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White matter microstructural changes and episodic memory disturbances in late-onset bipolar disorder
(2018)
Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts.
Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) (n = 16)], late-onset bipolar disorder [(LOD)(n = 14)] and healthy controls (n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups.
Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups.
Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.
Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study.
Introduction: The aim of this study was to ascertain whether the testing format of an OSPE (Objective Structured Practical Examination) in conservative dentistry (sixth semester) predicts the scores on the practical section of the state examination (11th semester) in the same subject. Taking general student profiles into consideration (score on the school-leaving exam [Abitur], score on the preliminary exam in dental medicine [Physikum], length of university study, cohorts, and sex), we also investigated if any correlations or differences exist in regard to the total and partial scores on the OSPE and the corresponding state examination.
Methods: Within the scope of this longitudinal retrospective study, exam-specific data spanning 11 semesters for dental students (N=223) in Frankfurt am Main were collected and analyzed. Statistical analysis was carried out by calculating Spearman rank correlations, partial correlations, Pearson’s correlation coefficients, and multiple regressions (SPSS Statistics 21, IBM Corporation, New York).
Results: The results show that the OSPE (Cronbach’s α=.87) correlates with level of success on the practical section of the state exam in conservative dentistry (p=.01, r=.17). Length of university study also emerged to correlate significantly with the state exam score (p=.001, r=.23). Together, these two variables contribute significantly to predicting the state exam score (p=.001, R2=.076). This was seen extensively among female students. It was also discovered that these female students had higher school-leaving exam scores than male students (F=6.09, p=.01, η2=.027), and that a significant correlation between scores on the Physikum (preliminary exam in dental medicine) and OSPE scores existed only for male students (r=.17, p=.01).
Conclusion: This study was able to demonstrate the predictive effect of a clinical OSPE regarding scores achieved on the state exam. Taking the limitations of this study into account, we are able to recommend using the OSPE testing format in the sixth semester during the clinical phase of dental study.
Sex differences in the relationship between conduct disorder and cortical structure in adolescents
(2017)
Objective: Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure.
Method: As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status−matched controls (14–18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume.
Results: CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset.
Conclusion: We found both similarities and differences between males and females in CD–cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments.
Objective: Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research.
Design: Retrospective, descriptive study.
Setting: The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools.
Results: We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil.
Conclusions: The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries.
Einleitung: Ziel dieser Studie war es zu evaluieren, ob das Prüfungsformat einer OSPE (Objective Structured Practical Examination) durchgeführt im Fach Zahnerhaltungskunde (6. Fachsemester) den Studienerfolg im praktischen Teil des Staatsexamens (11. Fachsemester) im selben Fach prädiziert. Ferner sollte unter Berücksichtigung allgemeiner Angaben der StudienteilnehmerInnen (Abitursnote, Physikumsnote, Studiendauer, Kohorte und Geschlecht) analysiert werden, ob bezüglich der Gesamt- sowie Teilnoten der OSPE und der adäquaten Staatsexamensprüfung Zusammenhänge oder Unterschiede bestehen.
Methoden: Im Rahmen dieser longitudinalen, retrospektiven Studie wurden für einen Zeitraum von 11 Semestern prüfungsbezogene Daten von Studierenden (N=223) des Fachbereichs Zahnmedizin in Frankfurt am Main erhoben und untersucht. Für die statistische Auswertung der Daten wurden Spearman Rangkorrelationen, Partialkorrelationen, Korrelationskoeffizienten nach Pearson, und Multiple Regressionen (SPSS Statistics 21, IBM Corporation, New York) berechnet.
Ergebnisse: Die Ergebnisse zeigen, dass OSPE (Cronbachs α=.87) mit dem Erfolg im praktischen Teil des Staatsexamens im Fach Zahnerhaltungskunde korreliert (p=.01, r=.17). Als eine weitere signifikante Korrelation mit der Examensleistung erwies sich die Dauer des Studiums (p=.001, r=.23). Gemeinsam leisten diese beiden Variablen einen signifikanten Beitrag zur Vorhersage der Examensnote (p=.001, R2=.076). Das zeigte sich im größeren Umfang bei weiblichen Studierenden. Zudem wurde festgestellt, dass diese bessere Abiturnoten als männliche Studierende aufweisen (F=6.09, p=.01, η2=.027) und dass es lediglich bei männlichen Studierenden eine signifikante Korrelation zwischen der Physikumsnote (Zahnärztliche Vorprüfung) und der OSPE-Benotung gab (r=.17, p=.01).
Schlussfolgerung: In der vorliegenden Untersuchung konnte der prädiktive Effekt einer klinischen OSPE auf die Prüfungsleistung im Staatsexamen gezeigt werden. Unter Berücksichtigung der Limitation der Studie empfiehlt sich aus unserer Sicht die Durchführung eines solchen Prüfungsformats im Rahmen des klinischen Studienabschnitts im 6. Semester im Fach Zahnmedizin.
Die Vermittlung der Zusammenhänge zwischen psychologischen Funktionen und körperlichen Veränderungen sowie deren Relevanz für die Entstehung und Aufrechterhaltung von Krankheiten stellt ein zentrales Ziel der Ausbildung in Medizinischer Psychologie dar. Zur Veranschaulichung dieser Zusammenhänge führten wir ein Psychophysiologie-Praktikum im ersten vorklinischen Semester ein. Die Studierenden führten in Vierergruppen mit Hilfe ausführlicher schriftlicher Instruktionen jeweils ca. 30 Minuten andauernde praktische Übungen durch, die die folgenden Themen behandelten: (1) Stress (abhängige Variable: Herzrate), (2) "Lügendetektor" (abhängige Variable: Hautleitwertsreaktionen), (3) Biofeedback (abhängige Variable: Hauttemperatur) und (4) Elektroenzephalogramm (abhängige Variable: Amplituden der vier klassischen Frequenzbänder). Die praktischen Übungen wurden durch theoretische Gruppenarbeiten und einen Termin zur Zusammenfassung der Ergebnisse der Übungen ergänzt. Die studentische Evaluation des Praktikums war durchweg positiv. So wurde das Praktikum als Bereicherung des Kurses angesehen, und der selbstbeurteilte Kenntnisstand auf dem Gebiet der Psychophysiologie zeigte eine signifikante Verbesserung. Diese Ergebnisse sowie unsere Eindrücke während des Praktikums bekräftigten unseren Entschluss, ein Psychophysiologie-Praktikum als Teil des Kurses der Medizinischen Psychologie und Medizinischen Soziologie fest zu etablieren.
Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease.
Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established.
Results: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates.
Conclusions: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.
Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.
The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people’s mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups (“recovered,” 9.0%; “resilient,” 82.6%; “delayed dysfunction,” 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants’ psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.
Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors) rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC) performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors) reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM—encoding and maintenance—are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.
Background: Previous magnetic resonance imaging (MRI) research suggests that, prior to the onset of psychosis, high risk youths already exhibit brain abnormalities similar to those present in patients with schizophrenia.
Objectives: The goal of the present study was to describe the functional organization of endogenous activation in young adolescents who report auditory verbal hallucinations (AVH) in view of the “distributed network” hypothesis of psychosis. We recruited 20 young people aged 13–16 years who reported AVHs and 20 healthy controls matched for age, gender and handedness from local schools.
Methods: Each participant underwent a semi-structured clinical interview and a resting state (RS) neuroimaging protocol. We explored functional connectivity (FC) involving three different networks: 1) default mode network (DMN) 2) salience network (SN) and 3) central executive network (CEN). In line with previous findings on the role of the auditory cortex in AVHs as reported by young adolescents, we also investigated FC anomalies involving both the primary and secondary auditory cortices (A1 and A2, respectively).
Further, we explored between-group inter-hemispheric FC differences (laterality) for both A1 and A2. Compared to the healthy control group, the AVH group exhibited FC differences in all three networks investigated. Moreover, FC anomalies were found in a neural network including both A1 and A2. The laterality analysis revealed no between-group, inter-hemispheric differences.
Conclusions: The present study suggests that young adolescents with subclinical psychotic symptoms exhibit functional connectivity anomalies directly and indirectly involving the DMN, SN, CEN and also a neural network including both primary and secondary auditory cortical regions.
Forgotten features of head zones and their relation to diagnostically relevant acupuncture points
(2011)
In the 1890s Sir Henry Head discovered certain areas of the skin that develop tenderness (allodynia) in the course of visceral disease. These areas were later termed ‘Head zones’. In addition, he also emphasized the existence of specific points within these zones, that he called ‘maximum points’, a finding that seems to be almost forgotten today. We hypothesized that two important groups of acupuncture points, the diagnostically relevant Mu and Shu points, spatially and functionally coincide with these maximum points to a large extent. A comparison of Head's papers with the Huang Di Neijing (Yellow Thearch's Inner Classic) and the Zhen Jiu Jia Yi Jing (Systematic Classic of Acupuncture and Moxibustion), two of the oldest still extant Chinese sources on acupuncture, revealed astonishing parallels between the two concepts regarding both point locations and functional aspects. These findings suggest that the Chinese discovery of viscerocutaneous reflexes preceded the discovery in the West by more than 2000 years. Furthermore, the fact that Chinese medicine uses Mu and Shu points not only diagnostically but also therapeutically may give us new insights into the underlying mechanisms of acupuncture.
Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.
Several regions in human temporal and frontal cortex are known to integrate visual and auditory object features. The processing of audio–visual (AV) associations in these regions has been found to be modulated by object familiarity. The aim of the present study was to explore training-induced plasticity in human cortical AV integration. We used functional magnetic resonance imaging to analyze the neural correlates of AV integration for unfamiliar artificial object sounds and images in naïve subjects (PRE training) and after a behavioral training session in which subjects acquired associations between some of these sounds and images (POST-training). In the PRE-training session, unfamiliar artificial object sounds and images were mainly integrated in right inferior frontal cortex (IFC). The POST-training results showed extended integration-related IFC activations bilaterally, and a recruitment of additional regions in bilateral superior temporal gyrus/sulcus and intraparietal sulcus. Furthermore, training-induced differential response patterns to mismatching compared with matching (i.e., associated) artificial AV stimuli were most pronounced in left IFC. These effects were accompanied by complementary training-induced congruency effects in right posterior middle temporal gyrus and fusiform gyrus. Together, these findings demonstrate that short-term cross-modal association learning was sufficient to induce plastic changes of both AV integration of object stimuli and mechanisms of AV congruency processing.
Objective: To determine whether the performance of multiple sclerosis (MS) patients in the sound-induced flash illusion (SiFi), a multisensory perceptual illusion, would reflect their cognitive impairment.
Methods: We performed the SiFi task as well as an extensive neuropsychological testing in 95 subjects [39 patients with relapse-remitting MS (RRMS), 16 subjects with progressive multiple sclerosis (PMS) and 40 healthy control subjects (HC)].
Results: MS patients reported more frequently the multisensory SiFi than HC. In contrast, there were no group differences in the control conditions. Essentially, patients with progressive type of MS continued to perceive the illusion at stimulus onset asynchronies (SOA) that were more than three times longer than the SOA at which the illusion was already disrupted for healthy controls. Furthermore, MS patients' degree of cognitive impairment measured with a broad neuropsychological battery encompassing tests for memory, attention, executive functions, and fluency was predicted by their performance in the SiFi task for the longest SOA of 500 ms.
Conclusions: These findings support the notion that MS patients exhibit an altered multisensory perception in the SiFi task and that their susceptibility to the perceptual illusion is negatively correlated with their neuropsychological test performance. Since MS lesions affect white matter tracts and cortical regions which seem to be involved in the transfer and processing of both crossmodal and cognitive information, this might be one possible explanation for our findings. SiFi might be considered as a brief, non-expensive, language- and education-independent screening test for cognitive deficits in MS patients.
Background: Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children. Methods: Forty four Caucasian children (ages 8-14) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 1994) were randomly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells (n = 21) or a wait-list control group (n = 23). The primary outcome measure was clinical improvement. Secondary outcomes included improvements in anxiety coping, dysfunctional cognitions, interaction frequency and comorbid symptoms. Outcome measures included child report and clinican completed measures as well as a diagnostic interview. Results: Significant differences between treatment participants (4 dropouts) and controls (2 dropouts) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children. Furthermore, in the treatment group, significantly more children were free of diagnosis than in wait-list group at post-test. Additional child completed and clinician completed measures support the results. Discussion: The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia. Future research will need to compare this treatment to an active treatment group. There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate. Conclusion: Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children. Active comparators should be established with other evidence-based CBT programs for anxiety disorders, which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation (e.g. Coping Cat).
Purpose: Collaborative care is effective in improving symptoms of patients with depression. The aims of this study were to characterize symptom trajectories in patients with major depression during one year of collaborative care and to explore associations between baseline characteristics and symptom trajectories.
Methods: We conducted a cluster-randomized controlled trial in primary care. The collaborative care intervention comprised case management and behavioral activation. We used the Patient Health Questionnaire-9 (PHQ-9) to assess symptom severity as the primary outcome. Statistical analyses comprised latent growth mixture modeling and a hierarchical binary logistic regression model.
Results: We included 74 practices and 626 patients (310 intervention and 316 control recipients) at baseline. Based on a minimum of 12 measurement points for each intervention recipient, we identified two latent trajectories, which we labeled "fast improvers" (60.5%) and "slow improvers" (39.5%). At all measurements after baseline, "fast improvers" presented higher PHQ mean values than "slow improvers". At baseline, "fast improvers" presented fewer physical conditions, higher health-related quality of life, and had made fewer suicide attempts in their history.
Conclusions: A notable proportion of 39.5% of patients improved only "slowly" and probably needed more intense treatment. The third follow-up in month two could well be a sensible time to adjust treatment to support "slow improvers".
Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day–night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD.
Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up.
Discussion: This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.
Trial registration: German Clinical Trials Register, DRKS00011666. Registered on 9 February 2017. ClinicalTrials.gov, NCT03371810. Registered on 13 December 2017.
In the later stages of addiction, automatized processes play a prominent role in guiding drug-seeking and drug-taking behavior. However, little is known about the neural correlates of automatized drug-taking skills and drug-related action knowledge in humans. We employed functional magnetic resonance imaging (fMRI) while smokers and non-smokers performed an orientation affordance task, where compatibility between the hand used for a behavioral response and the spatial orientation of a priming stimulus leads to shorter reaction times resulting from activation of the corresponding motor representations. While non-smokers exhibited this behavioral effect only for control objects, smokers showed the affordance effect for both control and smoking-related objects. Furthermore, smokers exhibited reduced fMRI activation for smoking-related as compared to control objects for compatible stimulus-response pairings in a sensorimotor brain network consisting of the right primary motor cortex, supplementary motor area, middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the incompatible condition, we found higher fMRI activation in smokers for smoking-related as compared to control objects in the right primary motor cortex, cingulate gyrus, and left fusiform gyrus. This suggests that the activation and performance of deeply embedded, automatized drug-taking schemata employ less brain resources. This might reduce the threshold for relapsing in individuals trying to abstain from smoking. In contrast, the interruption or modification of already triggered automatized action representations require increased neural resources.