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Infant carrying may have beneficial effects on the parent-infant relationship but only limited research has been conducted in this area. Therefore, the main aim of the current study was to investigate whether infant carrying is associated with parental reflective functioning, parental bonding, and parental (emotional) and behavioral responses to infant crying, key elements within the parent-infant relationship, promoting infant development. Parents reporting high levels (N = 389) of infant carrying (six times a week or daily) and parents reporting low levels (N = 128) of infant carrying (less than once a week or not at all) who participated in an online survey about the developing parent-infant relationship in Germany were included in the present study. Standardized questionnaires were used to assess parental reflective functioning, parental bonding impairments, and emotional responses to infant crying. Further insensitive (non-responsive and hostile) behaviors in response to infant crying were assessed. Parents with high levels of infant carrying showed better parental reflective functioning, lower parental bonding problems, less negative emotions, and less insensitive behaviors in response to infant crying., (© 2024 The Authors. Infant Mental Health Journal published by Wiley Periodicals LLC on behalf of Michigan Association for Infant Mental Health.)

Background: Recent studies report that LGBTQ + people have experienced high levels of mental health problems during COVID-19-related social distancing. Given the well-established association between social isolation and mental health, the main aim of the current study was to investigate differences in mental health and (perceived) social isolation and social support in LGBTQ + individuals compared to heterosexual, cisgender people and to explore whether the hypothesized higher mental health burden in LGBTQ + individuals is (partly) mediated by (perceived) social isolation or social support., Methods: N = 531 participants indicating belonging to the LGBTQ + community and N = 1826 not identifying as LGBTQ + participated in a cross-sectional online survey during the initial COVID-19-related lockdown in Germany. Standardized questionnaires were used to assess depression, anxiety, suicidality, loneliness and social support. Further, perceived social isolation and face-to-face communication during the lockdown were assessed., Results: LGBTQ + people had higher levels of depression, anxiety and suicidal thought, were lonelier and experienced less social support than non-LGBTQ + identifying individuals. Mediation analysis showed that the higher levels of mental health burden in LGBTQ + people were (partly) mediated by reduced social connectedness. Further face-to-face contact positively affected mental health by reducing feelings of loneliness., Conclusion: Given the high impact of loneliness on mental health, governmental actions should be taken to promote social connectedness particularly among LGBTQ + identifying individuals to ensure that the COVID-19 pandemic does not exacerbate the health inequalities that already exist between LGBTQ+-identifying and heterosexual, cisgender people., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Studies using transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) revealed an imbalance between cortical excitation and inhibition (E/I) in the dorsolateral prefrontal cortex (DLPFC) in depression. As adolescence is a developmental period with an increase in depression prevalence and profound neural changes, it is crucial to study the relationship between depression and cortical excitability in adolescence. We aimed to investigate the cortical excitability of the DLPFC in adolescents with depression and a dependency of the TMS-evoked potential N100 on the depression severity. 36 clinical patients (12-18 years of age; 21 females) with a major depressive episode were assessed twice in a longitudinal design: shortly after admission (T0) and after six weeks of intervention (T1). GABA-B-mediated cortical inhibition in the left and right DLPFC, as assessed by the N100, was recorded with EEG. Significantly higher depression scores were reported at T0 compared to T1 (p < 0.001). N100 amplitudes were significantly increased (i.e., more negative) at T0 compared to T1 (p = 0.03). No significant hemispheric difference was found in the N100 component. The correlation between the difference in depression severity and the difference in N100 amplitudes (T0-T1) obtained during stimulation of the left DLPFC did not remain significant after correction for testing in both hemispheres. Higher N100 amplitudes during a state of greater depression severity are suggestive of an E/I imbalance in the DLPFC in adolescents with an acute depressive episode. The N100 reduction potentially reflects a normalization of DLPFC over inhibition in association with decreased depressive symptomatology, indicating severity dependency., (© 2022. The Author(s).)

Childhood adversity has been suggested to affect the vulnerability for developmental psychopathology, including both externalizing and internalizing symptoms. This study examines spontaneous attention biases for negative and positive emotional facial expressions as potential intermediate phenotypes. In detail, typically developing boys (6-13 years) underwent an eye-tracking paradigm displaying happy, angry, sad and fearful faces. An approach bias towards positive emotional facial expressions with increasing childhood adversity levels was found. In addition, an attention bias away from negative facial expressions was observed with increasing childhood adversity levels, especially for sad facial expressions. The results might be interpreted in terms of emotional regulation strategies in boys at risk for reactive aggression and depressive behaviour., (© 2022. The Author(s).)

Background: A deficit in empathy has repeatedly been described in individuals with conduct disorder (CD), and in particular in those with callous unemotional traits. Until now, little is known about the neural basis of empathy in children and adolescents with early onset conduct disorder. The aim of this study was to examine neural responses during empathizing in children and adolescents with CD with a task that allowed to differentiate between the judgment of the emotional states of other people and the own emotional response to other people's emotional state. Moreover, we investigated associations of callous-unemotional traits and neural activations during empathizing. Methods: Using functional magnetic resonance imaging (fMRI) we investigated 14 boys with early onset CD and 15 typically developing (TDC) age matched controls between 8 and 16 years of age. Happy and sad faces were presented, and participants were asked to either infer the emotional state from the face (other-task) or to judge their own emotional response (self-task). A perceptual decision on faces was used as a control task. Individual empathic abilities and callous unemotional traits were assessed. Results: During the other task, TDC boys showed significantly larger right amygdala responses than CD boys. Higher empathic abilities (as assessed with the Bryant Index of Empathy) were associated with higher responses in the right amygdala within the CD boys and across the entire sample. Moreover, across the entire sample, callous-unemotional traits were negatively related to the BOLD-response in the right amygdala. CD boys showed larger responses in the dorsal and ventral medial prefrontal cortex across tasks and increased activation in dorsal medial prefrontal cortex specifically during the self-conditions, which were also related to empathic abilities within the CD boys. Conclusions: The data emphasize the important role of the amygdala in empathy related emotional processing. Diminished amygdala responses and their association with low empathy suggest a pivotal influence of impaired amygdala processing in early-onset CD, in particular for deficits in empathic behavior and related callous-unemotional-traits. Elevated response in the medial prefrontal cortex in boys with CD point toward increased involvement of brain areas related to self-referential processing and cognitive empathy during empathizing., (Copyright © 2020 von Polier, Greimel, Konrad, Großheinrich, Kohls, Vloet, Herpertz-Dahlmann and Schulte-Rüther.)

Background: Early intervention for children identified as late talkers (LTs) at the age of 24 months is still a controversial issue in research and clinical routine. Previous studies have shown inconsistent results regarding predictors of early lexical deficits on school-age outcomes of late-talking toddlers., Methods: In a five-wave follow-up study, we investigated various aspects of language and literacy abilities in 39 German-speaking third-graders who had been identified as LTs at the age of 24 months, compared to 39 typically developing children (TDC) also attending the third grade. The duration of auditory sensory memory was examined at the age of 4 years using mismatch negativity (MMN) of tones - an event-related potential not confounded by any language skill. In addition, the predictive value of memory performance was examined in a longitudinal perspective., Results: Overall, LTs scored within normal range in language and literacy assessments. However, LTs differed from TDC in vocabulary size, verbalization of semantic relations, non-word repetition, and spelling. The findings can be explained by phonological working memory. The duration of auditory sensory memory and spatial working memory did not account for any variance., Conclusions: LTs sustain persistent phonological processing limitations even though their native language and literacy performance lay within the normal range at school age. Further research on second language acquisition, academic achievements, and the efficacy of early intervention in late-talking toddlers is recommended., (© 2019 John Wiley & Sons Ltd.)

This paper presents the results of an online survey in Germany in which 296 adult children of mentally ill parents were interviewed. The aim of the study was to record the respondents' attachment-related experiences and to investigate possible predictors of reported childhood experiences on adult attachment patterns. The German version of the revised Adult Attachment Scales (AAS-R) was used to record basic adult attachment dimensions. Data analysis yielded lower values in the dimension "intimacy/trust" compared to the general population, whereas very high values were found in the dimension "anxiety". A clinical relevant anxious-avoiding attachment style could be assigned to 39 % of the respondents. In regression analyses, the safety experienced in childhood, communication deficits in the family and stigmatisation experiences proved to be significant predictors of adult attachment styles. In the concluding discussion of the research findings, we consider possible help offers for adult children of mentally ill parents., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Reduced social motivation is a hallmark of individuals with autism spectrum disorders (ASDs). Although the exact neural mechanisms are unclear, oxytocin has been shown to enhance motivation and attention to social stimuli, suggesting a potential to augment social reinforcement learning as the central mechanism of behavioral interventions in ASD. We tested how reinforcement learning in social contexts and associated reward prediction error (RPE) signals in the nucleus accumbens (NAcc) were modulated by intranasal oxytocin. Male adults with a childhood diagnosis of ASD (n = 15) and healthy controls (n = 24; aged 18-26 years) performed a probabilistic reinforcement learning task during functional magnetic resonance imaging in a single-center (research center in Germany), randomized double-blind, placebo-controlled cross-over trial. The interventions were intranasal oxytocin (Syntocinon ® , Novartis; 10 puffs = 20 international units (IUs) per treatment) and placebo spray. Using computational modeling of behavioral data, trial-by-trial RPE signals were assessed and related to brain activation in NAcc during reinforcing feedback in social and non-social contexts. The order of oxytocin/placebo was randomized for 60 participants. Twenty-one participants were excluded from analyses, leaving 39 for the final analysis. Behaviorally, individuals with ASD showed enhanced learning under oxytocin when the learning target as well as feedback was social as compared to non-social (social vs. non-social target: 87.09% vs. 71.29%, 95% confidence interval (CI): 7.28-24.33, p = .003; social vs. non-social feedback: 81.00% vs. 71.29%, 95% CI: 2.81-16.61, p = .027). Correspondingly, oxytocin enhanced the correlation of the RPE signal with NAcc activation during social (vs. non-social) feedback in ASD (3.48 vs. -1.12, respectively, 95% CI: 2.98-6.22, p = .000), whereas in controls, this effect was found in the placebo condition (2.90 vs. -1.14, respectively, 95% CI: 1.07-7.01, p = .010). In ASD, a similar pattern emerged when the learning target was social (3.00 vs. -0.64, respectively, 95% CI: -0.13 to 7.41, p = .057), whereas controls showed a reduced correlation for social learning targets under oxytocin (-0.70 vs. 2.72, respectively, 95% CI: -5.86 to 0.98, p = .008). The current data suggest that intranasal oxytocin has the potential to enhance social reinforcement learning in ASD. Future studies are warranted that investigate whether oxytocin can potentiate social learning when combined with behavioral therapies, resulting in greater treatment benefits than traditional behavior-only approaches.

A negative mood-congruent attention bias has been consistently observed, for example, in clinical studies on major depression. This bias is assumed to be dysfunctional in that it supports maintaining a sad mood, whereas a potentially adaptive role has largely been neglected. Previous experiments involving sad mood induction techniques found a negative mood-congruent attention bias specifically for young individuals, explained by an adaptive need for information transfer in the service of mood regulation. In the present study we investigated the attentional bias in typically developing children (aged 6-12 years) when happy and sad moods were induced. Crucially, we manipulated the age (adult vs. child) of the displayed pairs of facial expressions depicting sadness, anger, fear and happiness. The results indicate that sad children indeed exhibited a mood specific attention bias toward sad facial expressions. Additionally, this bias was more pronounced for adult faces. Results are discussed in the context of an information gain which should be stronger when looking at adult faces due to their more expansive life experience. These findings bear implications for both research methods and future interventions.

Background: Moderate to vigorous endurance and strength-training exercise was suggested as a treatment option for major depression. However, there is little evidence to support this suggestion in adolescent patients. The present study investigates the effects of a whole-body vibration strength-training intervention on symptoms in medication-naïve adolescent inpatients experiencing a major depressive episode. Potential underlying endocrinological and neurobiological mechanisms are explored., Methods/design: A double-blinded randomized controlled trial is conducted at the University Hospital of Cologne in Germany, comparing a 6-week, whole-body vibration strength-training with a 6-week placebo-intervention, as add-on therapy to inpatient treatment as usual. Forty-one subjects (13-18 years of age) will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients' change in the Children's Depression Rating Scale raw-score, from baseline until the end of the intervention. As secondary endpoints, the effects of exercise treatment on patients' cortisol awakening response as well as on brain-derived neurotrophic factor, insulin-like growth factor 1 and inflammatory markers (tumor necrosis factor-alpha, interleukin-6 and C-reactive protein) serum levels will be assessed., Discussion: This study will provide evidence on the effectiveness of whole-body vibration strength-training as an add-on therapy in adolescent inpatients experiencing a major depressive episode. After completion of data collection, the present study will be the largest randomized controlled trial so far to investigate the effectiveness of an exercise intervention in inpatient adolescents suffering from a major depressive episode. Moreover, the present study may help to determine the underlying mechanisms of potential anti-depressant effects of exercise in depressed adolescent inpatients., Trial Registration: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00011772 . Registered on 20 March 2017.

More right-sided frontal brain resting activity has been postulated to be a correlate of major depression in adults. In children and adolescents, more right-sided activity (as indicated by more left-sided alpha activity) seems to be associated with psychosocial risk factors. However, an association of frontal asymmetry and manifest unipolar depression has not been shown in adolescents so far. We analyzed frontal asymmetry in 20 adolescents (12-17 years) with unipolar depression (12 with first episode, 8 with recurrent depression) and 31 healthy age-matched controls. We found significantly less left-sided alpha power over frontal Regions of Interest in patients, while controls exhibited no asymmetry. In the control group, more left-sided frontal alpha correlated with higher depression scores, which was not observed in the patient group. Our results suggest developmental effects on frontal asymmetry, and prompt further investigations in adolescents to clarify the role of frontal asymmetry in adolescent major depression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To date, little is known about sex differences in the neurophysiological correlates underlying auditory information processing. In the present study, auditory evoked potentials were evoked in typically developing male (n = 15) and female (n = 14) adolescents (13-18 years) during an auditory oddball task. Girls compared to boys displayed lower N100 and P300 amplitudes to targets. Larger N100 amplitudes in adolescent boys might indicate higher neural sensitivity to changes of incoming auditory information. The P300 findings point toward sex differences in auditory working memory and might suggest that adolescent boys might allocate more attentional resources when processing relevant auditory stimuli than adolescent girls.

Background: Recent studies have proposed the process of emotion regulation as a promising target to study the neurophysiological basis of adolescent depression. Emotion regulation has repeatedly been studied with emotional go/no-go paradigms. To date, no study has examined if the left-frontal hypoactivation associated with depression generalizes to active tasks. The aim of this study was therefore to investigate the hemispheric asymmetry of the N2 component in depressed adolescents in an emotion regulation paradigm., Methods: Twenty-four adolescents diagnosed with major depression (age 11-18) and 30 healthy controls (age 11-18) performed two emotional go/no-go tasks exhibiting negative faces as go trials and positive faces as no-go trials and vice versa., Results: On the behavioral level, no significant group differences emerged. On the neural level, we found a more right-lateralized N2-amplitude in depressed subjects, while it was more left-lateralized in controls. Furthermore, both groups showed a less negative N2-amplitude to positive no-go stimuli., Conclusion: This study provides strong support for a general left-frontal hypoactivity in adolescent depression, which also applies to active emotional go/no-go paradigms. Furthermore, the less negative N2 to positive stimuli is consistent with a generally enhanced impulsivity of adolescents toward appetitive stimuli, which is possibly the base of the differential clinical pattern of adolescent in contrast to adult depression., (© 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.)

Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC). A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The last few years have seen much research on girls with conduct disorder (CD). This article summarizes the gender-specific data regarding prevalence, differences with respect to symptomatology (e.g., subtypes of aggression, callous-unemotional (cu)-traits), and it presents data on the autonomic and neuroendocrine stress system as well as genetic, neurocognitive, and neuroimaging data. Differences in the impact of environmental factors on boys and girls for the development of CD are discussed. Taken together, the data indicate that there is great overlap in symptomatology, personality traits, and neurobiological aberrations in girls and boys with CD. Since fewer girls than boys exhibit CD symptomatology, further investigations on CD in girls might help to identify resilience factors that could improve future therapeutic interventions.

During the last decade, repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become established as a treatment for various mental diseases. The rational of prefrontal stimulation has been adapted from the mode of action known from rTMS using motor-evoked potentials though little is known about the precise effect of rTMS at prefrontal sites. The objective of the current study is to investigate the inhibitory effect of prefrontal 1 Hz rTMS by stimulating the generators of event-related potentials (ERP) which are located in the prefrontal cortex. Thus, 1 Hz rTMS was applied offline over the left dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (MPFC) in 18 healthy subjects who subsequently underwent a GoNogo task. Both active conditions were compared to sham rTMS within a randomized and counterbalanced cross-over design in one day. ERPs were recorded during task performance and the N2 and the P3 were analysed. After 1 Hz rTMS of the left DLPFC (but not of the MPFC), an inhibitory effect on the N2 amplitude was observed, which was related to inhibitory control. In contrast, after 1 Hz rTMS of the MPFC (but not at the left DLPFC) a trend towards an increased P3 amplitude was found. There was no significant modulation of latencies and behavioural data. The results argue in favour of an inhibitory effect of 1 Hz rTMS on N2 amplitudes in a GoNogo task. Our findings suggest that rTMS may mildly modulate prefrontally generated ERP immediately after stimulation, even where behavioural effects are not measurable. Thus, combined rTMS-ERP approaches need to be further established in order to serve as paradigms in experimental neuroscience and clinical research.

Background: Until now German language tests have been rarely evaluated for their diagnostic accuracy. The goal of the study was to determine whether frequently used German language instruments are valid measures for identifying developmental language disorders in 3-year-old children., Material and Methods: The language test SETK 3-5 (including the short version SSV) and the parent questionnaire SBE-3-KT were administered to 88 children with and without language impairment. The procedure of the selection of children enabled an extrapolation to general population. A language sample rating was used as a gold standard., Results: Depending on case definition 6-22% of children were classified as language impaired by SETK 3-5, 9% by SSV and 15% by SBE-3-KT. Sensitivity, specificity and positive predictive values of SETK 3-5 for specified cut-offs were 35-93%, 86-97% and 41-58%, respectively. The corresponding values of SSV were 49%, 96%, 56% and of SBE-3-KT 92%, 93%, 59%., Conclusions: 3-year-old children with developmental language disorders can been identified with sufficient accuracy by means of SETK 3-5, an individual language test, as well as by SBE-3-KT, a parent questionnaire. However, the number of false positive classifications is relatively high. The hit rate of SSV, an individual short test, was too low for clinical use., (© Georg Thieme Verlag KG Stuttgart · New York.)

The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.

Psychomotor symptoms related to an impairment of the nigrostriatal dopaminergic system are frequent in major depression (MD). Repetitive transcranial magnetic stimulation (rTMS) has been discussed as a new treatment option for MD. In neurobiological terms, an influence of high-frequency rTMS on dopaminergic neurotransmission has previously been shown by several studies in animals and humans. Therefore, an improvement of psychomotor symptoms by rTMS could be assumed. The aim of this pilot study was to investigate the effect of high-frequency rTMS on psychomotor retardation and agitation in depressive patients. We investigated the effect of left prefrontal 10 Hz rTMS on psychomotor retardation and agitation in 30 patients with MD. Patients were randomly assigned to real or sham rTMS in addition to a newly initiated standardized antidepressant medication. We found a trend in the reduction of agitation (t(28) = 1.76, p = 0.09, two-tailed), but not in the reduction of retardation. Furthermore, no general additional antidepressant effect of rTMS was observed. Although there was no statistical significant influence of high-frequency rTMS on psychomotor symptoms in depressive patients, the results showed a trend in the reduction of psychomotor agitation in MD. This effect should be systematically investigated as the primary end point in further studies with larger sample sizes.

Background: Because standard repetitive transcranial magnetic stimulation (rTMS) protocols exhibit post-stimulus effects of short duration, novel protocols such as theta burst stimulation (TBS), are promising approaches to enhance the effectiveness of rTMS. However, little is known about the side effect profile of such protocols. Thus, the present study explores whether TBS is safe particularly in terms of effects on cognition, mood, and electroencephalogram (EEG) measures in healthy subjects., Methods: Twenty-four healthy volunteers participated in 2 randomized, placebo-controlled, cross-over experiments and underwent continuous TBS (cTBS), intermittent TBS (iTBS), and shamTBS either over the left dorsolateral prefrontal cortex (DLPFC, n = 12) or the medial prefrontal cortices (mPFC, n = 12). Clinical side effects, performance in a neuropsychological battery, mood changes, and resting EEG were recorded., Results: Neither a seizure nor epileptiform EEG activity was observed. The most prominent side effect was the occurrence of vagal reactions during TBS; otherwise no serious side effects were found. Standardized low-resolution brain electromagnetic tomography showed current density changes in the alpha2 band after iTBS of the DLPFC, which remained detectable up to 50 min after stimulation. The few changes in neuropsychological performance were concordant with stimulation site. No impact on mood was detected., Conclusions: Although TBS protocols of the human prefrontal cortex seem to be safe in healthy subjects, future studies need to address the occurrence of vagal reactions. Excitatory and inhibitory properties of motor cortex TBS might not be transferable to prefrontal sites, and the action of specific TBS protocols needs to be further investigated prior to clinical application.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients., Methods: In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted., Results: Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors., Limitations: No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites., Conclusions: In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables.

Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been shown to increase striatal dopaminergic activity. Here we investigated dopaminergic neurotransmission using single photon emission computed tomography (SPECT) and [(123)I]IBZM to indirectly assess the change in endogenous striatal dopamine concentration upon rTMS as compared with d-amphetamine challenge. SPECT imaging was performed twice each in five patients during rTMS, and in two patients who received 0.3 mg/kg D-amphetamine. Administration of rTMS led to a mean relative decrease in striatal IBZM binding by 9.6+/-6.2%, and d-amphetamine challenge (n=4) induced a mean relative reduction by 8+/-2.95% (difference not statistically significant). Acute rTMS challenge showed similar striatal dopaminergic effects to those associated with the administration of d-amphetamine, a substance known to increase synaptic dopamine.

Given that a considerable portion of depressed patients does not respond to or remit during pharmacotherapy, there is increasing interest in non-pharmacological strategies to treat depressive disorders. Several brain stimulation approaches are currently being investigated as novel therapeutic interventions beside electroconvulsive therapy (ECT), a prototypic method in this field with proven effectiveness. These neurostimulation methods include repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), deep brain stimulation (DBS) and transcranial direct current stimulation (tDCS). It is via different neuroanatomically defined "windows" that the various approaches access the neuronal networks showing an altered function in depression. Also, the methods vary regarding their degree of invasiveness. One or the other method may finally achieve antidepressant effectiveness with minimized side effects and constitute a new effective treatment for major depression.