Hippocampal volume is related to body mass index in Alzheimer's disease

Obesity is associated with lower brain volumes in early Alzheimer's disease, but its effects on hippocampal volumes are unclear, as weight loss is also associated with Alzheimer's disease. To address this question, we applied an automated hippocampal mapping method to brain MRI scans for 162 patients with Alzheimer's disease. We hypothesized that obesity, measured by body mass index, would be associated with lower hippocampal volumes in mildly affected patients. Statistical maps showed a selective pattern of hippocampal volume differences that were significantly associated with body mass index. Associations were detected in the anterior hippocampus, and confirmed by permutation testing. Cardiovascular risk factors, such as high body mass index, may promote additional neurodegenerative changes, and should therefore be considered in epidemiological studies and clinical trials.     

The development of an observer-scale for measuring social dysfunction and aggression

Scales for measuring aggressive cognitions and behaviour have mainly been administered by nursing-staff or been self-ratings. During recent years we have made an attempt to construct an observer-scale for aggression analogous to the Hamilton scale for depression. The Social Dysfunction and Aggression Scale (SDAS) consists of 9 items (SDAS-9) covering outward aggression and 2 items (SDAS-2) covering inward aggression. The inter-observer reliability of the SDAS has been found adequate in terms of intra-class coefficients. In a pilot study on 82 inpatients from different centres in Denmark and Sweden the SDAS was compared to three-item scales for outward and inward aggression and to a global scale for outward aggression. The results showed that the SDAS-9 correlated positively with the other outward observer-scales, and the SDAS-2 with the other inward scale. A divergent validity was seen between the outward and inward scales, indicating that it is necessary to measure both dimensions. Preliminary ranks-according-to-frequency scores showed the following order of the nine outward items: irritability, dysphoric mood, social disturbances, nondirected verbal aggressiveness, negativism, directed verbal aggressiveness, physical violence towards staff, physical violence towards things, and physical violence towards persons other than staff.     

Maternal subjective social standing is related to inflammation during pregnancy

BackgroundThe association of socioeconomic status (SES) with health and disease risk is well established. Low-grade inflammation represents a key pathway believed to underlie this association. Previous research has suggested that subjective social standing (SSS) is more consistently associated with health outcomes than objective measures of SES such as income and education. Given the importance of maternal inflammatory state in a wide array of pregnancy, birth and fetal/child developmental and health outcomes, we examine here the independent association of maternal SSS relative to objective SES with pro-inflammatory state during pregnancy.MethodsWe conducted a longitudinal study of an ethnically diverse sample of 250 pregnant women with 3 study visits in early, mid and late gestation. We obtained objective measures of SES (income, education), and SSS with reference to the community and to the nation using the MacArthur Scale of Subjective Social Status. At each study visit, a composite maternal pro-inflammatory score was derived from circulating levels of inflammatory markers (IL-6, CRP, TNF-α).ResultsIn hierarchical linear models, SSS but not objective SES was significantly and negatively associated with maternal inflammatory state. Moreover, the relationship between SSS and inflammatory state remained significant after accounting for objective SES. SSS with reference to the community was a stronger predictor of inflammatory state than SSS with reference to the nation.DiscussionOur finding adds to the scientific literature on SSS and health, highlights the importance of including SSS measures in this context, and supports future research on the relative role and biological pathways by which SSS may impact pregnancy, birth and fetal/child development and health.     

C-reactive protein is related to memory and medial temporal brain volume in older adults

Recent research suggests a central role for inflammatory mechanisms in cognitive decline that may occur prior to evidence of neurodegeneration. Limited information exists, however, regarding the relationship between low-grade inflammation and cognitive function in healthy older adults. This study examined the relation between inflammation, verbal memory consolidation, and medial temporal lobe volumes in a cohort of older community-dwelling subjects. Subjects included 141 functionally intact, community-dwelling older adults with detectable (n = 76) and undetectable (n = 65) levels of C-reactive protein. A verbal episodic memory measure was administered to all subjects, and measures of delayed recall and recognition memory were assessed. A semiautomated parcellation program was used to analyze structural MRI scans. On the episodic memory task, analysis of covariance revealed a significant CRP group by memory recall interaction, such that participants with detectable levels of CRP evidenced worse performance after a delay compared to those with undetectable levels of CRP. Individuals with detectable CRP also demonstrated lower performance on a measure of recognition memory. Imaging data demonstrated smaller left medial temporal lobe volumes in the detectable CRP group as compared with the undetectable CRP group. These findings underscore a potential role for inflammation in cognitive aging as a modifiable risk factor.     

Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume

Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 T–MRI protocol including high-resolution 3D–T1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.     

Delayed development of song control nuclei in the zebra finch is related to behavioral development

The postnatal development of two visual areas (nucleus rotundus and ectostriatum) and two song control areas (hyperstriatum ventrale pars caudale, HVc, and nucleus robustus archistriatalis, RA) of the zebra finch brain was followed from birth to adulthood. The following parameters were investigated: (1) neuron size, (2) volume of the brain nuclei, and (3) myelination of axons. The nucleus rotundus, the diencephalic station of the tectofugal pathway, exhibits the fastest development: rotundal neurons reach their maximum size at 20 days of age; the volume of this structure reaches adult size at the same time. The process of myelination begins between day 5 and day 10 and is completed at 40 days of age. A similar temporal sequence of development is seen in the ectostriatum, except myelination starts some days later. Thus the development of these visual areas is completed at 40 days. In contrast, the development of the song control nuclei is delayed. Neurons in RA and HVc grow steadily up to 40 days of age, attaining a size larger than that observed in adults. Whereas the volume of HVc increases until day 40 and remains stable thereafter, RA volume increases until day 70 and evidences a decrease thereafter. It is not until postnatal day 20 (RA) and day 40 (HVc) that the myelination process starts in the song control areas. Adult myelin density is achieved by 70 days in RA and by 100 days in HVc. It can be demonstrated that the development of the visual system parallels the development of visual performance of the birds. Delayed growth of song control nuclei coincides with development of song.     

Executive performance is related to regional gray matter volume in healthy older individuals

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail‐making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community‐dwelling individuals (50–81 years). Task performance was analyzed relative to brain structure using voxel‐based morphometry, corrected for age and sex. Improved task performance was associated with increased local gray matter volume in task‐specific patterns that showed partial, but not complete overlap with known task‐specific functional imaging patterns. While all three tasks showed associations with prefrontal gray matter volume as expected for executive functioning, the strongest overlap between the three tasks was found in insular cortex, suggesting that it has a previously underestimated role for executive functions. The association between the insular cortex and executive functioning was corroborated using stereological region‐of‐interest measurement of insular volume in a subgroup of 93 subjects. Quantitatively, the volume of the single most strongly related region explained 2.4 ± 1.1% of the variance in executive performance over and above the variance explained by age, which amounted to 7.4 ± 4.1%. The age‐independent peak associations between executive performance and gray matter described here occurred in regions that were also strongly affected by age‐related gray matter atrophy, consistent with the hypothesis that age‐related regional brain volume loss and age‐related cognitive changes are linked. Hum Brain Mapp 34:3333–3346, 2013. © 2012 Wiley Periodicals, Inc.     

Globus pallidus volume is related to symptom severity in neuroleptic naive patients with schizophrenia

This study compares globus pallidus (GP) volume between neuroleptic naive patients with schizophrenia and healthy controls using structural MRI. The volume of the external segment of the GP (GPe) was positively correlated with the severity of global symptoms, as measured by the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms (SANS/SAPS, Andreasen and Olsen, 1982). The volume for the GP, GPe, and internal segment (GPi) did not differ between groups.     

Suicidality and trait aggression related to childhood victimization in patients with alcoholism

The relationship between physical abuse in childhood and suicide attempts in adulthood has long been known. However, the phenomenon has not been examined in patients who are undergoing treatment for alcoholism. In this study we seek an answer to the questions of whether exposure to physical abuse in childhood predisposes to violence, which in turn increases the likelihood of suicidal behavior in adulthood. The sample studied comprised 172 patients with alcohol dependence and with data for childhood physical abuse, trait aggression and lifetime suicide attempts. The measuring instruments used for the investigation were the European Addiction Severity Index, the Buss and Perry Aggression Questionnaire and the Janus Questionnaire. Generalized Linear Model analysis revealed a significant gender-dependent association between physical abuse by the parents suffered in childhood and later suicide attempts. In females, childhood victimization by parents increased the likelihood of suicide attempts by approximately 15 times; in males, the increase was about twofold. Association of suicide attempts with the overall level of trait aggression also significantly interacted with gender. In females, the increase in the level of total scores of the trait aggression from 0 to 50 points (approximately the mean level in the study population) elevated the likelihood of the suicide attempts by almost ninefold, whereas the analogous increase in males was about threefold. The results draw attention to the importance of preventing suicide in clinical populations of alcohol-dependent patients.     

Mushroom body feedback interneurones in the honeybee show GABA-like immunoreactivity

The distribution of the transmitter substance GABA was investigated in the mushroom body neuropile of the honeybee by means of immunohistochemistry. The protocerebro-calycal tract (PCT) links a mushroom body output area with the calycal input sites. Interneurones contained within the PCT exhibit GABA-like immunoreactivity and may function as negative feedback loop.     

Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression.

BACKGROUND: Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression. METHODS: Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior. RESULTS: Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces. CONCLUSIONS: These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.     

Severity of vascular dementia is related to volume of metabolically impaired tissue.

The relation between dementia severity and regional cerebral metabolic rate of glucose was studied in 28 patients with vascular dementia (VD) in comparison with 20 age-matched patients who were suffering from Alzheimer's disease (AD) and 24 normal subjects by using positron emission tomography with fludeoxyglucose F 18. Similar metabolic impairment was found in the temporoparietal and frontal association cortex in patients with VD and in those with AD. Metabolism of the basal ganglia, thalamus, and cerebellum was reduced significantly in patients with VD only. The total volume of regions with metabolism below the 95% confidence interval of control values was significantly related to the severity of dementia but did not differ between patients with VD and those with AD. A metabolic ratio of regional cerebral glucose metabolism of association areas divided by regional cerebral glucose metabolism of structures that were typically not affected by AD was significantly lower in patients with AD than in those with VD. This ratio was also related to dementia severity in both types of dementia.     

Neuropsychological performance is related to current social and occupational functioning in veterans with posttraumatic stress disorder

Background: Several studies have reported deficits in both immediate and delayed recall of verbal memory in patients with posttraumatic stress disorder (PTSD). However, most of these studies had several methodological disadvantages. None of these studies assessed parameters related to social or occupational functioning. Methods: Fifty Dutch veterans of UN peacekeeping missions (25 with PTSD and 25 without PTSD) were assessed with a comprehensive neuropsychological test battery consisting of four subtests of the Wechsler Adult Intelligence Scale‐III, California Verbal‐Learning Test, and the Rey Auditory Verbal‐Learning Test. Veterans with PTSD were free of medication and substance abuse. Results: Veterans with PTSD had similar total intelligence quotient scores compared to controls, but displayed deficits of figural and logical memory. Veterans with PTSD also performed significantly lower on measures of learning and immediate and delayed verbal memory. Memory performance accurately predicted current social and occupational functioning. Conclusions: Deficits of memory performance were displayed in a sample of medication‐ and substance abuse‐free veterans with PTSD. Deficits in memory performance were not related to intelligence quotient, length of trauma exposure, or time since trauma exposure. This study showed that cognitive performance accurately predicted current social and occupational functioning in veterans with PTSD. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Adult social attachment disturbance is related to childhood maltreatment and current symptoms in borderline personality disorder

We characterized borderline personality disorder (BPD) along two fundamental dimensions of adult social attachment and evaluated attachment associations with childhood maltreatment and current symptoms using self-report measures in 40 outpatients with DSM-IV BPD. The BPD group had significantly greater dimensional attachment impairment and rate of fearful attachment type compared with a healthy control group. Among BPD subjects, dimensional attachment-anxiety was specifically associated with sexual abuse, whereas attachment-avoidance was associated with all five maltreatment types. The two attachment dimensions showed divergent associations with current interpersonal problems, impulsivity subtypes and mood symptoms. We conclude that (1) BPD is characterized by adult attachment disturbance; (2) these attachment problems are strongly related to childhood maltreatment, and to current interpersonal problems and clinical symptoms that are considered core features of BPD; and (3) the diverse problems of BPD patients may arise from two basic mechanisms, each tied to a different type of attachment disturbance, developmental history, and clinical outcome.     

Mushroom body neuronal remodelling is necessary for short-term but not for long-term courtship memory in Drosophila

The remodelling of neurons during their development is considered necessary for their normal function. One fundamental mechanism involved in this remodelling process in both vertebrates and invertebrates is axon pruning. A well-documented case of such neuronal remodelling is the developmental axon pruning of mushroom body γ neurons that occurs during metamorphosis in Drosophila. The γ neurons undergo pruning of larval-specific dendrites and axons at metamorphosis, followed by their regrowth as adult-specific dendrites and axons. We recently revealed a molecular cascade required for this pruning. The nuclear receptor ftz-f1 activates the expression of the steroid hormone receptor EcR-B1, a key component for γ remodelling, and represses expression of Hr39, an ftz-f1 homologous gene. If ectopically expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. The mushroom bodies are a bilaterally symmetric structure in the larval and adult brain and are involved in the processing of different types of olfactory memory. How memory is affected in pruning-deficient adult flies that possess larval-stage neuronal circuitry will help to explain the functional role of neuron remodelling. Flies overexpressing Hr39 are viable as adults and make it possible to assess the requirement for wild-type mushroom body pruning in memory. While blocking mushroom body neuron remodelling impaired memory after short-term courtship conditioning, long-term memory was normal. These results show that larval pruning is necessary for adult memory and that expression of courtship short-term memory and long-term memory may be parallel and independent.