Hippocampal and amygdalar volumes in dissociative identity disorder

OBJECTIVE: Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. METHOD: The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. RESULTS: Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. CONCLUSIONS: The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.     

A meta-analysis of structural brain abnormalities in PTSD

This series of meta-analyses examined structural abnormalities of the hippocampus and other brain regions in persons with PTSD compared to trauma-exposed and non-exposed control groups. The findings were significantly smaller hippocampal volumes in persons with PTSD compared to controls with and without trauma exposure, but group differences were moderated by MRI methodology, PTSD severity, medication, age and gender. Trauma-exposed persons without PTSD also showed significantly smaller bilateral hippocampal compared to non-exposed controls. Meta-analyses also found significantly smaller left amygdala volumes in adults with PTSD compared to both healthy and trauma-exposed controls, and significantly smaller anterior cingulate cortex compared to trauma-exposed controls. Pediatric samples with PTSD exhibited significantly smaller corpus callosum and frontal lobe volumes compared to controls, but there were no group differences in hippocampal volume. The overall findings suggested a dimensional, developmental psychopathology systems model in which: (1) hippocampal volumetric differences covary with PTSD severity; (2) hippocampal volumetric differences do not become apparent until adulthood; and (3) PTSD is associated with abnormalities in multiple frontal-limbic system structures.     

Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study.

BACKGROUND: Previous investigations suggest that maltreated children evidence alterations of chemical mediators of stress and adverse brain development. Previous anatomical magnetic resonance imaging (MRI) brain studies have not controlled for socioeconomic status. METHODS: In this study, 28 psychotropic na?ve children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) and 66 sociodemographically similar healthy control subjects underwent comprehensive clinical assessments and anatomical MRI brain scans. RESULTS: Compared with control subjects, subjects with PTSD had smaller intracranial, cerebral, and prefrontal cortex, prefrontal cortical white matter, and right temporal lobe volumes and areas of the corpus callosum and its subregions (2, 4, 5, 6, and 7), and larger frontal lobe cerebrospinal fluid (CSF) volumes than control subjects. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller in subjects with PTSD, whereas right, left, and total lateral ventricles and frontal lobe CSF were proportionally larger than in control subjects, after adjustment for cerebral volume. Brain volumes positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Significant gender x group effect demonstrated greater lateral ventricular volume increases in maltreated male subjects with PTSD than maltreated female subjects with PTSD. No hippocampal differences were seen. CONCLUSIONS: These data provide further evidence to suggest that maltreatment-related PTSD is associated with adverse brain development. These data also suggest that male children may be more vulnerable to these effects.     

Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder

Borderline personality disorder (BPD) is a common disorder associated with emotional dysregulation and other symptoms that have been hypothesized to be related to dysfunction of limbic brain areas including hippocampus and amygdala. The purpose of this study was to measure hippocampal and amygdala volumes in BPD. Hippocampal and amygdala volumes were measured with magnetic resonance imaging (MRI) in 10 patients with BPD and 23 control subjects. Patients with BPD had a 21.9% smaller mean amygdala volume and a 13.1% smaller hippocampal volume, compared to controls. These findings are consistent with the hypothesis that alterations in the hippocampus and amygdala are associated with BPD.     

Smaller hippocampal volume in Dutch police officers with posttraumatic stress disorder.

BACKGROUND: Previous magnetic resonance imaging studies of posttraumatic stress disorder (PTSD) have reported smaller hippocampal volume, especially in war and sexual abuse victims. Our aim was to assess hippocampal volume in traumatized police officers with and without PTSD in the absence of alcohol abuse and moderate to severe major depression. METHODS: In a case-matched control study, 14 police officers with current PTSD and 14 traumatized police officers without lifetime PTSD were examined using magnetic resonance imaging. Three temporal lobe areas were manually segmented: hippocampus, amygdala, and parahippocampal gyrus. Volumetric analysis was used to measure gray matter, white matter, and cerebrospinal fluid. RESULTS: After controlling for total brain volume, the hippocampal volume in the PTSD group was significantly smaller in comparison with the traumatized control group (total 10.6%; left 12.6%). Volumes of amygdala, parahippocampal gyrus, gray matter, white matter, and cerebrospinal fluid were not significantly altered. A significant negative correlation was found between reexperiencing symptoms and hippocampal volume in the PTSD group. CONCLUSIONS: We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of police officers, excluding comorbidity as a confounder. The finding of smaller hippocampal volume was specific to PTSD.     

Hippocampal volume reduction in major depression

OBJECTIVE: Elevated levels of glucocorticoids in depression have been hypothesized to be associated with damage to the hippocampus, a brain area involved in learning and memory. The purpose of this study was to measure hippocampal volume in patients with depression. METHOD: Magnetic resonance imaging was used to measure the volume of the hippocampus in 16 patients with major depression in remission and 16 case-matched nondepressed comparison subjects. RESULTS: Patients with depression had a statistically significant 19% smaller left hippocampal volume than comparison subjects, without smaller volumes of comparison regions (amygdala, caudate, frontal lobe, and temporal lobe) or whole brain volume. The findings were significant after brain size, alcohol exposure, age, and education were controlled for. CONCLUSIONS: These findings are consistent with smaller left hippocampal volume in depression.     

Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up

BACKGROUND: Although the hippocampus has been found to be smaller in patients with depression, prospective longitudinal in vivo studies are necessary to investigate whether depression can result in a further diminution of hippocampal volumes or whether a smaller hippocampal volume predisposes an individual to the development of depression. METHOD: Thirty patients with DSM-IV major depressive disorder as well as 30 healthy control subjects matched for age, gender, and handedness were examined at admission to the hospital and 1 year later using a documentation of the medical history and high-resolution magnetic resonance imaging (MRI) for the presence of depression and to determine changes in hippocampal as well as amygdala volumes. Patients were enrolled from March 2000 to August 2002. RESULTS: No significant hippocampal and amygdala volume changes were observed in patients or controls between baseline and 1-year follow-up investigations. However, the subgroup of patients who were nonremitted at the time of the follow-up investigation showed significantly reduced left and right hippocampal volumes at both baseline and the 1-year follow-up compared with remitted patients. Moreover, the right hippocampal volumes of nonremitted patients were significantly smaller compared with matched healthy controls. CONCLUSION: These results do not support the hypothesis that hippocampal volumes diminish during the 1-year follow-up period. However, smaller hippocampal volumes may be related to a poor clinical outcome after 1 year.     

Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression

CONTEXT: Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity, which is believed to be altered in patients with major depression. OBJECTIVE: To examine the effect of the BDNF Val66Met polymorphism on hippocampal and amygdala volumes in patients with major depression and in healthy control subjects. DESIGN: Cross-sectional comparison between patients and controls. SETTING: Inpatients with major depression from the Department of Psychiatry and Psychotherapy and healthy controls from the community were recruited. PARTICIPANTS: The study population of 120 subjects included 60 patients with major depression and 60 healthy controls. MAIN OUTCOME MEASURES: Using a combined strategy, hippocampal and amygdala volumes were estimated on high-resolution magnetic resonance images, and genotyping was performed for the BDNF Val66Met polymorphism. RESULTS: Patients had significantly smaller hippocampal volumes compared with controls (P = .02). Significantly smaller hippocampal volumes were observed for patients and for controls carrying the Met-BDNF allele compared with subjects homozygous for the Val-BDNF allele (P = .006). With respect to amygdala volumes, no significant differences between patients and controls and no significant main effects for the BDNF Val66Met polymorphism were observed. CONCLUSIONS: These genotype-related alterations suggest that Met-BDNF allele carriers might be at risk to develop smaller hippocampal volumes and may be susceptible to major depression. This study supports findings from animal studies that the hippocampus is involved in brain development and plasticity.     

Hippocampal volume in adult burn patients with and without posttraumatic stress disorder

OBJECTIVE: Increasing evidence suggests that posttraumatic stress disorder (PTSD) is associated with small hippocampal size. The authors compared trauma-exposed subjects with PTSD and trauma-exposed subjects without PTSD to clarify whether small hippocampal size is related to PTSD or to mere trauma exposure. METHOD: Three-dimensional structural magnetic resonance imaging was used to assess hippocampal volumes in 30 men who had recently been exposed to a severe burn trauma and 15 matched healthy comparison subjects. RESULTS: Relative to the comparison subjects, the trauma-exposed subjects with PTSD (N=15) as well as the trauma-exposed subjects without PTSD (N=15) had significantly smaller volumes of the right hippocampus (subjects with PTSD: -12%; subjects without PTSD: -13%). Larger total areas of burned body surface were significantly related to smaller left hippocampal volumes. Use of analgesic/sedative treatment with the N-methyl-d-aspartic acid (NMDA) antagonist ketamine was significantly related to larger right hippocampal volumes and to stronger PTSD symptoms. CONCLUSIONS: PTSD is not a necessary condition for small hippocampal size in trauma-exposed individuals. Rather, the results provide evidence that smaller hippocampal size in trauma-exposed individuals is a result of traumatic stress. The posttraumatic application of NMDA antagonists may protect against hippocampal damage induced by traumatic stressors but increases the patient's risk of developing PTSD symptoms.     

Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis

Little work has directly examined the course of hippocampal volume in children and adults with childhood maltreatment-related posttraumatic stress disorder (PTSD). Data from adults suggest that hippocampal volume deficits are associated with PTSD, whereas findings from children with PTSD generally show no hippocampal volume deficits in PTSD. Additionally, the role of the amygdala in emotional response makes it a possible region for investigation in children and adults with childhood maltreatment-related PTSD. The objectives of this study were 2-fold: (1) to meta-analytically determine whether hippocampal and amygdala volumes in children and adults with PTSD from childhood maltreatment differ from those in healthy controls, and (2) to use cross-sectional findings performed with meta-analyses as a proxy for longitudinal studies to estimate the course of hippocampal and amygdala volumes in child and adult subjects with PTSD from childhood maltreatment. Using electronic databases, we identified articles containing hippocampal and amygdala data for children with PTSD and adults with PTSD from childhood maltreatment. Data were extracted and effect sizes were calculated using Comprehensive Meta-Analysis Version 2.0. Reduced bilateral hippocampal volume was found in adults with childhood maltreatment-related PTSD compared with healthy controls, but this deficit was not seen in children with maltreatment-related PTSD, suggesting hippocampal volume deficits from childhood maltreatment may not be apparent until adulthood. Greater left than right hippocampal volume was found in the adult healthy control group but not in the PTSD group. Amygdala volume in children with maltreatment-related PTSD did not differ from that in healthy controls. Hippocampal volume is normal in children with maltreatment-related PTSD but not in adults with PTSD from childhood maltreatment, suggesting an initially volumetrically normal hippocampus with subsequent abnormal volumetric development occurring after trauma exposure. However, longitudinal studies are needed to support these preliminary findings.     

Magnetic resonance imaging volumes of the hippocampus in drug-naïve patients with post-traumatic stress disorder without comorbidity conditions

Most brain imaging studies have showed smaller hippocampal volume in adults with chronic PTSD; however, some other studies have not replicated this finding. Most of these investigations included subjects with other psychiatric comorbidities, such as major depression or alcohol abuse.

The prevalence of psychiatric comorbidities in PTSD is generally high and this makes it difficult, if not impossible, to disentangle the contribution of other disorders to hippocampal volume.

Therefore, the main goal of the current study is to compare hippocampal volumes of healthy subjects and drug-naïve patients with PTSD caused by different types of mixed civilian traumas (i.e. car accident, physical abuse, sudden death of a family member, assault or robbery, natural disaster and traumatic abortion) and without comorbidity conditions.

Magnetic resonance imaging (MRI) was used to measure the hippocampi, total cerebrum, gray matter, white matter and cerebrospinal fluid volumes in 34 patients with single diagnosis of PTSD, and 34 case-matched non-PTSD comparison subjects.

The patients with single diagnosis of PTSD had an 11.8% smaller left hippocampus (p < 0.001) and an 8.7% smaller right hippocampus (p = 0.003) than the healthy controls. The results were controlled for the total brain volume and for gray matter volumes. Subjects with PTSD also displayed lower overall gray matter volume (p = 0.006).

There were no significant correlations between hippocampal volumes and illness duration or severity of PTSD. The findings indicate the presence of smaller hippocampal volumes in drug-naïve patients with single diagnosis of PTSD, compared with healthy subjects.     

Hippocampal size and dementia in stroke patients: the Sydney stroke study

BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.     

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.     

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non‐traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma‐exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head‐body‐tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma‐related than PTSD‐specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD‐specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.     

Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies

Over the last decade a significant number of studies have reported smaller hippocampal volume in individuals with symptoms of post-traumatic stress disorder (PTSD) relative to control groups, and in some cases hemispheric asymmetries in this effect have been noted. However these reported asymmetries have not been in a consistent direction, and other well-controlled studies have failed to observe any hippocampal volume difference. This paper reports a systematic review and meta-analysis of studies in which hippocampal volume was estimated from magnetic resonance images in adult patients with PTSD. After applying a variety of selection criteria intended to minimize potential confounds in pooled effect-size estimates, the meta-analysis included 13 studies of adult patients with PTSD that compared the patients to well-matched control groups, for a total of 215 patients and 325 control subjects. The studies varied with respect to participant age, gender distribution, source of trauma, severity of symptoms, duration of disorder, the nature of the control groups, and the methods employed for volumetric quantification. Despite these differences, pooled effect size calculations across the studies indicated significant volume differences in both hemispheres. On average PTSD patients had a 6.9% smaller left hippocampal volume and a 6.6% smaller right hippocampal volume compared with control subjects. These volume differences were smaller when comparing PTSD patients with control subjects exposed to similar levels of trauma, and larger when comparing PTSD patients to control subjects without significant trauma exposure. Such differences are consistent with the notion that exposure to stressful experiences can lead to hippocampal atrophy, although prospective studies would be necessary to unambiguously establish such a relationship.     

Smaller right hippocampus in war veterans with posttraumatic stress disorder

Chronic stress can putatively cause damage in the human hippocampus, but evidence of damage has not been consistently shown in studies on hippocampal morphology in posttraumatic stress disorder (PTSD). We compared hippocampal volumes in PTSD patients and normal subjects. Using a 3D T1-weighted GRE magnetic resonance imaging sequence, we measured hippocampal volumes in 15 war veterans with combat-related chronic PTSD and 15 case-matched normal controls. Although war veterans, our PTSD subjects were not professional soldiers and were mobilized shortly before they were exposed to a very specific combat-related trauma over a 3-day period. In our study, the period between traumatic exposure and imaging was considerably shorter, on average, 9 years, compared with at least two decades in previous studies on subjects with combat-related PTSD. Moreover, our subjects were free of any comorbidity, treatment or medication. The right hippocampus was significantly smaller in PTSD subjects than in healthy controls. The left hippocampus was also smaller in PTSD subjects than in controls, but the difference was not significant. In all PTSD subjects, the right hippocampus was smaller than the left (on average, 7.88%). Our results show smaller volume of the right hippocampus in PTSD patients than in normal subjects.     

Hippocampal volume, PTSD, and alcoholism in combat veterans

Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted.     

Amygdala and hippocampal volumes and cognition in adult survivors of childhood abuse with dissociative disorders

Objective: Trauma‐exposed individuals with post‐traumatic stress disorder (PTSD) display reduced amygdala and hippocampal size and impaired cognition. However, studies on trauma‐exposed individuals with dissociative amnesia (DA) or dissociative identity disorder (DID) are lacking. Method: Twenty‐three young women who had experienced severe childhood sexual/physical abuse, diagnosed with DA/DID or PTSD, and 25 healthy control subjects were subjected to 3D structural magnetic resonance imaging of amygdala and hippocampus and a clinical and neuropsychological investigation. Results: Compared with controls, trauma‐exposed subjects with PTSD (n = 10) displayed significantly reduced amygdala and hippocampal size and significantly impaired cognition. By contrast, trauma‐exposed subjects with DA or DID (n = 13) displayed normal amygdala and hippocampal size and normal cognition. Conclusion: We report for the first time volumetric results in subjects with DA/DID without PTSD as comorbid diagnosis. Our results indicate preserved amygdala and hippocampal size and preserved cognition in subjects with these disorders.     

Segmented hippocampal volume in children and adolescents with posttraumatic stress disorder.

BACKGROUND: Although many studies of adults with posttraumatic stress disorder (PTSD) have reported smaller hippocampal volume compared with control subjects, comparable studies of children and adolescents have failed to replicate these findings or have noted opposite trends suggesting a larger hippocampus. We therefore performed a secondary analysis combining data from prior studies to examine the hypothesis that hippocampus would be larger in pediatric subjects with PTSD compared with non-maltreated control subjects. We also hypothesized that differences in PTSD subjects would be observed between boys and girls. METHODS: Sixty-one subjects (31 boys, 30 girls) with maltreatment-related PTSD and 122 control subjects matched on age and gender underwent magnetic resonance imaging. RESULTS: As hypothesized, we observed a significantly larger hippocampus controlling for cerebral volume in PTSD subjects compared with control subjects. Segmented hippocampal white-matter volume was greater in PTSD subjects but not gray-matter volume. Hippocampal volume was positively related to age of trauma onset and level of psychopathology, particularly externalizing behavior. No interactions with group were observed for age or gender. CONCLUSIONS: Future longitudinal studies with trauma control subjects and neuropsychological measures are indicated to further elucidate the relationship between hippocampus and behavioral abnormalities in young PTSD subjects.     

Traumatic stress: effects on the brain

Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effects on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD.