2008, volume 24, issue 1

Only for Pharmacotherapy in Psychiatry and Neurology

Mechanism of RNA interference and application of RNAi in therapy

Katarzyna Sipa, Barbara Nawrot
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 7–18

RNA interference (RNAi) is a newly discovered mechanism of the post-transcriptional regulation of gene expression. This phenomena is induced by coded in genome micro RNA (miRNA) or by synthetic, short interfering RNA (siRNA). Both types of RNA molecules after binding to RISC protein complex, exhibiting nucleolytic activity, operate as guides which recognize the complementary sequence in target mRNA. Formation of the siRNA/RISC complex with mRNA results in hydrolysis of the mRNA, and in consequence, in degradation of the translation template. Binding of the miRNA-loaded RISC to mRNA inhibits formation of the translational complex. Discovery of the RNA interference was a breakthrough for development of the functional genomics as well as kindled a new hope for revitalization of the therapeutic use of nucleic acids. At present the siRNA duplexes are widely used as universal, sequence specific inhibitors of gene expression for research purposes. In numerous biotechnological companies intensive studies are focused on introduction of siRNA molecules into therapies of diverse diseases. The most advanced (clinical trials phase II) are the studies on the siRNA directed towards mRNA of VEGF or of its receptor as an approach for treatment of age-related macular degeneration (AMD).

Original article

Val/Met polymorphism of COMT and prophylactic effect of lithium in bipolar affective illness

Agnieszka Permoda-Osip, Janusz Rybakowski, Aleksandra Suwalska, Monika Dmitrzak-Węglarz, Maria Skibińska, Piotr Czerski, Joanna Hauser
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 19–24

Objectives. The aim of this study was to assess a relation between Val/Met COMT polymorphism and bipolar affective illness in a group of lithium-treated patients and also an analysis of this polymorphism in these patients, in relation to lithium prophylaxis effects.
Methods. The study was performed on 101 patients with bipolar affective illness (41 male, 60 female) treated with lithium for at least 5 years (5-20 years). The patients were divided into three groups in respect to their response to prophylactic lithium administration (ER – excellent responders, PR – partial responders, NR – lithium non responders). The control group consisted of 437 healthy persons (166 male, 271 female). All patients and healthy subjects were genotyped for Val/Met COMT polymorphism using PCR method.
Results. The distribution of genotypes Met/Met, Val/Met, and Val/Val of COMT polymorphism was significantly different in bipolar patients treated lithium compared with control group. In bipolar illness group, significantly higher percentage of Met/Met homozygotes and significantly lower percentage of Val/Met heterozygotes appeared. Genotype distribution was not accordant to Hardy-Weinberg principle. In lithium-treated patients a presence of Met/Met genotype was the most frequent in the group of NR patients (44%) and the least frequent in ER group (29%).
Conlusions. The results obtained show a difference of genotype distribution between lithium-treated bipolar patients and healthy control subjects. The preponderance of Met/Met homozygotes in bipolar patients may suggest an association of bipolar affective illness with a tendency to higher dopaminergic activity in prefrontal cortex. A finding of the study was also an association between Met/Met genotype and poorer response to prophylactic lithium treatment.

Original article

Associations between the course of schizophrenia in first years of ilness and cognitive dysfunctions after 31 years from onset

Agnieszka Kałwa, Małgorzata Rzewuska, Agnieszka Piróg-Balcerzak, Małgorzata Luks, Janina Skalska, Alina Borkowska
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 25–32

The aim of this work is to assess the relationship between the course of schizophrenia in first 9 years from the onset and cognitive, clinical and social outcome after many years from onset. We investigated 33 patients with chronic schizophrenia who took part in 9 year-long follow-up in first years of disease; with medium duration of ilness 31 years. We found relationship between the type of ilness (severe process with higher number of hospitalizations vs longer periods of remissions, no need to be hospitalized) and present functioning of working memory and psychomotor speed, however no relationship between performance on neuropsychological tests (exept TMT part A and B) and the course of ilness (treated vs untreated psychosis) has been found. Our results show also significant relationship between functional outcome at the baseline and cognitive flexibility, psychomotor speed and nonverbal working memory. Ability to complete correctly categories in the WCST was connected with better social adjustment at the baseline and longer periods of regular pharmacological treatment in first years of ilness. Present social outcome was assessed as better comparing to baseline.

Original article

Clinic and pharmacotherapy of addiction to opioids and psychostimulants

Karina Steinbarth-Chmielewska, Helena Baran-Furga
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 33–42

Taking psychoactive substances can cause psychiatric symptoms as well as behavioral disturbances. Opioids and psychostimulants such as cocaine and amphetamine have strong addictive potential. Substitute treatment with agonists of opioid receptors, mainly methadone, or antagonist of opioid receptors –naltrexone, is available only in few places in Poland.There are no algorithms in the treatment of substance dependence, although trials with antidepressants, mood stabilizers or with drugs acting by “disrupting the reward circuit”, such as flupenthixol, disulfiram or naltrexone have been conducted. The efficacy of the pharmacotherapy in the treatment of the relapse in addictive disturbances is minimal. In recent two decades there has been a growing interest in the patients showing comorbidity of psychiatric disorder and various substance use. Clinical observations have shown that such patients stay shorter in treatment, have more frequent hospitalizations, exhibit more aggressive and suicidal behaviour, and the results of their treatment are worse compared to the patients with only one diagnosis.

Review article

Aipiprazole in the management of patients with nonschizophrenic mental disorders

Justyna Holka-Pokorska
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 43–52

An overview of recent research findings shows that Aripiprazole is more and more often used in the treatment of not only schizophrenia, but also other psychiatric disorders. In the paper psychopharmacological and clinical aspects of Aripiprazole use are discussed regarding the management of acute manic or mixed episodes associated with Bipolar I Disorder; the prevention of relapse into depression in stabilized patients with bipolar or unipolar affective disorder; potentialization of antidepressant treatment efficacy in patients with drug-resistant major depressive disorder; the treatment of core symptoms of borderline personality disorder, as well as psychotic symptoms in the course of Alzheimer’s disease or acute confusional states (delirium).

Aripiprazole turned out to be an effective normothymic agent in manic episodes treatment and relapse prevention in bipolar disorder. However, in clinical trials no beneficial effect of Aripiprazole monotherapy was found as regards either the reduction of depression severity or prevention of relapse into depression in bipolar disorder. On the other hand, combined Aripiprazole and antidepressant treatment turned out to ameliorate depressive symptoms in non-responding patients with unipolar affective disorder.

In the treatment of patients with borderline personality disorder Aripiprazole was reported to reduce depressive and anxiety symptoms, readiness to respond with aggression, and paranoid thinking. Since Aripiprazole is safe and well tolerated, it can be used to treat psychotic symptoms in the course of dementing syndromes or persistent confusional states of various etiologies in different somatic diseases. However, further research involving large-size patient populations is needed to verify Aripiprazole efficacy in the treatment of the latter two conditions.

Review article

The Bipolar Depression Rating Scale: the description and clinical utility

Wiktor Dróżdż, Alina Borkowska, Michael Berk
Farmakoterapia w Psychiatrii i Neurologii, 2008, 1, 53–63

Bipolar depression was diagnosed in the majority of patients attending psychiatric outpatients clinics in Poland in a survey recently published. Psychometric tools for assessment of depressive disorders currently used (i.e. the Hamilton Depression Scale or the Montgomery-Asberg Depression Rating Scale) were designed around the features of classic unipolar depression. A growing body of evidence suggests that there are phenomenological as well as psychopathological and pathogenetic differences between unipolar and bipolar depression. Hence, the principles of treatment of bipolar depression are distinct from the treatment algorithms for unipolar depression, and the metrics for symptom assessment need to reflect the unique phenomenological signature of bipolar depression. Here we present a newly elaborated scale for the assessment of symptoms of bipolar depression which has showed strong internal consistency, inter-rater reliability and correlations with other rating scales for depression. Additionally, Polish translation of the Bipolar Depression Rating Scale is enclosed.