Volume 7, Issue 2, June 2005
Anna Székely, Zsolt Rónai, Mária Sasvári-Székely
For some human traits heritability estimates are well known based on results from twin studies. However, the study of connecting these characteristics to candidate genes in the Human Genom has just been started. The main goal of the recently formulated Human Fenom Project is to define “endophenotypes”, characteristics that have considerable heritable component, and can be empirically measured with objective tools, standardized across cultures. Based on our recent findings the VNTR polymorphism in the coding region of the dopamin D4 receptor gene is a candidate gene of the “persistence” trait. Individuals carrying the 7-repeat polymorphism of this allele describe themselves as less persistent. In line with these results the 7-repeat polymorphism was associated to the “persistence” trait as measured by the Junior version of the TCI in a psychiatric sample of children diagnosed with ADHD. Based on these findings our main goal was to define an objective, behavioral measure which could be used as an “endophenotype” in genetic association studies. “Persistence” could be related to responsiveness in a reaction time task demanding sustained attention, for example. This hypothesis was tested using a sample of 35 healthy Caucasian subjects, participating in a extended cognitive reaction time task and filling out the TCI personality questionnaire. Non-invasive DNA sampling was used to determine the candidate polymorphism of the DRD4-VNTR. Results using self-report data replicated our previous findings: the 7-repeat polymorphism was significantly associated to lower “persistence” scores. Individual differences of reaction time were compared using the 7-repeat present/absent grouping as well. Results indicate that responses of individuals with the 7-repeat allele were significantly slower and more variable than of those without this candidate allele. Based on self-report and behavioural measures “persistence” trait is a possible endophenotype of psychogenetic associations.
KEYWORDS: genetic association study, endophenotype, temperament and character inventory, persistence personality trait, reaction time, dopamine D4 receptor gene polymorphism
There are three various approaches in the pharmacological treatment of posttraumatic stress disorder (PTSD) among the published data. The most frequently implemented approach is to treat patients suffering from the diagnosis of PTSD. Both short-term acute and long-term relapse prevention treatments represent a curative paradigm: with an intention to diminish the symptoms associated with the disorder. Data about efficacy of monoamine oxidase inhibitors and selective serotonin reuptake inhibitors (SSRIs) in the treatment of PTSD are heterogeneous. Data are relatively consistent with regards of efficacy of SSRIs in the treatment of civilian, predominately female population, regardless of the type of trauma: interpersonal or non-interpersonal trauma. Placebo controlled trial data in the treatment of combat-related PTSD are inconclusive or negative. Three recently published studies provide new approaches to the treatment of male patients, suffering from combat-related PTSD. A relatively young, recently traumatized male, combat-related population showed significant improvement for fluoxetine compared to placebo. An adjuvant 5HT2 antagonist profile may improve the SSRI effect in the treatment of PTSD: nefazodone was significantly superior compared to placebo in the treatment of combat-related PTSD, and risperidone treatment add-on to antidepressants showed significant benefits compared to antidepressant monotherapy in the treatment of combat-related PTSD. The goal of sedative paradigm is to minimize the immediate consequences of the traumatic stress, decrease the fear, anxiety and sleeplessness. Data published about benzodiazepines failed to show effectiveness in the acute management of post-traumatic mental consequences. The intention of the third treatment paradigm is characterized by the secondary prevention of PTSD. Benzodiazepines administered shortly after the traumatic event, failed to prevent the mental consequences of traumatic stress. Two small trials with propranolol administration after the trauma have been shown some benefits compared to placebo or no treatment. PTSD represents a complex disregulation of numerous neurotransmitters and neuromodulators, therefore the complex pharmacological treatment has to consider approaches beyond the current treatment regimens characterized by modulation of monoamine neurotransmission.
KEYWORDS: posttraumatic stress disorder, sedative paradigm, curative paradigm, secondary prevention
Ákos Ferencz, Enikő Bartók, Roland Berecz, Teodóra Glaub, István Degrell
Background. Relationship between schizophrenia and cognitive functions has been reported by several studies. Our workgroup examined the changes of cognitive functions in prepsychotic patients without any relevant psychiatric disorder in their anamnesis, and also in schizophrenic patients with predominantly negative symptoms. Methods. Measures were carried out by Cambridge Neuropsychological Test Automated Battery (CANTAB), a complex computer-based test battery of 13 tests covering a wide range of cognitive functions. 11 prepsychotic (9 male, 2 female) and 14 negative-symptom schizophrenic patients (all male) took part in the study.
Results. Prepsychotic patients showed significant (p<0,05) impairment in the tests of visual memory, spatial recognition memory, spatial working memory and sustained attention. In patients with negative-symptoms significant deficits were also found (p><0,05) in the delayed matching to sample, the working memory test, and in the intra- extradimensional shift – an analogue of Wisconsin Card Sorting Test.>>0,05). impairment in the tests of visual memory, spatial recognition memory, spatial working memory and sustained attention. In patients with negative-symptoms significant deficits were also found (p<0,05) in the delayed matching to sample, the working memory test, and in the intra- extradimensional shift – an analogue of Wisconsin Card Sorting Test.><0,05) in the delayed matching to sample, the working memory test, and in the intra- extradimensional shift – an analogue of Wisconsin Card Sorting Test.
Conclusion. The present results show CANTAB may be a useful tool to detect the emergence of psychosis in an early phase, and also it has been found that in schizophrenic patients with predominantly negative symptoms further areas of cognition are also affected. The results may provide a better understanding about the background of the disorder, and the early recognition of the cognitive deficits may help to initiate a specific therapy in proper time. This could result in the slowing of the progression and an improved chance of recovery.
KEYWORDS: neuropsychological, neurocognitive, CANTAB, schizophrenia, prepsychosis
Viktor Vörös, Sándor Fekete, Anthea Hewitt, Péter Osváth
Despite of the decreasing suicide rates, the number of suicide attempts – peculiarly in the adolescent population – shows a growing tendency. Due to the small amount of study results the problem remains hard to assess. Child and Adolescent Self-harm in Europe (CASE) study, allows us to explore self-reported suicidal behavior among adolescents more exactly. This European multicentre study has a special focus on adolescent suicidal behavior (suicidal thoughts, ideation, deliberate self harm, suicide attempt) and other self destructive behavior (drug, alcohol) as well as psychopathological symptoms (anxiety, depression, impulsivity, aggression) and it also investigates coping strategies, life events and family background. In the representative school-based community study an anonymous, self-reported questionnaire were conducted with 4408 (males: 2388, females: 2020) 15 and 16 year-old pupils. Out of the 4408 pupils 7.8% (males: 4.6%, females: 11.6%) of the adolescents reported former suicide attempt, 1.6% of the boys and 3.6% of the girls reported about more than one suicide attempts. According to the statistical analysis the suicidal group greatly differs from the non-suicidal one. Suicidal adolescents were more likely to use alcohol, drugs or nicotine than their non-suicidal peers. Drug abuse was four times more common among suicidal boys, and five times more common among suicidal girls than in the non-suicidal group. 30% of the boys and 13% of the girls used more than one kind of drug. The use of ecstasy and sedatohypnotic drugs showed the most spectacular difference between suicidal and non-suicidal teenagers in both genders. Suicide attempters usually had higher scores in scales measuring anxiety, depression, impulsivity, while their self-esteem was significantly lower. The comparative analysis has revealed that suicide attempters compose a subgroup with more severe psychopathology (anxiety, depression, and impulsivity), lower self-esteem and ineffective coping strategies. Suicidal behavior frequently appeared with addictive problems. The results of our study may help in recognizing the role of risk factors coexisting with suicidal behavior and thus making it easier for schools to have adequate and effective prevention programs.
KEYWORDS: suicide attempt, adolescent population, epidemiology, addict behavior, psychopathology
The concurrent use of more than one drug to treat syndromes and diseases is common in medicine as well as in psychiatry. Despite strong recommendation by experts to employ monotherapy whenever possible, the prevalence of antipsychotic polypharmacy (APP) has greatly increased, particularly since the advent of the Second Generation Antipsychotics (SGA). The literature which consists of three RCTs, several naturalistic cohort studies and numerous case reports does not show convincing evidence of APP efficacy. The best results were seen in studies of augmentation of clozapine response by a second antipsychotic. Studies which examined the side effect burden showed higher rates of anticholinergic and extrapyramidal side effects of APP compared to monotherapy, but these differences tended to disappear when total dosage was controlled for. The relative cost of APP may be higher than monotherapy, but very little data are available. Experts recommend APP in a few special clinical situations: a) for augmentation when a patient fails to respond to adequate antipsychotic trials, especially with clozapine; b) in some instances of failed cross-taper of antipsychotics; c) adding a FGA to a SGA for agitation during acute treatment of psychosis. Indiscriminate condemnation of APP is misdirected, the real culprit being incompetent pharmacotherapy. Improved education and advances in the science of psychopharmacology will lead to more specific antipsychotic therapies and ultimately to less need for APP.
KEYWORDS: polypharmacy, monotherapy, first generation antipsychotics, second generation antipsychotics
Henriette Walter, Alexander Dvorak, Karin Gutierrez, Werner Zitterl, Otto Michael Lesch
Human substance use is complex, being influenced by many psychopathological and sociological factors as well as the substance’s pharmacological effects. Dependence development is not attributable directly to the consumed substance, but takes also all the other issues into regard. One of all these issues might be that gender represents an influencing factor and impacts on tolerance of a substance, on abuse patterns and finally on development of dependence as well as on addiction related disorders. Therapeutic programs´ needs might be different too. In general, more men than women are alcohol dependent or have alcohol problems, but women are at greater risk for adverse effects and alcohol related diseases. Death rates among female alcoholics are 50 to 100 percent higher than those of men. Major impairments, diagnosis, medical and psychosocial consequences and their implication on treatment will be outlined.
The strategy and points of medication and the use of antipsychotics in the phase of psychosocial rehabilitation substantially different from that we use in the acute treatment. While in the acute phase the primary goal is the symptomreduction as soon as possible, the goal in the psychosocial rehabilitation is the maintenance of the symptom-free remission state, as long as possible in a stable way, providing the best functioning and best available quality of life with minimal loss of capacities and skills. The basis of the lasting, stable remission and of the successful psychosocial rehabilitation is the effective, safe and tolerable pharmacotherapy, in which the antipsychotics play essential role. Second generation antipsychotics are more favorable for patients and for clinicians, then the first generation ones.
KEYWORDS: psychosocial rehabilitation, antipsychotics, remission, cooperation, therapeutic alliance