Posterior Hippocampal Volumes Research Articles

Hippocampal volume reduction and autobiographical memory deficits in chronic schizophrenia

Although autobiographical memory (AM) deficits and hippocampal changes are frequently found in schizophrenia, their actual association remained yet to be established. AM performance and hippocampal volume were examined in 33 older, chronic schizophrenic patients and 21 healthy volunteers matched for age, gender and education. Psychopathological symptoms and additional neuropsychological parameters were assessed by using appropriate rating scales; magnetic resonance imaging (MRI) 3-T data were analyzed via an automated region-of-interest procedure. When compared with the control subjects, patients showed significantly decreased left anterior and posterior hippocampal volumes. Episodic but not semantic AM performance was significantly lower in the patients than in the healthy controls. Both episodic and semantic AM deficits were significantly correlated with volume of the left hippocampus in the patient group. In contrast, deficits in verbal memory, working memory and remote semantic memory observed in the patients did not relate to hippocampal volume. Our findings indicate that AM deficits in chronic schizophrenia are associated with hippocampal volume reductions and underline the importance of this pathology in schizophrenia.

Estrogen and the male hippocampus: Genetic variation in the aromatase gene predicting serum estrogen is associated with hippocampal gray matter volume in men

The neurosteroid 17-beta estradiol (E2) plays an important role in neuronal plasticity, neurogenesis and neuroprotection of hippocampal neurons in slice cultures and the female brain. While some effects of E2 on hippocampal neurons observed in females were also seen in the male hippocampus, others seem to be specific to females. The current study aimed to further explore the effect of E2 on the male hippocampus by investigating the relationship between genetic variations in E2 synthesis and hippocampal gray matter (GM) volume. We chose a single nucleotide polymorphism (rs700158, SNP) in the gene CYP19A1 coding for the final enzyme (aromatase) in E2 synthesis. Men homozygous for the A allele of rs700518 have repeatedly been shown to have higher E2 serum levels than male carriers of the G allele. Two independent cohorts of healthy young men were genotyped for rs700518 and voxel-based morphometry (VBM) was performed on structural magnetic resonance images to determine genotype dependent group differences. Men homozygous for the A allele of rs700518 had greater bilateral posterior hippocampal GM volumes in both cohorts. Thus, the genotype associated with higher E2 serum levels was also associated with greater hippocampal gray matter.

Anatomical and functional correlates of human hippocampal volume asymmetry

Hemispheric asymmetry of the human hippocampus is well established, but poorly understood. We studied 110 healthy subjects with 3-Tesla MRI to explore the anatomical and functional correlates of the R>L volume asymmetry. We found that the asymmetry is limited to the anterior hippocampus (hemisphere×region interaction: F(1,109)=42.6, p<.001). Anterior hippocampal volume was correlated strongly with the volumes of all four cortical lobes. In contrast, posterior hippocampal volume was correlated strongly only with occipital lobe volume, moderately with the parietal and temporal lobe volumes and not with the frontal lobe volume. The degree of R>L anterior hippocampal volume asymmetry predicted performance on a measure of basic cognitive abilities. This provides evidence for regional specificity and functional implications of the well-known hemispheric asymmetry of hippocampal volume. We suggest that the developmental profile, genetic mechanisms and functional implications of R>L anterior hippocampal volume asymmetry in the human brain deserve further study.

State dependent posterior hippocampal volume increases in patients with major depressive disorder

The hippocampal formation has been implicated in etiology and therapy response in major depressive disorder (MDD). However, prospective longitudinal studies investigating volumes in hippocampal subregions and their association with clinical findings are still lacking. Global and regional hippocampal volumes and neuropsychological performance were assessed longitudinally in 15 young patients with unipolar early onset MDD who responded to therapy and 13 matched healthy control subjects. Although volumes at baseline did not differ between groups, patients with MDD showed significant posterior hippocampal volume increases during the treatment course (mean observation period 161.4 ± 58.6 days). Posterior hippocampal volume increases were seen in every single patient. The detected posterior hippocampal volume increases were significantly correlated with the number of solved problems in a planning task at baseline. The study is limited by the small sample size. Moreover, future studies should include patients who do not respond to antidepressant treatment. Patients with MDD showed selective increases in posterior hippocampal volumes which were not correlated to the degree of functional restitution. However, posterior hippocampal volume increases might constitute a surrogate parameter of neuroplasticity taking place during antidepressant therapy which might be predicted by executive functioning at baseline.

Hippocampal volume in postmenopausal cynomolgus macaques with behavioral depression.

Magnetic resonance imaging (MRI) studies report hippocampal (HC) volume reductions in depression. Despite observations of functional heterogeneity and ovarian steroid influence in the hippocampus, few studies report regional volume alterations or control for menstrual cycle phase. Using in vitro methods, we recently observed reduced anterior HC volume in antidepressant-naive, ovarian-intact, behaviorally depressed adult female monkeys. The purpose of this study was to confirm these findings in vivo and examine whether lack of ovarian steroids affects the relationship between depression and HC volume. MRI was used to measure whole, anterior, and posterior HC volumes in a matched sample of antidepressant-naive, surgically postmenopausal adult female cynomolgus macaques characterized for behavioral depression (six depressed, six nondepressed). High-resolution structural MRIs were acquired, and HC regions of interest were manually segmented. HC volumes were normalized to whole brain volumes before analysis. Similar to the previous in vitro study, HC volume measured in vivo was associated with depression. In contrast to the previous study of ovarian-intact female monkeys, whole, anterior, and posterior volumes of both the left and right hippocampi were significantly smaller in depressed compared with nondepressed surgically postmenopausal female monkeys. These findings confirm and extend previous observations of smaller HC volumes in behaviorally depressed female monkeys and suggest a possible role for ovarian steroids in HC protection in depression. Further studies of the potential modulating effects of ovarian function on the relationship between depression and HC volume are warranted.

Reduced right posterior hippocampal volume in women with recurrent familial pure depressive disorder

Volumetric changes in mood-relevant distributed limbic/paralimbic structures have been reported in the recent literature on the course of mood disorders. Patients with unipolar and bipolar disorders have been found to have smaller hippocampal and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior cingulate cortex (ACC) volumes in female patients with recurrent familial pure depressive disorder (rFPDD). We used semi-automated software for magnetic resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial recurrent major depression (MD) and 15 healthy female subjects. Analysis of covariance, with whole brain volume as covariate, was used to compare volumetric measurements in the two groups. Volumes of the right hippocampal body and tail were significantly smaller in female patients with familial depressive disorder than in healthy subjects. Our data provide evidence of structural lateralized hippocampal body and tail abnormalities in women with familial history and recurrent episodes of depression. Although global reduction of hippocampal volume has been widely reported, data on lateralized regional reductions in familial recurrent depression had not been previously reported. Reduced volume of the right posterior hippocampus could be a structural endophenotype for recurrent depressive disorders in women.

Abnormal hippocampal shape in offenders with psychopathy

Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 +/- 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 +/- 10.8) were used for statistical modelling of local changes with a surface-based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2-3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear-conditioning.

Anterior hippocampal and orbitofrontal cortical structural brain abnormalities in association with cognitive deficits in schizophrenia

Objective Numerous studies have implicated the hippocampus and prefrontal cortex in schizophrenia. However, precisely which subregions of the hippocampus and prefrontal cortex are abnormal remain unknown. Our study goal was to investigate the structure of the anterior hippocampus, posterior hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) simultaneously in thirty-eight patients with schizophrenia and twenty-nine controls to determine which of these subregions are abnormal in schizophrenia. As an exploratory study goal, we investigated the relation of neurocognition to brain structure in schizophrenia patients. Method We generated detailed structural magnetic resonance imaging data and compared hippocampal and prefrontal subregional structural brain volumes between schizophrenia and control groups. We obtained a neurocognitive test battery in schizophrenia patients and studied the association of abnormal brain structures to neurocognition. Results Structural brain abnormalities were pinpointed to the left anterior hippocampus and left OFC in schizophrenia patients, which were both significantly reduced in volume. The DLPFC and posterior hippocampus, though numerically decreased in volume, were not significantly decreased. Anterior hippocampal volumes were more strongly associated with OFC volumes in schizophrenia patients compared to controls. By contrast, DLPFC volume was unrelated to anterior or posterior hippocampal volume. Both the anterior hippocampus and OFC were independently related to cognitive abnormalities common in schizophrenia, including indices of verbal, language, and executive functions. The DLPFC and posterior hippocampal volumes were unrelated to cognitive measures. Conclusions These findings highlight related abnormalities of the anterior hippocampus and OFC in schizophrenia, which may shed light on the pathophysiology of the disorder.

Anterior hippocampal volume is reduced in behaviorally depressed female cynomolgus macaques

Hippocampal (HC) function and morphology have been implicated in the pathophysiology of depression. Reduced HC volume has been observed in depressed humans, although the effect is not always significant. Studies of functional differentiation of the HC have revealed that the anterior portion is associated with emotional and anxiety-related functioning, and the posterior portion with memory processing. As such, measuring whole HC volume may mask differences seen only in the anterior or posterior HC. We used unbiased stereology to measure whole, anterior, and posterior HC volumes in 12 adult female cynomolgus macaques, half of which exhibited spontaneously occurring depressive behavior defined as a slumped/collapsed body posture with open eyes, and a relative lack of responsivity to environmental stimuli. The two groups were otherwise matched on circulating estradiol, progesterone, and cortisol levels, social status, estimated age, and body weight. Frozen postmortem HC tissue from depressed and nondepressed monkeys was serially sectioned and thionin-stained. According to established neuroanatomical guidelines and with the aid of Neurolucida software (MBF Bioscience), every 10th section throughout the extent of the HC was manually traced and used to reconstruct the 3D models used to determine volumes. Anterior and posterior HC were delineated by the presence or absence of the uncus. No significant differences were found between depressed and nondepressed monkeys for whole or posterior HC volume, although the average HC volume was 4% smaller in depressed than nondepressed monkeys. Anterior HC volumes were significantly smaller (15.4%) in depressed compared to nondepressed monkeys. These results indicate that reduced volume in the anterior HC, an area previously implicated in emotional functioning, may be associated with a depressive phenotype in female cynomolgus macaques.

Hippocampal Volumes in First-Episode Psychosis

Hippocampal Volumes in First-Episode Psychosis

Hippocampal Volumes in First-Episode Psychosis

Studies have shown that patients with schizophrenia have smaller hippocampi than healthy comparison subjects. There are, however, inconsistencies regarding the relationship between clinical characteristics and topographical differences in hippocampal volumetry. The authors investigated hippocampal volumes in minimally treated patients with first-episode schizophrenia spectrum disorders, relative to comparison subjects. Thirty-nine consecutive patients and 29 matched comparison subjects were scanned using 1.5 tesla MR system. Patients had significantly smaller right anterior, right, and anterior hippocampal volumes than comparison subjects. There was a gender by diagnosis effect: female patients showed significantly smaller anterior and right hippocampal volumes than female comparison subjects, an effect not seen in male patients. Our results suggest that smaller hippocampal volumes are present even in early stages of the illness.

Schizophrenia diagnosis and anterior hippocampal volume make separate contributions to sensory gating

Impaired P50 gating is thought to reflect a core deficit in schizophrenia, but the relevant neural network is not well understood. The present study used EEG and MEG to assess sensory gating and volumetric MRI to measure hippocampal volume to investigate relationships between them in 22 normal controls and 22 patients with schizophrenia. In the schizophrenia group, anterior but not posterior hippocampal volume was smaller, and both the P50 and M50 gating ratios were larger (worse) than in controls. Independent of group, left-hemisphere M50 gating ratio correlated negatively with left anterior hippocampal volume, and right-hemisphere M50 gating ratio correlated negatively with right anterior hippocampal volume. Schizophrenia diagnosis predicted M50 gating independent of hippocampal volume. These results are consistent with the finding that hippocampus is a critical part of a fronto-temporal circuit involved in auditory gating.

Posterior Hippocampal Volumes Are Associated with Remission Rates in Patients with Major Depressive Disorder

The hippocampus (HC) is smaller in patients with recurrent major depressive disorder (MDD), but few longitudinal studies have examined whether volume is associated with clinically meaningful outcomes such as response to treatment. We compared regional (head and body/tail) HC volumes in 46 patients with MDD, 14 of whom remitted after 8 weeks of first treatment to HC volumes of 32 patients who were not in remission after 8 weeks. Patients who remitted had larger pretreatment hippocampal body/tail volumes bilaterally compared with those who were not in remission at 8 weeks. This difference was not apparent in either the right or left hippocampal head. These findings extend a small number of previous reports, suggesting that regional brain volumes might be associated with rate and extent of clinical response to antidepressant medication.

Reduced Posterior Hippocampal Volume in Posttraumatic Stress Disorder

Hippocampal volume is reduced in posttraumatic stress disorder (PTSD). In the present study, we sought to determine whether volume loss is homogenously distributed or confined to a certain part of the structure. Twenty-two adult outpatients with PTSD (11 after prolonged prepubertal trauma and 11 after single adult trauma) and 22 matched healthy subjects were scanned at the National Institute of Mental Health using high-resolution 3T magnetic resonance imaging between September 2003 and August 2004. PTSD diagnosis was conferred using the Structured Clinical Interview for DSM-IV. Volumes of whole, anterior, and posterior hippocampus and subiculum were compared between groups. Total hippocampal volume was lower in patients with PTSD (p = .02), with a significant diagnosis by hippocampal-subregion interaction (p = .02). Post hoc analysis revealed significantly smaller posterior hippocampi in PTSD (p = .006), with no difference in the volumes of anterior hippocampus or subiculum. No volume differences were found between PTSD participants with prolonged childhood abuse compared to single adult trauma exposure. The posterior hippocampus has been associated with storage, processing, and retrieval of spatiotemporal memories, central to the protective function of fear conditioning. Volume deficit in the posterior hippocampus may indicate malfunction in this faculty, leading to the exaggerated conditioned fear response observed in PTSD.

Structural brain abnormalities in psychopaths—a review

The biological basis of psychopathy has not yet been fully elucidated. Few studies deal with structural neuroimaging in psychopaths. The aim of this article is to review these studies in order to contribute to our understanding of the biological basis of psychopathy. Data in the literature report a reduction in prefrontal gray matter volume, gray matter loss in the right superior temporal gyrus, amygdala volume loss, a decrease in posterior hippocampal volume, an exaggerated structural hippocampal asymmetry, and an increase in callosal white matter volume in psychopathic individuals. These findings suggest that psychopathy is associated with brain abnormalities in a prefrontal-temporo-limbic circuit-i.e. regions that are involved, among others, in emotional and learning processes. Additionally, data indicate that psychopathic individuals cannot be seen as a homogeneous group. The associations between structural changes and psychopathic characteristics do not enable causal conclusions to be drawn, but point rather to the important role of biological brain abnormalities in psychopathy. To gain a comprehensive understanding of this, psychopathy must be viewed as a multifactorial process involving neurobiological, genetic, epidemiological and sociobiographical factors.

Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits

Polydipsic hyponatremic schizophrenic patients (PHS) exhibit enhanced plasma arginine vasopressin (pAVP) and hypothalamic pituitary adrenal (HPA) axis responses to stress that appear attributable to anterior hippocampal dysfunction. Neuroanatomic and electrophysiologic studies indicate oxytocin activity in PHS patients should also be affected. Furthermore, oxytocin normally diminishes HPA responses to stress and facilitates cognitive and behavioral functions impaired in schizophrenia, suggesting that diminished oxytocin activity could contribute to this subsets' neuropsychiatric disorder. In the present study, we measured plasma oxytocin levels at intervals before and after stress induction in six polydipsic hyponatremic (PHS), four polydipsic normonatremic (PNS), five nonpolydipsic normonatremic schizophrenic (NNS) patients and seven healthy controls. Most of these subjects also completed studies measuring their medial temporal lobe volumes, their hippocampal-mediated HPA feedback and their ability to discriminate different facial emotions (an oxytocin-sensitive measure which is markedly impaired in schizophrenia). Results demonstrated that 1) plasma oxytocin levels were lower ( p = .006) in hyponatremic patients relative to the other three groups, whose levels were similar and did not change. Oxytocin levels across all subjects were 2) inversely correlated with anterior hippocampal ( p = .004) (but not posterior hippocampal or amygdala volumes), and 3) directly correlated with the integrity of hippocampal-mediated HPA feedback ( p = .039). Finally, 4) oxytocin levels predicted schizophrenic patients' ability to correctly identify facial emotions ( p = .004). These preliminary data provide further evidence that neuroendocrine dysfunction in PHS reflects anterior hippocampal pathology and contributes to a characteristic neuropsychiatric syndrome.

Spatial cognition and the human navigation network in AD and MCI

The mechanisms underlying navigation impairments in Alzheimer disease (AD) are unknown. We characterized navigation in AD and mild cognitive impairment (MCI) to test the hypothesis that navigation disability reflects selective impairments in spatial cognition and relates to atrophy of specific brain regions. We compared 13 mild AD and 21 MCI patients with 24 controls on a route-learning task that engaged various spatial processes. Using structural MRI and optimized voxel-based morphometry, we also investigated the neural correlates of spatial abilities in a subset of subjects (10 AD, 12 MCI, 21 controls). AD and MCI patients recognized landmarks as effectively as controls, but could not find their locations on maps or recall the order in which they were encountered. Half of AD and one-quarter of MCI patients got lost on the route, compared with less than 10% of controls. Regardless of diagnosis, patients who got lost had lower right posterior hippocampal and parietal volumes than patients and controls who did not get lost. The ability to identify locations on a map correlated with right posterior hippocampal and parietal volumes, whereas order memory scores correlated with bilateral inferior frontal volumes. The navigation disability in Alzheimer disease and mild cognitive impairment (MCI) involves a selective impairment of spatial cognition and is associated with atrophy of the right-lateralized navigation network. Extensive spatial impairments in MCI suggest that navigation tests may provide early markers of cognitive and neural damage.

Left posterior hippocampal density reduction using VBM and stereological MRI procedures in schizophrenia

Structural deficits in the hippocampus have been implicated in the pathophysiology of schizophrenia. However the role played by structural impairments in the hippocampus in the memory deficits of schizophrenic patients remains unclear. Magnetic resonance imaging was used in this study to investigate left, right, anterior and posterior hippocampal volume and density in 28 schizophrenic patients and 33 normal controls. Voxel-based morphometry analysis showed that schizophrenics had significantly lower density in the right and posterior hippocampus than controls. MRI stereological analysis revealed significant differences in left posterior hippocampus than controls. MRI stereological analysis revealed significant differences in anterior and posterior on both sides, with the left posterior region predominating. Schizophrenics showed significant impairments in verbal learning and long term retention ( P < 0.001). The correlation analyses between hippocampal density and memory variables yielded a significant correlation between forgetting and density of the anterior hippocampus. These findings support the hypothesis of a regional atrophy within the hippocampus in schizophrenic patients.

Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients

Diminished hippocampal volume occurs in the anterior segment of some schizophrenic patients, and in the posterior segment in others. The significance of hippocampal pathology in general and these segmental differences in specific is not known. Several lines of evidence suggest anterior hippocampal pathology underlies the life-threatening hyponatremia seen in a subgroup of patients with schizophrenia; therefore our goal was to determine if this region was preferentially diminished in hyponatremic patients. We studied seven polydipsic hyponatremic, ten polydipsic normonatremic, and nine nonpolydipsic normonatremic schizophrenic inpatients, as well as 12 healthy controls. All underwent structural scanning on a high resolution (3.0 T) magnetic resonance imaging (MRI) scanner. Hippocampal formation, amygdala, and third ventricle volumes were manually traced in each subject. The hippocampus was divided at the posterior extent of the uncus, and all structural volumes were corrected for whole brain volume and other significant recognized factors (i.e., age, gender, height, parental education). Despite being overhydrated, anterior hippocampal formation volume was diminished in those with polydipsia and hyponatremia relative to each of the other three groups. Third ventricle volume was larger in this group than in healthy controls but similar to the two patient groups. Posterior hippocampal and amygdala volumes did not differ between groups. Other potential confounds (e.g., water imbalance) either had no effect or accentuated these differences. We conclude the anterior hippocampal formation is smaller in hyponatremic schizophrenic patients, thereby linking an important and objective clinical feature of schizophrenia to a neural pathway that can be investigated in animal models. The findings strengthen the hypothesis that anterior hippocampal formation pathology disrupts functional connectivity with other limbic structures in schizophrenia.

Intrapair Differences in Hippocampal Volume in Monozygotic Twins Discordant for the Risk for Anxiety and Depression

Current biological psychiatric models assume that genetic and environmental risk factors for anxiety and depression act on the same brain structures. To test this assumption, we assessed brain anatomy by using optimized voxel-based morphometry on magnetic resonance images obtained in monozygotic twin pairs who were discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs who were concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. We observed volume reductions in the temporal lobe, most notably in the left posterior hippocampal region in subjects at high risk for anxiety and depression, but exclusively in the intrapair comparison of discordant monozygotic twins. Because monozygotic twins are genetically identical, any discordance in their risk for anxiety and depression and hippocampal volume must arise from differential exposure to environmental influences. A group comparison between pairs concordant for low or high risk, which is more likely to reflect differences in genetic vulnerability, did not show reduced temporal-lobe and posterior hippocampal volumes in the pairs at high risk for anxiety and depression. This pattern of results suggests that damage to temporal-lobe structures may be specific to an environmentally driven etiology of anxiety and depression.