The Relationship between Alcohol-Cannabis Use and Stressful Events with the Development of Incident Clinical Psychosis in a Community-Based Prospective Cohort. / Toplum Tabanli Bir Örneklemin Ileriye Dönük Izleminde, Alkol- Esrar Kullaniminin ve Stresli Yasam Olaylarinin Klinik Psikoz Gelisimi ile Iliskisi.

OBJECTIVE: The aim of this study is to evaluate the associations between alcohol-cannabis use and forensic/stressful events with the risk of incident clinical psychosis during follow-up. METHOD: A community-based sample (n: 2142) was screened for clinical psychosis (schizophrenia and other psychotic disorders, affective disorders with psychotic features) at baseline and follow-up. Thus, incident clinical psychosis cases to develop during follow-up (individuals with no clinical psychosis at the baseline assessment and with clinical psychosis at the follow-up assessment) were detected (n: 27). These cases and the controls who did not report any psychotic symptoms at the follow-up assessment (n: 1691) were compared for exposure to environmental risk factors during follow-up (total n: 1718). RESULTS: Individuals reporting heavy alcohol drinking or cannabis use during follow-up had significantly higher risk of incident clinical psychosis. The monthly frequency of drinking and cannabis use was also associated with the risk. Higher number of stressful life events exposed predicted higher risk of incident clinical psychosis. The risk of incident clinical psychosis was significantly higher in case of coexistence of two risk factors (heavy drinking, cannabis use, ≥3 stressful events), in comparison with the existence of a single risk factor (17.7 vs. 1.6%, p<0.001). CONCLUSION: Heavy drinking, cannabis use, forensic events and stressful events were associated with the risk of incident clinical psychosis. The coexistence of multiple stressful events and disorders related to abuse of alcohol/cannabis should be considered as a warning for the development of clinical psychosis.

Izmir Mental Health Cohort for Gene-Environment Interaction in Psychosis (TürkSch): Assessment of the Extended and Transdiagnostic Psychosis Phenotype and Analysis of Attrition in a 6-Year Follow-Up of a Community-Based Sample.

Objective: TürkSch is a prospective, longitudinal study in a representative community sample (Izmir, Turkey), consisting of several data collection stages, to screen and follow-up mental health outcomes, with a special focus on the extended and transdiagnostic psychosis phenotype. The aim of the present paper is to describe the research methodology, data collection results, and associations with noncontact and refusal in the longitudinal arm. Methods: Households were contacted in a multistage clustered probability sampling frame, covering 11 districts and 302 neighborhoods at baseline (n = 4,011) and at 6-year follow-up (n = 2,185). Both at baseline and at follow-up, participants were interviewed with the Composite International Diagnostic Interview. Participants with probable psychotic disorder were reinterviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID)-I either at the hospital or at the participant's residence. Relevant neighborhood-level measures were assessed in a separate sample (n = 5,124) in addition to individual-level measures. Candidate gene-by-environment interactions were investigated using two nested case-control studies. Results: Individuals with a mental health problem had lower refusal rates. Older and lower educated individuals had a lower probability of noncontact. Discussion: The TürkSch study has an advanced design to meet the challenges of evaluating the multidimensional etiological and phenomenological nature of the extended and transdiagnostic psychosis phenotype.

Bilateral keratoconus, acute hydrops and unilateral corneal perforation due to Tourette syndrome.

A 27-year-old male with a repetitive behavior of eyeball pressing for six months presented with decreasing visual acuity for three months. Upon arrival his best corrected visual acuity was 0.2 on the right and 0.6 on the left eyes. Scheimpflug camera system demonstrated grade 4 and grade 2 keratoconus, respectively. Psychiatric consultation revealed Tourette syndrome and treatment was started. Despite psychiatric treatment, acute hydrops occurred in both eyes decreasing visual acuity to hand motions bilaterally. Left corneal perforation due to ongoing habit of eyeball pressure was experienced which led the loss of light perception and phtisis bulbi. Although Tourette syndrome is rare, it might cause bilateral acute onset keratoconus when the repetitive movements affect periocular region. Psychiatric treatment should be considered as early as possible in these patients in order to prevent unfavorable complications.

Psychotic experiences and mood episodes predict each other bidirectionally: a 6-year follow-up study in a community-based population.

BACKGROUND: Psychotic experiences (PEs) are not exclusive to psychotic disorders and highly correlated with mood episodes. In this representative general population-based study, longitudinal bidirectional associations between the extended psychosis phenotype and mood episodes were investigated, accounting for other possible causes. METHODS: Households were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011) and at 6-year follow-up (n = 2185). Participants were interviewed with the relevant sections of the composite international diagnostic interview both at baseline and at follow-up. Sociodemographic, familial and environmental risk factors associated with the extended psychosis phenotype and mood episodes were assessed. Logistic regression and cross-lagged panel correlation models were used for the associations between the extended psychosis phenotype and mood episodes. RESULTS: PEs were associated with subsequent depressive and manic episodes. There was bidirectionality in that mood episodes were associated with subsequent PEs, and PEs were associated with subsequent mood episodes. The associations occurred in a sub-additive pattern. There were substantial synchronous and cross-lagged correlations between these psychopathology domains, with reciprocally similar cross-lagged correlations. Familial risk and adverse life events were associated with both psychopathology domains, whereas some sociodemographic risk factors and alcohol/cannabis use were associated with only one domain. CONCLUSION: The sub-additive bidirectional associations between PEs and mood episodes over time and the similarity of cross-lagged correlations are suggestive of mutually causal connections between affective and psychotic domains of psychopathology.

Is BDNF-Val66Met polymorphism associated with psychotic experiences and psychotic disorder outcome? Evidence from a 6 years prospective population-based cohort study.

There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population-based prospective cohort study, the longitudinal associations between BDNF-Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case-control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re-appraisal at follow-up 6 years later (n = 254). The BDNF-Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF-Val66Met polymorphism impacted in a dose-response but extra-linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF-Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum.

DSM outcomes of psychotic experiences and associated risk factors: 6-year follow-up study in a community-based sample.

BACKGROUND: Psychotic experiences (PEs) may predict a range of common, non-psychotic disorders as well as psychotic disorders. In this representative, general population-based cohort study, both psychotic and non-psychotic disorder outcomes of PE were analysed, as were potential moderators. METHODS: Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011). Participants were interviewed with the Composite International Diagnostic Interview (CIDI) both at baseline and at 6-year follow-up. Participants with PE at baseline were clinically re-interviewed with the SCID-I at follow-up. The role of socio-demographics, characteristics of PE, co-occurrence of mood disorders and family history of mental disorders were tested in the association between baseline PE and follow-up diagnosis. RESULTS: In the participants with baseline PE, the psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the rates of DSM-IV mood disorders without psychotic features (42.8%) and other non-psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower socio-economic status, co-occurrence of mood disorders, family history of a mental disorder and persistence of PE predicted any follow-up DSM diagnosis. Furthermore, onset of psychotic v. non-psychotic disorder was predicted by younger age (15-30 years), co-presence of delusional and hallucinatory PE and family history of severe mental illness. CONCLUSION: The outcome of PE appears to be a consequence of baseline severity of multidimensional psychopathology and familial risk. It may be useful to consider PE as a risk indicator that has trans-diagnostic value.

[The Association between the Extended Psychosis Phenotype and COMT val158met and BDNF val66met polymorphisms]. / Genis Psikoz Fenotipinin COMT val158met ve BDNF val66met Polimorfizmleri ile Iliskisi.

OBJECTIVE: Psychotic disorders were previously associated with catechol- O-methyltransferase (COMT) val158met (rs4680) and brain-derived neurotrophic factor (BDNF) val66met (rs6265) polymorphisms. This article evaluates the association between COMT/BDNF polymorphisms and the extended psychosis phenotype which covers not only schizophrenia but also subclinical expressions of psychotic experiences. METHOD: The participants of this study were part of the TürkSch (Izmir Mental Health Survey for Gene-Environment Interaction in Psychoses), a longitudinal study Psychotic experiences and disorders were screened 437. The extended psychosis phenotype was grouped into four: (1) no psychotic experiences (n: 194), (2) subclinical psychotic experiences (n: 87), (3) clinically relevant psychotic experiences (n: 104), and (4) schizophrenia-like disorders (n: 52). BDNF rs6265 was genotyped occurred in every participant whereas COMT rs4680 genotyping could be done on 366 individuals. RESULTS: There was no association between the extended psychosis phenotype and BDNF rs6265/COMT rs4680 polymorphisms. The frequency of met carriers in the BDNF rs6265genotype was slightly higher in individuals with subclinical psychotic experiences than in the group with no psychotic experiences, which was just below the significance level (p=0.08). CONCLUSION: The lack of an association between different expression levels of the extended psychosis phenotype and the BDNF rs6265/ COMT rs4680 polymorphism might be related to sample characteristics, underlying gene-gene, gene-environment and gene-environment-gene interactions.

Early Onset Schizophrenia Associated With Obsessive-Compulsive Disorder: Clinical Features and Correlates.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is notably a comorbid disorder in patients with schizophrenia. This study aimed to evaluate clinical features and correlates of early onset patients with schizophrenia with OCD. METHODS: In the present study, we included 10 patients with both schizophrenia and OCD and 19 patients with schizophrenia without OCD. The mean antipsychotic doses the patients needed for treatment are standardized as chlorpromazine equivalent dose. RESULTS: The mean antipsychotic doses at first episode were 491 ± 376 mg/d in schizophrenia comorbid OCD group and 290 ± 209 mg/d in the schizophrenia without OCD group (P = 0.018). This significant difference was also found for the mean doses at the assessment for the study (512.40 ± 336.22 mg/d in schizophrenia comorbid OCD and 296.05 ± 147.25 mg/d in patients with schizophrenia without OCD, P = 0.012). There was no statistical difference in the mean scores of Clinical Global Impression and Positive and Negative Syndrome Scale between schizophrenia with and without OCD group, respectively. (Clinical Global Impression: 5 ± 0.66 vs 4.36 ± 0.83, P = 0.094; Positive and Negative Syndrome Scale: 67.60 ± 11.84 vs 69.84 ± 14.62, P = 0.573). CONCLUSIONS: Adolescents with schizophrenia and OCD needed more antipsychotic doses for acute exacerbation and the maintenance of reduction of psychosis severity than adolescents with only schizophrenia. We could suggest that OCD comorbidity in schizophrenia is more treatment resistant, although the severity of the schizophrenia was similar between study groups. There was no correlation between OCD and schizophrenia symptoms either.

Deficits of social-cognitive and social-perceptual aspects of theory of mind in remitted patients with schizophrenia: effect of residual symptoms.

Although ToM deficit in schizophrenia is widely accepted, findings regarding remitted schizophrenia patients are contradictory. Because residual symptoms are present out of psychotic exacerbation periods, the differences between definition of remission may be important to interpret these findings. The purpose of this study was to investigate the relationship between performance of 2 different aspects of theory of mind (ToM) and residual clinical symptoms and other cognitive deficits in schizophrenia. Ninety-one stable outpatients with schizophrenia and 55 healthy controls were assessed with a neuropsychological battery. Both social-cognitive and social-perceptual aspects of ToM were impaired in schizophrenia, even in patients who were totally free of residual symptoms. Still, the results showed that ToM deficit is related to residual symptoms of schizophrenia. Social-cognitive ToM abilities seem to be related to both positive and negative symptoms. The ToM deficits of fully remitted patients without persistent negative symptoms may be secondary to a more general cognitive dysfunction in schizophrenia.

Cognitive insight and acute psychosis in schizophrenia.

Cognitive insight is a new concept. There are very few data regarding the relationship between cognitive insight and positive symptoms. The goal of the present study was to investigate the impact of acute psychosis (delusions and hallucinations) on overconfidence in judgments and self-reflectiveness of patients with schizophrenia. The Beck Cognitive Insight Scale was used to compare the cognitive insight of schizophrenia patients with (n = 93) and without (n = 45) current psychotic symptoms. Clinical symptoms and clinical insight of the patients were also assessed. The present findings suggest that both overconfidence in judgments and impaired self-reflectiveness are associated with acute psychosis. Only diminished self-reflectiveness seem to be improved following hospitalization. Although overconfidence of schizophrenia patients in their judgments was more severe in schizophrenia patients with psychotic symptoms, self-certainty of schizophrenia patients may be a relatively persistent characteristic that is also present after recovery of psychosis. Studies with larger samples involving follow up for longer periods will be valuable to understand the nature of the relationship between cognitive insight and clinical symptoms of schizophrenia.

Social functioning, theory of mind and neurocognition in outpatients with schizophrenia; mental state decoding may be a better predictor of social functioning than mental state reasoning.

Few studies have directly investigated the relationship between theory of mind (ToM) deficits and social functioning in schizophrenia. At the same time, the impact of mental state decoding tasks on social dysfunction has also not yet been investigated. In this study, the relationship between theory of mind deficits and social functioning was investigated among 50 patients with schizophrenia. A mental state decoding task known as 'The Eyes test' and a mental state reasoning task 'The Hinting test' were applied to assess ToM abilities, while the Social Functioning Scale (SFS) was used to assess social functioning. Non-ToM neurocognitive tests were also given to the patients. Results of the study show how theory of mind and working memory performances of patients with good functional outcome proved to be significantly better than those of inadequately functioning patients. Results also indicate that performance on the Eyes test was the best predictor of social functioning and that negative symptoms also contributed to poor social functioning. It is concluded in this study that mental state decoding skills appear to be the most important cognitive mediator of social functioning.

Psychological outcomes of an outpatient pulmonary rehabilitation program in patients with chronic obstructive pulmonary disease.

STUDY/PRINCIPLES: The effects of an outpatient pulmonary rehabilitation program on psychological morbidity (anxiety and depressive symptoms) were examined in patients with chronic obstructive pulmonary disease (COPD). METHODS: The 26 rehabilitation patients with COPD were compared with 19 control patients with COPD similar in age, gender, COPD severity and other variables. Initial assessment included lung function testing, health status, exercise tolerance, dyspnea intensity and psychiatric interviews using Hamilton depression rating scale (HAM-D) and Hamilton anxiety rating scale (HAM-A). A pulmonary rehabilitation program was carried out during the following 2 months; psychiatric interviews and measurements of health status, exercise tolerance and dyspnea intensity were done again on completion of the study at 2 months. RESULTS: There was a decrease in HAM-A scores in the rehabilitation group and the decrease was statistically significant (P=0.010). On the contrary the HAM-A scores did not change in control group. The decrease in HAM-A scores in rehabilitation group was also statistically significant compared with the control group (P=0.042). There was no significant difference in HAM-D scores within the two groups and also there was no significant difference between the two groups in HAM-D scores. The health status, exercise tolerance and dyspnea intensity improved significantly in the rehabilitation group compared to the control group. CONCLUSION: This study shows that our outpatient rehabilitation program leads to a benefit in anxiety and depressive symptoms in COPD patients. The benefit was especially significant in anxiety symptoms. In addition to the improvement in psychological symptoms, the health status, exercise tolerance and dyspnea intensity were also significantly improved in COPD patients who underwent the rehabilitation program. This outpatient-based rehabilitation program was well accepted by the patients. The relatively simple design of the program makes it feasible independently of expensive equipment.

[Obsessive-compulsive symptoms in schizophrenia]. / Sizofrenide Obsesif Kompulsif Belirtiler.

Schizophrenia and obsesive compulsive disorder (OCD) are among the oldest described psychiatric disorders. Although they appear to be two distinct psychiatric disorders, early literature about the existence of obsessive-compulsive symptoms in schizophrenia dates back to the 1920's. The findings that atypical antipsychotics exacerbate obsessive-compulsive symptoms among schizophrenic patients and the emergence of a possible biological relation between the two diseases increased interest in this subject. Until the 1990's information about the aetiology of obsessive-compulsive symptoms which are observed in about 60% of schizophrenic patients, was insufficient. Recently there has been progress in explaining the structural and functional abnormalities in both OCD and schizophrenia. Knowledge of the cortico-subcortical circuits might explain the co-incidence of symptomatology in the two disorders. It is shown that there is prefrontal cortex dysfunction in both disorders but the bases of dysfunctions are distinct from each other. These dyfunctions derive from two different neuro-anatomical systems partially connected with each other and with different neuro-anatomical connections. It is suggested that dorsolateral prefrontal cortex (DLPC) dysfunction occurs in schizophrenia and ventro-medial prefrontal cortex dysfunction (VMPC) in OCD. In this review, the incidence of obsessive-compulsive symptoms in schizophrenia, their effect on the disorder, the features of the schizo-obsessive patient group and the mechanism of how atypical antipsychotics exacerbate obsessive compulsive symptoms are discussed. Thus, we aimed to highlight the neurobiologic heterogeneity and phenomenology of schizophrenic disorder.

The effect of galantamine added to clozapine on cognition of five patients with schizophrenia.

Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials.

Obsessive-compulsive symptoms in schizophrenia: prevalance and clinical correlates.

Obsessive-compulsive symptoms (OCS) have been observed in a substantial proportion of schizophrenic patients. In this study, the rate of occurrence of OCS and obsessive-compulsive disorder (OCD) in schizophrenic patients, and also the interrelationship between OCS and schizophrenic symptoms and depressive symptoms were assessed. A total of 100 subjects with a diagnosis of schizophrenia from the 4th edition of the Diagnostic and Statistical Manual (DSM-IV) were evaluated by the structured and clinical interview for axis-1 DSM-IV disorders-patient edition (SCID-P), the Positive and Negative Syndrome Scale (PANSS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Calgary Depression Rating Scale for Schizophrenia. The prevalance of OCS in individuals meeting criteria for schizophrenia was 64%. A total of 30 of these patients (Y-BOCS total score > or =7) also met the DSM-IV criteria for OCD. The total score on Y-BOCS was significantly correlated with total score on PANSS, Positive-PANSS score, General-PANSS score and total score on Calgary Depression Rating Scale for Schizophrenia. OCS and OCD relatively frequent in schizophrenic patients and OCS are significantly correlated with the severity of psychosis, positive symptoms, and depressive symptoms in schizophrenic patients. These findings provide further evidence for the importance of OCS in schizophrenia.

Psychosocial skills training on social functioning and quality of life in the treatment of schizophrenia: a controlled study in Turkey.

OBJECTIVE This study assessed the impact of a psychosocial skills training program, consisting of psychoeducation, interpersonal group therapy and family education incorporated into social skills training, as an integrative approach on social functioning and quality of life of patients with schizophrenia, in comparison to standard care for an 8-month period. METHOD Thirty patients with DSM-IV schizophrenia were included in the study. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS), Quality of Life Scale (QLS), Social Functioning Scale (SFS), and Global Assessment of Function (GAF) at baseline. Fifteen patients underwent an 8-month psychosocial skills training group program and another fifteen patients (waiting list) continued in standard care. Both groups were reassessed and analyzed at the end of the study. RESULTS Two groups were not statistically different in terms of total PANSS, QLS, SFS, GAF scores, and demographic characteristics at baseline. However, there was a significant improvement in the mean total QLS, SFS, GAF, and even in total PANSS scores (respectively from 64.46±19.58 to 89.67±24.10, P<0.001, from 93.20±22.85 to 132.60±33.85, P<0.002, from 57.40±8.78 to 63.86±7.57, P<0.012, and from 63.53±14.48 to 53.33±15.71, P<0.029) for those who underwent the PSST program, but there was no statistically significant change for those on standard care at the end of the study. CONCLUSION This study highlights the 'social functioning' and 'quality of life' benefits of the psychosocial skills training program for patients with schizophrenia. It can be concluded that this comprehensive psychosocial skills training program might be an important contribution to the functioning of the patients.

Paroxetine augmentation to tianeptine treatment causes exacerbation of depressive symptoms: presentation of two cases.

We present two cases whose depressive symptoms partially remitted with tianeptine treatment but exacerbated after paroxetine augmentation to tianeptine. Although tianeptine has structural similarities with tricyclic antidepressants, unlike tricyclic agents or selective serotonin- reuptake inhibitors(SSRIs), it enhances 5-HT reuptake in brain, leading to decreased availability of the transmitter in the synaptic cleft. Thus, efficacy of tianeptine as an antidepressant agent caused a challenge to the concept of serotonergic deficit theory in depression. Both paroxetine and tianeptine are found equivalently effective in treatment of major depression, but no data are available for combined use of these two agents.

Reduced short-term obsessive-compulsive symptoms in schizophrenic patients treated with risperidone: a single-blind prospective study.

BACKGROUND: Risperidone is a widely used agent as first-line treatment in schizophrenia with a favorable side-effect profile. However, a number of case reports have suggested an increase in obsessive-compulsive symptoms in patients treated with risperidone. OBJECTIVE: The aim of this study was to investigate the effect of risperidone on obsessive-compulsive symptoms in the treatment of schizophrenia. METHOD: Forty patients with DSM-IV diagnosis of schizophrenia were included in the study. The Yale-Brown obsessive compulsive scale was administered before, at the end of first and second months of treatment. Paired-samples t-test was used to compare the three assessments. RESULTS: There was not an increase, but a significant decrease, in YBOCS scores over time during risperidone treatment (p<0.05). CONCLUSION: In the present study risperidone caused a significant decrease in obsessive-compulsive symptoms in the treatment of schizophrenia.