Microstructural thalamic changes in schizophrenia: a combined anatomic and diffusion weighted magnetic resonance imaging study

Objective

Several magnetic resonance imaging (MRI) and postmortem studies have supported the role of the thalamus in the pathophysiology of schizophrenia. Interestingly, a recent small diffusion weighted imaging (DWI) study showed abnormal thalamic microstructure in patients with schizophrenia. The objective of our study was to use structural MRI and DWI to explore for the first time both thalamic volumes and integrity in schizophrenia.

Methods

We measured thalamic volumes and apparent diffusion coefficient (ADC) measures bilaterally in 71 patients with schizophrenia, representative of those living in the geographically defined catchment area of South Verona (i.e., 100 000 inhabitants), and 75 individuals without schizophrenia. The presence of the adhesio interthalamica was also detected.

Results

We found no significant differences in thalamus size between patients with schizophrenia and participants in the control group, with only a trend for decreased left volumes. No abnormal frequency of the adhesio interthalamica was found. In contrast, significantly increased thalamic ADC values were shown in schizophrenia patients. Age significantly inversely correlated with thalamic volumes in both groups and correlated positively with posterior ADCs in patients with schizophrenia. No significant associations between clinical variables and either volumes or ADC values were reported.

Conclusion

Widespread altered microstructure integrity and partially preserved thalamus size were found in schizophrenia patients. Therefore, subtle thalamic structural abnormalities are present in schizophrenia, even with maintained volumes. This may result from disruption at the cytoarchitecture level, ultimately supporting corticothalamic misconnection. Future imaging studies should further explore thalamic tissue coherence and its role for cognitive disturbances in patients at high risk for schizophrenia and in first-degree relatives.Medical subject headings: psychotic disorders, magnetic resonance, neurosciences     

Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high Risk for Psychosis: A Preliminary Study

Objective

Recent neuroimaging studies have suggested that brain changes occur in subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal symptoms, among which depression may increase the risk of developing a psychotic disorder. The goal of this study is to examine brain metabolite levels in the anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left thalamus in subjects at UHR for psychosis and to compare brain metabolite levels between the UHR subjects with comorbid major depressive disorder and healthy controls.

Methods

Proton magnetic resonance spectroscopy was used to examine brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence quotient (IQ)-matched healthy controls were included in this study.

Results

Overall, no significant differences were observed in any metabolite between the UHR and healthy control group. However, UHR subjects with major depressive disorder showed significantly higher myo-inositol (Ins) levels in the left thalamus, compared to the healthy control.

Conclusion

Our results demonstrate that increased thalamic Ins level is associated with prodromal depressive symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are required to investigate the function of Ins concentrations as a biomarker of vulnerability to psychosis.     

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Background

Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.

Methods

We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.

Results

Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.

Limitations

Our study had a small sample size, and we were unable to control for the effects of medication.

Conclusion

Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.     

Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study

Objective

According to the stress-toxicity hypothesis of depression, hippocampal volumes may diminish as the disease progresses. We sought to examine the changes in hippocampal and amygdala volumes at baseline and at 3 years after an acute depressive episode, and the impact of reduced hippocampal volumes on the outcome.

Methods

In a prospective, longitudinal study, we examined the hippocampus and amygdala of 30 inpatients with major depression from the Department of Psychiatry and Psychotherapy and 30 healthy participants from the community (control group) using high-resolution magnetic resonance images at baseline and after 3 years. Psychopathology was assessed at baseline, weekly during the inpatient phase and then after 1, 2 and 3 years.

Results

During the 3-year follow-up period, neither hippocampal nor amygdala volumes changed significantly among patients or participants in the control group. However, in the subgroup of patients who took antidepressants over the full 3 years, the left hippocampal volumes increased significantly. Patients with small hippocampal volumes and previous depressive episodes had a worse clinical outcome compared with patients with large hippocampal volumes and previous depressive episodes.

Conclusion

Overall, our results suggest that a relatively small hippocampal volume may be a vulnerability factor for a bad treatment response in major depression. Subtle changes in hippocampal volumes may be detectable during continuous antidepressant therapy. Such changes may be the result of neuroplastic processes.Medical subject headings: hippocampus, amygdala, magnetic resonance imaging, depressive disorder, major     

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study

Background

Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis.

Methods

We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]).

Results

We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group.

Limitations

The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination.

Conclusion

P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.     

Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study

Background

Late-life depression is associated with decreased brain volumes, particularly in frontal and temporal areas. Evidence suggests that depressive symptoms at a subclinical level are also associated with brain atrophy in these regions, but most of these associations are based on cross-sectional data. Our objective was to investigate both cross-sectional and longitudinal relations between sub-threshold depressive symptoms and brain volumes in older adults and to examine whether these associations are modified by age.

Methods

In total, 110 dementia-free adults from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging aged 56 years and older at baseline participated in this study. Participants received annual evaluations for up to 9 years, during which structural magnetic resonance imaging (MRI) scans were acquired and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale.

Results

Mean depressive symptom scores over time were associated with grey matter volume reductions in the left temporal lobe. Depressive symptoms were associated with brain volume reductions with advancing age in the cingulate gyrus and orbitofrontal cortex. Moreover, individuals with higher mean depressive symptom scores showed a faster rate of volume decline in left frontal white matter. Depressive symptoms were not associated with hippocampus volumes.

Limitations

Limitations include the relative homogeneity of our primarily white and highly educated sample, the lack of information about age at onset of depressive symptoms and potential limitations of the automated brain volume registration.

Conclusion

Our results suggest that depressive symptoms, even at a subthreshold level, are associated with volume reductions in specific frontal and temporal brain regions, particularly with advancing age.     

Hippocampus and amygdala morphology in adults with attention-deficit hyperactivity disorder

Objective

Attention-deficit hyperactivity disorder (ADHD) in adulthood is a serious health problem with a prevalence of up to 4%. Limbic structures have been implicated in the genesis of ADHD; it has been suggested that they mediate mood and cognitive disturbances in affected individuals. Recently, a large study involving children and adolescents with ADHD reported bilateral enlargement of the hippocampus and indirect evidence of amygdala volume loss in this patient sample. We sought to test the hypothesis that, like in pediatric patients, there might be hippocampus and amygdala volume abnormalities in adult patients with ADHD.

Methods

We studied 27 adult patients with ADHD and 27 group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements of the regions mentioned.

Results

In contrast to previous findings in children and adolescents, we found no significant differences in hippocampus and amygdala volumes among adults with and without the disorder.

Conclusion

Findings of hippocampus enlargement and amygdala volume loss are not very stable across different samples of patients with ADHD. Contradictory findings may be related to the different locations of alterations along the complex circuits responsible for the different symptoms of ADHD. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed.Medical subject headings: hippocampus, amygdala, attention deficit disorder with hyperactivity     

Measurement of Precuneal and Hippocampal Volumes Using Magnetic Resonance Volumetry in Alzheimer's Disease

Background and Purpose

Alzheimer''s disease (AD) is associated with structural alterations in the medial temporal lobe (MTL) and functional alterations in the posterior cortical region, especially in the early stages. However, it is unclear what mechanisms underlie these regional discrepancies or whether the posterior cortical hypometabolism reflects disconnection from the MTL lesion or is the result of local pathology. The precuneus, an area of the posteromedial cortex that is involved in the early stages of AD, has recently received a great deal of attention in functional neuroimaging studies. To assess the relationship between the precuneus and hippocampus in AD, we investigated the volumes of these two areas using a magnetic resonance volumetric method.

Methods

Twenty-three subjects with AD and 14 healthy age-matched controls underwent T1-weighted three-dimensional volumetric brain magnetic resonance imaging. Volumetric measurements were performed in the precuneus and hippocampus.

Results

Compared to controls, AD patients exhibited a significant reduction in total precuneal volume, which was more prominent on the right side, and significant bilateral reductions in hippocampal volume. No correlation was found between the total volumes of the precuneus and hippocampus in the AD group.

Conclusions

These results suggest that volumetric measurements of both the precuneus and hippocampus are useful radiological indices for the diagnosis of AD. Furthermore, the lack of correlation is attributable to local pathology rather than being a secondary consequence of MTL pathology.     

Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder

Background

Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD.

Methods

We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T₁- and T₂-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala.

Results

Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD.

Limitations

Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size.

Conclusion

Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.     

Reduced amygdalar and hippocampal size in adults with generalized social phobia

Background

Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking.

Methods

In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation.

Results

Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity.

Limitations

Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative.

Conclusion

We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.     

Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment

Background

Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD.

Methods

We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sex-matched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm × 0.5 mm × 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume.

Results

We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients.

Limitations

This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment.

Conclusion

Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD.     

Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder

Background:

Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).

Methods:

One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.

Results:

Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.

Conclusions:

Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.Key words: psychosis, cognition, brain volume, neurodevelopmental, neuroprogressive     

Structural covariance in the hallucinating brain: a voxel-based morphometry study

Background

Neuroimaging studies have indicated that a number of cortical regions express altered patterns of structural covariance in schizophrenia. The relation between these alterations and specific psychotic symptoms is yet to be investigated. We used voxel-based morphometry to examine regional grey matter volumes and structural covariance associated with severity of auditory verbal hallucinations.

Methods

We applied optimized voxel-based morphometry to volumetric magnetic resonance imaging data from 26 patients with medication-resistant auditory verbal hallucinations (AVHs); statistical inferences were made at p < 0.05 after correction for multiple comparisons.

Results

Grey matter volume in the left inferior frontal gyrus was positively correlated with severity of AVHs. Hallucination severity influenced the pattern of structural covariance between this region and the left superior/middle temporal gyri, the right inferior frontal gyrus and hippocampus, and the insula bilaterally.

Limitations

The results are based on self-reported severity of auditory hallucinations. Complementing with a clinician-based instrument could have made the findings more compelling. Future studies would benefit from including a measure to control for other symptoms that may covary with AVHs and for the effects of antipsychotic medication.

Conclusion

The results revealed that overall severity of AVHs modulated cortical intercorrelations between frontotemporal regions involved in language production and verbal monitoring, supporting the critical role of this network in the pathophysiology of hallucinations.     

Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

Background

Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.

Methods

We obtained high-resolution 3-dimensional T₁-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.

Results

We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psycho-pathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.

Limitations

This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.

Conclusion

Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.     

Grey matter alterations in patients with depersonalization disorder: a voxel-based morphometry study

Background

To our knowledge, no whole brain investigation of morphological aberrations in dissociative disorder is available to date. Previous region-of-interest studies focused exclusively on amygdalar, hippocampal and parahippocampal grey matter volumes and did not include patients with depersonalization disorder (DPD). We therefore carried out an explorative whole brain study on structural brain aberrations in patients with DPD.

Methods

We acquired whole brain, structural MRI data for patients with DPD and healthy controls. Voxel-based morphometry was carried out to test for group differences, and correlations with symptom severity scores were computed for grey matter volume.

Results

Our study included 25 patients with DPD and 23 controls. Patients exhibited volume reductions in the right caudate, right thalamus and right cuneus as well as volume increases in the left dorsomedial prefrontal cortex and right somatosensory region that are not a direct function of anxiety or depression symptoms.

Limitations

To ensure ecological validity, we included patients with comorbid disorders and patients taking psychotropic medication.

Conclusion

The results of this first whole brain investigation of grey matter volume in patients with a dissociative disorder indentified structural alterations in regions subserving the emergence of conscious perception. It remains unknown if these alterations are best understood as risk factors for or results of the disorder.     

Pervasive microstructural abnormalities in autism: a DTI study

Background

Recent studies have reported abnormal functional connectivity patterns in the brains of people with autism that may be accompanied by decreases in white matter integrity. Since autism is a developmental disorder, we aim to investigate the nature and location of decreases in white and grey matter integrity in an adolescent sample while accounting for age.

Methods

We used structural (T₁) imaging to study brain volumetrics and diffusion tensor imaging (DTI) to investigate white and grey matter integrity in people with autism. We obtained magnetic resonance images for adolescents aged 12–18 years with high-functioning autism and from matched controls. Fractional anisotropy and mean diffusivity, as well as grey and white matter volumetrics were analyzed.

Results

There were 17 participants with autism and 25 matched controls included in this study. Participants with autism had lower fractional anisotropy in the left and right superior and inferior longitudinal fasciculus, but this effect was not significant after adjusting for age and intelligence quotient (IQ). The kurtosis of the white matter fractional anisotropy probability distribution was higher in this participant group, with and without adjustment for age and IQ. Most notably, however, the mean diffusivity levels were markedly increased in the autism group throughout the brain, and the mean diffusivity probability distributions of both grey and white matter were shifted toward a higher value, particularly with age and IQ adjustment. No volumetric differences in grey and white matter were found.

Limitations

We corrected for age and IQ using a linear model. The study was also limited by its sample size, investigated age range and cross-sectional design.

Conclusion

The findings suggest that autism is characterized by a generalized reduction of white matter integrity that is associated with an increase of interstitial space. The generalized manifestation of the white matter abnormalities provides an important new perspective on autism as a connectivity disorder.     

Gyrification,cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities

Background

Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification.

Methods

We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1.

Results

Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions.

Conclusions

The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype.     

Thalamic morphology in schizophrenia and schizoaffective disorder

Background

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia.

Method

T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape.

Results

Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions.

Conclusions

Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.     

Structural MRI correlates for vulnerability and resilience to major depressive disorder

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.     

Thalamic chronotaraxis: isolated time disorientation

Background

Acute isolated disorientation of time, chronotaraxis, is an uncommon manifestation of thalamic stroke. To our knowledge, acute thalamic chronotaraxis with MRI findings has not previously been reported.

Objective

To describe five patients with chronotaraxis after thalamic stroke and attempt to demonstrate the correlation between lesion location and neurological findings.

Patients, methods and results

Isolated time disorientation and loss of time sense were found in five of 120 patients (4%) with ischaemic thalamic stroke in our centre. All patients had disorientation to actual date, inability to know the exact time of the day and under or overestimation of the time passed during examination. Patients expressed themselves as having time blindness with an inability to estimate and guess the actual time.

Conclusion

Acute thalamic chronotaraxis is a specific clinical picture that accurately predicts a small artery disease of the thalamus involving the mediodorsal nucleus of the thalamus. This clinical syndrome appears to have a good clinical recovery.Disorientation of time, place and person, and distortion of personal and extrapersonal memory systems may occur after mediodorsal thalamotomy, and may also be observed in paramedian or polar artery infarction.^1,2 Isolated prominent disorientation of time is extremely rare, and the term chronotaraxis has been used to describe this phenomenon.³ The meaning of the Greek name chronotaraxis is distortion or disorientation of the sense of time, such as for dates, seasons of the year, times of the day, and overestimation or underestimation of duration of time.We present a consecutive series of five patients with chronotaraxis, and attempt to clarify the correlation between lesion location and related behavioural findings.