Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: A meta-analysis

Background

Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.

Methods

In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls.

Results

Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls.

Conclusions

Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.     

Hippocampal function in posttraumatic stress disorder

Recent studies have reported memory deficits and reduced hippocampal volumes in posttraumatic stress disorder (PTSD). The goal of the current research was to use functional neuroimaging and a validated explicit memory paradigm to examine hippocampal function in PTSD. We used positron emission tomography (PET) and a word-stem completion task to study regional cerebral blood flow (rCBF) in the hippocampus in 16 firefighters: 8 with PTSD (PTSD group) and 8 without PTSD (Control group). During PET scanning, participants viewed three-letter word stems on a computer screen and completed each stem with a word they had previously encoded either deeply (High Recall condition) or shallowly (Low Recall condition). Relative to the Control group, the PTSD group exhibited significantly smaller rCBF increases in the left hippocampus in the High vs Low Recall comparison. However, this finding reflected relatively elevated rCBF in the Low Recall condition in the PTSD group. Collapsing across High and Low Recall conditions, (1) the PTSD group had higher rCBF in bilateral hippocampus and left amygdala than the Control group, and (2) within the PTSD group, symptom severity was positively associated with rCBF in hippocampus and parahippocampal gyrus. The groups did not significantly differ with regard to accuracy scores on the word-stem completion task. The PTSD group had significantly smaller right (and a trend for smaller left) hippocampal volumes than the Control group. The results suggest an abnormal rCBF response in the hippocampus during explicit recollection of nonemotional material in firefighters with PTSD, and that this abnormal response appears to be driven by relatively elevated hippocampal rCBF in the comparison condition.     

Hippocampal function during associative learning in patients with posttraumatic stress disorder

In the last decade several studies have shown memory deficits in patients with posttraumatic stress disorder (PTSD) which have been associated with a reduced hippocampus volume. However, until now we do not know how or whether these structural abnormalities turn into functional abnormalities. Thus, the primary purpose of the present study was the investigation of the hippocampal function using functional magnet resonance imaging (fMRI).We compared PTSD patients and healthy control participants using an associative learning paradigm consisting of two encoding and one retrieval condition. During fMRI scanning participants had to learn face-profession pairs. Afterwards only faces were presented as cue stimuli for associating the category of the prior learned target profession and the participants had to decide whether this face belonged to a scientific or an artistic profession. Additionally, cognitive functioning, i.e. memory and attention, was examined using neuropsychological standard tests.During encoding PTSD patients showed stronger hippocampal and weaker prefrontal activation compared to healthy control participants. During retrieval the two groups did not differ neither in hippocampus activation nor in accuracy of retrieval. PTSD patients however showed a reduced activation in the left parahippocampal gyrus and other memory-related brain regions. We did not find any significant memory differences between PTSD patients and healthy control participants.The results suggest that PTSD has an effect on memory-related brain function despite intact memory functioning. In particular the hippocampal/parahippocampal regions and the prefrontal cortex show functional alterations during associative learning and memory.     

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.     

Sleep findings in young adult patients with posttraumatic stress disorder.

BACKGROUND: Laboratory sleep studies in posttraumatic stress disorder (PTSD) have not provided consistent evidence of sleep disturbance, despite apparent sleep complaints. Most of these studies have investigated middle-aged chronic PTSD subjects with a high prevalence of comorbidities such as substance dependence and/or personality disorder. METHODS: Ten young adult PTSD patients (aged 23.4 +/- 6.1 years) without comorbidities of substance dependence and/or personality disorder underwent 2-night polysomnographic recordings. These sleep measures were compared with those of normal control subjects and were correlated with PTSD symptoms. RESULTS: Posttraumatic stress disorder patients demonstrated significantly poorer sleep, reduced sleep efficiency caused by increased wake time after sleep onset, and increased awakening from rapid eye movement (REM) sleep (REM interruption). We found significant positive correlations between the severity of trauma-related nightmare complaints and the percentage of REM interruption, as well as wake time after sleep onset. CONCLUSIONS: The results indicate that trauma-related nightmares are an important factor resulting in increased REM interruptions and wake time after sleep onset in PTSD.     

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.     

Hippocampal and amygdalar volumes in breast cancer survivors with posttraumatic stress disorder

Although smaller hippocampi and amygdalae were found in cancer survivors with intrusions, associations between cancer-related posttraumatic stress disorder (PTSD) and these volumes are unknown. The authors performed MRI volumetric analyses of these regions in 15 cancer survivors with PTSD, 15 cancer survivors without PTSD, and 15 healthy comparison subjects. The authors also examined the correlation between PTSD symptom scores of the Impact of Event Scale and these volumes in the PTSD group. These volumes were not significantly different among the groups, but the intrusion score was inversely associated with the hippocampal volume. Results suggest intrusions, not PTSD diagnosis, might be associated with hippocampal volume.     

Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: A meta-analysis

Trauma exposure itself in the absence of posttraumatic stress disorder (PTSD) may be associated with hippocampal volume deficits. We meta-analytically compared hippocampal volumes in PTSD subjects, in trauma-exposed subjects without PTSD, and in trauma-unexposed subjects. Using the words and phrases PTSD, neuroimaging, hippocampus, brain, violence, trauma, abuse, rape, war, combat, accident, and disaster, we searched major computerized databases to obtain candidate studies through 2008 for inclusion. We identified 39 hippocampal volumetric studies in adults with PTSD compared to control groups consisting of either trauma-exposed controls without PTSD or trauma-unexposed controls, or both. We meta-analytically compared left, right, and total hippocampal volumes between 1) PTSD subjects and a trauma-unexposed group, 2) PTSD subjects and a trauma-exposed group without PTSD, and 3) a trauma-unexposed group and a trauma-exposed group without PTSD. Hippocampal volumes were smaller in the PTSD group and trauma-exposed group without PTSD compared to the trauma-unexposed group. Further, the right hippocampus was smaller in the PTSD group compared to the trauma-exposed group without PTSD. Additionally, the right hippocampus was larger than the left in the PTSD and trauma-unexposed groups but not in the trauma-exposed group without PTSD. Hippocampal volume reduction is associated with trauma exposure independent of PTSD diagnosis, albeit additional hippocampal reduction was found in PTSD compared to the trauma-exposed group without PTSD.     

Neuropsychological function in college students with and without posttraumatic stress disorder

Previous research on the neuropsychology of posttraumatic stress disorder (PTSD) has identified several neurocognitive deficits that co-occur with the disorder. However, it remains unclear whether these deficits are due to trauma exposure, PTSD symptomatology or psychiatric/substance abuse comorbidity. We examined trauma exposure, PTSD symptoms and neuropsychological performance in 235 undergraduate students, i.e. a non-clinical sample. The sample comprised 146 subjects with trauma exposure (38 with current PTSD and 108 without lifetime PTSD) and 89 no-trauma comparison (NC) subjects who were administered tests of attention, working memory, psychomotor speed, word generation and executive functioning. Relationships of neuropsychological functioning to measures of psychiatric symptoms and substance abuse were examined. Current PTSD (PTSD+), trauma-exposed without PTSD (PTSD-) and NC subjects did not differ significantly on the vast majority of neuropsychological tests. There were very few significant associations between neuropsychological performance and clinical variables, and those that were statistically significant were small in magnitude. The striking lack of differences in neuropsychological performance between the three groups suggests that college students with trauma exposure, regardless of the presence of PTSD symptoms, may be cognitively resilient. Neuropsychological impairment may not be an invariant feature of PTSD, but when it is present, it may be associated with poorer functional outcomes.     

Absence of hippocampal volume differences in survivors of the Nazi Holocaust with and without posttraumatic stress disorder

It remains unclear whether smaller hippocampal volume is a consistent feature of chronic posttraumatic stress disorder (PTSD) and whether it accounts for the associated memory deficits observed in this illness. Hippocampal volume, comparison regions and memory performance were examined in Holocaust survivors with PTSD (PTSD+: n=14; 5 men, 9 women) and without PTSD (PTSD-: n=13; 6 men, 7 women) and a non-exposed control group of healthy Jewish adults (n=20; 13 men, 7 women). The subjects had medical examinations, high-resolution magnetic resonance imaging, and memory testing. PTSD+ subjects had poorer memory performance than non-exposed subjects and PTSD- subjects, but they did not differ from either group in right or left hippocampal volume when gender and head size were taken into account. Older age and smaller left hippocampal volume were more strongly associated in the PTSD+ group than in the PTSD- groups. Holocaust survivors had larger superior temporal gyral and lateral temporal lobe volumes bilaterally than non-exposed subjects. Smaller hippocampal volume is not invariably associated with chronic PTSD and does not explain the substantial explicit memory impairment observed in Holocaust survivors with this disorder. Larger temporal lobe volumes may be associated with early traumatization and survival or may reflect some other characteristic of Holocaust survivors.     

Nefazodone in patients with treatment-refractory posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic disorder among combat veterans, persisting in as many as 15% of Vietnam veterans for at least 20 years. Treatment response in veterans with combat-related PTSD has been disappointing. Although anxiolytics, anticonvulsants, antipsychotics, and antidepressants have been tried, none has been consistently associated with improvement in all primary symptom domains (i.e., intrusive recollections, avoidance/numbing, and hyperarousal). This open-label study evaluated the use of nefazodone in a group of Vietnam veterans with chronic, treatment-refractory symptoms of PTSD. METHOD: Male outpatients with DSM-IV PTSD who had failed a minimum of 3 previous medication trials were eligible for the study. Nineteen Vietnam combat veterans entered the study and were treated with nefazodone, 100-600 mg/day, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functioning, and adverse events were assessed weekly. RESULTS: Severity of depression lessened, as did PTSD symptoms of intrusive recollections, avoidance, and hyperarousal. Depressive symptom severity as measured by the Beck Depression Inventory decreased by a mean of 30%. Similarly, there was an overall drop in the intensity of PTSD symptoms as measured by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addition, improvements in sleep and sexual functioning were reported. The mean daily dose of nefazodone after 12 weeks was 430 mg (range, 200-600 mg/day). The most frequently reported side effects were headaches (53%), dry mouth (42%), and diarrhea (42%), but side effects tended to be mild and transient. CONCLUSION: In this group of Vietnam veterans with chronic treatment-refractory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone was well tolerated and effective. Larger, controlled studies are warranted.     

Clonidine in Cambodian patients with posttraumatic stress disorder

Some symptoms of posttraumatic stress disorder (PTSD) are related to central nervous system adrenergic hyperarousal. It has been suggested that an adrenergic receptor-blocker could be used to diminish, if not alleviate, the target symptoms of PTSD. Severely traumatized Cambodian refugee patients (N = 68) who suffered from chronic PTSD and major depression improved symptomatically when treated with a combination of clonidine and imipramine. A prospective pilot study of nine patients using this combination of an alpha-2 adrenergic agonist and a tricyclic antidepressant resulted in improved symptoms of depression in six patients, five to the point that DSM-III-R diagnoses were no longer met. The average decrease in the Hamilton Rating Scale for Depression score was 16. PTSD global symptoms improved in six patients but only in two to the point that DSM-III-R diagnoses were not met. There was no further sleep disorder in five and the frequency of nightmares lessened in seven patients. Startle reaction improved only in four patients; avoidance behavior showed little improvement in any of the nine. The imipramine-clonidine combination was well tolerated and presents a promising treatment for severely depressed and traumatized patients, although further studies are needed.     

Predictors of posttraumatic stress disorder after burn injury.

OBJECTIVE: The authors' goal was to examine subjective and objective predictors of posttraumatic stress disorder (PTSD). METHOD: Hospitalized burn patients were assessed 1 week after injury with both objective predictors (percent of burned area and facial disfigurement) and subjective predictors (emotional distress and perceived social support). The patients were then assessed 2, 6, and 12 months later for development of PTSD. RESULTS: Among 51 patients, 18 (35.3%) met PTSD criteria at 2 months. High rates of PTSD were also found at 6 months (N = 16, 40.0% of the 40 available patients) and 12 months (N = 14, 45.2% of the 31 available patients). PTSD was predicted by subjective variables assessed at baseline, but patients with more severe burns were not more likely to develop PTSD. CONCLUSIONS: The DSM-III-R diagnosis of PTSD relies on an objective evaluation of the stressor's severity. The prospective data in this study support those who argue that evaluations of the severity of the stressor might also take into account subjective factors.     

Social integration and inflammation in individuals with and without posttraumatic stress disorder

BackgroundPosttraumatic stress disorder (PTSD) is associated with increased risk for morbidity and mortality, which may be mediated through elevated inflammation. In contrast, social support appears to protect against morbidity and mortality, reduce levels of inflammation, and improve PTSD outcomes.MethodsWe examined relationships among social isolation, perceived social support, and inflammation in Veterans Affairs (VA) patients with and without PTSD. Our sample included 735 (35% PTSD+) participants from the Mind Your Heart Study (mean age = 58 ± 11; 94% male). Social isolation was assessed with the Berkman Syme Social Network Index; perceived social support with the Multidimensional Scale of Perceived Social Support; and PTSD with the Clinician Administered PTSD Scale. Inflammation was indexed by high sensitivity C-reactive protein, white blood cell count, and fibrinogen. Hierarchical linear regression was used to examine associations between social measures and inflammation. PROCESS was used to examine the interactive effects of social relationships and PTSD on inflammation.ResultsSocial isolation, but not low perceived social support, trended towards an association with elevated inflammation in the full sample. However, considering groups with and without PTSD separately, social isolation was significantly associated with all inflammatory markers among individuals without PTSD, but not among those with PTSD.ConclusionsSocial integration is associated with reduced inflammation in individuals without, but not with, PTSD. Socially integrated individuals with PTSD did not have lower levels of inflammatory markers than socially isolated individuals with PTSD.     

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.     

Mineralocorticoid receptor function in patients with posttraumatic stress disorder

OBJECTIVE: The study examined whether enhanced limbic mineralocorticoid receptor activity resulting in negative glucocorticoid feedback could contribute to the diminished basal and stress-induced cortisol output reported in patients with posttraumatic stress disorder (PTSD). METHOD: The effects of acute antimineralocorticoid (spironolactone) versus placebo pretreatment on levels of plasma cortisol at baseline and after stimulations with corticotropin-releasing hormone (CRH) and on adrenocorticotropic hormone (ACTH) level were measured in 12 PTSD patients and 12 healthy comparison subjects. RESULTS: Spironolactone significantly elevated basal cortisol and ACTH concentrations as well as cortisol secretion after CRH stimulation, but no differential effect between PTSD patients and comparison subjects was detected. CONCLUSIONS: The results indicate intact, but not enhanced, mineralocorticoid receptor function in PTSD. The study's experimental conditions did not allow determination of whether other compensatory factors might have masked the putative mineralocorticoid receptor changes.     

Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: relation to risk and resilience factors

OBJECTIVE: To examine whether there are post-traumatic stress disorder (PTSD) related differences in hippocampal volume in middle-aged and elderly veterans and to examine the relationship of neuroendocrine activity, memory performance, and measures of risk and resilience for PTSD to hippocampal volume in this cohort. METHODS: Seventeen veterans with chronic PTSD and 16 veterans without chronic PTSD received an MRI scan followed by neuroendocrine assessment (24-h urinary cortisol excretion and the lysozyme IC(50-DEX), a measure of glucocorticoid receptor (GR) responsiveness), and cognitive testing. RESULTS: Veterans with PTSD did not differ from those without PTSD in hippocampal volume, but they did show significantly lower urinary cortisol levels, and poorer memory performance on the Wechsler Logical Memory test and Digit Span test. Smaller left hippocampal volumes were observed in veterans who developed PTSD in response to their first reported traumatic exposure, compared to veterans who had first experienced a traumatic event to which they did not develop PTSD, prior to experiencing a subsequent event that led to PTSD. In contrast, the two neuroendocrine measures were associated with risk factors related to early trauma exposure. CONCLUSION: Although hippocampal volume was not found to differ between subjects with and without PTSD, smaller hippocampal volumes in PTSD may be associated with specific risk and resilience factors. These may be distinct from vulnerability markers associated with increased responsiveness to glucocorticoids and/or other neuroendocrine measures that have been observed in combat-related PTSD.     

Development of posttraumatic stress disorder in adult bipolar patients with histories of severe childhood abuse

Little is known about the nature and extent of posttraumatic stress disorder (PTSD) in adults with bipolar disorder, particularly in relation to the presence of past childhood or adult forms of abuse, and its impact on course of illness. The authors studied 100 consecutive DSM-IV bipolar patients who were evaluated for childhood physical, sexual and emotional abuse, traumatic events in adulthood, and lifetime PTSD. Adult comorbid PTSD was evident in 24% of subjects and was significantly associated with childhood sexual abuse, adult sexual assault, and adult survival of the suicide, homicide, or accidental death of a close friend or relative. Severe childhood abuse was reported by about half of bipolar patients, but only one-third of abused patients developed PTSD. Risk for PTSD rose in linear fashion to the number of childhood abuse subtypes present. Adult sexual assault was significantly more likely to be associated with PTSD if childhood sexual abuse was present rather than absent. The findings suggest that about one-third of bipolar patients with severe childhood abuse histories, particularly sexual abuse, manifest comorbid adult PTSD. Childhood sexual abuse, as well as severe interpersonal loss, may sensitize individuals who are predisposed to bipolar disorder also to develop eventual PTSD.