Disclosing common biological signatures and predicting new therapeutic targets in schizophrenia and obsessive-compulsive disorder by integrated bioinformatics analysis.

Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive-compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence of a concept entitled "schizo-obsessive disorder" as a new specific clinical entity with more severe psychiatric symptoms. Many studies have been done on SCZ and OCD, but the common pathogenesis between them is not clear yet. Therefore, this study aimed to identify shared genetic basis, potential biomarkers and therapeutic targets between these two disorders. Gene sets were extracted from the Geneweaver and Harmonizome databases for each disorder. Interestingly, the combination of both sets revealed 89 common genes between SCZ and OCD, the most important of which were BDNF, SLC6A4, GAD1, HTR2A, GRIN2B, DRD2, SLC6A3, COMT, TH and DLG4. Then, we conducted a comprehensive bioinformatics analysis of the common genes. Receptor activity as the molecular functions, neuron projection and synapse as the cellular components as well as serotonergic synapse, dopaminergic synapse and alcoholism as the pathways were the most significant commonalities in enrichment analyses. In addition, transcription factor (TFs) analysis predicted significant TFs such as HMGA1, MAPK14, HINFP and TEAD2. Hsa-miR-3121-3p and hsa-miR-495-3p were the most important microRNAs (miRNAs) associated with both disorders. Finally, our study predicted 19 existing drugs (importantly, Haloperidol, Fluoxetine and Melatonin) that may have a potential influence on this co-occurrence. To summarize, this study may help us to better understand and handle the co-occurrence of SCZ and OCD by identifying potential biomarkers and therapeutic targets.

Does insular cortex lesion cause tinnitus in rats?

Objectives: Tinnitus is defined as ringing of the ears that is experienced when there is no external sound source, and is an auditory phantom sensation. The insula as a multimodal cortex has been shown to be involved in the processing of auditory stimuli rather than other sensory and motor processing and reported to correlate with some aspects of tinnitus. However, its exact role is not clear. The present study aimed to investigate the effect of excitotoxic lesions limited to the insular cortex on the ability to detect a gap in background noise. Materials and Methods: Gap detection test and prepulse inhibition, two objective measurements of auditory startle response, were measured, in 33 male Wistar rats, before and up to four weeks after insular lesion in three experimental groups (sham, control, and lesion). Results: The ability to detect the gap interposed between 60 db background noise was impaired at weeks 2, 3, and 4 following insular lesion, while prepulse inhibition remained intact up to four weeks after surgery. Conclusion: These findings indicated that excitotoxic lesions of the insular cortex may produce a tinnitus-like phenomenon in rats while sparing the hearing sensitivity; suggesting that the insular cortex may have a role in the development of tinnitus.

The effect of insular cortex lesion on hyperacusis-like behavior in rats.

Background and objectives: Hyperacusis is hypersensitivity and extreme response to the intensity of sound that is tolerable in normal subjects. The mechanisms underlying hyperacusis has not been well understood, specially the role of insular cortex. The aim of this study is to investigate the role of insular cortex in hyperacusis like behavior. Material and methods: The number of 33 male wistar rats weighting 170-250 gr were allocated randomly in three groups; control, sham, and insular lesion. Auditory startle responses (ASR) to different intensities of stimuli (70, 80, 90, 100, and110 dB without background noise as well as 110 dB in the presence of 70, 80 dB background noise) were measured before and up to four weeks after intervention. Results: Data analyses showed an increase in ASR to 100 dB stimulus without background noise one week after insular lesion, and increased responses to other intensities two weeks after lesion. Furthermore, there was a decrease in ASR to 110 dB stimulus with 80 dB background noise two weeks after insular lesion. However, no significant difference was observed in 70 dB background noise. The changes in ASR lasts at least four weeks.Conclusion: The findings indicated that there was an increase in ASR in the absence of background noise following cortical excititoxic lesion limited to insular cortex, while there was a decrease in responses in the presence of background noise which suggests possible increased sensitivity to sound loudness as a hyperacusis-like phenomenon. The study showed a significant relationship between insular cortex lesion and ASR in rats.

Does 5, 7-Dihydroxytryptamine injection into nucleus accumbens cause hyperacusis?

Hyperacusis may be defined as diminishing tolerance to moderate and high intensity sounds in people with normal hearing sensitivity. Serotonin plays a critical role in some of auditory tasks including startle reflex and prepulse inhibition. Serotonin deficiency can cause some diseases which can coincide with hyperacusis. The aim of the present study was to investigate the probable influence of serotonergic depletion in nucleus accumbens (NAcc) on the startle reflex. The startle reflexes were examined in Wistar rats (n: 48) in different intensities with and without the background noise. The amplitude of startle reflex significantly increased in NAcc-injected rats without background noise, while this difference disappeared in the presence of background noise in all intensities. These data proposed that the injection of 5, 7-Dihydroxytryptamine (5, 7-DHT) into nucleus accumbens will cause hyperacusis-like behavior, and strengthens the possibility of the role of serotonin and nucleus accumbens in hyperacusis.