Psychiatric heredity and posttraumatic stress disorder: survey study of war veterans

Aim

To explore the prevalence of psychiatric heredity (family history of psychiatric illness, alcohol dependence disorder, and suicidality) and its association with the diagnosis of stress-related disorders in Croatian war veterans established during psychiatric examination.

Methods

The study included 415 war veterans who were psychiatrically assessed and diagnosed by the same psychiatrist during an expert examination conducted for the purposes of compensation seeking. Data were collected by a structured diagnostic procedure.

Results

There was no significant correlation between psychiatric heredity of psychiatric illness, alcohol dependence, or suicidality and diagnosis of posttraumatic stress disorder (PTSD) or PTSD with psychiatric comorbidity. Diagnoses of psychosis or psychosis with comorbidity significantly correlated with psychiatric heredity (φ = 0.111; P = 0.023). There was a statistically significant correlation between maternal psychiatric illness and the patients’ diagnoses of partial PTSD or partial PTSD with comorbidity (φ = 0.104; P = 0.035) and psychosis or psychosis with comorbidity (φ = 0.113; P = 0.022); paternal psychiatric illness and the patients’ diagnoses of psychosis or psychosis with comorbidity (φ = 0.130; P = 0.008), alcohol dependence or alcohol dependence with comorbidity (φ = 0.166; P = 0.001); psychiatric illness in the primary family with the patients’ psychosis or psychosis with comorbidity (φ = 0.115; P = 0.019); alcohol dependence in the primary family with the patients’ personality disorder or personality disorder with comorbidity (φ = 0.099; P = 0.044); and suicidality in the primary family and a diagnosis of personality disorder or personality disorder with comorbidity (φ = 0.128; P = 0.009).

Conclusion

The study confirmed that parental and familial positive history of psychiatric disorders puts the individual at higher risk for developing psychiatric illness or alcohol or drug dependence disorder. Psychiatric heredity might not be necessary for the individual who was exposed to severe combat-related events to develop symptoms of PTSD.There are several risk factors associated with the development of posttraumatic stress disorder (PTSD), such as factors related to cognitive and biological systems and genetic and familial risk (1), environmental and demographic factors (2), and personality and psychiatric anamnesis (3).They are usually grouped into three categories: factors that preceded the exposure to trauma or pre-trauma factors; factors associated with trauma exposure itself; and post-trauma factors that are associated with the recovery environment (2,4).There are many studies which support the hypothesis that pre-trauma factors, such as ongoing life stress, psychiatric history, female sex (3), childhood abuse, low economic status, lack of education, low intelligence, lack of social support (5), belonging to racial and ethnic minority, previous traumatic events, psychiatric heredity, and a history of perceived life threat, influence the development of stress related disorders (6). Many findings suggest that ongoing life stress or prior trauma history sensitizes a person to a new stressor (2,7-9). The same is true for the lack of social support, particularly the loss of support from significant others (2,9-11), as well as from friends and community (12-14). If the community does not have an elaborated plan for providing socioeconomic support to the victims, then the low socioeconomic status can also be an important predictor of a psychological outcome such as PTSD (2,10,15). Unemployment was recognized as a risk factor for developing PTSD in a survey of 374 trauma survivors (16). It is known that PTSD commonly occurs in patients with a previous psychiatric history of mental disorders, such as affective disorders, other anxiety disorders, somatization, substance abuse, or dissociative disorders (17-21). Epidemiological studies showed that pre-existing psychiatric problems are one of the three factors that can predict the development of PTSD (2,22). Pre-existing anxiety disorders, somatoform disorders, and depressive disorders can significantly increase the risk of PTSD (23). Women have a higher vulnerability for PTSD than men if they experienced sexually motivated violence or had pre-existing anxiety disorders (23,24). A number of studies have examined the effects of gender differences on the predisposition for developing PTSD, with the explanation that women generally have higher rates of depression and anxiety disorders (3,25,26). War-zone stressors were described as more important for PTSD in men, whereas post-trauma resilience-recovery factors as more important for women (27).Lower levels of education and poorer cognitive abilities also appear to be risk factors (25). Golier et al (25) reported that low levels of education and low IQ were associated with poorer recall on words memorization tasks. In addition, this study found that the PTSD group with lower Wechsler Adult Intelligence Scale-Revised (WAIS-R) scores had fewer years of education (25). Nevertheless, some experts provided evidence for poorer cognitive ability in PTSD patients as a result or consequence rather than the cause of stress-related symptoms (28-31). Studies of war veterans showed that belonging to racial and ethnic minority could influence higher rates of developing PTSD even after the adjustment for combat exposure (32,33). Many findings suggest that early trauma in childhood, such as physical or sexual abuse or even neglect, can be associated with adult psychopathology and lead to the development of PTSD (2,5,26,34,35). Surveys on animal models confirm the findings of lifelong influences of early experience on stress hormone reactivity (36).Along with the reports on the effects of childhood adversity as a risk factor for the later development of PTSD, there is also evidence for the influence of previous exposure to trauma related events on PTSD (9,26,28). Breslau et al (36) reported that previous trauma experience substantially increased the risk for chronic PTSD.Perceived life threats and coping strategies carry a high risk for developing PTSD (9,26). For instance, Ozer et al (9) reported that dissociation during trauma exposure has high predictive value for later development of PTSD. Along with that, the way in which people process and interpret perceived threats has a great impact on the development or maintenance of PTSD (37,38).Brewin et al (2) reported that individual and family psychiatric history had more uniform predictive effects than other risk factors. Still, this kind of influence has not been examined yet.Keeping in mind the lack of investigation of parental psychiatric heredity on the development of stress-related disorders, the aim of our study was to explore the prevalence and correlation between the heredity of psychiatric illness, alcohol dependence, suicidality, and the established diagnosis of stress-related disorders in Croatian 1991-1995 war veterans.     

Pharmacotherapy of treatment-resistant combat-related posttraumatic stress disorder with psychotic features

Aim

To assess retrospectively the clinical effects of typical (fluphenazine) or atypical (olanzapine, risperidone, quetiapine) antipsychotics in three open clinical trials in male Croatian war veterans with chronic combat-related posttraumatic stress disorder (PTSD) with psychotic features, resistant to previous antidepressant treatment.

Methods

Inpatients with combat-related PTSD were treated for 6 weeks with fluphenazine (n = 27), olanzapine (n = 28) risperidone (n = 26), or quetiapine (n = 53), as a monotherapy. Treatment response was assessed by the reduction in total and subscales scores in the clinical scales measuring PTSD (PTSD interview and Clinician-administered PTSD Scale) and psychotic symptoms (Positive and Negative Syndrome Scale).

Results

After 6 weeks of treatment, monotherapy with fluphenazine, olanzapine, risperidone, or quetiapine in patients with PTSD significantly decreased the scores listed in trauma reexperiencing, avoidance, and hyperarousal subscales in the clinical scales measuring PTSD, and total and subscales scores listed in positive, negative, general psychopathology, and supplementary items of the Positive and negative syndrome scale subscales, respectively (P<0.001).

Conclusion

PTSD and psychotic symptoms were significantly reduced after monotherapy with typical or atypical antipsychotics. As psychotic symptoms commonly occur in combat-related PTSD, the use of antipsychotic medication seems to offer another approach to treat a psychotic subtype of combat-related PTSD resistant to previous antidepressant treatment.In a world in which terrorism and conflicts are constant threats, and these threats are becoming global, posttraumatic stress disorder (PTSD) is a serious and global illness. According to the criteria from the 4th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1), exposure to a life-threatening or horrifying event, such as combat trauma, rape, sexual molestation, abuse, child maltreatment, natural disasters, motor vehicle accidents, violent crimes, hostage situations, or terrorism, can lead to the development of PTSD (1,2). The disorder may also be precipitated if a person experienced, saw, or learned of an event or events that involved actual or threatened death, serious injury, or violation of the body of self or others (3,4). In such an event, a person’s response can involve intense fear, helplessness, or horror (3,4). However, not all persons who are exposed to a traumatic event will develop PTSD. Although the stress reaction is a normal response to an abnormal situation, some extremely stressful situations will in some individuals overwhelm their ability to cope with stress (5).PTSD is a chronic psychiatric illness. The essential features of PTSD are the development of three characteristic symptom clusters in the aftermath of a traumatic event: re-experiencing the trauma, avoidance and numbing, and hyperarousal (1,6). The core PTSD symptoms in the re-experiencing cluster are intrusive memories, images, or perceptions; recurring nightmares; intrusive daydreams or flashbacks; exaggerated emotional and physical reactions; and dissociative experiences (1,6,7). These symptoms intensify or re-occur upon exposure to reminders of the trauma, and various visual, auditory, or olfactory cues might trigger traumatic memories (3,4). The avoidance and numbing cluster of symptoms includes efforts to avoid thoughts, feelings, activities, or situations associated with the trauma; feelings of detachment or alienation; inability to have loving feelings; restricted range of affect; loss of interest; and avoidance of activity. The hyperarousal cluster includes exaggerated startle response, hyper-vigilance, insomnia and other sleep disturbances, difficulties in concentrating, and irritability or outbursts of anger. PTSD criteria include functional impairment, which can be seen in occupational instability, marital problems, discord with family and friends, and difficulties in parenting (3,4,8). In addition to this social and occupational dysfunction, PTSD is often accompanied by substance abuse (9) and by various comorbid diagnoses, such as major depression (10), other anxiety disorders, somatization, personality disorders, dissociative disorders (7,11), and frequently with suicidal behavior (12). Combat exposure can precipitate a more severe clinical picture of PTSD, which may be complicated with psychotic features and resistance to treatment. War veterans with PTSD have a high risk of suicide, and military experience, guilt about combat actions, survivor guilt, depression, anxiety, and severe PTSD are significantly associated with suicide attempts (12).The pharmacotherapy treatment of PTSD includes the use of antidepressants, such as selective serotonin reuptake inhibitors (fluvoxamine, fluoxetine, sertraline, or paroxetine) as a first choice of treatment, tricyclic antidepressants (desipramine, amitriptyline, imipramine), monoamine oxidase inhibitors (phenelzine, brofaromine), buspirone, and other antianxiety agents, benzodiazepines (alprazolam), and mood stabilizers (lithium) (13-16). Although the pharmacotherapy of PTSD starts with antidepressants, in treatment-refractory patients a new pharmacological approach is required to obtain a response. In treatment-resistant patients, pharmacotherapy strategies reported to be effective include anticonvulsants, such as carbamazepine, gabapentine, topiramate, tiagabine, divalproex, lamotrigine (14,17); anti-adrenergic agents, such as clonidine (although presynaptic α2-adrenoceptor agonist, clonidine blocks central noradrenergic outflow from the locus ceruleus), propranolol, and prazosin (13,14), opiate antagonists (13), and neuroleptics and antipsychotics (14,17,18).Combat exposure frequently induces PTSD, and combat-related PTSD might progress to a severe form of PTSD, which is often refractory to treatment (19-21). Combat-related PTSD is frequently associated with comorbid psychotic features (11,14,17,19-21), while psychotic features add to the severity of symptoms in combat-related PTSD patients (19,22-24). These cases of a more severe subtype of PTSD, complicated with psychotic symptoms, require the use of neuroleptics or atypical antipsychotic drugs (14,17,25-27).After the war in Croatia (1991-1995), an estimated million people were exposed to war trauma and about 10 000 of the Homeland War veterans (15% prevalence) have developed PTSD, with an alarmingly high suicide rate (28). The war in Croatia brought tremendous suffering, not only to combat-exposed veterans and prisoners of war (29), but also to different groups of traumatized civilians in the combat zones, displaced persons and refugees, victims of terrorist attacks, civilian relatives of traumatized war veterans and terrorist attacks victims, and traumatized children and adolescents (30). Among Croatian war veterans with combat-related PTSD, 57-62% of combat soldiers with PTSD met criteria for comorbid diagnoses (8-11), such as alcohol abuse, major depressive disorder, anxiety disorders, panic disorder and phobia, psychosomatic disorder, psychotic disorders, drug abuse, and dementia. In addition to different comorbid psychiatric disorders, a great proportion of war veterans with combat-related PTSD developed psychotic features (8,11,25,26), which consisted of psychotic depressive and schizophrenia-like symptoms (suggesting prominent symptoms of thought disturbances and psychosis). Psychotic symptoms were accompanied by auditory or visual hallucinations and delusional thinking in over two-thirds of patients (25,26). Delusional paranoid symptoms occurred in 32% of patients (25,26). The hallucinations were not associated exclusively with the traumatic experience, while the delusions were generally paranoid or persecutory in nature (25,26). Although psychotic PTSD and schizophrenia share some similar symptoms, there are clear differences between these two entities, since PTSD patients still retain some insight into reality and usually do not have complete disturbances of affect (eg, constricted or inappropriate) or thought disorder (eg, loose associations or disorganized responses).This proportion of veterans with combat-related PTSD refractory to treatment (18-20) and with co-occurring psychotic symptoms requires additional pharmacological strategies, such as the use of neuroleptics (25) or atypical antipsychotics (14,17,26). Studies evaluating the use of antipsychotics in combat-related PTSD with psychotic features are scarce, and antipsychotics were frequently added to existing medication in the treatment of PTSD.In this study, we compared retrospectively the clinical effects of four antipsychotic drugs – a neuroleptic drug (fluphenazine) and three atypical antipsychotics (olanzapine, risperidone and quetiapine) – in treatment-resistant male war veterans with combat-related PTSD with psychotic features.     

Patients with Combat-related and War-related Posttraumatic Stress Disorder 10 Years After Diagnosis

Aim

To establish how many patients diagnosed with posttraumatic stress disorder (PTSD) in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later, and assess their sociodemographic characteristics, comorbid disorders, and type of treatment.

Methods

Medical records of patients diagnosed with PTSD in 1996 were reviewed in the period 2007-2009 and the patients who contacted a psychiatrist in that period (n = 85) and those who did not (n = 158) were compared.

Results

There were 36.7% of men and 20% of women diagnosed with PTSD in 1996 who contacted a psychiatrist in the period 2007-2009. Patients who contacted a psychiatrist and those who did not did not differ in sex, age, the number of visits and hospitalizations in 1996, and employment status. The majority of patients still had PTSD and/or were enduring personality change in the period 2007-2009, and 54.8% had some comorbidity (mostly depression, alcohol-related disorders, and personality disorders). Patients were most often treated with anxiolytics and antidepressants.

Conclusion

Ten years after the traumatic experience, one third of patients with PTSD received psychiatric help, regardless of their sex, age, and employment status. Half of them had comorbid disorders and the majority of them were treated with anxiolytics and antidepressants.Posttraumatic stress disorder (PTSD) is a mental disorder that develops in 9-25% of war veterans (1-4), mainly in the first two years after the traumatic experience (5,6), but sometimes can develop years later (7,8). A similar prevalence was also found among Croatian war veterans (5-9). In the majority of cases (80-98%), PTSD is comorbid with other mental disorders: alcohol abuse, depression, anxiety disorders, and somatization (5,9-11).PTSD can also develop after a war-related trauma that is not necessarily combat-related, and the lifetime prevalence of PTSD in this population is 15-38% (12) and the prevalence of anxiety and depressive disorders is even higher (13,14).Many patients in Croatia had symptoms of PTSD and used health facilities for treatment years after the war (5-9). In the former Yugoslavia, 84% of untreated war-related PTSD patients still had PTSD symptoms years after the war (15). Resolution of PTSD is observed in 50-60% of cases (4,16).Combat-related PTSD causes more functional impairment and is less responsive to treatment than PTSD related to other traumas (17-19). It is unclear whether this happens because there is indeed a difference between the two types of PTSD or some of the patients aggravate their symptoms in order to get compensation (17,18,20). Some studies show that the use of health facilities decreases after obtaining war veteran status and compensation, but others show that the patients who had obtained the status and compensation used medical facilities more often than those who had not (20-23).The aim of this study was to establish how many patients diagnosed with PTSD in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later and assess their comorbidities, sociodemographic characteristics, and type of treatment.     

Heterogeneity of posttraumatic stress disorder symptoms in Croatian war veterans: retrospective study

Aim

To determine the relationship between the intensity of combat-related posttraumatic stress disorder (PTSD) and the intensity of predominating symptoms.

Method

The study included 151 veterans from 1992-1995 war in Croatia with PTSD, aged 38.3 ± 7.3 years (mean ± standard deviation). The veterans were psychologically tested with the Mississippi Scale for Combat-related PTSD (M-PTSD), Questionnaire on Traumatic Combat and War Experiences (USTBI-M), and Minnesota Multiphasic Personality Inventory-version 201 (MMPI-201).

Results

The discriminative analysis of the data revealed that the group with lower PTSD intensity had the highest scores on MMPI scales D (depression, T-score 95.7 ± 5.6), Hs (hypochondriasis, 87.6 ± 5.1), and Hy (hysteria, 85.6 ± 4.9), whereas the group with higher PTSD intensity, besides these three scales (D = 98.3 ± 5.3; Hs = 90.1 ± 4.3; Hy = 89.5 ± 4.7), also had clinically significantly elevated Pt (psychastenia, 80.6 ± 5.6), Sc (schizophrenia, 79.6 ± 4.8), and Pa (paranoia, 85.6 ± 5.4) scales, with the highest Pa scale.

Conclusion

It was possible to differentiate study participants with different PTSD intensity on the basis of their MMPI profile. More intense PTSD was associated with externalized symptoms, such as aggression, acting-out, hostility, and mistrust, whereas less intensive PTSD was associated with mostly depressive symptoms. Our study showed that different intensity of PTSD has different symptom patterns.A person’s reaction to trauma depends on the traumatic situation itself, personality characteristics of the person exposed to trauma, and posttraumatic social environment. Most people develop some form of acute stress reaction to traumatic event, but in the majority of cases the stress-related difficulties spontaneously withdraw once the person is removed from the situation (1). Fewer people will develop chronic disorders which may evolve into a clinical picture of posttraumatic stress disorder (PTSD) (2). Symptoms that characterize PTSD include repeated re-experiencing of the trauma, emotional numbing, detachment, lack of affect, anhedonia, and avoidance of activities and situations reminiscent of the traumatic event (3).PTSD is often comorbid with other psychiatric disorders (4-7). Patients with PTSD often complain of psychosomatic disturbances, ranging from anxiety accompanied with tremor and restlessness to depressive problems with predominant cognitive aspects of depression (dark thoughts, shame, guilt, and suicidal thoughts and intentions) and to vegetative symptoms (insomnia and loss of appetite) (8). Comorbidity of PTSD with anxiety or depressive disorders is diagnosed in cases where anxiety or depressive symptoms are prevalent. Due to these psychiatric problems, patients with PTSD often resort to alcohol or drug abuse (4). Memory and concentration impairment, often present in PTSD, may seriously interfere with everyday functioning of these patients (9).Because PTSD symptoms are so heterogeneous, many researchers presume that there are different subtypes of the disorder. Previous attempts to determine different types of PTSD used different methodologic approaches (10-12). Some studies analyzed characteristics of PTSD with respect to predominant symptomatology (6,8), whereas others tried to associate PTSD symptoms with different types of stressors (12,13). Electrophysiological indicators of PTSD as well as the possibility to determine different types of PTSD on the basis of specific electrophysiological indicators were investigated (14,15).Further attempts to discern among different types of PTSD were based on personality tests, primarily Minnesota Multiphasic Personality Inventory (MMPI) (16), response to specific pharmacotherapy (17), and existing aggressive behavior (18-20). Recently, intensity of PTSD has been investigated as a factor that determines the type of the disorder (21-23).The aim of the present study was to determine the relationship between the intensity of PTSD and predominating symptoms in a sample of Croatian 1991-1995 war veterans.     

Circulating lymphocyte subsets, natural killer cell cytotoxicity, and components of hypothalamic-pituitary-adrenal axis in Croatian war veterans with posttraumatic stress disorder: cross-sectional study

Aim

To determine peripheral blood lymphocyte subsets – T cells, helper T cells, cytotoxic T cells, B cells, and natural killer cells, natural killer cell cytotoxicity, serum cortisol concentration, and lymphocyte glucocorticoid receptor expression in Croatian combat veterans diagnosed with chronic posttraumatic stress disorder (PTSD); and to examine the relationship between the assessed parameters and the time passed since the traumatic experience.

Methods

Well-characterized group of 38 PTSD patients was compared to a group of 24 healthy civilians. Simultaneous determination of lymphocyte subsets and the expression of intracellular glucocorticoid receptor was performed using three-color flow cytometry. Natural killer cell cytotoxicity was measured by ⁵¹Cr-release assay and the serum cortisol concentration was determined by radioimmunoassay.

Results

We found higher lymphocyte counts in PTSD patients than in healthy controls (2294.7 ± 678.0/μL vs 1817.2 ± 637.0/μL, P = 0.007) and a positive correlation between lymphocyte glucocorticoid receptor expression and the number of years that passed from the traumatic experience (r_s = 0.43, P = 0.008). Lymphocyte glucocorticoid receptor expression positively correlated with serum cortisol concentration both in PTSD patients (r = 0.46, P = 0.006) and healthy controls (r = 0.46, P = 0.035).

Conclusion

This study confirmed that the immune system was affected in the course of chronic PTSD. Our findings also indicated that the hypothalamic-pituitary-adrenal axis profile in PTSD was associated with the duration of the disorder. Due to the lack of power, greater sample sizes are needed to confirm the results of this study.Prolonged or frequently repeated stress response during symptomatic episodes in chronic posttraumatic stress disorder (PTSD) can result in neuroendocrine and immune alterations, posing serious threat to mental and physical health (1,2). Evidence suggests that PTSD is related to increased medical morbidity, particularly from cardiovascular and autoimmune diseases (3). With controversial findings when neurobiology of PTSD is concerned, the patophysiological mechanisms underlying increased susceptibility to disease are not clear (4,5). However, it has been implicated that the sympathetic-adrenal-medullary (SAM) and the hypothalamic-pituitary-adrenal axes are the key mediators in this process (6,7).The immune system interacts with the hypothalamic-pituitary-adrenal axis in a bidirectional fashion to maintain homeostasis. Being the primary effector of the stress response, cortisol modifies the complex cytokine network and, consequently, leukocyte function and recirculation (8). These effects are achieved through its interaction with the specific intracellular glucocorticoid receptors (9).Studies of the leukocyte recirculation (10,11), immune cells function (12), and hypothalamic-pituitary-adrenal axis activity (5) in PTSD yielded controversial results. Overall findings support the hypothesis that immune activation in PTSD may be associated with Th2 cytokine shift and alterations in the proinflammatory cytokine system (4). Besides, it is believed that PTSD is linked with low plasma cortisol levels and higher glucocorticoid receptor expression, suggesting enhanced feedback sensitivity to cortisol (13). In contrast to these findings, Gotovac et al (14) showed that Croatian combat veterans with PTSD, approximately 6 years after traumatic event, had lower expression of glucocorticoid receptor in lymphocyte subsets, with higher serum cortisol concentration than healthy subjects. Majority of other studies did not take into account the time passed since the trauma and their samples mainly included Vietnam veterans (15) or Holocaust survivors (16), who had greater time gap since the traumatic experience than Croatian war veterans.Considering the strong discrepancies in the results published to date, we performed a cross-sectional study to evaluate the correlation between PTSD in Croatian combat war veterans and the percentages of circulating lymphocyte subsets, natural killer cell cytotoxicity as a measure of immune function, and the serum cortisol concentration with lymphocyte glucocorticoid receptor expression as components of hypothalamic-pituitary-adrenal axis. The emphasis was put on the relationship between the assessed parameters and the time passed since the traumatic experience.     

Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder

Aim

To test the differences in serum lipid concentrations between veterans with chronic posttraumatic stress disorder (PTSD) and veterans without PTSD.

Methods

We determined plasma lipid parameters and calculated risk factors for 50 veterans in the PTSD group and 50 veterans in the non-PTSD group. Trauma exposure, coping strategies, and quality of life were assessed with Life Stressor List, Manchester Short Assessment of Quality of Life Scale, and Folkman-Lazarus Coping Strategies Questionnaire.

Results

There was no difference between the groups in the exposure to combat trauma. PTSD group had significantly lover education than non-PTSD group (10.6 ± 1.8 vs 12.4 ± 2.6 years, P = 0.007) and lower monthly income per family member (€67.8 ± 51.3 vs €281.9 ± 208.2, P < 0.001). PTSD group had significantly higher levels of all plasma lipid parameters (cholesterol: 6.54 ± 1.24 vs 5.40 ± 1.09 mmol/L, P < 0.001; triglycerides: 2.55 ± 0.68 vs 1.73 ± 0.77 mmol/L, P < 0.001; very low density lipoprotein-cholesterol: 1.14 ± 0.32 vs 0.78 ± 0.35 mmol/L, P < 0.001; low density lipoprotein-cholesterol: 4.49 ± 1.06 vs 3.46 ± 0.93 mmol/L, P < 0.001). High-density lipoprotein cholesterol concentration was significantly lower in PTSD group (0.96 ± 0.18 vs 1.15 ± 0.24 mmol/L, P < 0.001). Established risk factor for arteriosclerosis (6.96 ± 1.19 vs 4.71 ± 0.88, P < 0.001) and Adult Treatment Panel III ten years risk for coronary disease (19.44 ± 7.27% vs 9.74 ± 4.10%, P < 0.001) were significantly higher in the PTSD group. Secondary traumatization was significantly more frequent in the PTSD group (3.8 ± 5.7 vs 1.3 ± 4.7 events; P < 0.001).

Conclusions

Chronic PTSD is associated with dyslipidemia, leading to an increased risk of coronary artery disease. Environmental factors and coping strategies should be considered as important factors for the occurrence and persistence of PTSD.“The body keeps the score: memory and the evolving psychobiology of post traumatic stress” by Bessel van der Kolk (1) was published in the Harvard Review of Psychiatry in 1994. Although it may not be the first article on neurobiology of posttraumatic stress disorder (PTSD), the strong metaphor contained in the first part of its title summarizes the research results in this field. Studies looking for biological causes of a disorder that is clearly precipitated by environmental or man-made causes were largely outnumbered by studies on the psychosocial nature of the disorder decades after the delayed first recognition of PTSD in the diagnostic manuals – 1980 in Diagnostic and Statistical Manual of Mental Disorders III (DSM III) (2) and 1990 in the International Classification of Diseases-10 (ICD-10) (3). A small number of studies appeared in literature in parallel with the recognition of the disorder, but the number of biological studies since September 11, 2001 has grown 5-fold and keeps growing (4).Research interest mainly focused on alterations of neuroendocrine regulation (5,6) and neuroanatomical (7) and neuroimmunological alterations (8,9). From the neuroendocrine point of view, in PTSD there is an increased noradrenergic activity in absence of shutdown by serum cortisol that has been found to be decreased in this disorder due to dysregulation of the hypothalamo-pituitary-adrenal axis (10-12). Studies on changes in serum lipid concentrations were based on clinical observations and the results of epidemiological studies indicating increased cerebrovascular and cardiovascular morbidity and mortality in survivors of prolonged traumatic and combat stress (13-17). Kagan’s pioneer study (18) of changes in lipid status of Vietnam veterans was published in 1999 and was followed by the work of other researchers who confirmed its results (19-23).The population of Bosnia and Herzegovina suffered massive and prolonged traumatization in the 1992-1995 war (24-26). Increase in the prevalence and incidence of PTSD in comparison with the period before the war, as well as the increase in trauma-related disorders in overall psychiatric morbidity, represents a logical consequence of these events (27). In our work with people suffering from chronic PTSD, we had frequently noticed alterations of serum lipids, associated with an increased risk of cardiovascular diseases. This is consistent with our clinical observation of increased cardiovascular and cerebrovascular morbidity in patients who had been treated in the Unit for Trauma-related Disorders of the Department of Psychiatry of the University Clinical Center in Sarajevo and the literature (13-17). Therefore, we aimed to explore the differences in concentrations of serum cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), index of arteriosclerosis, established risk factor for arteriosclerosis (ERF), and 10 years-risk for coronary disease according to Adult Treatment Panel III (ATP III) (28) between veterans with the diagnosis of chronic PTSD and veterans without the diagnosis of PTSD. Our second aim was to compare and analyze the differences between the two groups in socio-demographic characteristics, trauma exposure measures, secondary traumatization (after the war), PTSD symptoms, coping strategies, and quality of life, to obtain information on the factors influencing the development and persistence of PTSD in veterans with combat stress exposure.There are divided opinions in literature whether this disorder develops in individuals with certain predisposing factors or all people have equal chances of developing PTSD (29-32). There is also a question whether biological markers of PTSD are trait markers or state markers, as well as whether PTSD can be explained by stress-diathesis model as schizophrenia (33). To explore these claims, we also compared socio-demographic characteristics of the sample, trauma events inventory, coping strategies, and quality of life indicators.     

Breast and gynecological cancers in Croatia, 1988-2008

Aim

To analyze and interpret incidence and mortality trends of breast and ovarian cancers and incidence trends of cervical and endometrial cancers in Croatia for the period 1988-2008.

Methods

Incidence data were obtained from the Croatian National Cancer Registry. The mortality data were obtained from the World Health Organization (WHO) mortality database. Trends of incidence and mortality were analyzed by joinpoint regression analysis.

Results

Joinpoint analysis showed an increase in the incidence of breast cancer with estimated annual percent of change (EAPC) of 2.6% (95% confidence interval [CI], 1.9 to 3.4). The mortality rate was stable, with the EAPC of 0.3% (95% CI, -0.6 to 0.0). Endometrial cancer showed an increasing incidence trend, with EAPC of 0.8% (95% CI, 0.2 to 1.4), while cervical cancer showed a decreasing incidence trend, with EAPC of -1.0 (95% CI, -1.6 to -0.4). Ovarian cancer incidence showed three trends, but the average annual percent change (AAPC) for the overall period was not significant, with a stable trend of 0.1%. Ovarian cancer mortality was increasing since 1992, with EAPC of 1.2% (95% CI, 0.4 to 1.9), while the trend for overall period was stable with AAPC 0.1%.

Conclusion

Incidence trends of breast, endometrial, and ovarian cancers in Croatia 1988-2008 are similar to the trends observed in most of the European countries, while the modest decline in cervical cancer incidence and lack of decline in breast cancer mortality suggest suboptimal cancer prevention and control.Breast and gynecological cancers are among the seven most common female cancers in Croatia: in 2008 breast cancer was the most common cancer with the proportion of 26% of all cancer sites, endometrial cancer ranked fourth (6%), ovarian cancer (with fallopian tubes cancer) sixth (5%), and cervical cancer seventh (4%) (1).Breast, endometrial, and ovarian cancers share some similar risk factors like early menarche, late menopause, obesity, and low parity (2-5). Also, breast cancer in personal history increases the risk of endometrial and ovarian cancer (6). Delayed childbearing increases the risk of breast cancer but seems to have no impact on the development of ovarian and endometrial cancer (3-5). Diabetes mellitus increases the risk of endometrial and breast cancer (7,8). Use of tamoxifen or other selective estrogen receptor modulators increases the risk of endometrial and ovarian cancer, while the use of combined oral contraceptives is a protective factor (2,9,10). Also, tobacco smoking and alcohol intake reduce the risk of endometrial cancer (2,11,12). Alcohol intake and both oral contraceptives and hormonal replacement therapy are risk factors for breast cancer (2,13,14). Multiparty and physical activity are protective factors for all three cancers (2,4,15,16). Low socioeconomic status, sexually transmitted diseases, promiscuity, unprotected sexual behavior, earlier age of first intercourse, and smoking are risk factors for cervical cancer (2,17-23). Infection with human papillomavirus is considered as a necessary cause of cervical cancer (24).The aim of this study was to report the incidence and mortality of breast and ovarian cancers and incidence of endometrial and cervical cancers, analyze the trends in the period 1988-2008, and compare them to other European countries.     

Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study

Aim

To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.

Methods

In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.

Results

HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter.

Conclusion

The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.Adverse drug reactions (ADR) are among the leading causes of mortality and morbidity responsible for causing additional complications (1,2) and longer hospital stays. Magnitude of ADRs and the burden they place on health care system are considerable (3-6) yet preventable public health problems (7) if we take into consideration that an important cause of ADRs are drug-drug interactions (8,9). Although there is a substantial body of literature on ADRs caused by drug-drug interactions, it is difficult to accurately estimate their incidence, mainly because of different study designs, populations, frequency measures, and classification systems (10-15).Many studies including different groups of patients found the percentage of potential drug-drug interactions resulting in ADRs to be from 0%-60% (10,11,16-25). System analysis of ADRs showed that drug-drug interactions represented 3%-5% of all in-hospital medication errors (3). The most endangered groups were elderly and polimedicated patients (22,26-28), and emergency department visits were a frequent result (29). Although the overall incidence of ADRs caused by drug-drug interactions is modest (11-13,15,29,30), they are severe and in most cases lead to hospitalization (31,32).Potential drug-drug interactions are defined on the basis of on retrospective chart reviews and actual drug-drug interactions are defined on the basis of clinical evidence, ie, they are confirmed by laboratory tests or symptoms (33). The frequency of potential interactions is higher than that of actual interactions, resulting in large discrepancies among study findings (24).A valuable resource for detecting drug-drug interactions is a spontaneous reporting database (15,34). It currently uses several methods to detect possible drug-drug interactions (15,29,35,36). However, drug-drug interactions in general are rarely reported and information about the ADRs due to drug-drug interactions is usually lacking.The aim of this study was to estimate the incidence of actual and potential drug-drug interactions in the national Spontaneous Reporting Database of ADRs in Croatia. Additionally, we assessed the clinical significance and seriousness of drug-drug interactions and their probable mechanism of action.     

Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia

AimTo present and evaluate a new screening protocol for amblyopia in preschool children.MethodsZagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic.Results78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively.ConclusionThe ZAPS study used the most discriminative VA test with optotypes in lines as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia.Vision disorders in children represent important public health concern as they are acknowledged to be the leading cause of handicapping conditions in childhood (1). Amblyopia, a loss of visual acuity (VA) in one or both eyes (2) not immediately restored by refractive correction (3), is the most prevalent vision disorder in preschool population (4). The estimated prevalence of amblyopia among preschool children varies from 0.3% (4) to 5% (5). In addition, consequences of amblyopia include reduced contrast sensitivity and/or positional disorder (6). It develops due to abnormal binocular interaction and foveal pattern vision deprivation or a combination of both factors during a sensitive period of visual cortex development (7). Traversing through adulthood, it stands for the leading cause of monocular blindness in the 20-70 year age group (8). The main characteristic of amblyopia is crowding or spatial interference, referring to better VA when single optotypes are used compared to a line of optotypes, where objects surrounding the target object deliver a jumbled percept (9-12). Acuity is limited by letter size, crowding is limited by spacing, not size (12).Since amblyopia is predominantly defined as subnormal VA, a reliable instrument for detecting amblyopia is VA testing (13-15). Moreover, VA testing detects 97% of all ocular anomalies (13). The gold standard for diagnosing amblyopia is complete ophthalmological examination (4). There is a large body of evidence supporting the rationale for screening, as early treatment of amblyopia during the child’s first 5-7 years of life (8) is highly effective in habilitation of VA, while the treatment itself is among the most cost-effective interventions in ophthalmology (16). Preschool vision screening meets all the World Health Organization’s criteria for evaluation of screening programs (17). Literature search identified no studies reporting unhealthy and damaging effects of screening. The gold standard for screening for amblyopia has not been established (4). There is a large variety of screening methodologies and inconsistent protocols for referral of positives to complete ophthalmological examination. Lack of information on the validity (18,19) and accuracy (4) of such protocols probably intensifies the debate on determining the most effective method of vision screening (8,20-29). The unique definition of amblyopia accepted for research has not reached a consensus (4,5,30,31), further challenging the standardization of the screening protocols.Overall, two groups of screening methods exist: the traditional approach determines VA using VA tests, while the alternative approach identifies amblyogenic factors (27) based on photoscreening or automated refraction. The major difference between the two is that VA-based testing detects amblyopia directly, providing an explicit measure of visual function, while the latter, seeking for and determining only the level of refractive status does not evaluate visual function. In addition, the diagnosis and treatment of amblyopia is governed by the level of VA. On the other hand, amblyogenic factors represent risk factors for amblyopia to evolve. There are two major pitfalls in screening for amblyogenic factors. First, there is a lack of uniform cut-off values for referral and second, not all amblyogenic factors progress to amblyopia (19).Besides the issue of what should be detected, amblyopia or amblyogenic factors, a question is raised about who should be screened. Among literate children, both 3- and 4- year-old children can be reliably examined. However, 3-year-old children achieved testability rate of about 80% and positive predictive rate of 58% compared to >90% and 75%, respectively in the 4-year-old group (32). In addition, over-referrals are more common among 3-year-old children (32). These data determine the age of 4 years as the optimum age to screen for amblyopia. Hence, testability is a relevant contributor in designating the optimal screening test.If VA is to be tested in children, accepted standard tests should be used, with well-defined age-specific VA threshold determining normal monocular VA. For VA testing of preschool children Lea Symbols (33) and HOTV charts (22,32) are acknowledged as the best practice (34), while tumbling E (28,35,36) and Landolt C (28,37-39) are not appropriate as discernment of right-left laterality is still not a fully established skill (34,40). The Allen picture test is not standardized (34,41). Both Lea Symbols and HOTV optotypes can be presented as single optotypes, single optotypes surrounded with four flanking bars, single line of optotypes surrounded with rectangular crowding bars, or in lines of optotypes (22,33,34,41-53). The more the noise, the bigger the “crowding” effect. Isolated single optotypes without crowding overestimate VA (24), hence they are not used in clinical practice in Sweden (32). If presented in lines, which is recognized as the best composition to detect crowding, test charts can be assembled on Snellen or gold standard logMAR principle (34,42,51,54). Age-specific thresholds defining abnormal VA in preschool screening for amblyopia changed over time from <0.8 to <0.65 for four-year-old children due to overload of false positives (20).The outline of an effective screening test is conclusively demonstrated by both high sensitivity and high specificity. Vision screening tests predominately demonstrated higher specificity (4). Moreover, sensitivity evidently increased with age, whereas specificity remained evenly high (4). The criteria where to set the cut-off point if the confirmatory, diagnostic test is expensive or invasive, advocate to minimize false positives or use a cut-off point with high specificity.On the contrary, if the penalty for missing a case is high and treatment exists, the test should maximize true positives and use a cut-off point with high sensitivity (55). A screening test for amblyopia should target high sensitivity to identify children with visual impairment, while the specificity should be high enough not to put immense load on pediatric ophthalmologists (14). Complete ophthalmological examination as the diagnostic confirmatory gold standard test for amblyopia is neither invasive nor elaborate technology is needed, while the penalty for missing a case is a lifetime disability.In devising the Zagreb Amblyopia Preschool Screening (ZAPS) study protocol, we decided to use Lea Symbols in lines test and to screen preschool children aged 48-54 months to address the problems declared. Near VA testing was introduced in addition to commonly accepted distance VA testing (14,22,24,32,45,56-69) due to several reasons: first, hypermetropia is the most common refractive error in preschool children (70), hence near VA should more reliably detect the presence of hypermetropia; second, the larger the distance, the shorter the attention span is; and third, to increase the accuracy of the test.The pass cut-off level of ≤0.1 logMAR was defined because of particular arguments. Prior to 1992 Sweden used the pass cut-off level for screening of 0.8 (20). A change in the referral criteria to <0.65 for four-year-old children ensued, as many children referred did not require treatment (20). In addition, amblyopia treatment outcome of achieved VA>0.7 is considered as habilitation of normal vision (3,14). At last, the pass cut-off value ≤0.1 logMAR at four years can hardly mask serious visual problems, and even if they are present, we presume they are mild and can be successfully treated at six years when school-entry vision screening is performed. The aim of the ZAPS study is to present and evaluate new screening protocol for preschool children aged 48-54 months, established for testing near and distance VA using Lea Symbols in lines test. Furthermore, we aimed to determine the threshold of age-specific and chart-specific VA normative, testability of the ZAPS study protocol, and the prevalence of amblyopia in the City of Zagreb County. By delivering new evidence on amblyopia screening, guideline criteria defining optimal screening test for amblyopia in preschool children can be revised in favor of better visual impairment clarification.     

The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

Aim

To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity.

Methods

Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α₂-adrenoreceptor agonist), yohimbine (α₂-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine.

Results

Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity.

Conclusion

The results suggest that α₂-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity.Benzodiazepines are used for their anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant properties in the treatment of a variety of neuropsychiatric disorders (1,2), including anxiety and depression, which are often related to disturbances in the activity of hypothalamic-pituitary-adrenal (HPA) axis (3,4). Although these drugs exert most of their pharmacological effects via γ-aminobutyric acid_A (GABA_A) receptors (5,6), benzodiazepine administration has been associated with alterations in neuroendocrine function both in experimental animals and humans (7-9). However, even after years of extensive studies, the complex mechanisms by which these widely used drugs produce their effects on the HPA axis are still not known.Although most of the previous studies have demonstrated that classical benzodiazepines such as diazepam decrease the HPA axis activity in stressful contexts (10-14), under basal conditions they have been shown to stimulate (9,11,15-18), inhibit (15,19-22), and not affect (17,23-25) the HPA axis activity. Such diverse results might be related to several factors such as the dose and gender (15,16,20,21,26-28), or may also be a consequence of the net effect of non-selective benzodiazepines on the various GABA_A receptor isoforms (9).Our previous studies demonstrated that while diazepam (1 mg/kg) produced no change in plasma corticosterone levels in male rats (15,20), it decreased basal levels of corticosterone in female rats (15,26). However, although diazepam inhibited the HPA axis activity of female rats following administration of lower doses (1 or 2 mg/kg) (15,20,21,26), it stimulated the HPA axis activity following administration of high doses (10 mg/kg) (15,16,26). Moreover, whereas the suppressive effect of the lower doses of diazepam (2.0 mg/kg) on the HPA axis activity in female rats involves the GABA_A receptor complex (21), increases in corticosterone levels by a higher dose of diazepam (10 mg/kg) do not involve the stimulation of GABA_A receptors (16). In addition, stimulatory effect of 10 mg/kg diazepam on the HPA axis activity in rats seems not to be mediated by the benzodiazepine/GABA/channel chloride complex or by peripheral benzodiazepine receptors, but rather by a cyclic adenosine monophosphate (AMP)-dependent mechanism (18).Since our previous results suggested that the effect of a high dose of diazepam on the activity of the HPA axis in female rats might be due to a blockade of α₂-adrenergic receptors (16), the aim of this study was to elucidate whether noradrenergic system also has a modulatory role in the inhibitory effect of 2.0 mg/kg diazepam on basal plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in female rats.     

Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

Aim

To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects.

Methods

The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery.

Results

Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting.

Conclusion

Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects.Registration No: IRCT201103255764N2Postoperative pain has not only a pathophysiologic impact but also affects the quality of patients’ lives. Improved pain management might therefore speed up recovery and rehabilitation and consequently decrease the time of hospitalization (1). Surgery causes tissue damage and subsequent release of biochemical agents such as prostaglandins and histamine. These agents can then stimulate nociceptors, which will send the pain message to the central nervous system to generate the sensation of pain (2-4). Neuroendocrine responses to pain can also cause hypercoagulation state and immune suppression, leading to hypoglycemia, which can delay wound healing (5).Tonsillectomy is a common surgery in children and post-tonsillectomy pain is an important concern. Duration and severity of pain depend on the surgical technique, antibiotic and corticosteroid use, preemptive and postoperative pain management, and patient’s perception of pain (6-9). There are many studies that investigated the control of post tonsillectomy pain using different drugs such as intravenous opioids, non-steroidal anti-inflammatory drugs, steroids, ketamine, as well as peritonsillar injection of local anesthetic, opioid, and ketamine (6,7,10-14).Ketamine is an intravenous anesthetic from phencyclidin family, which because of its antagonist effects on N methyl-D-aspartate receptors (that are involved in central pain sensitization) has regulatory influence on central sensitization and opium resistance. It can also band with mu receptors in the spinal cord and brain and cause analgesia. Ketamine can be utilized intravenously, intramuscularly, epidurally, rectally, and nasaly (15,16). Several studies have shown the effects of sub-analgesic doses of ketamine on postoperative pain and opioid consumption (7,13,15-17). Its side effects are hallucination, delirium, agitation, nausea, vomiting, airways hyper-secretion, and increased intra cerebral pressure and intra ocular pressure (10,11,15,16).Tramadol is an opium agonist that mostly effects mu receptors, and in smaller extent kappa and sigma receptors, and like anti depressant drugs can inhibit serotonin and norepinephrine reuptake and cause analgesia (6,12,18). Its potency is 5 times lower than morphine (6,12), but it has lower risk of dependency and respiratory depression, without any reported serious toxicity (6,12). However, it has some side effects such as nausea, vomiting, dizziness, sweating, anaphylactic reactions, and increased intra-cerebral pressure. It can also lower the seizure threshold (6,12,18,19).Several studies have confirmed the efficacy of tramadol and ketamine on post-tonsillectomy pain (6,10-12,20). In previous studies, effects of peritonsillar/ IV or IM infiltration of tramadol and ketamine were compared to each other and to placebo, and ketamine and tramadol were suggested as appropriate drugs for pain management (6,7,10-19,21). Therefore, in this study we directly compared the effect of peritonsillar infiltration of either tramadol or ketamine with each other and with placebo.     

Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

Aim

To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress.

Methods

Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed.

Results

Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033).

Conclusion

Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males.Maintaining homeostasis is often challenged by different types of stressors (1). Homeostasis is regulated by a complex endocrine processes engaging the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic autonomic system (2-4). Stress can occur either in acute or chronic form with different consequences – the acute stress mostly induces the ˝fight or flight˝ response, while chronic stress promotes long term changes, which can lead to a variety of diseases (5,6). If stress is of sufficient magnitude and duration, the action of HPA is unsuppressed and results in prolonged elevation of cortisol (7), induced production of energy, vasoconstriction, lipolysis, proteolysis, immunosuppression, and suppression of reproductive function to save energy and retain overall homeostasis (8). Women are generally less susceptible to chronic stress up to the period of menopause, when the loss of protective hormones, estrogen and progesterone, occurs and thus they become prone to development of depression, anxiety, or schizophrenia (9). In contrast, men are generally more susceptible and sensitive to chronic stress, showing changes in feeding habits and decreased body weight (10,11).Chronic stress can cause the development of cardiovascular disorder, obesity, and diabetes, which can be reflected in serum cholesterol, glucose, and decreased glucose tolerance (12-14). There is a strong correlation between stress and sexual hormones, but the mechanisms by which estrogen, testosterone, and progesterone exert their possible protective role under stress conditions are not fully explored. Sexual hormones affect stress outcome and stress hormones affect the levels of sexual hormones (15-17). Testosterone is activated during stress response in rats and humans (18,19) and tends to increase more in men than women (20). Estrogen lowers the stress-induced response in women and men (9,21). Estrogens and progesterone are produced even after ovariectomy by adrenal glands (22) but it is not known if such compensation can withstand additional challenge like stress. Another possible player in stress response is leptin (Ob), hormone responsible for maintaining body weight, which is synthesized and secreted by adipose tissue (23), exerting its effects through the leptin receptor (Ob-R) (24). Chronic stress models imply a direct link between stress response and leptin (25,26). Receptors for leptin are present in the adrenal gland (27). The aim of this study was to investigate cardiovascular risk parameters and changes in leptin and sexual hormone receptors in adrenal gland during chronic stress. There is a clinically relevant change in the onset of cardiometabolic risk between healthy women and women with premature ovarian failure (28) and because of that ovariectomized female rats were included in the study.     

Disorder of extreme stress not otherwise specified (DESNOS) in Croatian war veterans with posttraumatic stress disorder: case-control study

Aim

To determine the presence of disorder of extreme stress not otherwise specified (DESNOS) in Croatian war veterans who suffer from combat-related posttraumatic stress disorder (PTSD).

Methods

The research included 247 veterans of the 1991-1995 war in Croatia who suffered from PTSD and were psychiatrically examined at four clinical centers in Croatia during a month in 2008. It was based on the following self-assessment instruments: The Harvard Trauma Questionnaire (HTQ): Croatian Version, the Structured Interview for Disorder of Extreme Stress (SIDES-SR), and the Mini International Neuropsychiatric Interview (MINI)

Results

Based on the SIDES-SR results, we formed two groups of participants: the group with PTSD (N = 140) and the group with both PTSD and DESNOS (N = 107). Forty three percent of participants met the criteria for DESNOS. There was a significant difference in the intensity of posttraumatic symptoms between the group with both PTSD and DESNOS and the group with PTSD only (U = 3733.5, P = 0.001). Respondents who suffered from both PTSD and DESNOS also reported a significantly larger number of comorbid mental disorders (U = 1123.5, P = 0.049) and twice more frequently reported comorbid depression with melancholic features (OR = 2.109, P = 0.043), social phobia (OR = 2.137, P = 0.036), or panic disorder (OR = 2.208, P = 0.015).

Conclusion

Our results demonstrate that PTSD and DESNOS can occur in comorbidity, which is in contrast with the ICD-10 criteria. A greater intensity of symptoms and a more frequent comorbidity with other psychiatric disorders, especially depression, panic disorder, and social phobia require additional therapy interventions in the treatment processes.Posttraumatic stress disorder (PTSD) is a common, but not the only disorder that develops as an effect of a traumatic experience. The prevalence of PTSD in general population is 1 to 14% (1-4). In case of war veterans, the rate ranges from 15 to 57% (3,5,6). As much as 79% of persons suffering from PTSD suffer from another mental disorder and 44% suffer from three or more mental disorders. This means that in case of a large number of traumatized persons, PTSD diagnosis covers only a few mental disturbances (7-11).Chronic or complex PTSD and DES or DESNOS (disorder of extreme stress not otherwise specified) have been investigated since the 1990s (12-15). DESNOS is defined and viewed as a group of symptoms within associated features of PTSD, and as such it may be included in future classifications (2,9). On the other hand, the ICD-10 introduced a diagnostic category of Enduring Personality Change After Catastrophic Events (F62.0), which includes features such as hostility and mistrustful attitude toward the world, social isolation, a feeling of emptiness and hopelessness, irritability, and estrangement. The diagnosis can be given only after two years of the illness duration and it excludes the diagnosis of concurrent PTSD because the enduring change is seen only as an adverse outcome of a long-lasting PTSD, not as a separate entity that can exist in comorbidity with PTSD (1). After its full development, enduring personality change cannot be treated that easily. The ICD-10 classification does not allow diagnosing the comorbidity of PTSD and Enduring Personality Change After Catastrophic Experience or DESNOS as a corresponding diagnostic category proposed by the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV classification (2).The correlation of DESNOS and PTSD is still not completely clear. It is not specified whether DESNOS is a separate clinical entity or a complication of PTSD. Potential factors are severity of traumatic experience, correlation with the severity of PTSD, comorbidity in Axes I and II of the DSM-IV classification system, and a range of personal and social factors that add to the development of the disorder (9,16,17). In spite of clinical experience and results speaking in favor of the presence of the entity that can be developed as an effect of trauma independently of PTSD or in comorbidity with PTSD, the DSM IV classification has not included this category (2,16-19).However, over the past 15 years a number of studies have discussed the possible inclusion of DESNOS in the DSM-V classification (16-19), many criteria have been defined, and even a specific questionnaire, Structured Interview for Disorder of Extreme Stress (SIDES), has been formed (9). Six clusters of symptoms have been proposed for establishing the DESNOS diagnosis: 1) alterations in regulation of affect and impulses (eg, extreme and unmodulated emotional states); 2) alterations in attention or consciousness (eg, dissociation); 3) alterations in self-perception (eg, image of self as fundamentally damaged); 4) alterations in interpersonal relations (eg, impaired relational boundaries); 5) alterations in biological self-regulation (eg, somatization), and 6) alterations in sustaining beliefs (eg, spiritual alienation) (18).[REMOVED HYPERLINK FIELD]DESNOS mostly occurs as a separate disorder, but also in comorbidity with PTSD. The prevalence of DESNOS is 1% in female student population (19), 2% in civil population exposed to war (18), and up to 57% in war veterans, 31% in comorbidity with PTSD and 26% as a separate diagnostic category (16). Furthermore, the prevalence of PTSD is the same in the general population and treatment-seeking population (17). Nearly a half of the treatment-seeking population meets the criteria for DESNOS, which suggests that symptoms of DESNOS, more likely than symptoms of PTSD, are the ones prompting patients to seek help (17).Clinical experience in working with war veterans in Croatia shows that there are patients suffering from chronic PTSD who report a range of symptoms meeting the criteria proposed for DESNOS (9). However, possible comorbidity of DESNOS and PTSD has not been assessed, probably to conform to the existing ICD classification (1). It may be assumed that DESNOS affects patients with severe clinical features of PTSD and that it also occurs in cases of Axis I comorbidity. These assumptions were the subject of our investigation.     

Awareness,knowledge, use,and attitudes toward evidence based medicine in a developing country: survey of physicians in a canton in Bosnia and Herzegovina

Aim

To assess awareness, knowledge, use, and attitudes toward evidence-based medicine (EBM) and The Cochrane Library (CL) among physicians from Zenica-Doboj Canton (ZDC), Bosnia and Herzegovina.

Methods

In this cross-sectional study, a self-administered anonymous questionnaire was sent by post to all state owned health institutions (2 hospitals and 11 Primary Health Care Institutions) in ZDC. The main outcome measures were physicians’ awareness of the Cochrane, awareness and use of CL, access to EBM databases, and access to internet at work. 358 of 559 physicians responded (63.69%).

Results

23.18% of respondents stated they had access to EBM databases, but only 3.91% named the actual EBM databases they used. The question on the highest level of evidence in EBM was correctly answered by 35.7% respondents, 34.64% heard about Cochrane and 32.68% heard about CL. They obtained information about CL mostly on the internet and from colleagues, whereas the information about EBM was obtained mainly during continuous medical education.

Conclusion

Although the attitudes toward EBM are positive, there is a low awareness of EBM among physicians in ZDC. Open access to the CL should be used more. Educational interventions in popularizing EBM and Cochrane are needed to raise awareness both among students and practicing physicians, and finally among lay audience.Evidence based medicine (EBM) is described as an integration of individual clinical expertise, the best available external clinical evidence from systematic research, and individual patients’ predicaments, rights, and preferences, in making clinical decisions about their care (1,2). However in many settings there are still barriers to its implementation (3-6).Awareness, knowledge, use, and attitudes toward EBM have been assessed worldwide (6,7). Attitudes toward EBM were mostly positive and participants welcomed the promotion of EBM (6-11). Barriers to practicing EBM differed between developing and developed countries. For example, respondents from Iran (8) reported that a major barrier was the lack of EBM training courses, while those from the Netherlands and Belgium reported limited time, attitudes, knowledge, and skills (5,12-14).Systematic reviews with or without meta-analysis produced by The Cochrane Library (CL) are considered as the “gold standard” in EBM (15-18). Cochrane systematic reviews (CSRs) can raise the quality of health care, especially in developing countries with scarce resources. For example, CSRs have been shown to provide invaluable evidence in creating national reimbursement lists (19).A nation-wide study among physicians in Croatia concluded that there was low awareness about EBM and the CL (30%), and additional educational interventions were required (6). Unlike Croatia, Bosnia and Herzegovina (BH) has no organized Cochrane activity (20). Our study aimed to assess the awareness, knowledge, use, and attitudes toward EBM and the CL (as the only available EBM database in BH with unrestricted access) among physicians in Zenica-Doboj Canton (ZDC), to help in the implementation of educational activities that would improve the use of EBM and the CL.     

Attitudes of Slovenian family practice patients toward changing unhealthy lifestyle and the role of family physicians: cross-sectional study

Aim

To assess patients’ attitudes toward changing unhealthy lifestyle, confidence in the success, and desired involvement of their family physicians in facilitating this change.

Methods

We conducted a cross-sectional study in 15 family physicians’ practices on a consecutive sample of 472 patients (44.9% men, mean age  [± standard deviation] 49.3 ± 10.9 years) from October 2007 to May 2008. Patients were given a self-administered questionnaire on attitudes toward changing unhealthy diet, increasing physical activity, and reducing body weight. It also included questions on confidence in the success, planning lifestyle changes, and advice from family physicians.

Results

Nearly 20% of patients planned to change their eating habits, increase physical activity, and reach normal body weight. Approximately 30% of patients (more men than women) said that they wanted to receive advice on this issue from their family physicians. Younger patients and patients with higher education were more confident that they could improve their lifestyle. Patients who planned to change their lifestyle and were more confident in the success wanted to receive advice from their family physicians.

Conclusion

Family physicians should regularly ask the patients about the intention of changing their lifestyle and offer them help in carrying out this intention.Unhealthy lifestyle, including unhealthy diet and physical inactivity, is still a considerable health problem all over the world. Despite publicly available evidence about the health risks of unhealthy lifestyle, people still find it hard to improve their unhealthy diet and increase physical activity. Previous studies have shown that attitudes toward lifestyle change depended on previous health behavior, awareness of unhealthy lifestyle, demographic characteristics, personality traits, social support, family functioning, ongoing contact with health care providers, and an individual’s social ecology or network (1-4).As community-based health education approaches have had a limited effect on health risk factors reduction (3,5), the readiness-to-change approach, based on two-way communication, has become increasingly used with patients who lead an unhealthy lifestyle (3,6,7). Family physicians are in a unique position to adopt this approach, since almost every patient visits his/hers family physician at least once in five years (8). Previous studies showed that patients highly appreciated their family physicians’ advice on lifestyle changes (9,10). Moreover, patients who received such advice were also more willing to change their unhealthy habits (3,7,11). The reason for this is probably that behavioral changes are made according to the patient’s stage of the motivational circle at the moment of consultation (12), which can be determined only by individual approach.Although family physicians are convinced that it is their task to give advice on health promotion and disease prevention, in practice they are less likely to do so (13). The factors that prevent them from giving advice are time (14,15), cost, availability, practice capacity (14), lack of knowledge and guidelines, poor counseling skills (16), and personal attitudes (17). It also seems that physicians’ assessment varies considerably according to the risk factor in question. For example, information on diet and physical activity are often inferred from patients’ appearance rather than from clinical measurements (14). Also, health care professionals seldom give advice on recommended aspects of intervention that could facilitate behavioral change (18). As a large proportion of primary care patients are ready to lose weight, improve diet, and increase exercise (19), it is even more important that their family physicians provide timely advice.So far, several studies have addressed patients’ willingness to make lifestyle change (2-5,20) and the provision of professional advice (3,5,7,10,11). However, none of these studies have investigated the relation between these factors. So, the aim of our study was to assess the relation between patients’ attitudes toward changing unhealthy lifestyle, confidence in success, and the desired involvement of their family physicians in facilitating the change.     

Effects of high fat diet,ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue

Aim

To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions.

Methods

The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue.

Results

StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group.

Conclusion

HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats.Obesity is one of the leading health issues worldwide, associated with an increased risk of morbidity and mortality (1). In 1997, the World Health Organization (WHO) formally recognized obesity as a global epidemic (2). Increase in body fat stores and obesity is caused by an imbalance between energy intake and energy expenditure (3,4). Since childhood obesity is a predictor of an increased death rate, the “obesity epidemic” may reverse the current declining rate of death from cardiovascular diseases (5). Factors that contribute to obesity can be environmental (6), social (7), behavioral (8), psychological (9), and genetic (10,11).Women generally have more body fat than men (12). Nevertheless similar odds ratios were recorded in women and men for the association of abdominal obesity with acute myocardial infarction (13). Weight gain is common after menopause, indicating an association between hormones and fat stores (14). A large scale observational study found that both the body mass index and the level of physical activity were independent predictors of mortality and that a higher level of physical activity did not eliminate the risk associated with adiposity. At the same time, women who were both lean and physically active had the lowest mortality (15). In animal studies menopause can be induced by ovariectomy (OVX) (16).Obesity can also be called a disorder of appetite and it is controlled by complex homeostatic mechanisms involving the hypothalamus and brainstem (17). Many gut peptides like cholecystokinin, ghrelin, glucagon-like peptide-1 (GLP-1), and -2 and peptide YY (PYY) act on the brain to control eating behavior (18). There are two different system for controlling feeding behavior: short-term and long-term (19). Short-term regulation involves neural signals from the GI tract and its hormones, like insulin, glucagon, and ghrelin (20). A hormone that functions mainly within long-term regulation is leptin (16 kD), a hormonal product of the obesity (ob) gen, primarily secreted by adipocytes (21) and released in the brain. It generates a feeling of satisfaction and acts like an appetite-suppressing agent. Circulating leptin levels are lower in ovariectomized rats (22).Food intake is regulated via neural circuits located in the hypothalamus (23). Leptin acts via its leptin or Ob receptors (Ob-R) and is primarily expressed in hypothalamic neurons (19) especially in arcuate, ventromedial, and dorsomedial nuclei (24). Leptin is transported across the blood-brain barrier (BBB) by a saturable transporter (25). Ob-R is also detected in nonhypothalamic areas in the mice and in human brain neocortex, cerebellum, entorinal cortex, amygdale, and rostral medulla (26). Adipocytes, endothelial cells, and macrophages also have leptin receptor at its surface, which suggests autocrine and paracrine action for leptin in human adipose tissue (27). Association between the expression of Ob-R in target tissues and physiological and hormonal controlled processes is still unclear. Leptin receptors mRNA is found in each of the major components of the CNS “feeding” circuitry – the brainstem, hypothalamus, and is distributed reward centers (Allan brain) (28). Therefore, the aim of the current study was to evaluate whether HFD affects Ob-R distribution compared with StD specifically in the barrel field and piriform cortex compared to standard feeding centers in the hypothalamus. We supposed that the combination of OVX and HFD is interesting for further research on selected brain regions, which might be alleviated by physical activity. We also supposed that changes in Ob-R level in white fat tissue would correlate with the changes in brain regions.     

Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis

The aim of this paper is to describe our surgical procedure for the treatment of osteonecrosis of the femoral head using a minimally invasive technique. We have limited the use of this procedure for patients with pre-collapse osteonecrosis of the femoral head (Ficat Stage I or II). To treat osteonecrosis of the femoral head at our institution we currently use a combination of outpatient, minimally invasive iliac crest bone marrow aspirations and blood draw combined with decompressions of the femoral head. Following the decompression of the femoral head, adult mesenchymal stem cells obtained from the iliac crest and platelet rich plasma are injected into the area of osteonecrosis. Patients are then discharged from the hospital using crutches to assist with ambulation. This novel technique was utilized on 77 hips. Sixteen hips (21%) progressed to further stages of osteonecrosis, ultimately requiring total hip replacement. Significant pain relief was reported in 86% of patients (n = 60), while the rest of patients reported little or no pain relief. There were no significant complications in any patient. We found that the use of a minimally invasive decompression augmented with concentrated bone marrow and platelet rich plasma resulted in significant pain relief and halted the progression of disease in a majority of patients.Osteonecrosis of the femoral head (ONFH) occurs when the cells of the trabecular bone and marrow in the femoral head spontaneously die, leading to fracture and collapse of the articular surface (1,2). In the US, every year ONFH occurs in 10 000-20 000 adults between the ages of 20 and 60 (1,3,4). Once collapse occurs, severe pain ensues, and the disease course rarely regresses (5-8). In order to halt disease progression and provide pain relief, 80% of patients suffering from ONFH will require a total hip arthroplasty (THA); typically at a younger age than patients undergoing a THA for osteoarthritis (9-11).Although ONFH is a common indication for THA, the etiology of the disease is still unknown (12,13). ONFH is thought to be a multifactorial disease, with patients reporting a history of exposure to one or more risk factors, including trauma to the hip, alcohol abuse, corticosteroid use, hemoglobinopathies, pregnancy, coagulopathies, organ transplant, chemotherapy, Caisson disease, HIV, and autoimmune conditions; however in some patients the risk factor remains unknown, and the disease is termed “idiopathic” ONFH (12-16). Recent studies looking at the gentics risks of ONFH have resulted in identifying an autosomal dominant mutation in collagen type II gene (COL2 A1 gene) (17); which has been associated with genetic polymorphisms in alcohol metabolizing enzymes and the drug transport proteins (18,19).If the disease course is recognized before collapse of the subchondral bone and cartilage, patients can be treated with core decompression of the femoral head including Ficat Stage I or II (12,20,21). This technique has been used for over four decades, however randomized control trials have failed to show that this procedure alone halts disease progression and collapse (4). Recently, concentrated bone marrow autograft has been used to augment the decompression site to attempt to repopulate the femoral head with human mesenchymal stem cells (hMSC) (13,22,23). This aim of this paper is to describe our surgical technique and early clinical results using autologous bone marrow concentrate with platelet rich plasma and a minimally invasive decompression for the treatment of ONFH.     

Psychological problems in children of war veterans with posttraumatic stress disorder in Bosnia and Herzegovina: cross-sectional study

Aim

To assess psychological problems in children as reported by their veteran fathers with war-related posttraumatic stress disorder (PTSD).

Method

The study group consisted of 154 veterans with war-related PTSD who were treated at the Mostar University Hospital. The control group consisted of 77 veterans without war-related PTSD who were selected from veteran associations by the snowball method. General Demographic Questionnaire, the first and fourth module of the Harvard Trauma Questionnaire–Bosnia and Herzegovina version, and the Questionnaire on Developmental, Emotional, and Behavioral Problems in Children, created specifically for the needs of this study, were used to collect data on veterans’ perception of psychological problems in their children.

Results

In comparison with veterans without PTSD, veterans with PTSD reported significantly more developmental (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.51-3.73), behavioral (OR, 3.92; 95% CI, 1.53-10.03), and emotional problems (OR, 17.74; 95% CI, 2.40-131.10) in their children.

Conclusion

Veterans with war-related PTSD more often reported developmental problems in their children. Father’s PTSD may have long-term and long-lasting consequences on the child’s personality.Posttraumatic stress disorder (PTSD) in one family member can negatively influence other family members and affect entire family dynamics (1-3). For many reasons, children in such families are especially vulnerable (4).Many studies have established that, in comparison with children of combat veterans without PTSD, the children of combat veterans with PTSD have more frequent and more serious developmental, behavioral, and emotional problems (2,5-10). Some of them also have specific psychiatric problems (11).Interviews with spouses and partners of combat veterans revealed that children of veterans with PTSD have more behavioral problems (5) and more frequent problems with authority, depression, anger, hyperactivity, and personal relationships (6-10) than children of veterans without PTSD. They are also more aggressive, use opiate drugs more often (6), and have learning difficulties and problems with diadic relations and emotional regulation (8). However, Harkness (8,12) did not find a significant association between the intensity of PTSD symptoms in veteran fathers and behavior of their children. On the other hand, it seems that the children of Vietnam War veterans did have behavioral problems, with veterans’ PTSD being a possible indirect factor in this association (13). It is assumed that direct war experience may disrupt the later capability of veterans to function as parents, leading to difficulties in the development and behavior of their children (12,13).With respect to the degree of individual and social traumatization caused by war trauma and post-war social situation in Bosnia and Herzegovina (BH), we assumed that war-related PTSD in veterans would have noticeable effect on the development of their children and that children of veterans with PTSD would have more psychological problems than children of veterans without PTSD.The aim of our study was to determine developmental, behavioral, and emotional problems of children in BH as reported by their veteran fathers with combat-related PTSD.     

War experiences and war-related distress in Bosnia and Herzegovina eight years after war

Aim

To examine the relationship between war experiences and war-related distress in Bosnia and Herzegovina.

Methods

The survey was performed in the late 2003 on a representative sample of 3313 respondents. The face-to-face interviews included 15 items on war-related distress and 24 items on war experiences. From these items we developed the War-related Distress Scale, the Direct War Experiences Scale, and the Indirect War Experiences Scale. Regression analysis was used to examine the relationship between war-related distress symptoms and war experiences variables, controlling for a range of other variables.

Results

Almost half of the respondents did not report any war-related distress symptoms, while about 13% reported 7 or more symptoms. Direct war experiences had a significant effect on war-related distress even eight years after the war, while indirect war experiences showed no significant effect on war-related distress. We found that marital status weakly decreased war-related distress, while household size increased it.

Conclusion

Direct war experiences seem to have a long-lasting traumatic effect on a substantial number of residents of Bosnia and Herzegovina.Bosnia and Herzegovina is a multi-ethnic state with Bosniacs (40%), Serbs (33%), and Croats (20%) as the largest ethnic groups. Their separate ethnic identities partly stem from different religious affiliations. Bosniacs belong to the Islamic, Croats to the Roman Catholic, and Serbs to the Orthodox tradition. The Bosnian war (1992-1995) was one of the most devastating wars in Europe since World War II. The most recent figures indicate that about 100 000 out of a population of 4.4 million were killed and at least as many were injured (1,2).Thousands were killed in many massacres throughout Bosnia. The worst one took place in Srebrenica where as many as 8000 Bosniac men and boys were killed by Serbian forces. This massacre was later described as genocide by the International Criminal Tribunal for Yugoslavia (ICTY) in The Hague (3,4). More than two million people were driven away from their homes in the process of ethnic cleansing. According to the World Bank estimates, about 60% of all houses in Bosnia and Herzegovina, half of the schools, and a third of the hospitals were damaged or destroyed (5). War of such an intensity can leave no inhabitants untouched, though some were harmed far more than others (6,7).Such traumatic, often life-threatening events have been reported to be the main factor predicting posttraumatic stress disorder (PTSD) (8-11). Research has also shown that the effects of war experiences may be present many years after the exposure to traumatic events (12-15). We will use the concept of war-related distress since our instrument measures war-related symptoms.Our main explanatory variables are based on reported war experiences. In addition, there are many factors that may affect war-related distress, such as social support as well as control variables, including sex, age, education, socio-economic status, and ethnicity.A number of studies showed that multiple exposures to traumatic events or cumulative traumas were associated with higher levels of psychological problems (16-21).Studies among Cambodian and Bosnian refugees have shown that the exposure to a variety of adverse events was associated with an increasing risk of PTSD (11,22). Similar findings were obtained among asylum seekers (23) and refugees from diverse cultural backgrounds (24).Some studies have shown that experiencing direct war violence is a stronger predictor of war-related distress than indirect war experiences (25,26). Another study found, however, high rates of war-related distress despite different degrees of direct exposure (27). We will argue that the distinction between direct and indirect war experiences influences the seriousness of the war distress. Our questionnaire included questions on events the respondents experienced directly, ie, witnessed personally, or that happened to their family or in their community; as well as questions on events the respondents experienced indirectly, ie, about which they were told, but did not personally witness.Lack of social support may have a negative impact on physical and psychological health, while availability of social support may have a positive impact (28-31). So far, only a few studies have examined the relationship between social support and mental health in social systems which have experienced serious traumatic events (26). Although there are several components of social support (28), we focused on social support from close family relations, which is why we examined respondents’ marital status and number of household members.Earlier research has identified a range of risk factors for developing posttraumatic stress symptoms, such as female sex (20,26,32,33), age (34,35), socioeconomic status (26,36), level of education (26,33,35), and urban residence (26). To estimate the effects of war experiences on war-related distress we controlled for several socio-demographic variables. In addition, we also controlled for belonging to different ethnic groups (Bosniacs, Croats, and Serbs) and ethnical heterogeneity of the neighborhood where one lives. The aim of this study was to examine whether war experiences have an effect on war-related distress even eight years after the end of the Bosnian war; whether direct war experiences have a stronger effect on war-related distress than indirect war experiences; and whether social support, such as marital status and household size buffers war-related distress.