Hippocampal atrophy

Activation of the HPA axis appears to play a critical role in mediating hippocampal atrophy 898... 

Sapolsky, R. M. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch. Gen. Psych. 57 925-935,... 

Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW. (1996). Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA. 93(9) 3908-13. 

As a possible consequence of direct neurotoxic effects of sustained hypercortisolism, hippocampal atrophy has now repeatedly been reported for depressed patients (Sheline et ah, 1996 Bremner et al., 2000a). Hippocampal atrophy may be associated with disinhi-bition of CRF secretion and further increases in cortisol secretion, which in turn may further damage the hippocampus. Impaired inhibition of the HPA axis is also evidenced by nonsuppression of cortisol by dexame-thasone and decreased GR numbers in depressed patients both findings parallel those in maternally separated rats. 

Interestingly, while peripheral neuroendocrine function appears normal in patients with panic disorder, decreased basal cortisol concentrations have been reported in most studies in PTSD patients. This relative hypocortisolism occurs in the context of increased feedback inhibition of the HPA axis (see Yehuda, 2000). However, a dissociation between central and adrenocortical (re)activity has been found in animal models of severe early-life stress as well as in abused children and women, suggesting that adrenal dysfunction may, at least in part, contribute to hypocortisolism in PTSD. In the face of hypocortisolism, it seems surprising that hippocampal atrophy is one of the most prominent findings in patients with PTSD, including adult survivors of childhood abuse with PTSD (see Newport and Nemeroff, 2000). While increased glucocorticoid sensitivity of hippocampal cells may play a role in the development of hippocampal atrophy, another potential mechanism may involve toxic effects of markedly increased cortisol responses to everyday stress in patients with PTSD. 

To the best of our knowledge, no studies with child and adolescent depressed cohorts have examined hippocampal volume. The one study that examined hippocampal volume in children and adolescents with PTSD (n = 43), about half of whom met criteria for comorbid MDD, failed to find evidence of hippocampal atrophy (De Beilis et ah, 1999). This finding is not surprising, as most of the children and adolescents in the study had not experienced more than one episode of depression, and hippocampal atrophy was found to be correlated with total lifetime duration of illness in the prior adult studies cited (Sheline et ah, 1996 Brem-ner et ah, 2000). Developmental factors may also account for the discrepant findings in child and adult studies. For example, age-dependent changes in sensitivity to some forms of N-methyl-D-aspartate (NMDA) receptor blockade neurotoxicity in corticolimbic regions have been reported in preclinical studies, with cell death minimal or absent prepuberty and reaching peak in early adulthood (Father et ah, 1995). 

Instead of hippocampal atrophy, the children and adolescents with PTSD were found to have smaller intracranial and cerebral volumes than matched controls increased right, left, and total lateral ventricle volume and decreased volume of the medial and posterior portions of the corpus callosum (CC) (De Beilis et ah, 1999). Consistent with this investigation, in a recent abstract, psychiatric inpatients with a history of mal-... 

Elgh, E., Lindqvist Astot, A., Fagerlund, M., Eriksson, S., Olsson, T., et al. (2006) Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer s disease. Biol Psychiatry 59, 155-161. 

Neuronal dysfunction on FDG-PET/fMRI -High CSF tau/p-tau -Cortical thinning/Hippocampal atrophy on sMRI. 

Dhikav V, Anand KS. 2007. Is hippocampal atrophy a future drug target Med Hypotheses 68 1300-1306. 

Cordoliani-Mackowiak M, Henon H, Pruvo J etal. (2003). Post stroke dementia influence of hippocampal atrophy. Archives of Neurology 60 585-590... 

Sapolsky, R. Glucocorticoids and Hippocampal Atrophy in neuropsychiatric Disorders Archives of General Psychiatry (2002) 57(10) pp. 925-935... 

Steroid-responsive encephalopathies can be considered vasculitic or non-vasculitic. Clinical features are suggestive of Creutzfeldt-Jakob disease (CJD), dementia with Lewy bodies (DLB), and parkinsonism, but pathological examination revealed only AD-related findings without evidence of Lewy bodies or prion disease in most cases. AD is not diagnosed in life due to the atypical clinical features, lack of hippocampal atrophy on brain imaging, and a dramatic symptomatic response to steroids [97], Some cases of new-variant CJD may also be misdiagnosed as AD. 

Lu PH, Thompson PM, Leow A, Lee GJ, Lee A, Yanovsky I et al (2011) Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults A tensor-based morphometry study. J Alzheimers Dis 23 433-442... 

Chiang GC, Insel PS, Tosun D, Schuff N, Truran-Sacrey D, Raptentsetsang ST et al (2010) Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects. Neurology 75 1976-1981... 

With increasing resolution due to higher Tesla images, volumetric studies show hippocampal and cerebellar volume loss of 3% and neocortical volume loss of 1.6% with an interscan interval of 3.5 years (Lemieux et al., 2000 Liu et al., 2001). Hippocampal atrophy, identified with hippocampal volume measurements, correlates well with hippocampal neuron loss, especially in the CAl sub-region. Decreased ipsilateral thalamic volume has also been documented in temporal lobe epilepsy (Dreifuss et al., 2001 Natsume et al., 2003). 

Starkman, M.N., Giordani, B., Gebarski, S.S., Berent, S., Schork, M.A., and Schteingart, D.E. 1999. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing s disease. Biol. Psychiatry 46 1595-1602. 

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