Dragica Kozarić-Kovačić

Dopamine beta‐hydroxylase (DBH) activity and ‐1021C/T polymorphism of DBH gene in combat‐related post‐traumatic stress disorder

The roles of dopamine (DA) and norepinephrine (NE) in posttraumatic stress disorder (PTSD) are unclear. The aim of the study was to determine plasma dopamine beta‐hydroxylase (DBH) activity and DBH‐1021C/T gene polymorphism in combat veterans with (N = 133) or without (N = 34) chronic PTSD. Similar frequencies in genotype or allele distribution were found between veterans with or without PTSD. War veterans with PTSD had lower DBH activity, associated with the DBH‐1021C/T variant in DBH genes, than veterans without PTSD. A significantly lower plasma DBH activity was found in combat veterans with PTSD carrying the CC genotype as compared to veterans without PTSD carrying the corresponding genotype. Since both groups were exposed to the same trauma, it is possible that a pre‐existing trait difference in regulation of NE function contributed to a differential vulnerability to develop PTSD, or that the regulation of DBH expression was different in response to trauma. The results suggest that that genotype‐controlled measurement of plasma DBH activity might be used as a potential biological marker of the response to trauma, and that further studies of DBH and other loci related to DA and NA in PTSD are warranted.

Prevalence of Psychotic Comorbidity in Combat-Related Post-Traumatic Stress Disorder

OBJECTIVE We explored the prevalence of comorbidity of psychotic symptoms among Croatian war veterans with combat-related post-traumatic stress disorder (PTSD) and the psychotic features among these patients, as well as the association between psychotic symptoms and personality disorders. METHODS The study included 680 men who had experienced combat stress and had diagnoses of PTSD confirmed before examination. They were compared with a group of 289 soldiers with combat experience under regular medical examination, who were still in active military service. The groups were matched in duration of combat experience, time elapsed between combat experience and the study, age, marital status, and education. Statistical analyses were performed using the t test and chi2 test. RESULTS The study showed that 15% of war veterans had current chronic PTSD and 45% had PTSD with one or more comorbid diagnoses. Psychotic disorders with PTSD were confirmed for 17% of those patients and major depressive disorder with psychotic features for 15%. Depression and psychotic symptoms were more often found among patients without personality disorders. Also, we found that 9% of the war veterans who were still in active military service had some psychiatric disorders. CONCLUSIONS Many patients demonstrated psychotic symptoms different from flashbacks and dissociative symptoms. Those psychotic symptoms are an integral part of PTSD and have a symbolic relation to the trauma.

Exaggerated platelet reactivity to physiological agonists in war veterans with posttraumatic stress disorder

An association between traumatic stress and cardiovascular disease (CVD) is supported by various epidemiological studies. Platelet activation and binding of activated platelets to leukocytes contributes to the pathophysiology of CVD. Evidence of hyperactive sympathetic nervous system, altered expression of platelet α(2)-adrenoreceptors (α(2)AR), and altered platelet adenylate cyclase activity in patients with posttraumatic stress disorder (PTSD) suggest that platelet reactivity in PTSD may be altered as well. We tested whether platelet reactivity to increasing doses of adenosine-diphosphate (ADP), epinephrine (EPI), or their combination differs between war veterans with PTSD (n=15) and healthy controls (n=12). For this purpose, citrated whole blood was incubated with increasing concentrations of ADP (0.1, 1, 10 μM), EPI alone (10 nM, 100 nM, 1000 nM), or EPI (10 nM, 100 nM, 1000 nM) in combination with 0.1 μM ADP. A subset of samples was also incubated with 10 μM yohimbine (YOH), α(2)AR antagonist, to distinguish receptor-specific effects. Platelet CD62P expression and formation of platelet-leukocyte aggregates (PLA) [platelet-monocyte (P-Mo), -lymphocyte (P-Ly), and -neutrophil (P-Ne) aggregates] were measured using three-color flow cytometry. Platelet reactivity was higher in war veterans with PTSD when compared to controls, as determined by greater CD62P expression and formation of PLA in response to ADP alone or in combination with EPI. Platelet reactivity also correlated with the severity of PTSD symptoms. Preliminary experiments with YOH indicate that stress-associated EPI elevations may contribute to platelet activation through a α(2)AR-dependent mechanism. The enhanced platelet reactivity observed in our study may be the underlying mechanism contributing to the development of CVD in PTSD patients.

Combat-experienced soldiers and tortured prisoners of war differ in the clinical presentation of post-traumatic stress disorder

The symptoms of the acute post-traumatic stress disorder (PTSD) were compared between 16 prisoners of war (POWs) tortured in detention camps and 20 soldiers with combat-related PTSD. PTSD was diagnosed in accordance with Watsons PTSD Questionnaire. Clinical symptoms were assessed in a structured clinical interview, using the Brief Symptom Inventory (BSI). Scores on PTSD scales were significantly higher in POWs. Dominant symptoms reported by POWs in a clinical interview were guilt feelings, psychic numbing, headache, and lack of energy. Soldiers with combat-related PTSD complained of panic attacks and more often reported uncontrolled aggressive behavior. The differences in the quality and quantity of PTSD symptoms and their clinical presentation between the soldiers who survived different traumas may be related to the specific combat and traumatic circumstances of their situation.

Epidemiological study of suicide in the Republic of Croatia – comparison of war and post-war periods and areas directly and indirectly affected by war

We examined the differences in the suicide characteristics between areas directly and indirectly affected by war activities and in war and post-war periods according to the following variables: suicide rate, sex, age and method of suicide. Analysis was done on 5349 suicides committed in the period 1993-1998 (war and post-war years). The suicide rates in the Republic of Croatia oscillated in the pre-war, war and post-war periods (1985-2000) but without significant differences. In the areas directly affected by war, the suicide rate was significantly lower than in other areas during the study period 1993-1998 (chi-square = 10.3245; P = 0.0017). The number of suicides in both sexes declined in the areas directly affected by war-more in men than in women; the difference between sexes was statistically significant (chi-square = 3.6697; P = 0.055). Middle- and old-aged people were the population with high suicide risk in both areas (t = 1.76; P = 0.078). There were significant differences in the methods of suicides between war and non-war areas (chi-square = 108.8473; P = 0.001). Firearms or explosive devices were the methods used more significantly for suicides in the areas directly affected by war than in other areas, whereas hanging was more frequently used in the areas indirectly affected by war.

Suicide attempt, smoking, comorbid depression, and platelet serotonin in alcohol dependence.

The risk of suicide in patients with alcoholism increases if alcoholism is related to comorbid depression. Both alcoholism and suicidal behavior are associated with reduced serotonin (5-hydroxytryptamine [5-HT]) function. Because suicide is enormous public health problem worldwide, to prevent suicide attempts, it is important to find peripheral marker of suicidal behavior. The aim of this study was to assess whether platelet 5-HT concentration is altered in alcoholic patients with or without suicide attempt. Platelet 5-HT concentration was evaluated in 397 male and 108 female ethnically homogenous medication-free patients with alcoholism, subdivided according to smoking status, comorbid depression, and a history of suicide attempt and in 450 male and 139 female healthy control (nonsuicidal) subjects. Suicide attempt was assessed by two measures: according to the score 4 on the item 3 from the Hamilton Rating Scale for Depression and according to the Structured Clinical Interview regarding suicidal attempt during lifetime. Both male and female patients with alcoholism who were nonsmokers had significantly lower platelet 5-HT concentration than the corresponding healthy subjects. Multifactor analyses of variance revealed the significant effects of alcoholism and smoking, but the lack of significant effects of suicide attempt, sex, or comorbid depression, and no interactions between variables, on platelet 5-HT concentration. Platelet 5-HT concentration did not differ significantly between suicidal patients compared with nonsuicidal patients with alcoholism. Because the results from the present study showed similar platelet 5-HT values between patients with or without a history of suicide attempt, our data did not support the hypothesis that platelet 5-HT concentration might be used as a peripheral marker of the pronounced suicidal behavior in alcoholism.

Outcome of influenza vaccination in combat-related post-traumatic stress disorder (PTSD) patients

Post‐traumatic stress disorder (PTSD) is an anxiety disorder that can occur after exposure to extreme traumatic experience such as war trauma, and is accompanied by fear, helplessness or horror. Exposure to trauma can result in immune dysregulation and influence susceptibility to infectious disease as well as vaccine efficacy. The aim of the study was to determine the relation of psychological stress and the immune response to influenza vaccination in combat‐related PTSD patients (n = 28). Detection of anti‐viral antibody titre was performed by inhibition of haemagglutination assay. Ex vivo tetramer staining of CD8+ T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)‐A*0201‐restricted influenza A haemagglutinin antigens before and after vaccination. Twenty patients showed a fourfold antibody titre increase to one or both influenza A viral strains, and 18 of them showed the same response for both influenza B viral strains. Ten of 15 healthy controls showed a fourfold rise in antibody titre to both influenza A viral strains and eight of them showed the same response for both influenza B viral strains. HLA‐A*0201+ PTSD patients (n = 10) showed a significant increase of influenza‐specific CD8 T cells after vaccination. Although those PTSD patients had a lower number of influenza‐specific CD8+ T cells before vaccination compared to HLA‐A*0201+ healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination. The generated humoral and cellular immune response in PTSD patients argues against the hypothesis that combat‐related PTSD in war veterans might affect protection following influenza vaccination.

Psychiatric aspects of normal and pathological lying

The paper outlines the difference between the so-called normal (common) lying and pathological lying. Pathological lying is an intriguing topic, still lacking any strong professional consensus, clear etiology, treatment options and prognoses. The paper explores some possible psychological mechanisms of pathological lying, reviews biological factors in pathological lying, and considers forensic significance of normal and pathological lying. The relationship between pathological lying and mental disorders is also discussed. The authors suggest that lying should be considered as a heterogenic and multidimensional behavioral pattern. The paper highlights how important it is to assess the patients control over lying, the function of lying, insight into and awareness of lying, as well as the effect of lying on everyday functioning.

Cognitive status of Croatian combat veterans and their compensation-seeking

Aim: To explore the differences in MMPI-2 scales and cognitive function scales (WAIS-III) in combat veterans submitted to expert examination for compensation-related purposes, compensation-seeking (CS) and war veterans who were under regular medical examination, non-compensation-seeking (NCS) veterans in Croatia. Methods: The study included 64 CS Croatian war veterans and 48 NCS war veterans. Both patient groups were assessed and diagnosed by a psychiatrist. Data were collected by Mini International Neuropsychiatric Interview (M.I.N.I) and Clinically Administered PTSD Scale. Psychological data on cognitive functions were collected by Wechsler Intelligence Scale- Revised (WAIS-III-R) and Minnesota Multi Personality Inventory-2 (MMPI-2). Results: Significant differences in CS and NCS groups on executive scales (digit-span and arithmetic), memory scales (numeric and visual), visual processing scales (visual completion), and control scales of MMPI-2 (F, Fb, K and L). There were no significant differences between compensation-seeking and non-compensation-seeking PTSD patients in verbal, non-verbal and global intelligence (VIQ, NIQ and IQ). Significantly lower results are shown on memory scales and higher results on control MMPI-2 scales for CS PTSD (with and without comorbid diagnoses) in comparison to NCS with PTSD or PTSD with comorbid diagnoses. Conclusion: Cognitive functions and over-reporting symptoms of PTSD are correlated especially in working memory, executive functions (digit-span, numeric memory and arithmetic) and visual completion and visual memory. Compensation-seeking could be an important artefact in neuropsychological measures and also offer additional help in the diagnosis of PTSD and cognitive impairment.

Comparison of ego strength between aggressive and non-aggressive alcoholics: a cross-sectional study

Aim To determine the differences between aggressive and non-aggressive alcoholics in sociodemographic and clinical characteristics and ego strength. Methods This cross-sectional study included 111 aggressive and 123 non-aggressive male alcoholics aged between 25 and 60 years who were admitted to the Department for Alcoholism, University Psychiatric Hospital Vrapče, Zagreb, Croatia, from January to December 2016. All participants met the diagnostic criteria for alcohol dependence according to the Croatian Mini International Neuropsychiatric Interview (MINI), 4th revised edition of Diagnostic and Statistical Manual of Mental Disorders, and the International Classification of Diseases. Participants were clinically assessed by an experienced psychiatrist using a clinical interview, MINI, Questionnaire from the Brown-Goodwin Lifetime History of Aggression, and Ego Identity Scale (EIS) according to Erikson. A clinical psychologist performed cognitive function measurements. EIS scores were analyzed using one-way analysis of variance. Results In comparison with non-aggressive alcoholics, aggressive alcoholics were more often divorced, unemployed, hospitalized, and first treated for alcoholism at an earlier age (P < 0.05 for all). They more frequently experienced depression (42.4% vs 19.4%, P = 0.013) and attempted suicide (34.7% vs 6.2%, P = 0.003), achieved a lower level of maturity at the second stage of psychosocial development related to shame and doubt (14.0 ± 4.1 vs 17.4 ± 3.7, P = 0.013) and at the fourth stage related to inferiority (13.1 ± 6.8 vs 18.1 ± 9.3, P = 0.011), and had lower total EIS score (75.8 ± 20.4 vs 85.2 ± 21.5, P < 0.012) than non-aggressive alcoholics. Conclusion Aggressive alcoholics had weaker ego-strength than non-aggressive alcoholics, experienced more depressive reactions and suicide attempts, and showed poorer psychosocial functioning. Oxford Centre for Evidence-based Medicine level of evidence: 3**