The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy

ABSTRACT

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy.

Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data.

Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance.

Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.     

Therapeutic efficacy of bilateral prefrontal slow repetitive transcranial magnetic stimulation in depressed patients with Parkinson's disease: an open study.

Recent studies have suggested that both high- and low-frequency repetitive transcranial magnetic stimulation (rTMS) have antidepressant effects in patients with major depression. We conducted an open study to assess the effects of slow rTMS on mood changes in patients with depression associated with Parkinson's disease (PD). Ten depressed patients with PD (four with major depression and six with dysthymia) received daily sessions of rTMS (frequency, 0.5 Hz; pulse duration, 0.1 msec; field intensity, 10% above the motor threshold) over both prefrontal regions (a total of 100 stimuli per prefrontal region daily) over 10 consecutive days. This treatment resulted in a moderate but significant decrease in scores of the Hamilton Depression Rating Scale (33-37%) and the Beck Depression Inventory (24-34%), which persisted 20 days after finishing the stimulation. In parallel, we observed mild improvement (18-20%) of motor symptoms. No significant adverse effects were reported. These preliminary results suggest the therapeutic potential of daily prefrontal low-frequency rTMS (0.5 Hz) in depression associated with PD.     

Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

BACKGROUND/AIM: Spasmodic dysphonia (DS) is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80-100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. METHODS: The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12-16 units each. In our study we applied indirect technique originally developed by Hocevar and Pirtosek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. RESULTS: The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index--(VHI) that was rated as rather significant one (t = 3.562; p = 0.006). CONCLUSION: Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.     

Novel stressors affected catecholamine stores in socially isolated normotensive and spontaneously hypertensive rats

Catecholamines in some central (hypothalamus and hippocampus) and peripheral tissues (adrenal glands and heart auricles) of long-term socially isolated normotensive and spontaneously hypertensive rats exposed to novel immobilization stress were determined by a simultaneous single isotope radioenzymatic assay. Long-term isolation (21 days) produced depletion of hypothalamic norepinephrine (NE) stores and hippocampal dopamine (DA) stores in both normotensive and spontaneously hypertensive rats. Acute immobilization stress (2 h) significantly decreased NE and DA stores in hypothalamus and hippocampus of naive normotensive and spontaneously hypertensive rats controls. However, novel immobilization stress applied to normotensive rats previously subjected to long-term isolation produced no changes in catecholamine levels in hypothalamus, while resulting in somewhat higher depletion of NE stores in hypothalamus of spontaneously hypertensive rats treated in the same way. Novel immobilization stress decreased NE and DA stores in hippocampus of normotensive but was without effect on NE and DA stores of spontaneously hypertensive rats. Social isolation did not affect catecholamine stores in peripheral tissues but novel immobilization stress produced a significant decrease in catecholamine content. The results suggest that some central and peripherals tissues of spontaneously hypertensive rats and normotensive rats differ with regard to catecholamine content and that there are certain differences in their responsiveness to stress.     

Long-term dynamic-oriented group psychotherapy of posttraumatic stress disorder in war veterans: prospective study of five-year treatment

Aim

To assess the effectiveness of the long-term group psychotherapy in the treatment of posttraumatic stress disorder (PTSD) in war veterans on the basis of clinical picture of PTSD, associated neurotic symptoms, and adopted models of psychological defense mechanisms.

Methods

Prospective cohort study involved 59 war veterans who participated in dynamic-oriented supportive group psychotherapy for five years. The groups met once a week for 90 minutes. Forty-two veterans finished the program. The Clinician-Administered PTSD Scale structured interview was used to assess the intensity of PTSD. Crown-Crisp Index was used to evaluate other neurotic symptoms, and Life Style Questionnaire was used to assess the defense mechanisms. The assessments were done at the beginning of psychotherapy, after the second, and after the fifth year of treatment. Comorbid diagnoses, hospitalizations, and outpatient clinic treatments were also recorded.

Results

Long-term group psychotherapy reduced the intensity of PTSD symptoms in our patients (the difference between Clinician-Administered PTSD Scale score at the beginning and the end of treatment, F = 9.103, P = 0.001). Other neurotic symptoms and the characteristic profile of defense mechanisms did not change significantly during the course of treatment. Predominant defense mechanisms were projection (M = 82.0 ± 14.4) and displacement (M = 69.0 ± 16.8). None of the symptoms or defense mechanisms present at the beginning of the treatment changed significantly after two or five years of treatment. The number of diagnosed major depressive episodes, which increased after the second year of psychotherapy, decreased by the end of treatment.

Conclusion

Psychotherapy can reduce the intensity of PTSD symptoms, but the changes in the personality of veterans with PTSD are deeply rooted. Traumatic experiences lead to the formation of rigid defense mechanisms, which cannot be significantly changed by long-term group psychotherapy.A traumatic experience greatly changes the perception of inner and outer world in a patient with posttraumatic stress disorder (PTSD) (1). Feelings of deep isolation, alienation, helplessness, and distrust, together with interpersonal problems and socially dysfunctional behavior, are the main psychological components of PTSD (1). Group psychotherapy, therefore, has the central role in the integrated psychiatric treatment of patients with PTSD (2).Since 1980, when the term “posttraumatic stress disorder” was introduced in psychiatric nomenclature, numerous studies have been conducted to establish the most appropriate psychotherapeutic methods for treating this disorder (3). Although recent guidelines recommend cognitive-behavioral approach, it seems that this type of therapy cannot be successfully applied in all war veterans, especially not in those with chronic PTSD (2-5). Deeply rooted changes in personality, which disturb biological, psychological, and social equilibrium, require long-term therapy. The corrective emotional experience and the feeling of security in a therapeutic group setting strengthen the healthy parts of the self, and neutralize and reintegrate the destructive ones (6). Dynamic-oriented group therapy is commonly used because the number of patients who need psychological help is relatively high, the availability of group therapists is limited, and the range of indications for this type of therapy is broad (2).After the 1991-1995 war in Croatia, the number of war veterans asking for psychiatric help has been increasing. In the first encounters with these patients, psychiatrists prescribed psychopharmaceuticals more often than short psychotherapeutic interventions. However, they soon realized that PTSD symptoms were recurring after an initial improvement and that the disorder had a strong and lasting impact on the patients'' professional, social, and family life. It was obvious that initially applied treatment methods could not successfully meet veterans’ needs for continuous and accessible mental health care. A more comprehensive and effective psychotherapeutic approach had to be adopted (6,7).Our aim was to assess the effectiveness of long-term group psychotherapy in the treatment of war veterans with PTSD by evaluating the clinical picture of PTSD, associated neurotic symptoms, and adopted models of psychological defense mechanisms after two and five years of treatment.     

Evaluation of examination stress based on the changes of sinus arrhythmia parameters

AIM: The aim of this study was to assess changes during the pre-examination, examination and postexamination period investigation in the sinus arrhythmia parameters. EXAMINEES AND METHODS: Twelve female subjects, first year students of Psychology, matched by age and previous experience in taking exams, participated in the study. The state of anxiety, high activation and exam apprehension were assessed. The R-R cardiac intervals were continuously recorded by an eight-channel polygraph (Powerlab). The measurements were made four times in the pre-examination period (days-20, -10, -1 and immediately before the exam), and on two occasions after the exam (days 1 and 10 days of the exam). The recording of R-R intervals also began five minutes before the exam and continued during the exam and five minutes after the exam. RESULTS AND DISCUSSION: The level of anxiety, exam apprehension and high activation changed in a similar way, showing almost linear increase with the approaching of the exam. The changes of R-R interval parameters showed that stress was highest during the exam. The measurements and analysis of results showed a decrease of stress in the postexamination period.     

The pituitary-adrenal axis of fetal rats after maternal dexamethasone treatment

Elevated glucocorticoid level in the gravid female circulation affects number of endocrine functions in fetuses and offspring. In this research female rats were injected with dexamethasone (Dx) in three consecutive daily doses of 1.0, 0.5, 0.5 mg/kg body weight, starting from day 16 of pregnancy. The influence of this treatment on the pituitary adrenocorticotrophic (ACTH) cells and adrenal glands of 19-day-old fetuses was examined immunocytochemically and by morphometric analysis. Moreover, the proliferative activity of adrenocortical cells was estimated after application of the mitotic inhibitor Oncovine. Administration of Dx to pregnant rats induced a decline of fetal ACTH cell immunopositivity and significant decreases of ACTH cell volume (23%, p<0.05), volume density (41%, p<0.05), and its number per unit area (17%, p<0.05) in comparison to the control 19-day-old fetuses. Reduced proliferative activity of adrenocortical cells (31%; p<0.05) in zona glomerulosa, as well as the volume of this zone were detected. The volume and number of fetal adrenocortical cells in the inner zone and chromoblasts were not significantly reduced after Dx treatment of pregnant rats. These results show that maternal Dx administration in the period when the fetal hypothalamo-pituitary-adrenal (PA) axis begins its function inhibited the PA axis. Reduced ACTH cell function and mitotic activity led to suppression of adrenocortical cell multiplication in zona glomerulosa, the region of the adrenal cortex where most proliferating cells were found in control 19-day-old fetuses. Thus, increased glucocorticoid levels during late pregnancy caused developmental modifications involving the fetal PA axis, which could be the basis of the altered endocrine responsiveness in adult life.