| 1 | Isr J Psychiatry Relat Sci 2006 -1 43: 52-6 |
|---|---|
| PMID | 16910386 |
| Title | Acute intermittent porphyria: psychosis as the only clinical manifestation. |
| Abstract | Acute intermittent porphyria (AIP) is the most common of the four forms of neuroporphyria. AIP mimics a variety of disorders and thus poses a diagnostic quagmire. Abdominal pain occurs in 90-95% of the attacks. Some patients develop psychiatric symptoms such as psychosis similar to schizophrenia. The diagnostic difficulty may lead to under-diagnosis of patients who present with strictly psychiatric symptoms. This assumption is supported by a high prevalence of AIP in psychiatric hospitals. Therefore, we encourage a high index of suspicion for AIP in psychiatric patients in order to prevent false psychiatric diagnosis. In addition we discuss psychotropic drugs that may exacerbate acute attacks in undiagnosed patients. We report a case in which the diagnosis of AIP was clouded by the presence of only psychiatric symptoms. The clue for diagnosis was an anamnestic detail of the use of a porphyrogenic drug prior to the admission. The diagnosis of AIP was supported by excess of alpha aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine concomitantly with a decrease in porphobilinogen deaminase (PBGD) activity in erythrocytes. The diagnosis was further strengthened by the fact that the patient's father was identified as an AIP carrier. However, in the absence of typical organic symptoms of porphyria, one cannot definitely rule out the presence of schizophrenia in this patient in addition to AIR |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychopharmacology (Berl.) 2009 Oct 206: 491-9 |
| PMID | 19680635 |
| Title | Genome-wide association study of antipsychotic-induced parkinsonism severity among schizophrenia patients. |
| Abstract | Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of neuroleptic treatment. Interindividual heterogeneity in AIP development and severity is associated with risk factors such as antipsychotic drug type, old age, and female gender. There is evidence for genetic predisposition to develop AIP but the variants that confer susceptibility or protection are mostly unknown. To identify genes related to AIP susceptibility, we performed a pharmacogenomic genome-wide association study (GWAS) for AIP severity. Three hundred ninety-seven American schizophrenia patients who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-GWAS project were included in our analysis. Patients had been randomized to treatment with antipsychotic monotherapy for periods ranging from 2 weeks to 18 months during phase 1 of the CATIE trial. They were regularly assessed for AIP severity using the modified Simpson-Angus Scale (SAS). For statistical analysis, patients were dichotomized as cases (average SAS mean global score > 0.3 during CATIE phase 1, N = 199) or controls (average SAS mean global score 0, N = 198). Using logistic regression and controlling for population stratification, age, gender, SAS score at baseline, and concomitant use of anticholinergic drugs, we identified several single-nucleotide polymorphisms associated with AIP severity. Although none reached the GWAS significance level of P < 4.2 x 10(-7), some promising candidate genes for further research on genetic predisposition to AIP were identified including EPF1, NOVA1, and FIGN. Our finding may contribute to understanding of the pathophysiology of AIP as well as to a priori identification of patients vulnerable for development of AIP. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Pharmacogenomics J. 2009 Apr 9: 103-10 |
| PMID | 18347610 |
| Title | Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region. |
| Abstract | RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study. EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69 Caucasian) treated for at least a month with typical antipsychotic drugs (n=45), risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695, rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Our results indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP), as measured by the Simpson Angus scale, in the overall sample and in the African-American subsample, the G (minor) allele having a protective effect. ORs for AIP among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample. In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We completely sequenced the RGS2 gene in nine patients with AIP and nine patients without, from the Israeli sample. No common coding polymorphisms or additional regulatory variants were revealed, suggesting that association of the rs4606 C/G polymorphism with AIP is biologically meaningful and not a consequence of linkage disequilibrium with another functional variant. Taken together, the findings of the current study support the association of RGS2 with AIP and focus on a possible protective effect of the minor G allele of SNP rs4606. This SNP is located in the 3'-regulatory region of the gene, and is known to influence RGS2 mRNA levels and protein expression. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Int J Psychiatry Med 2009 -1 39: 133-46 |
| PMID | 19860072 |
| Title | Factors related to admission of psychiatric patients to medical wards from the general hospital emergency department: a 3-year study of urgent psychiatric consultations. |
| Abstract | Emergency Rooms (ER) of Emergency Departments (ED) in General Hospitals (GH) have a role in providing for psychiatric evaluation. The aims of the present study were to examine the decision-making process of consultation psychiatry at the GH-ER and to analyze the differences between psychiatric patients admitted to a medical ward with those admitted to the psychiatry unit and those who are discharged from the ER. Over a period of 3 years, psychiatric consultations requested by ER of ED physicians to the GH Psychiatric service were recorded by using a form to describe epidemiological and clinical data on the consultation process. Of 1,962 psychiatric consultations, most regarded subjects who had had previous psychiatric contacts (76.2%) and at least one psychiatric admission (53.6%), and were currently cared for by the Mental Health Services (51.1%). Neurotic/stress-related syndromes (27.98%), schizophrenia (27.67%), and personality disorders (21.81%) were the most frequent ICD-10 diagnoses. The psychiatrist's disposal was to discharge the patient in 49.9% cases, to admit him/her to medical wards of the GH (MGH; 26.9%) or to the acute inpatient psychiatric ward (AIP; 23.1%). MGH group statistically differed from AIP group for being female (p < 0.01), older (p < 0.01), more likely having an ICD-10 diagnosis of neurosis/stress-related syndromes (p < 0.01) or organic mental disorder (p < 0.01), and less likely having a diagnosis of schizophrenia (p < 0.01), being in charge of the Mental Health Services (p < 0.01), and having had previous psychiatric admissions (p < 0.01). These results were confirmed by logistic regression analysis. The study shows that the medical wards of the General Hospital are a significant entry-point for providing psychiatric care of patients with ICD-10 neurotic and stress-related syndromes, even if without specific medical problems. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Biochem. J. 2011 May 435: 755-69 |
| PMID | 21323643 |
| Title | Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation. |
| Abstract | cAMP-specific PDE (phosphodiesterase) 4 isoforms underpin compartmentalized cAMP signalling in mammalian cells through targeting to specific signalling complexes. Their importance is apparent as PDE4 selective inhibitors exert profound anti-inflammatory effects and act as cognitive enhancers. The p38 MAPK (mitogen-activated protein kinase) signalling cascade is a key signal transduction pathway involved in the control of cellular immune, inflammatory and stress responses. In the present study, we show that PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1 (ultraconserved region 1) domain conserved among PDE4 long isoforms, by MK2 (MAPK-activated protein kinase 2, also called MAPKAPK2). Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. This modification confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP. Such reprogramming of cAMP accumulation is recapitulated in wild-type primary macrophages, but not MK2/3-null macrophages. Phosphorylation by MK2 also triggers a conformational change in PDE4A5 that attenuates PDE4A5 interaction with proteins whose binding involves UCR2, such as DISC1 (disrupted in schizophrenia 1) and AIP (aryl hydrocarbon receptor-interacting protein), but not the UCR2-independent interacting scaffold protein ?-arrestin. Long PDE4 isoforms thus provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Eur Neuropsychopharmacol 2012 May 22: 379-86 |
| PMID | 21982117 |
| Title | Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model. |
| Abstract | Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24 days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, pole test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the pole test. Results were most consistent for the 0.2 mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Neuropsychology 2012 Jul 26: 451-8 |
| PMID | 22612578 |
| Title | Revised associative inference paradigm confirms relational memory impairment in schizophrenia. |
| Abstract | Patients with schizophrenia have widespread cognitive impairments, with selective deficits in relational memory. We previously reported a differential relational memory deficit in schizophrenia using the Associative Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in schizophrenia (CNTRICS) initiative to examine relational memory. However, the AIP had limited feasibility for testing in schizophrenia because of high attrition of schizophrenia patients during training. Here we developed and tested a revised version of the AIP to improve feasibility. 30 healthy control and 37 schizophrenia subjects received 3 study-test sessions on 3 sets of paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After training, subjects were tested on the trained, noninferential Face-Face pairs (F3-F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of the trained House-Face pairs. schizophrenia patients were significantly more impaired on the inferential F1-F2 pairs than the noninferential F3-F4 pairs, providing evidence for a differential relational memory deficit. Only 8% of schizophrenia patients were excluded from testing because of poor training performance. The revised AIP confirmed the previous finding of a relational memory deficit in a larger and more representative sample of schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Psychopharmacology (Berl.) 2012 Apr 220: 519-28 |
| PMID | 21947317 |
| Title | Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients. |
| Abstract | Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants. The aim of this study was to validate our original AIP-GWAS susceptibility variants and to understand their possible function. We conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in an independent sample of 178 US schizophrenia patients treated for at least a month with typical or atypical antipsychotics. Then, a sample of 49 Jewish Israeli Parkinson's disease (PD) patients with available neuroimaging ([(123)I]-FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with level of dopaminergic deficits in the putamen. Using logistic regression and controlling for possible confounders, we found nominal association of the intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene with AIP (62 affected/116 unaffected), in the whole sample (p?=?0.009; P?=?5.97?×?10(-5) in the GWAS), and in the African American sub-sample (N?=?111; p?=?0.002). The same rs12678719-G AIP susceptibility allele was associated with lower levels of dopaminergic neuron related ligand binding in the contralateral putamen of PD patients (p?=?0.026). Our preliminary findings support association of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is associated with deficits in the nigrostriatal pathway in PD patients that may be related to latent subclinical deficits among AIP-prone individuals with schizophrenia. Further validation studies in additional populations are required. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Br J Psychiatry 2015 Dec 207: 556-7 |
| PMID | 26494868 |
| Title | Acute intermittent porphyria: comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden. |
| Abstract | Acute intermittent porphyria (AIP) has been associated with schizophrenia in some studies, but prior research is limited by the absence of comparison populations. Here, we linked Swedish registers to examine the risk of schizophrenia and bipolar disorder in 717 individuals diagnosed with AIP and their first-degree relatives, compared with matched individuals without AIP and their first-degree relatives. Individuals with AIP had a fourfold increased risk of schizophrenia or bipolar disorder. Similarly, relatives of individuals with AIP had double the risk of schizophrenia or bipolar disorder, suggesting that these associations may be as a result of common genetic influences. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Am J Addict 2015 Oct 24: 586-9 |
| PMID | 26332037 |
| Title | Amphetamine-induced psychosis: Transition to schizophrenia and mortality in a small prospective sample. |
| Abstract | We investigated transition from amphetamine-induced psychosis (AIP) to schizophrenia. A sample of 28 individuals was identified while hospitalized for AIP. We reviewed their hospital records after six years. During follow-up, seven individuals (25%) died and nine (32%) had moved from the area. Of the remaining 12, four individuals (25%) were diagnosed with schizophrenia. These individuals were, at baseline, characterized by fewer hallucinatory symptoms and more homelessness. Hospitalization for AIP was a relatively specific risk factor for schizophrenia and the mortality rate in AIP was high. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Front Neurol 2015 -1 6: 27 |
| PMID | 25750634 |
| Title | Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes. |
| Abstract | Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study. |
| SCZ Keywords | schizophrenia, schizophrenic |