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Background:Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP).Methods:Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models.Results:Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations.Conclusion:These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.

BackgroundWith the rapid and intensive spread of marihuana abuse among youth, Japanese society is focusing on law enforcement against drug abusers. In 2016, a mass killing allegedly committed by a marihuana abuser was reported in Japan.ObjectivesTo consider that common recognition of the diverse process and potential risks of cannabis psychosis should be shared among psychiatrists.AimsElicit differences between cannabis psychosis and methamphetamine psychosis, and determine whether specific guidelines for treatment of cannabis psychosis are required.MethodIntensive retrospective review of distinctive methamphetamine and cannabis psychosis through case studies in our hospital.ResultMajor symptoms of methamphetamine psychosis include auditory hallucination and paranoia, however recovery is achieved soon after undertaking treatment. In cannabis psychosis, distinctive features are megalomania and by a pseud-enlightenment experience of supernatural existence, abusers stick to an unrealistic self-estimate of omnipotent, which leads them to refuse the fading away of this feeling and repeat abuse.ConclusionPsychological substances have strong suggestibility so abusers’ symptoms are easily modified by their mental state. Involvement of syndicate or perception of illegality reflects abusers’ drastic symptoms, but after dehospitalisation, recurrences are relatively fewer. Cannabis, however, grows wild and is admitted legally in some countries, so abusers lack awareness of guilt by mistaken perception of omnipotence and unrealistic optimism. Due to addiction and depersonalization, they rather enjoy gaining contact with supernatural power and fall into social withdrawal and are implicated to social problems. Considering the difficulty of rehabilitating and returning abusers to the community, we should not disregard the risks of cannabis abuse.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Personality has been proposed as having a possible effect on the reaction that patients have toward auditory hallucination. However, this factor has not been studied previously. Thus, this study investigated the relationship among demographics, personality, cognition and emotional response in schizophrenics with persistent auditory hallucination. One-hundred and fourteen subjects with persistent auditory hallucination completed the Eysenck Personality Questionnaire, the revised Beliefs about Voices Questionnaire and the Chinese-version Hospital Anxiety and Depression Scale. Structural equation model showed that personality had an effect on beliefs about the hallucination (malevolent or benevolent), which then affected the reaction of patients toward these voices (engages or resists). Their reaction will further affect the anxious or depressed state of the patients. When these hallucinations were categorized into the three levels of omnipotence, beliefs and reactions, the model was more significant than that of one-level model. Persistent auditory hallucination only accounted for a portion of the emotional distress when malevolent or benevolent voices were perceived, and personality characteristics accounted for the remaining emotional distress in schizophrenics. This model helped us understand the relationship between personality, cognition and affective symptoms, such that, when therapists decide what “trait” to change, they can determine at which point to intervene.

IntroductionWhile 1–Hz repetitive transcranial magnetic stimulation (rTMS) has been found to be effective in reducing auditory hallucinations (AH), its effects are transient. cTBS, a patterned-rTMS technique induces sustained long-term-depression-like effects. Here, we demonstrate efficacy of twice daily, bilateral-cTBS in a patient with treatment-resistant AH, reflex hallucinations and vision-touch synesthesia.MethodA 25-year-old male with 5 years history of treatment-resistant AH (2nd/3rd person), vision-touch synesthesia and reflex hallucinations. He was on a combination of 200 mg clozapine and 300 mg amisulpride for the last 6 months with no improvement. He received two-weeks of twice daily, bilateral-cTBS [40,1 s-trains (bursts of 3-pulses at 50 Hz every 200 ms) given continuously at 90% motor threshold] over the temporoparietal junctions located using the International 10/20 system. Amisulpride was stopped and clozapine was increased to 300 mg/day. Change in AH and synesthesiae were assessed using auditory hallucination rating scale (AHRS) and clinical interview.ResultAHRS scores reduced from 35/41 to 0/41 at the end of 2 weeks, with substantial improvement being noticed at the end of the fifth day. Synesthesiae and reflex hallucinations also showed similar trends in improvement. No serious adverse events.DiscussionIntegration of auditory, visual and tactile perceptions is an important function of the temporoparietal junction. administering cTBS to this region bilaterally reduced our patient's perceptual abnormalities. Increasing dose of clozapine could be a confounding factor, however, the rapidity of treatment response enables us to attribute part of the improvement to cTBS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

BackgroundPsychiatric symptoms/disorders in brain diseases are not specific and may have the same clinical presentations as functional psychiatric disorders, so they can compromise early diagnosing of disease.ObjectiveThis paper's objective is to show (negative) influence of stigma in a diagnostic process of patients with predominantly psychiatric symptoms in their clinical pictures.Materials and methodsThe subject is a 46 year-old female patient with no history of psychiatric disease. Her symptoms includes: confusion, disorientation, perseveration, visual and auditory hallucination, lack of motivation, inability to understand questions, developed following a 10-day long period of febricity. During the outpatient care, she has been examined by a neurologist, a specialist of urgent and internal medicine, and a psychiatrist. As the CT scan made in that stage was interpreted as normal, the patient was hospitalised in a psychiatric hospital. She was treated both with typical and atypical antipsychotics but no therapeutic effects have been reached. Thinking of organic etiology, advanced diagnostics have been made (MR, LP). MR scan showed lesion that is a characteristic for herpetic meningitis, which is also confirmed with positive serological tests.ConclusionIn patients with a sudden onset of psychiatric symptoms, patients with unexpected changes in mental status or suddenly developed headaches, as in the therapy- resistant psychiatric disorders, it is important to keep in mind the possibility of the coexistence of brain disease. Removing the stigma from psychiatric patients is important in order to be able to give every patient the chance of getting the correct diagnose on time.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionCognitive impairment is present from the early stages of psychotic disorders. Alterations are found mainly in areas of attention, memory work and executive functions. During adolescence, ADHD patients often suffer from secondary disorders to lack of efficient procurement processes information by the poor development of executive functions.ObjectiveEvaluation of a patient whose diagnosis of ADD evolve to acute psychotic episode.MethodReview by clinical and psychometric tests developments in executive functions disorders.ResultsTwelve years old patient who comes to the hospital since 2012, was initially diagnosed with literacy difficulties and low academic performance, after MFF-20 speaks of Learning Disabilities. It presents lack of motivation, apathy, difficulty in scheduling and organization and adherence to schedules, so they diagnosed ADD. It is given treatment with methylphenidate and atomoxetine, presenting erratic path.After a year without treatment and the presence of a major stressful life event, at 17, has a first episode, consisting in mutiste attitude, phenomena of self-referenciality, experiences of control, enforcement and dissemination of ideas and auditory hallucination imperative type.ConclusionsThe presence of emocional dysregulation and alterations in the executive functions atribuyen to ADD, in this case, were premorbid symtomatology of a first psychotic episode. The presence of positive symptoms allows to clarify the diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionAuditory hallucination (AH) has been always concerned as a main core symptom of schizophrenia. However, the mechanisms of AH are still unclear.ObjectivesThe aim of this study is to further explore the complicated neuroimaging mechanism of AHs from a new insight by using voxel-mirrored homotopic connectivity (VMHC).MethodsForty-two patients with AH (APG), 26 without AHs (NPG) and 82 normal controls (NC) participated in resting state fMRI scan. Correlation analyses were used to assess the relationships between VMHC and Hoffman scores. Additionally, ROI analysis was used to further know about the functional connectivity between the brain areas with changed interhemispheric FC and the whole brain.ResultsAPG showed reduced VMHC in the parahippocapus, fusiform gyrus, rolandic operculum, insula, heschl's gyrus and superior temporal gyrus (STG). Hoffman score of APG group had negative correlation with VMHC in these regions. Besides, ROI analysis supported decreased interhemispheric FC in schizophrenia with AH and verified functional connectivity abnormalities in schizophrenia.ConclusionsThese findings suggest impairment of interhemispheric coordination and whole brain FC in schizophrenia with AH, which may be implicated to the neuroimaging mechanism of auditory hallucination. Furthermore, this research highly support dysconnectivity hypothesis that schizophrenia related to abnormalities in neuronal connectivity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Introduction the relationship between hypothyroidism and mood disorder espacially depressive disorder is well described. However, there are few studies reporting psychotic symptoms (such as delusions, auditory or/and visual hallucination) in the setting of thyroid hormone defeciency. Objectives this study highlights psychosis as a possible presenting symptom in hypothyroidism. Methods case report and review Results we report the case of a female patient aged 36 years old with no family or personal psychiatric history, who presented with delusion, depressive disorder and auditory hallucination . the CT scan was without abnormality . the thyroid screening finds a severe hypothyroidism after 3 months of radiotherapy witn Iodine131 [FT4 = 2.49 ρmol/l, TSH 135.28 μUI/ml] Conclusion psychotic symptoms are an uncommun presentation of hypothyroidism and treatement choices are contreversial.

Objective Our objective was to examine whether transcranial Direct current Stimulation (tDCS) applied over the left temporoparietal junction (assumed 'inhibitory' - cathode) and the left prefrontal cortex (assumed 'excitatory' - anode) can impact clinical symptoms and functional connectivity of targeted regions in patients with schizophrenia presenting treatment-resistant auditory verbal hallucinations. Method In a double blind sham-controlled randomized clinical trial, thirty patients with schizophrenia and treatment-resistant auditory verbal hallucinations were randomly allocated to receive either 20 minutes of active 2mA tDCS or sham stimulation twice a day during 5 consecutive working days. The anode was placed over the left prefrontal cortex according to 10/20 EEG international system (PFC/F3FP1) and the cathode over the left temporoparietal junction (TPJ/T3P3). Seed-based functional connectivity maps were compared before and after stimulation sessions (5 minutes resting state fMRI). Seed were placed in regards of the electrode locations. Analyses were done using Brain Voyager QX on resting state fMRI maps. Results Clinical impact of tDCS was investigated in the initial sample of 30 patients. tDCS resulted in an improvement of global symptoms (−12%) and auditory hallucination (−31%) for at least 3 months. The impact of tDCS on seed-based functional connectivity was investigated in a subsample of 21 patients. We reported a significant decrease of functional connectivity in fronto-temporal network (language-related brain areas including left TPJ, dorso-lateral PFC, Broca's area and their right homologues) after active tDCS compared to sham treatment. Conclusion tDCS seems to be a promising tool to modulate brain networks underlying clinical symptoms in schizophrenia.

The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists. The possible mechanism of the refractory schizophrenia included diagnostic errors, medical conditions and brain dysgensis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucination and persecutory delusion and so on. We reexamined all his possible medical conditions and found the patient had an abnormal enlarged Cavus Septum Pellucidum (CSP) combined with Cavum Vergae (CV) (maximum length>30 mm). Some reports suggested that abnormal CSP(length>6 mm) has an significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may lead to schizophrenia and worse prognosis.

Aim:To prove the clinical effect rTMS neuronavigation vs. standard coil positioning vs. controlls in the therapy of madication-resistant auditory hallucinations.Materials and methods:10 patients with medication-resistant auditory hallucinations on stabile antipsychotic medication, examined by MRI, PET, then treated by 1) neuronavigated, 2) standard positioning and 3) sham rTMS (controlls).Double-blind randomized sham-controlled parallel design was used in the study.rTMS parameters: 0.9Hz, 100%MT, 1080 pulses/session, 10 rTMS sessions within 2 weeks:1.Neuronavigated rTMS: coil focused over the highest contrast of metabolic activity in the left temporo-parietal (T-P) area (according to the SPM analyse 18FDG PET data).2.Standard rTMS: coil administered over the left T-P region defined as the midway between the T3 and P3 sites according to the international 10/20 EEG electrode system.3.Sham: coil angled 90° away from the skullPsychometric measurement: PANSS, Hallucination Change Scale (HCS) and the Auditory Hallucination rating scale (AHRS).Results and conclusion:Confirmation of a significant decrease in the Hallucination item as well as in the total of the positive score of PANSS, HCS and AHRS. Sham rTMS did not show a trend for improvement over time. Between-group comparisons of AHRS scores revealed significant differences, which confirmed efficiency of using neuronavigated rTMS.Compared to standard positioning in future studies, we believe to find rTMS neuronavigation more precise and effective. Studies monitoring a continuing effect of rTMS over long time periods are needed.Supported by the CNS, MZČ;R MZ0PCP2005 and MŠMT 1M0517, VZ 00 216 208 16.

Refuse to eat, resembling eating disorders, may be related to overvalued ideas; beginning during prodrome and transforming into delusions throughout psychosis.(2,3) Clarifying the reason is crucial, as antipsychotics’ side effects can aggravate comorbid eating disorder.(1)Female, age 16. Referred to our inpatient psychiatry clinic first, by an internist, for her refusal to eat. Height:155cm, Weight:26.3kg, BMI:10.95; was on wheelchair. She had primary amenorrhea. Complained about her fear of eating, excessive need to smoke, insomnia. 3 years ago, she began to refuse eating, reporting foods being fatty. After 6 months, persecutory delusions (being poisoned) and her unique auditory hallucination (“Don't eat, otherwise we'll kill you”) began. She was taken to practitioners and internists repeatedly, was hospitalized but didn't mention her psychotic symptoms. 2 years ago, she noticed that auditory hallucinations reduced when smoking; then became a heavy smoker. Her food intake had reduced in the last year and she had eaten nothing during last 2 months. Alimentation and Risperidone 1.5-3mg/day was administered via nasogastric tube. 3 weeks later; delusions and hallucinations remitted, eating behaviour normalized, smoking reduced explicitly. At 5th and 9th week of medication, weight/BMI were, 34kg/14.15 and 44.5kg/18.52 respectively. Except negative symptoms; she had no positive symptom, no fat phobia and no disturbed body perception. Eating behaviour was normal.Smoking may be a self-medication in Schizophrenia.(5) Cognitive and emotional component of eating refusal, like fat phobia and disturbed body perception, should be searched carefully after remission of positive symptoms, to exclude comorbid eating disorder.(4)

Hundreds of QEEG-related papers brought new information about the temporal dynamics of complex neuronal interactions that underlie impaired processing in many psychiatric diagnoses. Besides this fact, many researchers, clinical psychiatrists and neuroscientists prefer new imaging techniques (Positron Emission Tomography, PET; and functional Magnetic Resonance, fMRI) even if they are based on an indirect index of brain computing as metabolic or hemodynamic measurements which are blind to millisecond phenomena. We present the results of our studies provided with QEEG techniques (Low Resolution Electromagnetic Tomography, LORETA; EEG coherence, EEG cordance) in: 1) more than 60 patients with schizophrenia examined by means of QEEG and PET. We found significantly lower EEG coherence values, mainly from the left frontotemporal derivations in patients group and there was also significant correlation between the decrease of frontotemporal EEG coherence and elevated glucose metabolic uptake in the limbic structures (posterior cingulate and hippocampus). LORETA analysis showed almost the same results as analysis of PET images, not only in basal disease process, but also after successful application of rTMS in the subgroup of patients with treatment-resistant auditory hallucination. 2) in more than 30 patients with resistant depressive disorder we computed the new EEG indicator value (EEG cordance), and we showed, that the decrease in prefrontal EEG cordance in theta frequency band may indicate early changes of prefrontal activity and can become a useful tool in the prediction of response to antidepressants.The study was supported by MSMTCR project 1M0517.