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We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 × 10−7) and tetraspanin-8 (TSPAN8; P=6.11 × 10−7). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 × 10−8, TSPAN8; P=7.57 × 10−7 and EGFR; P=8.36 × 10−8). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case–control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case–Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.Molecular Psychiatry (2008) 13, 558–569; doi:10.1038/sj.mp.4002151; published online 4 March 2008 [ABSTRACT FROM AUTHOR]

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This study investigated the lifetime prevalence of suicide attempts (SA) and independent demographic and clinical correlates in stabilized schizophrenia inpatients. A cross-sectional study was conducted in three psychiatric hospitals in Anhui province, an agricultural province located in east China. Psychopathology and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Rating Scale (HAMD), respectively. A total of 315 stable schizophrenia inpatients were interviewed prior to discharge. The lifetime prevalence of SA was 22.2%. Multiple logistic regression analysis revealed that female gender (P < 0.001, OR = 3.4, 95%CI: 1.9–6.0), being married (P = 0.02, OR = 2.2, 95%CI: 1.1–4.4) and having more severe depressive symptoms (P = 0.014, OR = 1.2, 95%CI: 1.01–1.3) were independently and significantly associated with higher risk of SA. Lifetime SA is common among hospitalized schizophrenia patients living in agricultural areas of China. For suicide prevention, regular assessments, appropriate interventions and clinical management should be integrated into a community-based psychiatric service model for this population. [ABSTRACT FROM AUTHOR]

Neurons have highly developed Ca signalling systems responsible for regulating many neural functions such as the generation of brain rhythms, information processing and the changes in synaptic plasticity that underpins learning and memory. The signalling mechanisms that regulate neuronal excitability are particularly important for processes such as sensory perception, cognition and consciousness. The Ca signalling pathway is a key component of the mechanisms responsible for regulating neuronal excitability, information processing and cognition. Alterations in gene transcription are particularly important as they result in subtle alterations in the neuronal signalling mechanisms that have been implicated in many neural diseases. In particular, dysregulation of the Ca signalling pathway has been implicated in the development of some of the major psychiatric diseases such as bipolar disorder (BPD) and schizophrenia. [ABSTRACT FROM AUTHOR]

The alpha 1C subunit of the L-type voltage-gated calcium channel ( CACNA1C) gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the CACNA1C single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus. These results, however, are inconsistent with regard to the magnitude and directionality of effect. In the present study, brain activation was measured with fMRI during an episodic memory encoding and retrieval task using neutral faces in two independent samples of 94 and 111 healthy subjects, respectively. Within whole brain analyses, a main effect of genotype emerged mainly in the right hippocampus during encoding as well as retrieval within the first sample: Carriers of the minor allele (A) exhibited lower activations compared to G/G allele carriers. This effect could be replicated within the second sample, however, only for the retrieval condition. The results strengthen findings that rs1006737 is associated with neural systems related to memory processes in hippocampal regions which are detectable in healthy subjects. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine the prevalence and correlates of lifetime suicide attempts and current suicidal ideation in community-dwelling schizophrenia patients in China. Method: A sample of 540 schizophrenia patients was randomly selected in Beijing, China. All subjects were interviewed using standardized assessment instruments and their basic socio-demographic and clinical data including history of suicide attempts were collected. Results: The prevalence of lifetime suicide attempts and the point prevalence of suicidal ideation were 12.0 %, and 21.1 %, respectively. In multiple logistic regression analyses, the presence of lifetime suicide attempt was independently associated with rural residence, having major medical conditions and better social functioning, while higher likelihood of current suicidal ideation was associated with past suicide attempt, the severity of overall psychopathology and depressive symptoms and lower psychological quality of life (QOL). Conclusion: Among Chinese outpatients with schizophrenia, increased current symptoms and poorer QOL were correlated with current suicidal ideation, while demographic factors and indicators of greater social support were mostly correlated with lifetime suicide attempts. This study may help to identify important subgroups of patients with schizophrenia at particularly high risk of suicidal behavior. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex genetic disorder. Gene set-based analytic (GSA) methods have been widely applied for exploratory analyses of large, high-throughput datasets, but less commonly employed for biological hypothesis testing. Our primary hypothesis is that variation in ion channel genes contribute to the genetic susceptibility to schizophrenia. We applied Exploratory Visual Analysis (EVA), one GSA application, to analyze European-American (EA) and African-American (AA) schizophrenia genome-wide association study datasets for statistical enrichment of ion channel gene sets, comparing GSA results derived under three SNP-to-gene mapping strategies: (1) GENIC; (2) 500-Kb; (3) 2.5-Mb and three complimentary SNP-to-gene statistical reduction methods: (1) minimum p value (pMIN); (2) a novel method, proportion of SNPs per Gene with p values below a pre-defined α-threshold (PROP); and (3) the truncated product method (TPM). In the EA analyses, ion channel gene set(s) were enriched under all mapping and statistical approaches. In the AA analysis, ion channel gene set(s) were significantly enriched under pMIN for all mapping strategies and under PROP for broader mapping strategies. Less extensive enrichment in the AA sample may reflect true ethnic differences in susceptibility, sampling or case ascertainment differences, or higher dimensionality relative to sample size of the AA data. More consistent findings under broader mapping strategies may reflect enhanced power due to increased SNP inclusion, enhanced capture of effects over extended haplotypes or significant contributions from regulatory regions. While extensive pMIN findings may reflect gene size bias, the extent and significance of PROP and TPM findings suggest that common variation at ion channel genes may capture some of the heritability of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Suicide risk is high in schizophrenic patients and is further elevated in dual diagnosis patients. Suicide behaviour is a continuum from ideation, plans to attempts. Exposure to traumatic stress and co-morbid PTSD is elevated in schizophrenic patients. Suicide behaviour is also common in non-psychotic PTSD patients. This study aimed to investigate the effect of trauma and co-morbid PTSD on suicide behaviour in dual diagnosis patients and whether co-morbid PTSD would further elevate suicide risk. Method: This was a cross-sectional study in which suicide behaviour was compared in those with and without co-morbid PTSD in 110 patients suffering schizophrenia and alcohol and/or substance abuse. Results: 100 (91%) reported at least one traumatic event with an average of 4.3 events. 31 (28%) patients met criteria for full PTSD. Current suicidal ideation was reported by 39 (35%) and 23 (21%) reported plans and ideation, 69 (63%) reported at least one previous suicide attempt. Suicide behaviour was significantly associated with an increasing number of traumatic events. Suicidality was significantly associated and elevated with co-morbid PTSD. Analysis indicated that the effect of trauma on suicide behaviour appeared to be mediated by hopelessness. Conclusions: Suicide behaviour was not associated with exposure to trauma per se but was associated with incremental exposure to traumatic experiences. Consistent with the study hypotheses, co-morbid PTSD further adds to the risk of suicide behaviour in an already vulnerable group. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to explore the relationship between suicidal behavior and socio-demographic and clinical factors, including insight into illness, in patients with schizophrenia spectrum disorders. We evaluated 104 inpatients using the Self-Appraisal of Illness Questionnaire (SAIQ) for insight assessment, several Beck-related symptoms rating scales, and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. These patients were also evaluated for suicidal behavior and risk using the critical items of the Scale for Suicide Ideation (SSI) and lifetime suicide attempts. Patients with suicidal behavior generally had greater insight into illness than those who were non-suicidal. After controlling for depressive symptoms, the association of insight into illness with current suicidal ideation remained significant, whereas the association between insight and lifetime suicide attempts was no longer significant. As predicted, the regression analyses revealed that those with greater suicide risk had significantly higher levels of depressive symptoms and hopelessness and more lifetime suicide attempts. Moreover, greater insight into illness appeared to have a close, independent connection to suicidal behavior. Our findings suggest that depression, hopelessness, and greater insight into illness are major risk factors for suicide in patients with schizophrenia. It is plausible that depression mediates the relationship between greater insight into illness and suicidal behavior. Aggressive improvement of insight without the risk of deteriorating depressive symptoms may be warranted to reduce the risk of suicide. [ABSTRACT FROM AUTHOR]

Background: It is suggested that the incidence of schizophrenia is decreasing. However, changes in the number of psychiatric beds available and diagnostic practice have not always been taken into account. We studied the annual first-admission rate (per 100,000) for schizophrenia (FARsch) during a rapid deinstitutionalisation period in Finland. Method: From the National Finnish Hospital discharge register, we identified all 30,041, 15- to 64-year-old patients admitted for the first time with schizophrenia to hospitals in Finland between 1980 and 2003. Results: FARsch decreased from 56.39 in 1980 to 29.51 in 1991 and slightly increased thereafter. Changes in FARsch corresponded with changes in all admissions. FARsch was higher when using ICD-8, but lower when DSM-IIIR and ICD-10 were used. Conclusion: Changes in the number of psychiatric beds available, admission policy and diagnostic practice may explain the majority of variations in FARsch. Possibly, increased use of illegal drugs and improved treatment of depression are reflected in the increase in FARsch. [ABSTRACT FROM AUTHOR]

The management of suicide risk in patients with schizophrenia poses many challenges for clinicians. Compared with the general population, these patients have an 8.5-fold greater risk of suicide. This article reviews the literature dealing with the treatment of at-risk patients with schizophrenia. An integrated psychosocial and pharmacological approach to managing this population of patients is recommended. Although there is at least modest evidence suggesting that antipsychotic medications protect against suicidal risk, the evidence appears to be most favourable for second-generation anti- psychotics, particularly clozapine, which is the only medication approved by the US FDA for preventing suicide in patients with schizophrenia. In addition, treating depressive symptoms in patients with schizophrenia is an important component of suicide risk reduction. While selective serotonin receptor inhibitors (SSRIs) ameliorate depressive symptoms in patients with schizophrenia, they also appear to attenuate suicidal thoughts. Further research is needed to more effectively personalize the treatment of suicidal thoughts and behaviours and the prevention of suicide in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Copyright of Psychiatrie und Psychotherapie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article investigates the complicated relationship of suicide attempts and life events in adolescent schizophrenic patients. Instruments used to compare forty adolescents with a diagnosis of schizophrenia and 20 age-matched subjects with no psychiatric history, included Life Events Checklist and Sexual Abuse in Childhood Questionnaire. In conclusion, adolescent patients with schizophrenia, suicidal behavior is associated less with the number of life events.

Schizophrenia is a debilitating disorder, which is usually chronic, and is one of the most devastating medical illnesses. Early and appropriate treatment with antipsychotics is an important strategy for patients with first-episode schizophrenia. However, there are many possible safety issues for patients with schizophrenia that should be considered and properly addressed. Depressive symptoms and suicidal behaviour commonly occur in first-episode schizophrenic patients, and every effort should be made to treat and minimise these symptoms. There are also important issues and considerations in young and first-episode patients that should also be considered in the emergency treatment setting and for minimising medication nonadherence in this population. Most importantly, adverse effects should be considered, minimised and addressed. While first- and second-generation antipsychotics (SGAs) both appear to offer similar efficacy for amelioration of positive symptoms in first-episode patients, SGAs may offer better tolerability, specifically regarding extrapyramidal symptoms (EPS) and tardive dyskinesia risk, and some prolactin-sparing benefits. However, these medications do cause a host of adverse effects, including weight gain, metabolic disturbances, corrected QT interval prolongation and prolactin-related adverse effects, which are important considerations relating to both the short- and long-term safety of patients with schizophrenia being treated with SGAs. Clozapine and olanzapine are most likely to cause weight gain and metabolic effects, while risperidone is more likely to cause EPS and prolactin elevations. Most antipsychotics should be used in low doses to minimise adverse effects and each medication should be optimised in a highly individualised way to maximise adherence and treatment outcomes and minimise tolerability and safety concerns. At some point in their lives, these patients will most probably experience periods of depression, suicidal behaviours, adverse effects and nonadherence, and every effort should be made to minimise or prevent these from occurring. Thus, safety concerns in this group of young patients, in the beginning of their first psychotic episode, are a major issue as they are starting a journey of antipsychotic treatment that is likely to last for the remainder of their lives. [ABSTRACT FROM AUTHOR]

The relationship between psychotherapy and schizophrenia has undergone pronounced changes over the last several decades. The advent of psychiatric medication led to remarkable breakthroughs that obscured the existential issues inseparably tied to the lived experience of illness and overshadowed the role of psychotherapy in the treatment of schizophrenia. Recent years have brought renewed scrutiny of the place of psychotherapy in the treatment of persons with major mental illness but much less attention has been shown to matters of countertransference. The complex legacy of loss and grief assumes a special dimension in the therapeutic relationship and touches the lives of client and clinician alike. Both travel a common path and share privileged moments. It is the intersection of these life experiences, and how their confluence shapes the course of therapy that is the focus of this essay. [ABSTRACT FROM AUTHOR]

Ziprasidone is a novel antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical antipsychotics. In preclinical studies, ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. The drug has been administered orally to >300 patients with an acute exacerbation of schizophrenia or schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily, at dosages of between 80 and 160 mg/day, ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study, ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day. Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic schizophrenia who were treated for up to 1 year. In addition, significantly more ziprasidone than haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic schizophrenia. In general, oral ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the drug has a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The drug does not appear to be associated with sustained elevation of plasma prolactin concentrations. Preliminary data indicate that long-term oral ziprasidone treatment is well tolerated. Ziprasidone is the only novel antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular ziprasidone was effective and well tolerated in patients with acute agitation associated with psychosis. In addition, intramuscular ziprasidone reduced agitation scores by a significantly greater extent than haloperidol in a study involving patients with acute agitation associated with psychosis. Conclusions: Ziprasidone is a promising new antipsychotic that has shown significant efficacy in the oral treatment of patients with schizophrenia or schizoaffective disorder. The drug is well tolerated with a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and good tolerability in the treatment of acute agitation associated with psychotic disorders. [ABSTRACT FROM AUTHOR]

Depression is a common comorbid syndrome in patients with schizophrenia. A review of the literature highlights the multitude of different expressions used to describe depression in this context. This fact exemplifies the diagnostic and therapeutic inconsistencies found in literature. Former generations of psychiatrists considered that antidepressants could provoke psychotic symptoms. Although the evidence is still tentative, it appears to be current common practice for most psychiatrists, having ruled out confounding conditions such as extrapyramidal motor symptoms and negative symptoms, to prescribe antidepressant agents to patients who show depressive symptoms. There are controlled clinical trials that have demonstrated that tricyclic antidepressants are effective in the treatment of depression in patients with schizophrenia. In contrast, the newer antidepressants have yet to be tested in large scale controlled studies. Possible interactions between antipsychotics and antidepressants must be considered when these two classes of agent are prescribed. Monotherapy with novel antipsychotics may be a treatment option, as some such as zotepine, olanzapine and risperidone have shown advantages over traditional antipsychotics in reducing depressive symptoms in patients with schizophrenia. Others have some pharmacological properties that resemble antidepressant drugs. [ABSTRACT FROM AUTHOR]

A total of 149 inpatients were identified who had committed suicide in two Swiss psychiatric institutions in the years 1960-1981. Using Research Diagnostic Criteria, 49 were diagnosed as schizophrenics, 75 as depressives, and 9 as alcoholics. The first two groups were significantly overrepresented and the third one underrepresented when compared with a control sample. There were considerable differences between the individual diagnostic groups of clinical suicides: (1) schizophrenic suicides were characterized by a disturbed early social adjustment, a high degree of later disability and an unfavorable course of their illness, (2) depressive suicides were much less handicapped, although they presented a much higher long-term suicidal potential, and (3) alcoholic suicides demonstrated no signs of suicidal behavior in the clinic and committed suicide unexpectedly after experiencing negative life events. These findings have therapeutic implications. [ABSTRACT FROM AUTHOR]

The risk for suicidal behavior in schizophrenia is high with 10–15% committing suicide and 20–40% making suicide attempts. Due to the chronicity and complexity of schizophrenia and the multi-determined nature of suicidal behavior, the clinician must utilize a biopsychosocial approach to assessment and intervention. Clinical factors such as psychosis, depression and substance abuse increase the risk for suicidal behavior in schizophrenia. Social factors such as social adjustment and social supports also play a critical role. Ongoing assessment and intervention of suicidal behavior, clinical symptomatology, social environment and treatment issues are essential. Prediction and prevention of suicidal behavior are not always possible however. Treatment focused on the reduction of symptomatology and maintenance of an effective social environment may attenuate the risk for suicidal behavior in schizophrenia. [ABSTRACT FROM AUTHOR]