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The neurobiology and neuroendocrinology of stress. Implications for post-traumatic stress disorder from a basic science perspective.

Stress is a condition of the mind and a factor in the expression of disease that differs among individuals. In post-traumatic stress disorder (PTSD), traumatic events can create a long-lasting state of physiologic reactivity that amplifies and exacerbates the effects of daily life events. The elevated activities of physiologic systems lead to wear and tear, called "allostatic load." It reflects not only the impact of life experiences but also of genes, individual life-style habits (e.g., diet, exercise, and substance abuse), and developmental experiences that set life-long patterns of behavior and physiologic reactivity. Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation, but in the long run allostatic load causes changes in the body that lead to disease.

Aging↗

Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET).

BACKGROUND: We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM-III-R anxiety disorders. METHOD: Fifteen patients with obsessive -compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET. RESULTS: MANOVA revealed significant rCBF differences between diagnostic groups (F = 4.4; d.f. = 3, 57; P = 0.007) and between cerebral regions (F = 6.4; d.f. = 1, 57; P = 0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r = 0.24, n = 46, P = 0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r = -0.24, n = 46, P = 0.05) and right caudate rCBF (r = -0.31, n = 46, P = 0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r = -0.49, n = 16, P = 0.03) and with right caudate rCBF (r = -0.7, n = 16, P = 0.001). CONCLUSIONS: Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.

Adult↗

Errors in self-report of post-traumatic stress disorder after severe traumatic brain injury.

Assessing PTSD by questionnaire can lead to false positive diagnosis after severe traumatic brain injury. Sumpter and McMillan, reported quantitative data on 34 people with severe TBI; 59% were PTSD 'cases' by questionnaire assessment, but only 3% using a structured interview. The present paper describes ways in which these individuals made errors on questionnaires. Some did not follow questionnaire instructions because of inattention and concrete thinking or instead reported effects of brain injury. Symptom overlap between TBI and PTSD, including insomnia, irritability and impaired concentration can cause errors. Brain injury can also provoke curiosity about loss of memory (during coma, retrograde and post-traumatic amnesia), decreased participation, social withdrawal and difficulty adjusting to injury that may be mistaken for fear-associated PTSD symptoms. Assessment of PTSD by questionnaire can lead to erroneous conclusions and factors related to brain injury must be carefully considered when investigating PTSD.

Adult↗

Assessment of a new self-rating scale for post-traumatic stress disorder.

BACKGROUND: In post-traumatic stress disorder (PTSD) there is a need for self-rating scales that are sensitive to treatment effects and have been tested in a broad range of trauma survivors. Separate measures of frequency and severity may also provide an advantage. METHODS: Three hundred and fifty-three men and women completed the Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. These subjects comprised war veterans, survivors of rape or hurricane and a mixed trauma group participating in a clinical trial. Other scales were included as validity checks as follows: Global ratings, SCL-90-R, Eysenck Scale, Impact of Event Scale and Structured Clinical Interview for DSM-III-R. RESULTS: The scale demonstrated good test-retest reliability (r = 0.86), internal consistency (r = 0.99). One main factor emerged for severity and a smaller one for intrusion. In PTSD diagnosed subjects, and the factor structure more closely resembled the traditional grouping of symptoms. Concurrent validity was obtained against the SCID, with a diagnostic accuracy of 83% at a DTS score of 40. Good convergent and divergent validity was obtained. The DTS showed predictive validity against response to treatment, as well as being sensitive to treatment effects. CONCLUSIONS: The DTS showed good reliability and validity, and offers promised as a scale which is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD.

Adult↗

A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder.

Eighteen chronic post-traumatic stress disorder (PTSD+) combat veterans were administered nalmefene, a non-FDA approved oral opiate antagonist, based on the hypothesis that emotional numbing is an opiate-mediated phenomenon. Eight veterans showed a favorable response with a marked decrease of emotional numbing and other symptoms of PTSD, including startle response, nightmares, flashbacks, intrusive thoughts, rage and vulnerability. Veterans who responded favorably to the drug demonstrated a waxing and a waning of positive and negative PTSD symptoms with a general improvement in all these symptoms at higher nalmefene dosages. Case descriptions highlight some of the many changes veterans experienced on nalmefene dosage increases.

Adult↗

The prevalence of temporomandibular disorders in war veterans with post-traumatic stress disorder.

The purposes of this study were to assess the prevalence of temporomandibular disorders in Croatian war veterans suffering from post-traumatic stress disorder (PTSD) and to analyze the impact of the disease on mandibular function. One hundred eighty-two male subjects participated in the study. The examined group consisted of 94 subjects who had taken part in the war in Croatia and for whom PTSD had previously been diagnosed. Patients were compared with an age- and gender-matched group of subjects who had not taken part in the war and for whom PTSD was excluded by means of a psychiatric examination. The study used a clinical examination and standard questionnaire. Statistically significant differences were found in almost all measured parameters. With regard to restricted movements, overbite, and overjet, the differences obtained did not have clinical significance. The most significant differences were found in the parameters of pain. Headache was experienced by 63.83% of the subjects with PTSD, facial pain by 12.77%, and pain in the region of the jaw by 10.64%. Headache was the most intense pain, with an average intensity of 4.92 on a scale of 0 to 10. Pain on loading, temporomandibular joint clicking, and intrameatal tenderness were more prevalent in the PTSD group than in the healthy control group. The study supports the concept that PTSD patients are at increased risk for the development of temporomandibular disorder symptoms.

Adult↗

General practitioners' knowledge of post-traumatic stress disorder: a controlled study.

BACKGROUND: Post-traumatic stress disorder (PTSD) is common, is associated with substantial morbidity, and is often not recognised in primary care. AIM: To explore whether general practitioners (GPs) have significant gaps in their knowledge of PTSD. DESIGN OF STUDY: A controlled study. SETTING: Primary care in two Scottish regions. METHOD: A validated postal questionnaire consisting of clinical vignettes for PTSD, acute stress reaction, and depression was used to gather the data. The primary outcome measures were the proportion describing 'best practice' management of PTSD and the comparison of this with the control condition, the proportion describing 'best practice' management of depression. The secondary outcome measures were comparisons of PTSD and depression by recognition, drug treatment, and referral. RESULTS: Two-thirds (67.5%) of GPs included PTSD in their differential diagnosis for the PTSD vignette, and 86.8% made a referral to secondary care for the PTSD case. A minority of GPs (42.9%) and only 54.1% of a comparison group of psychiatrists specified the drug treatment of choice for PTSD, a selective serotonin reuptake inhibitor. Only 28.3% of GPs had the knowledge to recognise PTSD and prescribe appropriately, compared with 89.8% for depression (P <0.001). Only 10.2% of GPs described best practice for PTSD, compared with 47.7% for depression (P <0.001). CONCLUSION: Lack of knowledge is among the reasons for less than ideal recognition and management of PTSD in primary care. Further research should aim to explore the implementation of PTSD guidelines in primary care.

Antidepressive Agents↗

Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women.

Post-traumatic stress disorder is a common, chronic, and often disabling mental illness. Selective serotonin reuptake inhibitors are the usual first-line treatment for post-traumatic stress disorder, but many patients fail to respond adequately. Thus, other treatment options, including the atypical antipsychotics such as risperidone, need to be tested. Women between the ages of 19 and 64 years with post-traumatic stress disorder were enrolled. Symptom severity was rated at baseline using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8, Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinician Administered Post-traumatic Stress Disorder Scale. After washout from other psychotropic medications, 20 participants were randomized to either risperidone or placebo. Total score on the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 served as the primary outcome measure. Repeated-measures analysis of variance was followed by Newman-Keuls tests. A significant main effect exists for visits using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 raw score. For the treatment group, the difference between baseline Treatment Outcomes Post-traumatic Stress Disorder Scale-8 scores and treatment visit scores was significant beginning at visit 6 and continued through visit 11. No significant difference observed between baseline and any treatment visit for the placebo group. The Clinician Administered Post-traumatic Stress Disorder Scale, Hamilton Rating Scale for Anxiety, and Hamilton Rating Scale for Depression data revealed a similar pattern. In this small pilot study, risperidone monotherapy was more effective than placebo in the treatment of post-traumatic stress disorder.

Adult↗

Role of endocrine and inflammatory alterations in comorbid somatic diseases of post-traumatic stress disorder.

Since its first description in the Diagnostic and Statistical Manual for Mental Disorders, post-traumatic stress disorder (PTSD) has been characterized as a disorder of altered affective functioning which causes tremendous distress. In addition, it has been recognized that PTSD is not only accompanied by ''poor health'' but also by a number of specific and non-specific ''somatic'' pathologies, such as cardiovascular, autoimmune and physical complaints/chronic pain. It has been hypothesized that alterations of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) and the immune system may mediate or facilitate these somatic conditions. The aims of this review are to summarize studies that report altered somatic functioning in PTSD and to review how endocrine and immune function differentially affect PTSD-related somatic malfunction. It is hypothesized that alterations of HPA axis and SAM system permit disinhibition of inflammatory mechanisms, which in turn foster the development of somatic diseases as well as self-reported physical complaints.

Adult↗

Screening for trauma in children and adolescents: the validity of the Traumatic Stress Disorder Scale of the screen for child anxiety related emotional disorders.

Examined the validity of the Traumatic Stress Disorder scale of the Screen for Child Anxiety Related Emotional Disorders (SCARED), a recently developed self-report questionnaire measuring Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) defined anxiety disorders symptoms in children. A large sample of normal schoolchildren (N = 996) ages 7 to 19 years completed the SCARED. Children who scored high on the SCARED Traumatic Stress Disorder scale (i.e., trauma group; n = 43) and children who scored low on this scale (i.e., control group; n = 43) were then interviewed about their most aversive life event. In addition, children completed self-report questionnaires of traumatic experiences and posttraumatic stress disorder (PTSD) symptomatology. Results showed that children in the trauma group more frequently reported life events that independent judges considered to be 'potentially traumatic' than did control children. Furthermore, children in the trauma group reported having experienced more traumatic incidents and had higher scores on PTSD-related questionnaires compared with control children. Moreover, trauma group children more frequently fulfilled DSM-IV criteria for PTSD than did control children. The results of this study support the validity of the Traumatic Stress Disorder scale of the SCARED.

Adolescent↗

Psychometric detection of fabricated symptoms of combat-related post-traumatic stress disorder: a systematic replication.

Vietnam veterans with post-traumatic stress disorder (n = 11) and two other groups of Vietnam veterans (n = 24) instructed to fabricate symptoms of post-traumatic stress disorder completed the MMPI. A discriminant function analysis that used scale F and the post-traumatic stress disorder subscale correctly classified 91% of the subjects. This systematic replication supports the utility of the MMPI as a component in evaluating the validity of self-reported symptoms of post-traumatic stress disorder in Vietnam veterans.

Adult↗

[Many psychiatric disorders in Afghan refugees with residential status in Drenthe, especially depressive disorder and post-traumatic stress disorder].

OBJECTIVE: To assess the prevalence of psychiatric disorders and help-seeking behaviour of Afghan refugees with a residence status in the province of Drenthe, the Netherlands. DESIGN: Cross-sectional prevalence study. METHOD: By means of a modified multiflex snowball sampling with 3 primary informants, 55 Afghan households in 16 towns and villages in Drenthe were selected. After informed consent had been obtained, 51 adults completed a sociodemographic questionnaire and a culturally validated shortened 'Composite international diagnostic interview' (CIDI), DSM-IV version. Help-seeking behaviour was recorded. RESULTS: Half of the sample had resided in the Netherlands for at least 3 years. There was a high level of education, an unemployment level of 88% and moderate to poor language skills in 92% of the respondents. The prevalence of psychiatric disorders was 65% (95% CI: 52-78); depressive disorder occurred in 57% and posttraumatic stress disorder in 35%. Psychopathological findings were related to poor language skills, a lower level of education and unemployment. A total of 56% received treatment from a general practitioner and 4% were under psychiatric treatment. CONCLUSIONS: The prevalence of psychiatric disorders among adult Afghan refugees in Drenthe with a residence status was considerably higher than among the general population in the Netherlands.

Adult↗

Post-traumatic stress disorder.

The management of post-traumatic stress disorder depends on the nature of the stress, the personality of the victim, and the clinical orientation of the therapist. Traumatic situations may be experienced by individuals or by groups, and may be isolated incidents (such as unexpected civil disasters) or continuing occupational hazards, such as are experienced by soldiers, firemen or police. The first concern of therapists, whatever their methods of treatment, is an understanding of the nature of the trauma, and of the inherent differences in each type. This paper seeks to identify such differences. Some general therapeutic principles are then suggested.

Guilt↗

Pharmacotherapy of post-traumatic stress disorder: a family practitioners guide to management of the disease.

Post-traumatic stress disorder is a difficult to treat, yet common disorder, which is associated with significant morbidity, mortality and societal burden. Comprehensive management of post-traumatic stress disorder must include both psychotherapeutic and pharmacologic components. The current evidence-based pharmacologic management approaches to post-traumatic stress disorder, suggests that first-line treatments for monotherapy are the selective serotonin reuptake inhibitors, sertraline, paroxetine and fluoxetine. Other potential options include other monotherapies including venlafaxine, mirtazapine, tricyclic antidepressants, monoamine oxidase inhibitors, as well as adjunctive usage of atypical antipsychotics, lamotrigine, trazadone and a number of adrenergic agents. A trial of therapy should be at least 8 weeks and continue for at the very least 12 months, but is likely to be much longer. In light of the risks of untreated post-traumatic stress disorder (e.g., suicide and impaired psychosocial functioning), therapy may need to be continued for 2 years or more. Pharmacologic therapy instituted at the time of acute psychologic trauma shows promise for the prevention of post-traumatic stress disorder in the future and warrants further study.

Anticonvulsants↗

[Post-traumatic stress disorder in an anxiety disorder unit and in a victims support association].

The post-traumatic stress disorder (PTSD) represents an original and frequent pathological entity concerning people confronted with one or more significant traumatic events. We present here a comparative study concerning subjects who present a post-traumatic stress disorder received in an anxiety disorder unit (ADU) or in a victims support association (VSA). One hundred and twenty seven people have been included in the study, according to DSMIV for PTSD, during three years. Fifty-seven came from a victim support association, 54 came from an anxiety disorder unit and 16 were common to both structures. The PCL-S (PTSD Checklist Scale) was used to rate the intensity of the PTSD. Age, sex, marital statute, type of traumatism, comorbidity and previous traumatisms were compared. PCLS scores were equivalent in the two settings. More women, younger subjects and more aggression were received in the victim support association. In the anxiety disorder unit more psychiatric comorbidity and more frequent antecedents of traumatism were seen. In the whole sample, two thirds of the people lived alone. Our results show that a victim support association receives people suffering from a definite post-traumatic stress disorder as intense on the PCL-S as in an anxiety disorder unit. More work has to be done on support association in the community, as they are confronted with significant PTSD problems.

Adolescent↗

[Post-traumatic stress disorder with psychotic features].

Post-traumatic stress disorder (PTSD) is often accompanied by psychiatric comorbidity, usually depressive and anxiety disorders. Comorbidity with psychosis has seldom been described. We present 6 case-studies of Israeli military veterans with PTSD and psychosis (all men aged 28-43). All developed PTSD shortly after a period of months or even years, sometimes following trauma-related triggering. Psychotic symptoms such as delusions or auditory hallucinations usually had paranoid or depressive features related in content to the traumatic experience. The combined course and interaction between PTSD and psychotic disorder is discussed, as well as the diagnosis of PTSD with psychotic features.

Adult↗

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links.

OBJECTIVE: To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. METHODS: We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status-a marker of neurodegeneration-in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). RESULTS: Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). INTERPRETATION: Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.

Journal Article↗

Post-traumatic stress disorder. A brief overview.

BACKGROUND: Post-traumatic stress disorder (PTSD) is an anxiety disorder which occurs following exposure to a traumatic, potentially life threatening event. It is frequently comorbid with other anxiety and mood disorders, substance misuse and physical symptoms that may cloud its presentation. In itself, PTSD is a frequently chronic disabling condition associated with a marked impact on social, occupational and family functioning that also carries an increased risk of suicide. Early intervention once the disorder is present, represents the most effective chance of reducing disability. Appropriate diagnosis and referral are among the key skills required by the general practitioner to deal with this condition. OBJECTIVE: This article aims to provide an overview of PTSD for GPs including clinical features, epidemiological aspects, approach to assessment and treatment, and specialist resources available. DISCUSSION: Recent world events including terrorist attacks, wars in Afghanistan and Iraq, and Middle East turmoil have raised community awareness of the impact of trauma. General practitioners are in a unique position to be involved in the early diagnosis and treatment of PTSD, which has been shown to improve outcome.

Adult↗