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TRANSCRIPTOME STUDY IN OBSESSIVE COMPULSIVE DISORDERS
Abstracts
S927
SU72. TRANSCRIPTOME STUDY IN OBSESSIVE COMPULSIVE DISORDERS n
Bianca Lisboa ,1, Ana Carolina Tahira1, Arthur Sant'Anna2, Katia Oliveira1, Euripedes Constantino Miguel1, Marcelo Hoexter1, José Marcelo Farfel1, Helena Brentani3 1
University of Sao Paulo UFABC 3 Institute of Psychiatry HCFMUSP
gyri (ACC) in cortex are involved with affective circuitry; and Putamen (PT) in striatum and Orbitofrontal Cortex (OFC) are involved with ventral cognitive circuitry. We found differential gene expression between the areas with different biological functions. The next step will be the evaluation of the coexpression networks between the two circuitry.
Disclosure: Nothing to disclose.
2
http://dx.doi.org/10.1016/j.euroneuro.2017.08.261
Background: Obsessive Compulsive Disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions. The features of OCD are intrusive thoughts (obsessions) and repetitive behavior (compulsions). Functional neuroimaging studies indicate that OCD is a heterogeneous disorder related to the cortical-striatal thalamic circuitry (CSTC) and the areas that compose this circuitry include the nucleus accumbens (NAC), Putamen (PT), Caudate Nucleus (CN), Orbitofrontal Cortex (OFC) and subgenual cingulate gyri (ACC). Each brain area has a relevant role in the affective, dorsal cognitive and ventral cognitive corticostriatal loops (CSTC). Our proposal is compare the gene expression from transcriptome of post mortem brain from affective and ventral cognitive cortico-striatal circuitry. Methods: The brains are part of the psychiatric collection of Brain Bank of Brazilian Aging Brain Study Group (PsyBBBABSG). All cases and controls were 50 years and older, non-demented and without previous factors that could be cause hypoxia or autolysis of the brain. We analyzed 56 samples sourced from 8 OCD cases and 8 controls aligned by gender, age and hemisphere. The clinical, functional and psychiatric assessment evaluation was made by next-of-kin of the deceased answered a screening with semi-structured questionnaires. The library was constructed with ribosome depletion and the RNA sequencing was performed in automatic sequencer lluminaHiSeq 2500. The reads were evaluated to control quality using FastQC and aligned with genome using TopHat (genome reference hg38). We use Cuffilinks to perform the transcript assembly and HTSeqcount to determine the reads counts to gene in each sample. The gene expression was evaluated using DESeq2 and enrichment analysis was performed with WegGestalt. Results: To each circuitry we analyzed Differentially Expressed Genes (DEGs), comparing OCD and controls in each brain area. Were observed 400 DEG in NAC and 512 in the ACC in the affective circuitry, with 16 DEG common to each area. Enrichment analysis showed involvement of the exclusive DEGs from NAC in regulation of synaptic plasticity, glutamatergic and dopaminergic synapses, while exclusive DEGs from ACC enriched to infection disease and metabolic process. To ventral cognitive circuitry, were observed 619 DEG in PT and 444 in the OFC, with 25 DEG common and enrichment analysis showed exclusive DEGs from PT involved with regulation of neurological system process and stimulus responded, whereas exclusive DEGs from OFC involved with gliogenesis, ensheathment of neurons and drug metabolic process. Discussion: We analyzed 2 circuitry involved with OCD, the affective and ventral cognitive cortico-striatal circuitry. The Nucleus Accumbens (NAC) in striatum and subgenual cingulate
SU73. GENE EXPRESSION IN BLOOD OF ADOLESCENTS WITH PSYCHIATRIC DISORDERS n
Leticia Spindola ,1, Marcos Santoro1, Pedro Pan1, Fernanda Talarico1, Gabriela Xavier1, Carolina Carvalho1, Ary Gadelha1, Giovanni Salum Junior2, Euripedes Constantino Miguel3, Luis Rohde4, Evelin Aline Zanardo3, Leslie Domenici Kulikowski3, Rodrigo Bressan1, Vanessa Ota1, Sintia Belangero1 1
Federal University of Sao Paulo Hospital De Clinicas De Posto Alegre 3 University of Sao Paulo 4 Federal University of Rio Grande do Sul 2
Background: Neuropsychiatric disorders represent a large public health and economic burden at a national and global level, and delineating the genetic architecture of mental disorders across molecular levels will aid in the development of novel treatment and prevention strategies. Whereas most psychiatric disorders are moderately to highly heritable and there are evidences of shared genetic etiology for psychiatric disorders, we aimed to investigate gene expression profiling in adolescents with psychiatric disorders from a large prospective community school-based study in Brazil, the High Risk Cohort (HRC) Study for Psychiatric Disorders. Methods: This is a cross-sectional study comprised of adolescents from the HRC. Participants were assessed using the structured diagnostic interview Development and WellBeing Assessment (DAWBA) to evaluate psychiatric diagnosis according to the DSM-IV and psychopathology measures were assessed using Child Behavior Checklist (CBCL). Transcriptome in blood was compared between 23 adolescents with at least one psychiatric disorder (PD group) and 25 healthy controls (HC group) with no previous psychiatric disorder and low psychopathology symptoms. Blood gene expression profiling was measured using HumanHT-12 v4.0 Expression BeadChip (Illumina) and the 100 most associated genes list was brought forth to assess whether they were enriched for any Gene Ontology (GO) Biological Process category or canonical pathway (by KEGG - Kyoto Encyclopedia of Genes and Genomes) using the Enrichr tool. Results: The most prevalent diagnosis in PD group was anxiety disorders (44%), followed by major depression (28%), conduct disorders (28%) and attention deficit hyperactivity disorder (ADHD – 24%), knowing that some of those diagnoses were overlapped. We have not found
S927
SU72. TRANSCRIPTOME STUDY IN OBSESSIVE COMPULSIVE DISORDERS n
Bianca Lisboa ,1, Ana Carolina Tahira1, Arthur Sant'Anna2, Katia Oliveira1, Euripedes Constantino Miguel1, Marcelo Hoexter1, José Marcelo Farfel1, Helena Brentani3 1
University of Sao Paulo UFABC 3 Institute of Psychiatry HCFMUSP
gyri (ACC) in cortex are involved with affective circuitry; and Putamen (PT) in striatum and Orbitofrontal Cortex (OFC) are involved with ventral cognitive circuitry. We found differential gene expression between the areas with different biological functions. The next step will be the evaluation of the coexpression networks between the two circuitry.
Disclosure: Nothing to disclose.
2
http://dx.doi.org/10.1016/j.euroneuro.2017.08.261
Background: Obsessive Compulsive Disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions. The features of OCD are intrusive thoughts (obsessions) and repetitive behavior (compulsions). Functional neuroimaging studies indicate that OCD is a heterogeneous disorder related to the cortical-striatal thalamic circuitry (CSTC) and the areas that compose this circuitry include the nucleus accumbens (NAC), Putamen (PT), Caudate Nucleus (CN), Orbitofrontal Cortex (OFC) and subgenual cingulate gyri (ACC). Each brain area has a relevant role in the affective, dorsal cognitive and ventral cognitive corticostriatal loops (CSTC). Our proposal is compare the gene expression from transcriptome of post mortem brain from affective and ventral cognitive cortico-striatal circuitry. Methods: The brains are part of the psychiatric collection of Brain Bank of Brazilian Aging Brain Study Group (PsyBBBABSG). All cases and controls were 50 years and older, non-demented and without previous factors that could be cause hypoxia or autolysis of the brain. We analyzed 56 samples sourced from 8 OCD cases and 8 controls aligned by gender, age and hemisphere. The clinical, functional and psychiatric assessment evaluation was made by next-of-kin of the deceased answered a screening with semi-structured questionnaires. The library was constructed with ribosome depletion and the RNA sequencing was performed in automatic sequencer lluminaHiSeq 2500. The reads were evaluated to control quality using FastQC and aligned with genome using TopHat (genome reference hg38). We use Cuffilinks to perform the transcript assembly and HTSeqcount to determine the reads counts to gene in each sample. The gene expression was evaluated using DESeq2 and enrichment analysis was performed with WegGestalt. Results: To each circuitry we analyzed Differentially Expressed Genes (DEGs), comparing OCD and controls in each brain area. Were observed 400 DEG in NAC and 512 in the ACC in the affective circuitry, with 16 DEG common to each area. Enrichment analysis showed involvement of the exclusive DEGs from NAC in regulation of synaptic plasticity, glutamatergic and dopaminergic synapses, while exclusive DEGs from ACC enriched to infection disease and metabolic process. To ventral cognitive circuitry, were observed 619 DEG in PT and 444 in the OFC, with 25 DEG common and enrichment analysis showed exclusive DEGs from PT involved with regulation of neurological system process and stimulus responded, whereas exclusive DEGs from OFC involved with gliogenesis, ensheathment of neurons and drug metabolic process. Discussion: We analyzed 2 circuitry involved with OCD, the affective and ventral cognitive cortico-striatal circuitry. The Nucleus Accumbens (NAC) in striatum and subgenual cingulate
SU73. GENE EXPRESSION IN BLOOD OF ADOLESCENTS WITH PSYCHIATRIC DISORDERS n
Leticia Spindola ,1, Marcos Santoro1, Pedro Pan1, Fernanda Talarico1, Gabriela Xavier1, Carolina Carvalho1, Ary Gadelha1, Giovanni Salum Junior2, Euripedes Constantino Miguel3, Luis Rohde4, Evelin Aline Zanardo3, Leslie Domenici Kulikowski3, Rodrigo Bressan1, Vanessa Ota1, Sintia Belangero1 1
Federal University of Sao Paulo Hospital De Clinicas De Posto Alegre 3 University of Sao Paulo 4 Federal University of Rio Grande do Sul 2
Background: Neuropsychiatric disorders represent a large public health and economic burden at a national and global level, and delineating the genetic architecture of mental disorders across molecular levels will aid in the development of novel treatment and prevention strategies. Whereas most psychiatric disorders are moderately to highly heritable and there are evidences of shared genetic etiology for psychiatric disorders, we aimed to investigate gene expression profiling in adolescents with psychiatric disorders from a large prospective community school-based study in Brazil, the High Risk Cohort (HRC) Study for Psychiatric Disorders. Methods: This is a cross-sectional study comprised of adolescents from the HRC. Participants were assessed using the structured diagnostic interview Development and WellBeing Assessment (DAWBA) to evaluate psychiatric diagnosis according to the DSM-IV and psychopathology measures were assessed using Child Behavior Checklist (CBCL). Transcriptome in blood was compared between 23 adolescents with at least one psychiatric disorder (PD group) and 25 healthy controls (HC group) with no previous psychiatric disorder and low psychopathology symptoms. Blood gene expression profiling was measured using HumanHT-12 v4.0 Expression BeadChip (Illumina) and the 100 most associated genes list was brought forth to assess whether they were enriched for any Gene Ontology (GO) Biological Process category or canonical pathway (by KEGG - Kyoto Encyclopedia of Genes and Genomes) using the Enrichr tool. Results: The most prevalent diagnosis in PD group was anxiety disorders (44%), followed by major depression (28%), conduct disorders (28%) and attention deficit hyperactivity disorder (ADHD – 24%), knowing that some of those diagnoses were overlapped. We have not found