Background In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for ...illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD. Methods We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age- and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral DLPFC and dorsomedial prefrontal cortex DMPFC, anterior cingulate cortex ACC and basal ganglia) using a family-wise error correction ( p < 0.05) to control for multiple comparisons. Results There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls. Limitations The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size. Conclusion Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.
Abstract The anterior cingulate cortex (ACC) is located at the rostum of the corpus callosum and involved in both cognitive and emotional brain processes. It has been suggested to be involved in P300 ...event-related potential generation. A large sample of schizophrenia inpatients and controls was examined in order to assess the potential relationship between ACC volumes and P300 characteristics in patients with more pronounced negative symptoms. In 50 male schizophrenia patients and 50 matched controls, auditory P300 and structural magnetic resonance imaging volume measurements of the ACC were obtained. Patients' negative symptoms were assessed using the PANSS (Positive and Negative Syndrome Scale). Volumetry of ACC subregions revealed a volume reduction in patients with schizophrenia compared with controls in right hemispheric rostral ACC subregions that were most pronounced in more negative schizophrenia patients. There was a positive correlation between PZ P300 amplitude and total ACC volume in the right hemisphere in schizophrenia patients with less negative symptoms. The results support the assumption that structural changes of the ACC are more pronounced in subgroups of schizophrenia patients with more negative psychopathology. In addition, while right hemisphere ACC volumes significantly differ between schizophrenia subgroups, combining measures of event-related potential (ERP) and ACC volumetry does not add additional information.
Increased prevalence of cavum septi pellucidi (CSP) in schizophrenic patients in comparison to healthy subjects was reported previously. Our purpose was to evaluate the prevalence of variants of the ...septum pellucidum in healthy subjects in three different age groups.
151 healthy subjects, including 46 children (age 6 +/- 4 years), 72 young adults (age 31 +/- 8 years) and 33 elderly adults (age 59 +/- 7 years) were examined with high-resolution MRI. Three observers analysed the images using a standardised protocol. We evaluated the incidences of CSP, cavum vergae (CV) and their length.
CSP was detected in 80% of the cases in the paediatric group and 68% of young adults and in 72% of the elderly adults. A cavum vergae (CV) was noted in 22% of the children, in 39% of the young adults and in 36% of the elderly subjects. There was no significant difference between the age-related groups.
We detected a high prevalence of cavum septi pellucidi without a significant age dependence. Enlarged cava septi pellucidi are rare in healthy subjects.
Identification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance ...imaging-based diagnostic classification of neuropsychiatric patient populations.
To determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level.
Multivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs.
Departments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
The first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs.
Specificity, sensitivity, and accuracy of classification.
The 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases.
Different ARMSs and their clinical outcomes may be reliably identified on an individual basis by assessing patterns of whole-brain neuroanatomical abnormalities. These patterns may serve as valuable biomarkers for the clinician to guide early detection in the prodromal phase of psychosis.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. Core symptoms of ADHD, such as impulsivity, are caused by an interaction of ...genetic and environmental factors. Epigenetic modifications of DNA, such as DNA methylation, are thought to mediate the interplay of these factors. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to ADHD, e.g., showing that TPH2 G-703T (rs4570625) polymorphism influences response control and prefrontal signaling in ADHD patients. In this (epi)genetic imaging study we examined 144 children and adolescents (74 patients, 14 females) using fMRI at rest and during performing a waiting impulsivity (WI) paradigm. Both, TPH2 G-703T (rs4570625) genotype and DNA methylation in the 5' untranslated region (5'UTR) of TPH2 were associated with wavelet variance in fronto-parietal regions and behavioral performance, taking TPH2 genotype into account. In detail, comparisons between genotypes of patients and controls revealed highest wavelet variance and longest reaction times in patients carrying the T allele indicative for a gene-dosage effect, i.e., the WI phenotype is a direct result of the cumulative effect of ADHD and TPH2 variation. Regressions revealed a significant effect on one specific DNA methylation site in ADHD patients but not controls, in terms of a significant prediction of wavelet variance in fronto-parietal regions as well as premature responses. By the example of the TPH2 G-703T (rs4570625) polymorphism, we provide insight into how interactive genetic and DNA methylation affect the ADHD and/or impulsive endophenotype.
The use of electroconvulsive therapy (ECT) in mental retardation has been discussed in several case reports and case series. In this case, a 35-year-old patient with corpus callosum aplasia and ...severe therapy-resistant catatonia was treated with a series of unilateral ECT and improved considerably. Electroencephalographic recordings during ECT showed a complete interhemispheric synchronicity due to regular anterior and posterior commissural fibers. After ECT, the patient received long-term medication with quetiapine and lorazepam. Electroconvulsive therapy turned out to be a powerful tool for treating catatonic syndromes in patients with mental retardation and should be considered as a potent treatment option in otherwise therapy-resistant cases.
Background
In recent years, in vivo and post-mortem studies detected structural brain changes in schizophrenia. The aim of our analysis was to investigate potential changes of white matter in ...schizophrenic patients compared to controls, and the relationship to clinical characteristics.
Methods
Fifty male, right-handed schizophrenic patients who met DSM-IV criteria for schizophrenia were recruited. Fifty right-handed, age- and sex-matched subjects without a psychiatric disorder were enrolled as controls. Volumes of white matter in several brain regions were measured by 1.5 T MRI using a volumetry and segmentation software (BRAINS). Regions of interest including frontal, temporal, parietal, occipital and subcortical areas were determined using Talairach spaces.
Results
No significant differences in white matter volumes of total brain tissue and regions of interest were detected between patients and controls. A significant reduction of white matter in parietal cortex of right hemisphere was found in a subgroup of patients with pronounced negative symptoms. Furthermore, patients with first-grade relatives suffering from schizophrenia showed a reduction of subcortical white matter in the right hemisphere.
Conclusions
Our results indicate that subgroups of schizophrenic patients show alterations of white matter in distinct brain regions, including the right parietal lobe.
Many studies have shown a high prevalence of discrete neuromotor disturbances in schizophrenic patients. It was hypothesized that these disturbances are lateralized and reflect a neurodevelopmental ...disorder underlying schizophrenia. A new method for assessing subtle motor dysfunction and hemispheric asymmetries is the registration of hand movements with a digitizing tablet. Using this method, we studied hand–motor dysfunction and its lateralization in schizophrenics, as compared with healthy controls.
All subjects (27 schizophrenic patients, 13 of them without neuroleptic medication, the others under neuroleptics; 31 healthy controls) drew super-imposed concentric circles. We computed kinematic parameters reflecting velocity and automatization to quantify neurological soft signs (NSS).
The patients had significant impairments of regularity of repetitive hand movements, as compared with the healthy controls (F≥5.35;
p≤0.024
∗). Comparing differences of left- and right-hand performance between patients and controls, we found longer stroke duration (
F=(15,98);
p=0.000***) and decreased automatization (
F=18,14;
p=0.000***), especially on the left side in schizophrenic patients.
Measuring hand movements with a digitizing tablet is a sensitive method for assessing subtle motor dysfunction in schizophrenic patients, not reflected in the scores of clinical scales. Our findings show NSS in schizophrenic patients, independently of neuroleptics. Further, the hypothesis of lateralization of cerebral structures generating NSS towards the right hemisphere in schizophrenia is supported.
Amisulpride appears to be an effective atypical agent for treating schizophrenia in a dose-dependent manner.
29 patients suffering from schizophrenia or schizoaffective disorder were treated with a ...broad dose range of amisulpride (50-1 200 mg/day, mean: 455.2+/-278.8 mg/day). After 2 weeks, brain single photon emission tomography (SPET) scans were performed two hours after intravenous injection of 185 MBq 123IIBZM. Clinical evaluations and ratings of extrapyramidal symptoms were performed at baseline and after steady state treatment of two weeks with amisulpride.
In patients treated with amisulpride, specific binding of 123IIBZM to D2 receptors was significantly decreased (p<0.001) compared to healthy controls. D2 receptor blockade correlated well with administered doses and plasma concentrations of amisulpride. Extrapyramidal side effects, which had to be treated with biperiden, were observed in 31% of the patients. Clinical response was very good, without correlation between the response and striatal D2 occupancy.
Within the first two weeks of treatment with the atypical antipsychotic amisulpride a significant occupancy of striatal postsynaptic dopamine D2 receptors was achieved. At the same time amisulpride shows an excellent tolerability with good efficacy.
People experiencing possible prodromal symptoms of psychosis have a very high risk of developing the disorder, but it is not possible to predict, on the basis of their presenting clinical features, ...which individuals will subsequently become psychotic. Recent neuroimaging studies suggest that there are volumetric differences between individuals at ultra-high risk (UHR) for psychosis who later develop psychotic disorder and those who do not. However, the samples examined to date have been small, and the findings have been inconsistent.
To assess brain structure in individuals at UHR for psychosis in a larger and more representative sample than in previous studies by combining magnetic resonance imaging data from 5 different scanning sites.
Case-control study.
Multisite.
A total of 182 individuals at UHR and 167 healthy controls. Participants were observed clinically for a mean of 2 years. Forty-eight individuals (26.4%) in the UHR group developed psychosis and 134 did not.
Magnetic resonance images were acquired from each participant. Group differences in gray matter volume were examined using optimized voxel-based morphometry.
The UHR group as a whole had less gray matter volume than did controls in the frontal regions bilaterally. The UHR subgroup who later developed psychosis had less gray matter volume in the left parahippocampal cortex than did the UHR subgroup who did not.
Individuals at high risk for psychosis show alterations in regional gray matter volume regardless of whether they subsequently develop the disorder. In the UHR population, reduced left parahippocampal volume was specifically associated with the later onset of psychosis. Alterations in this region may, thus, be crucial to the expression of illness. Identifying abnormalities that specifically predate the onset of psychosis informs the development of clinical investigations designed to predict which individuals at high risk will subsequently develop the disorder.
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