Volume 10, Issue 1, March 2008

Editoral in Hungarian

István Degrell

An objective method for the assessment of expressed emotions and symptoms during direct family transactions in schizophrenia

Szabolcs Kéri, Oguz Kelemen

Abstract

Evidence suggests that expressed emotions (EEs) play a critical role in relapse in schizophrenia and adversely affect the long-term course of the disorder. In this paper we describe a method which is suitable for the objective assessment of EEs and associated psychopathological symptoms during direct family interactions. The patients and one of their family members participated in a 20-min interaction during which the number of relatives’ criticism and the number of patients’ unusual thoughts was measured (Rosenfarb IS, Goldstein MJ, Mintz J, Nuechterlein KH: Expressed emotion and subclinical psychopathology observable within the transactions between schizophrenic patients and their family members. J Abnorm Psychol 1995; 104:259-267). The results revealed that the mean number of criticism was 4.3 (SD=4.0), and the mean number of unusual thoughts was 3.2 (SD=3.9). The interrater reliability was high (kappa=0.78). Based on the assessment of this Hungarian sample, this method has been proven to be suitable for the evaluation of EEs and psychopathology during interpersonal transactions. Given that EE reactivity is related to cognitive functions, cognitive enhancers may have a positive effect.

Keywords: expressed emotion, unusual thought content, schizophrenia, family communication

Transcriptome alterations in the prefrontal cortex of subjects with schizophrenia who committed suicide

Krassimira Garbett, Rodica Gal-Chis, Gabor Gaszner, David A. Lewis, Karoly Mirnics

Abstract

To better understand the pathophysiological events associate with suicide in subjects with schizophrenia, we performed a DNA microarray expression profiling of the frontal cortex of subjects with schizophrenia who committed suicide, subjects with schizophrenia who died of non-suicidal causes and matched control subjects. Simultaneous expression profiling for >40,000 genes was performed using HU133A and HU133B Affymetrix oligonucleotide arrays. We conclude that suicide in schizophrenia is associated with a number of gene expression changes in the prefrontal cortex that are distinct from both of that observed in controls and subjects with schizophrenia who did not commit suicide. Furthermore, the observed gene expression signature contains a prefrontal cortical downregulation of the HTR2A serotonin receptor transcript, strengthening previously reported genetic susceptibility reports. As the observed transcript changes are likely developing over days or weeks, these data argue that the molecular predisposition to suicide develops significantly earlier than the act of suicide occurs. Finally, the presented data also strengthens previous reports of neuroimmune transcriptome disturbances in subjects with schizophrenia.

Keywords: schizophrenia, suicide, gene expression, DNA microarray, serotonin receptor, HTR2A

A comparison of the pharmacology of (-)-deprenyl to N-methylpropargylamine-1-aminoindane (J-508) and rasagiline, the desmethyl-analogue of J-508

Ildikó Miklya

Abstract

N-methylpropargylamine-1-aminoindane (J-508), a strong releaser of catecholamines was described 30 years ago as a more potent selective inhibitor of MAO-B than (-)-deprenyl (Knoll 1978). In 2007 the desmethyl-analogue of J-508 (rasagiline) was registered as a new selective inhibitor of MAO-B and a possible substitute for (-)-deprenyl in therapy. The discovery of the enhancer regulation, the realization that catecholaminergic and serotonergic neurons in the brain stem are enhancer-sensitive neurons, phenylethylamine (PEA) and triptamine are endogenous enhancer substances, (-)-deprenyl is a PEA-derived synthetic enhancer substance, and finally the development of (-)-BPAP, a tryptamine-derived, 100 times more potent synthetic enhancer substance than (-)-deprenyl, made it clear that the enhancer effect of (-)-deprenyl is primarily responsible for the therapeutic benefits of this drug. To compare the pharmacological spectrum of (-)-deprenyl and rasagiline was the aim of this study. The ability of rats to acquire a two way conditioned avoidance response (CAR) in the shuttle box was analyzed during 5 consecutive days. Tetrabenazine treatment (1 mg/kg, s.c.) depletes from their stores the transmitters of the catecholaminergic neurons of the brain stem. Since the activation of the cortical neurons via the noradrenergic neurons in the brain stem is sine qua non for the acquisition for a CAR, rats treated with tetrabenazine are unable to learn in the shuttle box. To block the activity of MAO-A (clorgyline) or to treat rats with an enhancer substance [(-)-BPAP] are the two possibilities to antagonize the learning deficit caused by tetrabenazine. We compared in shuttle box experiments the effect of (-)-deprenyl, (-)-desmethyl-deprenyl, J-508 and desmethyl-J-508 (rasagiline) on the learning ability of rats pretreated with tetrabenazine. We used as a reference substance clorgyline to demonstrate the effect of a selective MAO-A inhibitor, and (-)-BPAP to demonstrate the effect of a selective enhancer substance. (-)-Deprenyl and (-)-desmethyl-deprenyl acted, like (-)-BPAP, in low doses as enhancer substances and in very high doses as MAO-A inhibitors. J-508 and rasagiline proved to be devoid of the enhancer property and in doses which are known to block MAO-A, they antagonized the effect of tetrabenazine, like clorgyline. Thus, rasagiline can not be a substitute for (-)-deprenyl in therapy.

Keywords: (-)-BPAP, clorgyline, (-)-deprenyl, (-)-desmethyl-deprenyl, enhancer substances, J-508, rasagiline

SNAP-25: a novel candidate gene in psychiatric genetics

Reka Kovacs-Nagy, Jimmy Hu, Zsolt Ronai, Maria Sasvari-Szekely

Abstract

SNAP-25 (synaptosomal-associated protein of 25 kDa) is an integral part of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor), a docking complex for synaptic vesicle exocytosis and neurotransmitter release. Results with SNAP-25 deficient mouse models highly accelerated association studies of SNAP-25 as a candidate gene for psychiatric disorders, such as Attention Deficit Hyperactivity Disorder (ADHD) and Schizophrenia. Candidate gene studies implicate a large number of single nucleotide polymorphisms (SNPs). Among the numerous SNPs, the miR SNPs are novel functional variants affecting the binding of specific microRNA to their target mRNA. According to our in silico studies there are two putative miR SNPs in the 3’untranslated region (3’UTR) of the SNAP-25 gene. If the putative miR SNPs are shown to have a function in vivo their implication in further psychogenetic association studies will have a higher impact.

Keywords: SNAP-25, microRNA, psychiatric genetics, candidate gene study, ADHD, depression

Delusion assessment scales

L’Ubica Forgáčová

Abstract

Since the beginning of the 19th century, delusions have been classified mainly by their content or theme. Clinical psychopathological investigation requires additional variables that will allow investigators to describe the structure of delusional experience more accurately. Delusions are multidimensional constructs that may change across the various mental disorders. Several authors have developed rating scales with the aim to measure individual dimensions of delusional structure. In this paper, common rating scales are mentioned and the main characteristics of the Simple Delusional Syndrome Scale (SDSS) are summarized. The SDSS scale consists of 7 items (logical organization, systemization, stability, conviction, influence on the action, extension, and insertion), scored from 1 to 5. Results of the statistical analysis confirm good psychometric characteristics of the scale, Cronbach coefficient alpha=0.8327. The SDSS may contribute to a better understanding and diagnostics of delusional disorders and, using statistical methods, can help quantify the relationship between the delusional syndrome and the primary disease process. The SDSS scale may also be utilized in the assessment of changes occurring in delusional syndromes depending on the therapeutic effect of psychopharmacological drugs.

Keywords: delusions, rating scales, simple delusional syndrome, Simple Delusional Syndrome Scale

Mood stabilizers – past, present and future

András Sümegi

Abstract

Bipolar disorders are common, chronic, recurrent, and episodic mood disturbances, associated with variable dysfunctions in sleep, appetite, libido, activity, and cognition. These disorders are typically so severe that they impair occupational functioning. Until the discovery of lithium in the treatment of bipolar disorders, only electroconvulsive therapy was the available treatment of mania. After discovering the therapeutic effect of lithium in bipolar illness, the clinical outcome of the disorder has changed dramatically. Lithium has become the mainstay of the the treatment for bipolar disorders, however, the management of the illness has historically focused on the treatment of mania. Although the lifetime prevalence of bipolar disorder was originally estimated to be about 1%, the recent decade has brought more evidence, that the several clinical manifestations of the bipolar spectrum affects almost 5-6% of the general population. Lithium was absolutely helpful in euphoric mania, but with other types of disorder, especially bipolar depression and rapid cycling form, this efficacy significantly decreases. The newer mood stabilizers, carbamazepine and valproate have brought more possibilities to cover a broader zone of the bipolar spectrum. Although the new agents have offered a bit more protection against bipolar depression when used for prophylaxis, anyway, lithium, carbamazepine and valproate all are relatively ineffective against acute bipolar depression and rapid cycling. The third generation mood stabilizer lamotrigine has a broader and more effective efficacy in bipolar disorder, extending the therapeutic ranger especially in bipolar depression and in the difficult to treat rapid cycling subtype. This review provides a wide overview about the four most important mood stabilizers, lithium, carbamazepine, valproate and lamotrigine at the level of their synaptic and intracellular activities.

Keywords: bipolar disorder, bipolar depression, rapid cycle, lithium, carbamazepine, valproate, lamotrigine

The importance of depressive mixed states in suicidal behaviour

Annamaria Rihmer, Xenia Gonda, Judit Balazs, Gabor Faludi

Abstract

Research indicates that depressive mixed state (DMX) constitutes a very important suicide risk factor within the major affective episode. eral recently published studies demonstrated that DMX is present in one third of unipolar- and in two thirds of bipolar II major depressives, and substantially increases the risk of suicidal behaviour. Because of its nature and characteristics, this condition should be considered as part of the bipolar spectrum. The recognition and better understanding of DMX also have important implications for the recognition and prevention of suicide. The aim of this manuscript is to review the relationship between suicide attempt/completed suicide and depressive mixed state (DMX) (major depression plus 3 or more co-occurring intra-depressive non-euphoric hypomanic symptoms, which highly correspond to the well-recognised “agitated depression”). Our review establishes three important key points related to the role of depressive mixed states in suicidal behaviour: 1. In the majority of suicides, a current major mood episode is present; 2. DMX and agitated depression present a risk factor for suicidal behaviour; 3. DMX and agitated depression should be considered as bipolar spectrum. These should be taken into consideration in clinical and diagnostic work with affective disorder patients.

Keywords: suicide, depressive mixed states, agitated depression, bipolar spectrum disorder