Volume 9, Issue 2, June 2007
Eszter Dömötör, Andrea Sárosi, Gabriella Balogh, Anna Székely, Krisztina Héjjas,
Mária Sasvári-Székely and Gábor Faludi
Two well known polymorphic regions of the serotonin transporter gene (SLC6A4) are the 5HT-TLPR which consists of a 44-bp insertion or deletion in the promoter region and the STin2 consisting of variable number of tandem repeats in the second intron. Several studies focused on the association of the 5HTTLPR and behavioral or clinical factors of depression; on the other hand, the relation of the STin2 to major depressive disorder (MDD) is less widely investigated. We carried out a case-control study of 71 MDD patients and 99 healthy control subjects comparing frequencies of the STin2 allele- and genotype variants in the two populations. We found a significantly higher frequency of the STin2 10/10 homozygous genotype in the MDD patients’ group compared to controls (chi2 = 6,01, df = 2, p < 0.05). To further explore possible endophenotypes of neurocognitive functioning in the background of this disorder we measured performance of 71 cases and 30 matched controls using several tests of neurocognitive functioning. Our results indicated cognitive dysfunctions of the MDD patients in all tests as compared to control individuals. The clinical subgroup with at least one copy of the 10-repeat allele showed a decreased interference threshold in Stroop III as compared to patients without the 10-repeat allele. Average performance of the clinical subgroup without the 12-repat allele proved to be significantly weaker in the working memory and recall tasks (RAVLT) compared to patients having at least one copy of the 12-repeat allele. After further confirmation our results suggest that the presence of STin2.10 and absence of STin2.12 allele may be defined as a possible genetic endophenotype for cognitive dysfunctions detected in MDD.
Keywords: depression, serotonin transporter, STin2 gen polymorphism, neurocognition, endophenotype
Zoltán Rihmer, Péter Döme, Xénia Gonda, Huba Kiss G., Dénes Kovács, Krisztina Seregi, Zsófia Teleki
BACKGROUND: Epidemiological and clinical studies have found a significant association between smoking and suicidal behaviour.
METHOD: 334 outpatients with DSM-IV diagnosis of unipolar major depression, bipolar (I+II) disorder, schizophrenia, schizoaffective disorder and pure panic disorder were interviewed regarding to their smoking habits and previous suicide attempts.
RESULTS: With the exception of panic disorder patients, the rate of prior suicide attempt(s) was much higher among current and lifetime smokers than among never smokers in all diagnostic groups, but the difference was statistically significant only for lifetime smoker unipolar depressives and for current and lifetime smoker schizophrenics.
LIMITATIONS: Age, social class and alcohol/caffeine consumption was not controlled and dependent vs nondependent smokers were not distinguished.
CONCLUSIONS: The findings support previous results on the strong relationship between smoking and suicidal behaviour in psychiatric (particularly major depressive and schizophrenic) patients.
KEYWORDS:affective disorders, cigarette smoking, suicide attempt, panic disorder, schizophrenia
Ágnes Szilágyi, Csaba Barta, Krisztina Boór, Anna Székely, Zsolt Demetrovics, József Csorba, Huba Kalász, Mária Sasvári-Székely
Several studies suggested a possible link between substance use disorder and attention deficit hyperactivity syndrome (ADHD). The ADHD Rating Scale (ADHD-RS) completed by parents is a tool for diagnosing ADHD in childhood. We adapted this questionnaire for a self-report retrospective scale to estimate the presence of childhood ADHD symptoms in adults. This retrospective questionnaire was completed by 121 heroin dependent patients and 85 age- and sex-matched healthy controls. The ADHD Rating Scale Retrospective Questionnaire is a novel tool for assessing ADHD symptoms that demonstrated high validity. Our results showed strong gender difference in the prevalence of ADHD symptoms, since male subjects obtained higher mean scores of both attention-deficit and hyperactivity scales than females in both the control and the heroin dependent population. Besides, mean score of both scales were higher in the clinical population as a higher portion of substance abusers reported symptoms of childhood ADHD than controls. These results support the hypothesis that untreated childhood ADHD could be a risk factor for developing substance use disorder.
Keywords: ADHD, drug abuse, heroin
The hereditability of bipolar disorder (Bpd) and schizophrenia (Sch) is a well known fact, twin studies are applied to estimate the contribution of the genetic background. Gene linkage studies provided from suicidal brain samples are used to identify mutation of susceptibility genes involved in the etiology. Numerous genes are playing role in the altered signal transduction pathways. Based on the combined effects and functional interactions between the enzymes expressed by these key genes, it could be possible to estimate the genetic risk. Through targeting the intracellular enzymes we can affect the pathogenesis and modify neuronal plasticity of Bpd and Sch, thus developing new psychoactive drugs.
Keywords: bipolar disorder, schizophrenia, gene expression, signal transduction, neuronal plasticity
Neuropsychopharmacology is dedicated to the study of the pathophysiology and treatment of mental pathology with the employment of centrally acting drugs. In neuropsychopharmacological research the clinical effects of a psychotropic drug are linked to the effects of the substance on brain structures involved in its mode of action. It is assumed, that knowledge about the mode of action of a selectively effective psychotropic drug will provide clues about the pathophysiology of the illness, and conversely, that knowledge about the pathophysiology of an illness, will provide clues for developing clinically more effective psychotropic drugs. Since the currently employed clinical methodology for the demonstration of therapeutic efficacy links the mode of action of psychotropic drugs to pharmacologically heterogeneous populations, neuropsychopharmacological research does not provide the necessary feedback for developing more effective drugs. To resolve the pharmacological heterogeneity within currently used diagnoses, attempts were made to split syndrome-based psychiatric diagnoses into discrete neurobiological deficits, and to replace traditional psychiatric nosology by a genetic psychiatric nosology. Yet, to date, there is no alternative methodology to psychopathology-based psychiatric nosology for classifying mental pathology in a clinically relevant manner. As we are moving from the “neurotransmitter era” to a “genetic era” in neuropsychopharmacology, the need for identifying pharmacologically homogenous populations is becoming imminent. All primary targets of psychotropic drugs in the brain are encoded by genes which are identified, and any nosologic entity or psychiatric syndrome that corresponds with a treatment responsive population is a candidate for the generation of genetic hypotheses relevant to mental illness. Recognition that progress in neuropsychopharmacology, and molecular genetic research, depends on the speed clinical research can resolve the pharmacological heterogeneity within currently used diagnoses, led to the development of methodologies for the identification of treatment responsive form(s) of illness, such as the Composite Diagnostic Evaluation (CODE) System, and nosologic homotyping. The CODE System is a methodology for the identification of treatment responsive forms of illness if covered up by consensus-based diagnoses; it consists of a set of diagnostic algorithms that can assign simultaneously a diagnosis from several classifications to a patient. Nosologic homotypes are identical in elementary units of mental illness and are assigned the same position in the nosologic matrix, based on three “nosologic organizing principles. The empirically derived diagnostic categories are suitable for testing hypotheses relevant to the relationship between the “processing of mental events” and “signal transduction” in the central nervous system.
Keywords: alternative phenotypes, genetic classification, CODE System, CODE-DD, neuropsychopharmacological research; nosologic homotyping, nosologic matrix; polarity, psychopathologic symptoms, temporal organization, totality
We hospitalized a 50 year-old-woman because of prolonged violent suicide. Coming she had depressive symptoms, but her psychical observation and the heteroanamnestic data have shown psychotic symptoms–paranoid schizophrenia. During hospitalisation her checkup was very correct: long-lasting risperidone-therapy formed the centre of her psychopharmacotherapy. We applied close control and long-lasting antipsychotic treatment–, so the patient became well, without psychotic symptoms. So it was proved, that the long-lasting parenteral antipsychotic risperidone play important role of good compliance.
Keywords: schizophrenia, emotional emptyness, delusive symptoms, long-lasting antipsychotic treatment, good compliance