29) and healthy participants (n = 35). On the behavioral level, patients with PHA did not significantly differ from the control groups. However, on the neural-level patients with PHA in comparison to the control groups showed hyperactivation independent of condition in bilateral amygdala, right parietal lobe, and left nucleus accumbens. Moreover, patients with PHA, again in comparison to the control groups, showed hyperactivation in bilateral posterior parietal cortex and left dorsolateral prefrontal cortex during incongruent (i.e., harmless) versus congruent (i.e., dangerous) categorizations of body symptoms. Thus, body-symptom cues seem to trigger hyperactivity in salience and emotion processing brain regions in PHA. In addition, hyperactivity in brain regions involved in cognitive control and conflict resolution during incongruent categorization emphasizes enhanced neural effort to cope with negative implicit associations to body-symptom-related information in PHA. These results suggest increased neural responding in key structures for the processing of both emotional and cognitive aspects of body-symptom information in PHA, reflecting potential neural correlates of a negative somatic symptom interpretation bias.

Neural correlates of an attentional bias to health-threatening stimuli in individuals with pathological health anxiety.

BACKGROUND: An attentional bias to health-threat stimuli is assumed to represent the primary pathogenetic factor for the development and maintenance of pathological health anxiety (PHA; formerly termed "hypochondriasis"). However, little is known about the neural basis of this attentional bias in individuals with PHA. METHODS: A group of patients with PHA, a group of depressed patients and a healthy control group completed an emotional Stroop task with health-threat (body symptom and illness) words and neutral control words while undergoing functional MRI. RESULTS: We included 33 patients with PHA, 28 depressed patients and 31 controls in our analyses. As reflected in reaction times, patients with PHA showed a significantly stronger attentional bias to health-threat words than both control groups. In addition, patients with PHA showed increased amygdala and rostral anterior cingulate cortex activation for body symptom, but not for illness words. Moreover, only in patients with PHA amygdala activation in response to symptom words was positively associated with higher arousal and more negative valence ratings of the body symptom word material. LIMITATIONS: A control group of patients with an anxiety disorder but without PHA would have helped to define the specificity of the results for PHA. CONCLUSION: The attentional bias observed in patients with PHA is associated with hyperactivation in response to body symptom words in brain regions that are crucial for an arousal-related fear response (e.g., the amygdala) and for resolving emotional interference (e.g., the rostral anterior cingulate cortex). The findings have important implications for the nosological classification of PHA and suggest the application of innovative exposure-based interventions for the treatment of PHA.

Cough Is Dangerous: Neural Correlates of Implicit Body Symptoms Associations.

The negative interpretation of body sensations (e.g., as sign of a severe illness) is a crucial cognitive process in pathological health anxiety (HA). However, little is known about the nature and the degree of automaticity of this interpretation bias. We applied an implicit association test (IAT) in 20 subjects during functional magnetic resonance imaging (fMRI) to investigate behavioral and neural correlates of implicit attitudes toward symptom words. On the behavioral level, body symptom words elicited strong negative implicit association effects, as indexed by slowed reaction times, when symptom words were paired with the attribute "harmless" (incongruent condition). fMRI revealed increased activation in the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex for the comparison of incongruent words with control words, as well as with a lower significance threshold also in comparison to congruent words. Moreover, activation in the DLPFC, posterior parietal cortex, nucleus accumbens, and cerebellum varied with individual levels of HA (again, in comparison to control words, as well as with a lower significance threshold also in comparison to congruent words). Slowed reaction times as well as increased activation in dorsolateral prefrontal and posterior parietal cortex point to increased inhibitory demands during the incongruent IAT condition. The positive association between HA severity and neural activity in nucleus accumbens, dorsolateral prefrontal, and posterior parietal cortex suggests that HA is characterized by both intensified negative implicit attitudes and hampered cognitive control mechanisms when confronted with body symptoms.

Health anxiety and hypochondriasis in the light of DSM-5.

BACKGROUND: In the DSM-5, the diagnosis of hypochondriasis was replaced by two new diagnositic entities: somatic symptom disorder (SSD) and illness anxiety disorder (IAD). Both diagnoses share high health anxiety as a common criterion, but additonal somatic symptoms are only required for SSD but not IAD. DESIGN: Our aim was to provide empirical evidence for the validity of these new diagnoses using data from a case-control study of highly health-anxious (n = 96), depressed (n = 52), and healthy (n = 52) individuals. RESULTS: The individuals originally diagnosed as DSM-IV hypochondriasis predominantly met criteria for SSD (74%) and rarely for IAD (26%). Individuals with SSD were more impaired, had more often comorbid panic and generalized anxiety disorders, and had more medical consultations as those with IAD. Yet, no significant differences were found between SSD and IAD with regard to levels of health anxiety, other hypochondriacial characteristics, illness behavior, somatic symptom attributions, and physical concerns, whereas both groups differed significantly from clinical and healthy controls in all of these variables. CONCLUSION: These results do not support the proposed splitting of health anxiety/hypochondriasis into two diagnoses. Further validation studies with larger samples and additional control groups are warranted to prove the validity of the new diagnoses.

Simultaneous EEG-fMRI reveals brain networks underlying recognition memory ERP old/new effects.

The mapping of event-related potentials (ERP) on functional magnetic resonance imaging (fMRI) data remains difficult as scalp electroencephalography (EEG) is assumed to be largely insensitive to deep brain structures. Simultaneous recordings of EEG and fMRI might be helpful in reconciling surface ERPs with hemodynamic activations in medial temporal lobe structures related to recognition memory. EEG and imaging studies provide evidence for two independent processes underlying recognition memory, namely recollection and familiarity. Recollection reflects the conscious retrieval of contextual information about a specific episode, while familiarity refers to an acontextual feeling of knowing. Both processes were related to two spatiotemporally different ERP effects, namely the early mid-frontal old/new effect (familiarity) and the late parietal old new effect (recollection). We conducted an exploratory simultaneous EEG-fMRI study using a recognition memory paradigm to investigate which brain activations are modulated in relation to the ERP old/new effects. To this end we examined 17 participants in a yes/no recognition task with word stimuli. Single-trial amplitudes of ERP old/new effects were related to the hemodynamic signal in an EEG-informed fMRI analysis for a subset of 12 subjects. FMRI activation in the right dorsolateral prefrontal cortex and the right intraparietal sulcus was associated with the amplitude of the early frontal old/new effect (350-550ms), and activation in the right posterior hippocampus, parahippocampal cortex and retrosplenial cortex was associated with the amplitude of the late parietal old new effect (580-750ms). These results provide the first direct link between electrophysiological and hemodynamic correlates of familiarity and recollection. Moreover, these findings in healthy subjects complement data from intracranial ERP recordings in epilepsy patients and lesion studies in hypoxia patients.

A diary-based modification of symptom attributions in pathological health anxiety: effects on symptom report and cognitive biases.

OBJECTIVE: To examine whether a 2-week attribution modification training (AMT) changes symptom severity, emotional evaluation of health-threatening stimuli, and cognitive biases in pathological health anxiety. METHOD: We randomized 85 patients with pathological health anxiety into an electronic diary-based AMT group (AMTG; n = 42) and a control group without AMT (CG; n = 43). Self-report symptom measures, emotional evaluation, attentional bias, and memory bias toward symptom and illness words were assessed with an emotional Stroop task, a recognition task, and an emotional rating task for valence and arousal. RESULTS: After the 2-week period, the AMTG compared with the CG reported lower symptoms of pathological health anxiety, F(1, 82) = 10.94, p < .01, η2p = .12, rated symptom, F(1, 82) = 5.56, p = .02, η2p = .06, and illness words, F(1, 82) = 4.13, p = .045, η2p = .05, as less arousing, and revealed a smaller memory response bias toward symptom words in the recognition task F(1, 82) = 12.32, p < .01, η2p = .13. However, no specific AMT effect was observed for the attentional bias. CONCLUSION: The results support the efficacy of a comparatively short cognitive intervention in pathological health anxiety as a possible add-on intervention to existing treatment approaches to reduce symptom severity, as well as abnormalities in health-related emotional evaluation and memory processes.

Contextual fear conditioning in humans using feature-identical contexts.

Contextual fear conditioning studies in animals and humans found an involvement of the hippocampus and amygdala during fear learning. To exclude a focus on elements of the context we employed a paradigm, which uses two feature-identical contexts that only differ in the arrangement of the features and requires configural processing. We employed functional magnetic resonance imaging to determine the role of the hippocampus and neocortical areas during the acquisition of contextual fear in humans. For contextual fear acquisition, we paired one context (CS+) with an aversive electrical stimulus, whereas the other (CS-) was never followed by aversive stimulation. Blood oxygen level dependent activation to the CS+ was present in the insula, inferior frontal gyrus, inferior parietal lobule, superior medial gyrus and caudate nucleus. Furthermore, the amygdala and hippocampus were involved in a time-dependent manner. Psychophysiological interaction analyses revealed functional connectivity of a more posterior hippocampal seed region with the anterior hippocampus, posterior cingulate cortex and superior parietal lobule. The anterior hippocampus was functionally coupled with the amygdala and postcentral gyrus. This study complements previous findings in contextual fear conditioning in humans and provides a paradigm which might be useful for studying patients with hippocampal impairment.

Altered neural reward and loss processing and prediction error signalling in depression.

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

Childhood maltreatment is associated with depression but not with hypochondriasis in later life.

OBJECTIVE: Previous studies demonstrated that a history of childhood trauma is linked to mental disorders in adulthood, particularly to depression. Adverse childhood experiences are also considered to contribute to the risk of hypochondriasis, but the results of previous studies have not been conclusive with respect to the strength and specificity of this association. Therefore, we compared the association of adverse childhood experiences with both hypochondriasis and depression. METHODS: Fifty-eight patients with hypochondriasis, 52 patients with depression, and 52 healthy control participants completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 varieties of abuse and neglect. A clinical interview (SCID-I) was used to establish DSM-IV diagnoses. Associations between childhood maltreatment, hypochondriasis and depression were estimated by means of analyses of variance and multiple linear regression analyses. RESULTS: In comparison to hypochondriacal and healthy participants, patients with a current depressive disorder reported more emotional abuse as well as more emotional and physical neglect during childhood. Patients with hypochondriasis reported more emotional neglect than healthy individuals. However, when predicting the CTQ trauma types by diagnostic category adjusting for sex and comorbid DSM-IV diagnoses, emotional abuse, emotional neglect, physical abuse, physical neglect, as well as the CTQ total score were significantly associated with depression, but none of the CTQ scores was significantly related to hypochondriasis. CONCLUSIONS: The findings suggest a robust association of childhood maltreatment with depression but not with hypochondriasis. This result does not support etiological models of hypochondriasis which rely on childhood maltreatment as a risk factor for the development of this disorder.

Measuring depression with a well-being index: further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression.

BACKGROUND: In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS: The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD: Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS: In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION: Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

Does body shaping influence brain shape? Habitual physical activity is linked to brain morphology independent of age.

OBJECTIVES: Physical activity (PA) was found to influence human brain morphology. However, the impact of PA on brain morphology was mainly demonstrated in seniors. We investigated healthy individuals across a broad age range for the relation between habitual PA and brain morphology. METHODS: Ninety-five participants (19-82 years) were assessed for self-reported habitual PA with the "Baecke habitual physical activity questionnaire", and T1-weighted magnetic resonance images were evaluated with whole brain voxel based morphometry for gray and white matter volumes and densities. RESULTS: Regression analyses revealed a positive relation between the extent of physical activity and gray matter volume bilaterally in the anterior hippocampal and parahippocampal gyrus independent of age and gender. Age as well as leisure and locomotion activities were linked to enhanced white matter volumes in the posterior cingulate gyrus and precuneus, suggesting a positive interaction especially in seniors. CONCLUSIONS: Habitual physical activity is associated with regional volumetric gray and white matter alterations. The positive relation of hippocampal volume and physical activity seems not to be restricted to seniors. Thus, habitual physical activity should be generally considered as an influencing factor in studies investigating medial temporal lobe volume and associated cognitive functions (memory), especially in psychiatric research.

Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol.

Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects.

Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

Neuronal and behavioral correlates of health anxiety: results of an illness-related emotional Stroop task.

BACKGROUND: Health anxiety (HA) is defined as the objectively unfounded fear or conviction of suffering from a severe illness. Predominant attention allocation to illness-related information is regarded as a central process in the development and maintenance of HA, yet little is known about the neuronal correlates of this attentional bias. METHODS: An emotional Stroop task with body symptom, illness, and neutral words was employed to elicit emotional interference in healthy participants with high (HA+, n = 12) and low (HA-, n = 12) HA during functional magnetic resonance imaging. RESULTS: Prolonged reaction times for indicating the color of symptom words and a decrease in rostral anterior cingulate cortex (rACC) activation were seen in HA+ participants. Emotional interference effects on the behavioral level were negatively related to rACC activity over the whole group. Groups did not differ during the processing of threatening illness words. CONCLUSION: The results indicate stronger attention allocation toward body symptom words already in subclinical HA. This attentional bias appears to be linked to hypoactivity of the rACC which impedes effective emotional interference reduction, leading instead to a ruminative processing of the stimulus content.

Effects of age on the structure of functional connectivity networks during episodic and working memory demand.

The aim of the study was to investigate age-related differences in large-scale functional connectivity networks during episodic and working memory challenge. A graph theoretical approach was used providing an exhaustive set of topological measures to quantify age-related differences in the network structure on various scales. In a single session, 10 young (22-30 years) and 10 senior (62-77 years) subjects performed an episodic and a working memory task during functional magnetic resonance imaging. Networks of functional connectivity were constructed by correlating the blood oxygenation level-dependent (BOLD) signal for every pair of voxels. Statistical network parameters yield a global characterization of the network topology, the quantification of the importance of specific regions, and shifts in local connectivity. An age-related increase in the density and size of the networks and loss of small-worldness was observed, related to an expanded distribution of brain activity during both memory demands in seniors, and a more specific and localized activity in young subjects. In addition, we found highly symmetrical neural networks in young subjects accompanied by a strong coupling between parietal and occipital regions. In contrast, seniors showed pronounced left-hemispheric asymmetry with decreased connectivity within occipital areas, but increased connectivity within parietal areas. Moreover, seniors engaged an additional frontal network strongly connected to parietal areas. In contrast to young subjects, seniors showed an almost identical structure of network connectivity during both memory tasks. The chosen network approach is explorative and hypothesis-free. Our results extend seed-based and BOLD-signal intensity focused studies, and support present hypotheses like compensation and dedifferentiation.

A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression.

Major depressive disorder (MDD) is characterized by altered emotional and cognitive functioning. We performed a voxel-based whole-brain meta-analysis of functional neuroimaging data on altered emotion and cognition in MDD. Forty peer-reviewed studies in English-language published between 1998 and 2010 were included, which used functional neuroimaging during cognitive-emotional challenge in adult individuals with MDD and healthy controls. All studies reported between-groups differences for whole-brain analyses in standardized neuroanatomical space and were subjected to Activation Likelihood Estimation (ALE) of brain cluster showing altered responsivity in MDD. ALE resulted in thresholded and false discovery rate corrected hypo- and hyperactive brain regions. Against the background of a complex neural activation pattern, studies converged in predominantly hypoactive cluster in the anterior insular and rostral anterior cingulate cortex linked to affectively biased information processing and poor cognitive control. Frontal areas showed not only similar under- but also over-activation during cognitive-emotional challenge. On the subcortical level, we identified activation alterations in the thalamus and striatum which were involved in biased valence processing of emotional stimuli in MDD. These results for active conditions extend findings from ALE meta-analyses of resting state and antidepressant treatment studies and emphasize the key role of the anterior insular and rostral anterior cingulate cortex for altered emotion and cognition in MDD.

SCN1A affects brain structure and the neural activity of the aging brain.

BACKGROUND: The aging of the human brain is accompanied by changes in cortical structure as well as functional activity and variable degrees of cognitive decline. One-third of the observable inter-individual differences in cognitive decline are thought to be heritable. SCN1A encodes the sodium channel α subunit and is considered to be a susceptibility gene for several neurological disorders with prominent cognitive deficits. In a recent genome-wide association study the C allele of the SCN1A variant rs10930201 was observed to be significantly associated with poor short-term memory performance. rs10930201 was further observed to be related to differences in neural activity during a working memory task. METHODS: The aim of the present study was to explore whether SCN1A modifies the vulnerability to aging processes of the human brain. Therefore we assessed the interacting effects of the SCN1A vulnerability allele rs10930201 and age in terms of brain activity and brain morphology in 62 healthy volunteers between 21 and 82 years of age. RESULTS: In C allele carriers, activity in the right inferior frontal cortex and the posterior cingulate cortex increased with age. Moreover, exploratory analysis revealed regional effects of rs10930201 on brain structure, indicating reduced gray matter densities in the frontal and insular regions in the C allele carriers. CONCLUSIONS: Collectively, the present results suggest that the SCN1A polymorphism has modulatory effects on brain morphology and vulnerability to age-related alterations in brain activity of cortical regions that subserve working memory.