Temperamental patterns in female adolescents with borderline personality disorder.

A specific composition of temperament traits with high novelty seeking (NS), high harm avoidance (HA), and low reward dependence (RD) has been attributed to adult patients with borderline personality disorder (BPD). This study examined whether an analogue personality profile is specifically associated with adolescent BPD. The female study sample comprised 33 adolescents with BPD, 35 clinical controls (CCs), and 31 healthy controls (HCs). Dimensions of temperament and character were measured according to Cloninger's biopsychosocial model of personality. Significantly higher means of NS and HA but lower means of RD could be determined in the adolescents with BPD compared with the CCs and the HCs. The comparable findings of this specific temperament constellation in adolescents and adult patients with BPD suggest that heritable factors such as temperamental traits may contribute to the vulnerability for developing BPD. Early identification of a "borderline temperament" may facilitate early intervention and lower the risk for developing BPD.

Physical exercise training as preceding treatment to cognitive behavioral therapy in mild to moderate major depressive disorder: A randomized controlled trial.

BACKGROUND: Many patients with major depressive disorder (MDD) remain untreated or do not respond to cognitive behavioral therapy (CBT). Physical exercise shows antidepressive effects and may serve as an effective augmentation treatment. However, research on combining exercise with CBT is sparse in MDD and underlying mechanisms of exercise are not well understood to date. METHODS: 120 outpatients with MDD were randomized to either a high intensity exercise group (HEX), a low intensity exercise group (LEX), or a waiting list control group (WL). After 12 weeks of exercise training or waiting period, all patients received a manualized CBT. RESULTS: Seventy-five patients with MDD completed both the exercise program/ waiting period and the CBT. While physical fitness improved in HEX after the exercise program, it did not change in LEX and WL. Depressive symptoms improved in all three groups from baseline to post-CBT and the group by time interaction was not significant. Regression analyses revealed that the amount of fitness improvement during exercise predicted the subsequent CBT response. LIMITATIONS: The dropout rate was relatively high, preparatory CBT sessions during exercise / waiting period may have influenced depressive symptoms, and no patients with severe MDD were included. CONCLUSIONS: High intense physical exercise did not lead to a general enhancement of CBT outcome, but higher increases in physical fitness seem to improve symptom change during CBT. Our results suggest that the implementation of more individually tailored exercise programs could be a promising approach for future research and clinical practice.

Calendar age and puberty-related development of regional gray matter volume and white matter tracts during adolescence.

BACKGROUND: Adolescence is a critical time for brain development. Findings from previous studies have been inconsistent, failing to distinguish the influence of pubertal status and aging on brain maturation. The current study sought to address these inconsistencies, addressing the trajectories of pubertal development and aging by longitudinally tracking structural brain development during adolescence. METHODS: Two cohorts of healthy children were recruited (cohort 1: 9-10 years old; cohort 2: 12-13 years old at baseline). MRI data were acquired for gray matter volume and white matter tract measures. To determine whether age, pubertal status, both or their interaction best modelled longitudinal data, we compared four multi-level linear regression models to the null model (general brain growth indexed by total segmented volume) using Bayesian model selection. RESULTS: Data were collected at baseline (n = 116), 12 months (n = 97) and 24 months (n = 84) after baseline. Findings demonstrated that the development of most regional gray matter volume, and white matter tract measures, were best modelled by age. Interestingly, precentral and paracentral regions of the cortex, as well as the accumbens demonstrated significant preference for the pubertal status model. None of the white matter tract measures were better modelled by pubertal status. LIMITATIONS: The major limitation of this study is the two-cohort recruitment. Although this allowed a faster coverage of the age span, a complete per person trajectory over 6 years of development (9-15 years) could not be investigated. CONCLUSIONS: Comparing the impact of age and pubertal status on regional gray matter volume and white matter tract measures, we found age to best predict longitudinal changes. Further longitudinal studies investigating the differential influence of puberty status and age on brain development in more diverse samples are needed to replicate the present results and address mechanisms underlying norm-variants in brain development.

Reduced prefrontal and orbitofrontal gray matter in female adolescents with borderline personality disorder: is it disorder specific?

There is evidence that adults with borderline personality disorder (BPD) are characterized by abnormalities in frontolimbic brain areas. In this study we aimed to determine whether brain volume alterations already exist in adolescents with BPD. Sixty female right-handed individuals (age range, 14-18 years), 20 with a DSM-IV diagnosis of borderline personality disorder, 20 patients with a DSM-IV defined current psychiatric disorder and 20 healthy control subjects were included. Groups were matched for age and IQ. Using a 3 T MRI scanner, we collected 1 mm axial sections using a three-dimensional sagittal isotropic Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) sequence. Images were analyzed using voxel-based morphometry (VBM). Voxel-based analysis revealed that adolescents with BPD showed reduced gray matter in the dorsolateral cortex (DLPFC) bilaterally and in the left orbitofrontal cortex (OFC) relative to healthy control subjects. Adolescent clinical control subjects displayed significantly decreased gray matter volume in the right DLPFC in comparison with healthy control subjects. No significant gray matter differences were detected between the BPD group and the clinical control group. No group differences were found in the limbic system or in any white matter structures. The present study indicates that the early morphological changes in BPD are located in the PFC. However, these changes may not be BPD specific since similar changes were found in the clinical control group. Changes in limbic brain volumes and white matter structures might occur over the course of the illness.

Neuropsychological development in adolescents: Longitudinal associations with white matter microstructure.

Important neuropsychological changes during adolescence coincide with the maturation of white matter microstructure. Few studies have investigated the association between neuropsychological development and white matter maturation longitudinally. We aimed to characterize developmental trajectories of inhibition, planning, emotion recognition and risk-taking and examine whether white matter microstructural characteristics were associated with neuropsychological development above and beyond age. In an accelerated longitudinal cohort design, n = 112 healthy adolescents between ages 9 and 16 underwent cognitive assessment and diffusion MRI over three years. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for major white matter pathways using an automatic probabilistic reconstruction technique and mixed models were used for statistical analyses. Inhibition, planning and emotion recognition performance improved linearly across adolescence. Risk-taking developed in a quadratic fashion, with stable performance between 9 and 12 and an increase between ages 12 and 16. Including cingulum and superior longitudinal fasciculus FA slightly improved model fit for emotion recognition across age. We found no evidence that FA or MD were related to inhibition, planning or risk-taking across age. Our results challenge the additional value of white matter microstructure to explain neuropsychological development in healthy adolescents, but more longitudinal research with large datasets is needed to identify the potential role of white matter microstructure in cognitive development.

Serum brain-derived neurotrophic factor (BDNF) at rest and after acute aerobic exercise in major depressive disorder.

Physiological mechanisms of an anti-depressive effect of physical exercise in major depressive disorder (MDD) seem to involve alterations in brain-derived neurotrophic factor (BDNF) level. However, previous studies which investigated this effect in a single bout of exercise, did not control for confounding peripheral factors that contribute to BDNF-alterations. Therefore, the underlying cause of exercise-induced BDNF-changes remains unclear. The current study aims to investigate serum BDNF (sBDNF)-changes due to a single-bout of graded aerobic exercise in a group of 30 outpatients with MDD, suggesting a more precise analysis method by taking plasma volume shift and number of platelets into account. Results show that exercise-induced increases in sBDNF remain significant (p < .001) when adjusting for plasma volume shift and controlling for number of platelets. The interaction of sBDNF change and number of platelets was also significant (p = .001) indicating larger sBDNF-increase in participants with smaller number of platelets. Thus, findings of this study suggest an involvement of peripheral as well as additional - possibly brain-derived - mechanisms explaining exercise-related BDNF release in MDD. For future studies in the field of exercise-related BDNF research, the importance of controlling for peripheral parameters is emphasized.

Health-related quality of life among adolescents: A comparison between subjects at ultra-high risk for psychosis and healthy controls.

At risk status for psychosis has been robustly associated with decreased health-related quality of life (HRQoL) among adults. However, this relationship has not been examined in adolescents with ultra-high risk (UHR) for psychosis in comparison to healthy controls. Twenty-seven subjects with UHR and thirty healthy controls (14-18 years of age) were recruited in a multiphase screening and accessed with a HRQoL scale of KIDSCREEN-27. Comparisons indicated that subjects with UHR had poorer mean scores at a statistically significant level in the following scales: physical well-being, psychological well-being and school environment. In a logistic regression analysis, lower scores in the scale school environment explained at risk status for psychosis. Adolescents with UHR show significantly poorer HRQoL scores than healthy peers, identified predominantly by the evaluation of the school environment. These results might be interpreted as a self-perception of early mental and social functioning impairments, which seem to be recognized initially based on school demands. Considering these findings, institutes of education should be a good starting point to promote the awareness of the psychosis-risk state.

Reduced cortical thickness and its association with social reactivity in children with autism spectrum disorder.

Symptomatology and behavioral characteristics in autism spectrum disorders (ASD) have increasingly been linked to abnormalities in early brain growth patterns of affected children. Studies investigating specific components of gray matter structure, such as cortical thickness (CT), have produced conflicting results, and have rarely included additional measures of social impairment. In the present study, we applied a surface-based whole brain analysis to investigate CT in a sample of 36 pre-adolescent children [18 subjects with ASD (IQ mean: 111) and 18 healthy controls (IQ mean: 112.8), age range 6-12 years]. The CT analysis revealed widespread, but mostly left-hemispheric thinning in frontal, temporal, parietal and occipital brain areas related to the theory-of-mind network and the heteromodal association cortex. In an exploratory analysis, CT was observed to be differently associated with social impairment in children with ASD compared with typically developing children. The affected neuroanatomical regions are related to characteristic deficits in language, cognition and behavior that are often observed in the disorder. The relationship between social impairment and CT in children with ASD and controls seems to indicate aberrant developmental trajectories in ASD emerging early in life.

The optic radiation and the cerebellar peduncles in adolescents with first-admission schizophrenia--a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Previous studies have found gray matter alterations in the cerebellum and in the visual system in both adults and adolescents with schizophrenia. The present study was conducted to investigate whether white matter tracts associated with these regions are also affected in the early stages of the disorder. METHODS: Using a 1.5 Tesla magnetic resonance imaging (MRI) scanner and fiber tracking, the optic radiations and the middle cerebellar peduncles were examined in 13 adolescents with first-admission schizophrenia and 13 healthy controls matched for age, gender, school type, and handedness. RESULTS: Patients with schizophrenia displayed significantly decreased fractional anisotropy in the optic radiations, but no differences in the middle cerebellar peduncles compared to healthy controls. CONCLUSIONS: Our findings of altered fiber integrity in the optic radiations in adolescents with schizophrenia are in line with gray matter alterations in the visual cortices previously reported in the same sample and are in accordance with other studies that found decreased fractional anisotropy in these regions. These findings support the view that the visual system plays an important role in the pathogenesis of schizophrenia and may enhance our understanding of associations between the visual cortex and symptoms of the disorder.

Reduced cortical and subcortical volumes in female adolescents with borderline personality disorder.

Volumetric alterations in limbic structures have been detected in adults, but not in adolescents with borderline personality disorder (BPD). We examined adolescents in the early stages of BPD to provide a unique opportunity to investigate which parts of the brain are initially affected by the disorder before confounding factors such as long-term medication or chronicity can mask them. A group of 60 right-handed female adolescents between 14 and 18 years of age (20 patients with BPD, 20 clinical controls, and 20 healthy controls) underwent magnetic resonance imaging (MRI). Focus was on the examination of hippocampal and amygdalar volume differences. Furthermore, a cortical thickness analysis was conducted. FreeSurfer software detected significant group differences in the right and left hippocampus and in the right amygdala. Additionally, significant volume reductions in frontal (right middle frontal gyrus, orbital part of the inferior frontal gyrus bilaterally), and parietal regions (superior parietal gyrus bilaterally) were found in adolescents with BPD compared with controls. No group differences in cortical thickness were revealed.

Disorder-specific white matter alterations in adolescent borderline personality disorder.

BACKGROUND: The pathogenesis of borderline personality disorder (BPD) is complex and not fully understood. Using diffusion tensor imaging, recent studies suggest that white matter abnormalities may occur in adult patients with BPD. However, deeper insight into the disorder-specific developmental psychobiology (e.g., analysis of adolescents with BPD; inclusion of clinical control groups) is missing. METHODS: Twenty adolescent patients with BPD (aged 14-18 years), 20 healthy, and 20 clinical control subjects were assessed using diffusion tensor imaging. All subjects were right-handed girls, matched for age and IQ. Microstructural parameters were analyzed via tractography of the main bundles in the limbic system and using Tract-Based Spatial Statistics, an explorative, global approach. RESULTS: BPD was associated with decreased fractional anisotropy in the fornix when compared with clinical (p < .001) or healthy (nonsignificant trend) control subjects. Using Tract-Based Spatial Statistics, significant disorder-specific white matter alterations were found in the long association bundles interconnecting the heteromodal association cortex and in connections between the thalamus and hippocampus. CONCLUSIONS: The study strongly supports the hypothesis that white matter alterations play a key role in the pathogenesis of BPD. These disorder-specific alterations include white matter pathways involved in emotion regulation but also affect parts of the heteromodal association cortex that are related to emotion recognition. Our findings unify previously documented deficits in emotion recognition and regulation and suggest that a large-scale network of emotion processing is disrupted in BPD. Continued research is essential to evaluate the predictive value of these early disruptions in a clinical context.

Quantification of changes in language-related brain areas in autism spectrum disorders using large-scale network analysis.

PURPOSE: Diagnosis of autism spectrum disorders (ASD) is difficult, as symptoms vary greatly and are difficult to quantify objectively. Recent work has focused on the assessment of non-invasive diffusion tensor imaging-based biomarkers that reflect the microstructural characteristics of neuronal pathways in the brain. While tractography-based approaches typically analyze specific structures of interest, a graph-based large-scale network analysis of the connectome can yield comprehensive measures of larger-scale architectural patterns in the brain. Commonly applied global network indices, however, do not provide any specificity with respect to functional areas or anatomical structures. Aim of this work was to assess the concept of network centrality as a tool to perform locally specific analysis without disregarding the global network architecture and compare it to other popular network indices. METHODS: We create connectome networks from fiber tractographies and parcellations of the human brain and compute global network indices as well as local indices for Wernicke's Area, Broca's Area and the Motor Cortex. Our approach was evaluated on 18 children suffering from ASD and 18 typically developed controls using magnetic resonance imaging-based cortical parcellations in combination with diffusion tensor imaging tractography. RESULTS: We show that the network centrality of Wernicke's area is significantly (p<0.001) reduced in ASD, while the motor cortex, which was used as a control region, did not show significant alterations. This could reflect the reduced capacity for comprehension of language in ASD. CONCLUSIONS: The betweenness centrality could potentially be an important metric in the development of future diagnostic tools in the clinical context of ASD diagnosis. Our results further demonstrate the applicability of large-scale network analysis tools in the domain of region-specific analysis with a potential application in many different psychological disorders.

Reduced lateralization in early onset schizophrenia.

BACKGROUND AND PURPOSE: Previous imaging studies have described gray and white matter alterations in the cerebellum, the posterior aspects of the visual system and in the corpus callosum in patients with schizophrenia. Here, we investigated these regions in more detail using tract-based spatial statistics (TBSS). Additionally, we evaluated potential changes in lateralization of the optic radiation and the superior cerebellar peduncle. MATERIAL AND METHODS: We studied 12 patients with first-admission schizophrenia and a group of age-matched healthy controls. The diffusion tensor imaging data were preprocessed using tract-based spatial statistics and the obtained white matter skeleton was used to perform a regional analysis of fractional anisotropy in the corpus callosum, the optic radiation, and the superior and middle cerebellar peduncles. RESULTS: Using TBSS, a significant reduction of fractional anisotropy in the whole corpus callosum and the optic radiation but not in the middle and superior cerebellar peduncles was found. Furthermore, a significantly decreased lateralization of the optic radiation and the superior cerebellar peduncles in patients was observed. CONCLUSION: Our findings substantiate the concept that schizophrenia is a neurodevelopmental disorder and indicate that changes in lateralization may play a key role in the pathogenesis of this disease.

Impaired cerebral glucose metabolism in prodromal Alzheimer's disease differs by regional intensity normalization.

Using [(18)F] fluorodeoxyglucose (FDG) positron emission tomography (PET) patients with Alzheimer's disease show impairment of cerebral glucose metabolism in bilateral frontotemporoparietal association cortices and posterior cingulate cortex whereas in patients with mild cognitive impairment (MCI) results are heterogeneous. For the first time, the present study examined alterations of the cerebral glucose metabolism in patients with prodromal AD as compared to patients with AD dementia and healthy controls depending on intensity normalization. 15 patients with AD (69.8±8.5 years) and 28 with prodromal AD (67.4±9.1 years) as well as 10 healthy controls (58.8±5.9 years) underwent FDG PET under resting conditions. By statistical parametric mapping 8, analyses were performed using (a) cerebellar cortex or (b) whole brain as reference region for intensity normalization. Patients with AD dementia showed reductions in bilateral temporoparietal regions and posterior cingulate gyrus as compared to controls. By contrast, patients with prodromal AD had only reductions in the left posterior temporal lobe and left angular gyrus as compared with controls. Cerebellar normalization was superior in differentiating patients with prodromal AD or AD dementia from healthy controls, but global normalization provided slightly better contrasts for the differentiation between patients with prodromal AD and AD dementia in AD-typical regions. Unexpected hypermetabolism in patients was only revealed using global normalization and has to be regarded as an artifact of intensity normalization to a reference region affected by the disease.

Regional cerebral perfusion alterations in patients with mild cognitive impairment and Alzheimer disease using dynamic susceptibility contrast MRI.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess regional cerebral perfusion distribution in patients with Alzheimer disease (AD) or mild cognitive impairment (MCI) using dynamic susceptibility contrast magnetic resonance imaging. MATERIALS AND METHODS: Regional changes of perfusion were evaluated in 34 patients with AD, 51 patients with MCI, and 23 healthy controls (HCs). Using region of interest analyses, regional cerebral blood flow (CBF), cerebral blood volume, and mean transit time were measured bilaterally in the hippocampus; the temporal, temporoparietal, frontal, and sensomotoric cortices; the anterior and posterior cingulate gyri; the lentiform nucleus; and the cerebellum. RESULTS: A significant reduction of CBF in patients with AD compared to HCs was shown in the frontal and temporoparietal cortices bilaterally, the lentiform nuclei bilaterally, the left posterior cingulate gyrus, and the cerebellum. Compared with patients with MCI, patients with AD presented a reduction of CBF in the frontal cortices bilaterally, the left temporoparietal cortex, and the left anterior and posterior cingulate gyrus. In both hippocampi and the posterior cingulate gyrus, a trend to a slight increase of CBF in patients with MCI was noticed with a decrease in patients with AD. CONCLUSIONS: Using dynamic susceptibility contrast magnetic resonance imaging, pathologic alterations of regional brain perfusion can be demonstrated in patients with AD compared to patients with MCI or HCs.

White matter alterations in the corpus callosum of adolescents with first-admission schizophrenia.

Several diffusion tensor imaging (DTI) studies involving adults and adolescents with schizophrenia have examined fractional anisotropy (FA) in the corpus callosum (CC) with conflicting findings. This may be due to confounding factors such as the chronicity of the disorder, long-term medication with psychotropics or methodological differences. To provide a clearer picture of early alterations, we examined 13 adolescents with first-admission schizophrenia and 13 healthy controls using a region-of-interest approach based on probabilistic voxel classification. We quantified FA in four subdivisions of the CC and hypothesized that adolescents with schizophrenia display a reduced FA in the genu associated with 'hypofrontality' and a reduced FA in the body of the CC linked to the heteromodal association cortex. Fiber integrity measurements revealed significant FA decreases in the genu and body of the CC in adolescents with schizophrenia compared to healthy controls. These findings emphasize the central role of the CC in even the early stages of schizophrenia and lend weight to hypotheses about frontal alterations and the central role of the heteromodal association cortex in the aetiopathogenesis of the disorder.

Fronto-temporal disconnectivity and symptom severity in children with autism spectrum disorder.

OBJECTIVES: There is increasing evidence that many of the core behavioural impairments in autism spectrum disorders (ASD) emerge from disconnectivity of networks that are important for social communication. The present study aimed at investigating which specific fibre tracts are impaired in ASD and if possible alterations of white matter are associated with clinical symptomatology. METHODS: Eighteen children with ASD and 18 carefully matched typically developing controls aged 6-12 years were examined using diffusion tensor imaging (DTI) and voxel-based morphometry (VBM). Fractional anisotropy (FA) values were correlated with symptom severity as indexed by the children's scores on the Autisms Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: Decreased FA values were identified for the fornix (FO), the superior longitudinal fasciculus (SLF) the corpus callosum and the uncinate fasciculus (UF) in the ASD group compared to controls, with most prominent differences in the UF bilaterally and the right SLF. FA values of affected fibre tracts were negatively associated with clinical measures of autistic symptomatology. We did not observe significantly altered grey or white matter concentration after correction for multiple comparisons. CONCLUSION: Our findings support the hypothesis of abnormal white matter microstructure of fronto-temporal cortical networks in ASD, which are associated with core symptoms of the disorder.

Gray matter alterations in first-admission adolescents with schizophrenia.

BACKGROUND AND PURPOSE: Imaging studies of patients with schizophrenia have described a variety of cerebral alterations. However, long-term medication and the chronicity of the disorder may have contributed substantially to these alterations. Studies examining patients in the early stages of the disorder reduce the possibility of such confounding factors but are rare. In light of this, the aim of the present study was to examine adolescents in the early stages of the disorder to observe primary structural brain abnormalities. METHODS: Gray and white matter were measured in 13 adolescents with schizophrenia and 13 healthy controls matched for age, gender, handedness, and school type using voxel-based morphometry. RESULTS: Subjects with schizophrenia displayed decreased gray matter in the cerebellar vermis, and alterations in the left putamen and in several parts of the visual system. CONCLUSIONS: These findings support cerebellar involvement in the pathogenesis of schizophrenia, and the alterations observed in several parts of the visual system may provide insights into the nature of hallucinations and delusional interpretations.