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1.  Quality of life changes following inpatient and outpatient treatment in obsessive-compulsive disorder: a study with 12 months follow-up 
Background
Quality of life (QoL) is increasingly recognized as a critical outcome parameter in mental health studies. The aim of this study was to investigate different domains of the QoL in persons with obsessive-compulsive disorder (OCD) before and after a multimodal, disorder-specific in- and outpatient treatment.
Methods
Data of 73 persons with OCD treated in an inpatient setting followed by outpatient treatment were analyzed. The World Health Organization Quality of Life abbreviated (a multidimensional measure of the QoL) and the Beck Depression Inventory were administered prior to (baseline) and 12 months after the inpatient treatment (follow-up).
Results
At baseline, participants reported a significantly diminished psychological, social, physical, and global QoL compared to the German general population. Environmental QoL was not impaired in the present sample. The QoL was significantly improved at follow-up, except for social QoL, but remained below norm values. The QoL improvement was predicted by improvements of depressive symptoms.
Conclusions
The results indicate that persons with OCD suffer from a very low QoL. The QoL was significantly improved after 12 months of intensive state-of-the-art treatment. However, the QoL indices remained considerably lower than population norm values, indicating the need for additional research into novel treatment options for persons with OCD.
doi:10.1186/1744-859X-12-4
PMCID: PMC3586364  PMID: 23433285
Obsessive-compulsive disorder; Quality of life; Cognitive behavioral therapy; Exposure; Inpatient; WHOQOL; Functional impairment
2.  A structured interview guide for global impressions: increasing reliability and scoring accuracy for CNS trials 
Background
The clinical global impression of severity (CGI-S) scale is a frequently used rating instrument for the assessment of global severity of illness in Central Nervous System (CNS) trials. Although scoring guidelines have been proposed to anchor these scores, the collection of sufficient documentation to support the derived score is not part of any standardized interview procedure. It is self evident that the absence of a standardized, documentary format can affect inter-rater reliability and may adversely affect the accuracy of the resulting data.
Method
We developed a structured interview guide for global impressions (SIGGI) and evaluated the instrument in a 2-visit study of ambulatory patients with Major Depressive Disorder (MDD) or schizophrenia. Blinded, site-independent raters listened to audio recorded SIGGI interviews administered by site-based CGI raters. We compared SIGGI-derived CGI-S scores between the two separate site-based raters and the site-independent raters.
Results
We found significant intraclass correlations (p = 0.001) on all SIGGI-derived CGI-S scores between two separate site-based CGI raters with each other (r = 0.768) and with a blinded, site-independent rater (r = 0.748 and r = 0.706 respectively) and significant Pearson’s correlations between CGI-S scores with all MADRS validity comparisons for MDD and PANSS comparisons for schizophrenia (p- 0.001 in all cases). Compared to site-based raters, the site-independent raters gave identical “dual” CGI-S scores to 67.6% and 68.2% of subjects at visit 1 and 77.1% at visit 2.
Conclusion
We suggest that the SIGGI may improve the inter-rater reliability and scoring precision of the CGI-S and have broad applicability in CNS clinical trials.
doi:10.1186/1744-859X-12-2
PMCID: PMC3564924  PMID: 23369692
Inter-rater reliability; Global impressions; Ratings accuracy; Structured interviews
3.  Evidence review and clinical guidance for the use of ziprasidone in Canada 
While indicated for schizophrenia and acute mania, ziprasidone’s evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success
doi:10.1186/1744-859X-12-1
PMCID: PMC3564821  PMID: 23347694
Ziprasidone; Expert consensus; Schizophrenia; Bipolar disorder; Depression; Anxiety; Dosing; Off-label
4.  Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model 
The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.
A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.
The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.
Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.
doi:10.1186/1744-859X-11-29
PMCID: PMC3514336  PMID: 23157721
5.  Stress-related asthma and family therapy: Case study 
This paper applies the Biobehavioral Family Model (BBFM) of stress- related illness to the study and treatment of an adolescent with intractable asthma. The model is described, along with supportive research findings. Then a case study is presented, demonstrating how the model is clinically applied. We tell the story of an asthmatic adolescent presenting for therapy due to her intense asthmatic crises, and the case is presented to exemplify how the BBFM can help understand the family-psychobiological contribution to exacerbation of disease activity, and therefore guide treatment towards the amelioration of severe physical symptoms. Facets of the patient’s intra-familial interactions are consistent with the BBFM, which support clinical validation of the model. In the case described, it is likely that additional asthma medications would not have had the desired ameliorative effect, because they did not target the family relational processes contributing to the symptoms. The recognition of the influences of family relational processes on the disease was crucial for effective intervention. The therapy incorporates and weaves together BBFM understanding of family patterns of interaction and physiological/medical concerns integrated with Bowenian intervention strategies. This case study validates the importance and usefulness of BBFM for intervention with stress-sensitive illnesses such as asthma.
doi:10.1186/1744-859X-11-28
PMCID: PMC3537677  PMID: 23148727
Family; Differentiation; Asthma; Intervention
6.  Sexual obsessions and suicidal behaviors in patients with mood disorders, panic disorder and schizophrenia 
Background
The topic of sexual obsessions as a psychiatric symptom has not been well investigated. The aim of this study was twofold: 1) to explore the presence of sexual obsessions in patients with mood disorders (n=156), panic disorder (n=54) and schizophrenia (n=79), with respect to non-psychiatric subjects (n=100); 2) to investigate the relationship between sexual obsessions and suicidal behaviors, taking into account socio-demographic variables ad mental disorders.
Methods
289 psychiatric patients with mood disorders, panic disorder or schizophrenia, were recruited at the Italian University departments of psychiatry along with 100 non-psychiatric subjects, who presented for a routine eye exam at the ophthalmology department of the same Universities. The assessments included: the Structured Clinical Interview for DSM-IV-TR, the Brief Psychiatric Rating Scale (BPRS), the Obsessive-Compulsive Spectrum Self-Report (OBS-SR), for sexual obsession, and the Mood Spectrum-Self Report lifetime version (MOODS-SR). Suicidality was assessed by means of 6 items of the MOODS-SR.
Results
Sexual obsessions were more frequent in schizophrenia (54.4%), followed by mood disorders (35.9%). Among schizophrenia patients, males reported more sexual obsessions than females (P<0.01). Subjects who were more likely to report suicidal behaviors (suicidal ideation, plans and attempts) were female (adjusted OR=1.99), patients with mental disorders, specifically mood disorders (adjusted OR=11.5), schizophrenia (adjusted OR=3.7) or panic disorder (adjusted OR=2.9), and subjects who reported lifetime sexual obsessions (adjusted OR= 3.6). Sexual obsessions remained independently associated with all aspects of suicidal behaviors. Age, education, marital and employment status were not related to suicidal behaviors.
Conclusions
Special attention should be given to investigate and establish effective strategies of treatment for sexual obsessions, especially those with comorbid mood disorders or schizophrenia.
doi:10.1186/1744-859X-11-27
PMCID: PMC3549946  PMID: 23110965
Sexual obsessions; Suicidal ideation; Suicidal plans; Suicidal attempt; Mood disorders; Panic disorder; Schizophrenia
7.  Gender, trauma type, and PTSD prevalence: a re-analysis of 18 nordic convenience samples 
Background
The aim of the study was to examine a possible trauma type related variance in the gender difference of posttraumatic stress disorder (PTSD) prevalence.
Methods
An analysis was conducted on 18 convenience sample studies including data from a total of 5220 participants. The studies all applied the Harvard Trauma Questionnaire – part IV to assess PTSD. Cohen’s d was used to measure variance in gender differences. Trauma types included disasters and accidents, violence, loss, chronic disease and non-malignant diseases.
Results
The results showed an overall gender difference in PTSD prevalence similar to previous findings. Thus, women had a two-fold higher prevalence of PTSD than men. Besides categorical analyses, dimensional analyses of PTSD severity were also performed; the latter were associated with twice as large effect sizes. Females were more vulnerable to PTSD after disasters and accidents, followed by loss and non-malignant diseases. In violence and chronic disease, the gender differences were smallest.
Conclusions
The findings support the existence of a trauma type related variance in gender differences in PTSD prevalence.
doi:10.1186/1744-859X-11-26
PMCID: PMC3494556  PMID: 23107002
Posttraumatic Stress Disorder (PTSD); Gender differences; Trauma types
8.  Poor performance on the Iowa gambling task in children with obsessive-compulsive disorder 
Background
Several lines of evidence implicate orbitofrontal cortex dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of this study was to investigate neuropsychological dysfunction of the orbitofrontal cortex in children with OCD.
Methods
The Iowa Gambling Task (IGT), which reflects orbitofrontal cortex function, and the Wisconsin Card Sorting Test (WCST), which is associated with functioning of the dorsolateral prefrontal cortex, were administered to 22 children with OCD and 22 healthy controls matched for gender, age, and intelligence.
Results
OCD patients displayed poor performance on the IGT. In contrast, performance on the WCST was not impaired in OCD patients compared to controls.
Conclusions
These findings are in line with previous studies demonstrating that OCD in childhood is associated with a dysfunction of orbitofrontal-striatal-thalamic circuitry.
doi:10.1186/1744-859X-11-25
PMCID: PMC3508952  PMID: 23062199
Obsessive-compulsive disorder; Childhood-onset; Iowa gambling task; Wisconsin card sorting test; Orbitofrontal cortex
9.  No association between dietary patterns and depressive symptoms among a community-dwelling population in Japan 
Background
Studies of the associations between diet and depression have primarily focused on single nutrients or foods. Recently, dietary patterns representing a combination of foods have attracted more interest than individual nutrient. The objective of this study was to examine the association between dietary patterns and depressive symptoms among a community-dwelling population in Japan.
Methods
We examined the association between dietary patterns and the risk of depression among 791 Japanese community-dwelling individuals. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups [energy-adjusted food (g/d)] were extracted by principal component analysis. The Center for Epidemiologic Studies Depression Scale (CES-D) with a cut-off point of 16 was used to assess the prevalence of depression.
Results
A total of 97 subjects (12.3%) were classified as having depression. Four dietary patterns were identified: “Healthy”, “Western”, “Bread and confectionery”, and “Alcohol and accompanying” dietary patterns. After adjusting for potential confounders, the dietary patterns were not related to the risk of depression.
Conclusions
The present study failed to find associations between dietary patterns and the risk of depression. However, the interpretation of our results was hampered by the lack of certain data, including employment physical activity and longitudinal observations. Potential associations between dietary patterns and depressive symptoms were not completely ruled out. Future research exploring dietary patterns and depressive symptoms is warranted.
doi:10.1186/1744-859X-11-24
PMCID: PMC3532227  PMID: 23006931
10.  Clinical presentations of substance abuse in bipolar heroin addicts at time of treatment entry 
Background
Studies on the ‘self-medication hypothesis’ have focused on substance abuse as an attempt to alleviate emotional suffering.
Methods
We have investigated concomitant substances of abuse in 150 bipolar heroin addicts clustered according to their clinical presentation at treatment entry (depressive episode, hypomanic episode, manic episode and mixed episode). Bipolar heroin addicted patients were chosen because they tend to have a concomitant poly-substance abuse and because, as compared with patients suffering for other mental illnesses, they more clearly reveal a variety of identifiable affective states.
Results
Patients with a depressive episode more frequently used non-prescribed anxiolytic-hypnotics. They were found to use cocaine-amphetamines more frequently during a hypomanic episode, whereas the use of cannabis and cocaine-amphetamines occurred more frequently during a manic episode. The associated use of alcohol, cocaine-amphetamines and cannabinoids was more frequently encountered during a mixed episode. Limitations: apart from the difficulty in determining whether the substance use modifies the mood or the mood state determines the substance used, this is a report on a retrospective analysis, rather than a study specifically designed to elucidate the issue; in addition, no information was available on the temperament of our subjects. Assessments of the same subject in various clinical presentations would have provided a better level of information.
Conclusions
Besides one expected result – the prominent use of CNS stimulants during a depressive phase of bipolar patients – this study supports the hypothesis that mood elation is a pleasurable, rewarding experience that, in bipolar patients, can be started or prolonged by means of CNS stimulant drugs. Stimulant use was, therefore, more prevalent during the ‘up’ rather than the ‘down’ phase of the illness.
doi:10.1186/1744-859X-11-23
PMCID: PMC3473306  PMID: 22943591
11.  Assessment of pharmacological strategies for management of major depressive disorder and their costs after an inadequate response to first-line antidepressant treatment in primary care 
Background
The aim of the study was to determine the most common treatment strategies and their costs for patients with an inadequate response to first-line antidepressant treatment (AD) in primary care.
Method
A retrospective cohort study of medical records from six primary care centers was conducted. Adults with a major depressive disorder diagnosis, at least 8 weeks of AD treatment after the first prescription, and patient monitoring for 12 months were analyzed. Healthcare (direct cost) and non-healthcare costs (indirect costs; work productivity losses) were described.
Results
A total of 2,260 patients were studied. Forty-three percent of patients (N = 965) presented an inadequate response to treatment. Summarizing the different treatment approaches: 43.2% were switched to another AD, 15.5% were given an additional AD, AD dose was increased in 14.6%, and 26.7% remained with the same antidepressant agent. Healthcare/annual costs were 451.2 Euros for patients in remission vs. 826.1 Euros in those with inadequate response, and productivity losses were 991.4 versus 1,842.0 Euros, respectively (p < 0.001).
Conclusion
Antidepressant switch was the most common therapeutic approach performed by general practitioners in naturalistic practice. A delay in treatment change when no remission occurs and a significant heterogeneity in management of these patients were also found.
doi:10.1186/1744-859X-11-22
PMCID: PMC3426459  PMID: 22862816
Major depressive disorder; Remission; Primary care; First-line antidepressant treatment; Costs
12.  Does duration of untreated psychosis predict very long term outcome of schizophrenic disorders? results of a retrospective study 
Background
Studies performed to assess the relevance of duration of untreated psychosis (DUP) as a predictor of long-term outcome (i.e. follow-ups of ten years or more) are somewhat limited. The aim of this study was to evaluate the potential association between DUP and very long-term outcome (16-33 yrs) of schizophrenia by means of a retrospective design.
Methods
Retrospective data obtained from clinical records were collected regarding DUP and outcome variables (number of hospitalizations; number of attempted suicides; course of illness; GAF scores at last observation) for a cohort of 80 outpatients (52 Males, 28 Females, mean age 51.0+/-11.58 years) affected by schizophrenia according to DSMIVTR attending a university community mental health centre.
Results
Mean duration of follow up was 25.2 +/- 8.68 years; mean duration of untreated psychosis was 49.00 months (range 1-312 mo), with no significant difference according to gender. Patients with a shorter DUP (=/< 1 year) displayed more frequent “favourable” courses of illness (28.9% vs 8.6%) (p = 0.025), more frequent cases with limited (=/< 3) number of hospital admissions (85.7% vs 62.1%) (p = 0.047) and a better functioning (mean GAF score = 50.32+/-16.49 vs 40.26+/-9.60, p = 0.002); regression analyses confirmed that shorter DUP independently predicted a more positive outcome in terms of number of hospital admissions, course of illness, functioning (GAF scores).
Conclusion
A shorter DUP appears to act as a significant predictor of better outcome in schizophrenia even in the very long-term.
doi:10.1186/1744-859X-11-21
PMCID: PMC3416650  PMID: 22856624
13.  Reducing treatment delay for early intervention: evaluation of a community based crisis helpline 
Background
A limited number of studies have assessed the pathways to care of patients experiencing psychosis for the first time. Helpline/clinic programs may offer patients who are still functional but have potential for crisis an alternative that is free from judgment.
Methods
In this study we report on patient calling a round-the-clock crisis helpline for suicide prevention supported by psychiatric facilities in Mumbai, India. Chi-square and test of mean differences were used to compare outcomes between first-episode patients and those with a previous history.
Results
Within five years, the helpline received 15,169 calls. Of those callers, 2341 (15.4%) experienced suicidal ideation. Two hundred and thirty four patients opting for counseling lasting 12 months agreed to a psychiatric assessment. Of those, 32 were fist time psychosis sufferers, whereas, 54 had previously been psychotic. Of all psychiatric assessments, the clinic received 94 patients with ‘first-episode psychosis’. We found that the duration of illness was significantly shorter (17 vs. 28 months) and suicide attempts were fewer (16 vs. 21) in first-time psychosis sufferers compared to those with a treatment history.
Conclusions
We conclude that some first-episode patients of schizophrenia and other disorders do access services by using helplines. We also argue that helplines may be somewhat immune to stigma, allowing patients a safe alternative when finding help.
doi:10.1186/1744-859X-11-20
PMCID: PMC3416718  PMID: 22827835
Helpline; Stigma; Psychosis; Early intervention; Duration of treatment
14.  Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug 
Dopamine dysregulation syndrome (DDS) consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD). Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.
doi:10.1186/1744-859X-11-19
PMCID: PMC3465018  PMID: 22769562
Dopamine dysregulation syndrome (DDS); Aripiprazole; Dopamine D2 partial agonistic antipsychotic drug; Parkinson's disease; Dopamine replacement therapy (DRT)
15.  Pharmacoeconomic analysis of paliperidone palmitate for treating schizophrenia in Greece 
Background
Patients having chronic schizophrenia with frequent relapses and hospitalizations represent a great challenge, both clinically and financially. Risperidone long-acting injection (RIS-LAI) has been the main LAI atypical antipsychotic treatment in Greece. Paliperidone palmitate (PP-LAI) has recently been approved. It is dosed monthly, as opposed to biweekly for RIS-LAI, but such advantages have not yet been analysed in terms of economic evaluation.
Purpose
To compare costs and outcomes of PP-LAI versus RIS-LAI in Greece.
Methods
A cost-utility analysis was performed using a previously validated decision tree to model clinical pathways and costs over 1 year for stable patients started on either medication. Rates were taken from the literature. A local expert panel provided feedback on treatment patterns. All direct costs incurred by the national healthcare system were obtained from the literature and standard price lists; all were inflated to 2011 costs. Patient outcomes analyzed included average days with stable disease, numbers of hospitalizations, emergency room visits, and quality-adjusted life-years (QALYs).
Results
The total annual healthcare cost with PP-LAI was €3529; patients experienced 325 days in remission and 0.840 QALY; 28% were hospitalized and 15% received emergency room treatment. With RIS-LAI, the cost was €3695, patients experienced 318.6 days in remission and 0.815 QALY; 33% were hospitalized and 17% received emergency room treatment. Thus, PP-LAI dominated RIS-LAI. Results were generally robust in sensitivity analyses with PP-LAI dominating in 74.6% of simulations. Results were sensitive to the price of PP-LAI.
Conclusions
PP-LAI appears to be a cost-effective option for treating chronic schizophrenia in Greece compared with RIS-LAI since it results in savings to the health care system along with better patient outcomes.
doi:10.1186/1744-859X-11-18
PMCID: PMC3430591  PMID: 22747533
Paliperidone palmitate; Risperidone; Long-acting injectables; Schizophrenia; Pharmacoeconomic analysis; Greece
16.  Identifying the sociodemographic determinants of subjective health complaints in a cross-sectional study of Greek adolescents 
Background
Experience of common health symptoms without a clear physical or psychological cause, such as headache or dizziness, is often reported in adolescence. The present study attempted to investigate associations of self-reported subjective health complaints (SHC) with a number of sociodemographic factors of Greek adolescents.
Methods
Questionnaires were administered to a Greek nationwide random school-based sample of adolescents aged 12 to 18 years and their parents in 2003. Data from 922 adolescent-parent pairs were analyzed (response rate = 63%). Adolescents’ reported subjective health complaints were assessed for their association with a number of sociodemographic factors: age, sex, type of area of residence according to level of urbanization, immigration background, parental education and employment status, family socioeconomic status and perceived quality of financial resources (PQFR). Multiple linear regression analysis was used to assess the association of the aforementioned factors with subjective health complaints as the dependent variable.
Results
Most sociodemographic variables, apart from area of residence and immigration background, were independently associated with subjective health complaints in the univariate analyses. The multiple linear regression analysis, however, limited the factors that could predict adolescents’ subjective health complaints to four (age, sex, Family Affluence Scale score and perceived quality of financial resources). Some considerations regarding parental employment status and immigration background are highlighted.
Conclusions
Our study highlights the sociodemographic components of subjective health complaints in the Greek adolescent population. The need to include adolescent-specific measures when collecting information on adolescents’ social background is underlined. Identifying vulnerable adolescent populations could lead to effective health promoting and preventive interventions.
doi:10.1186/1744-859X-11-17
PMCID: PMC3441215  PMID: 22748205
Adolescence; Financial resources; Sociodemographic factors; Socioeconomic status; Subjective assessment; Subjective health complaints
17.  Psychiatric comorbidities in asperger syndrome and high functioning autism: diagnostic challenges 
Several psychiatric conditions, both internalizing and externalizing, have been documented in comorbidity with Asperger Syndrome (AS) and High Functioning Autism (HFA). In this review we examine the interplay between psychiatric comorbidities and AS/HFA. In particular, we will focus our attention on three main issues. First, we examine which psychiatric disorders are more frequently associated with AS/HFA. Second, we review which diagnostic tools are currently available for clinicians to investigate and diagnose the associated psychiatric disorders in individuals with AS/HFA. Third, we discuss the challenges that clinicians and researchers face in trying to determine whether the psychiatric symptoms are phenotypic manifestations of AS/HFA or rather they are the expression of a distinct, though comorbid, disorder. We will also consider the role played by the environment in the manifestation and interpretation of these symptoms. Finally, we will propose some strategies to try to address these issues, and we will discuss therapeutic implications.
doi:10.1186/1744-859X-11-16
PMCID: PMC3416662  PMID: 22731684
Asperger; High functioning autism; Comorbidities; Diagnostic challenges
18.  Effects of eszopiclone on safety, subjective measures of efficacy, and quality of life in elderly and nonelderly Japanese patients with chronic insomnia, both with and without comorbid psychiatric disorders: a 24-week, randomized, double-blind study 
Background
The primary objective of this study was to evaluate long-term (24-week) safety of eszopiclone in elderly and nonelderly Japanese patients with chronic insomnia. The secondary objectives were to evaluate short-term (4-week) efficacy and to assess for rebound insomnia or dependence after long-term treatment.
Methods
Patients (n = 164 elderly; n = 161 nonelderly), with or without psychiatric comorbidities, were randomized to receive low-dose (1 mg, elderly; 2 mg, nonelderly) or high-dose (2 mg, elderly; 3 mg, nonelderly) eszopiclone. The safety evaluation included adverse events, vital signs, clinical laboratory parameters, and electrocardiogram. Efficacy was assessed using patient reports of sleep latency (SL), total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NA), quality of sleep, depth of sleep, daytime sleepiness, daytime ability to function, and the 36-item Short Form (SF-36) Health Survey.
Results
The rate of adverse events was 81.5% in the 1-mg elderly group, 79.5% in the 2-mg elderly group, 82.1% in the 2-mg nonelderly group, and 87.0% in the 3-mg nonelderly group. Dysgeusia was the most common adverse event and was dose-related. Of 12 serious adverse events, none were considered by the investigator to be related to study medication. No rebound insomnia was observed. Eszopiclone significantly improved SL, TST, WASO, NA, and daytime sleepiness and function from baseline to Week 4, irrespective of age and psychiatric comorbidity. Improvements were also observed in SF-36 Mental Health Component scores in elderly and nonelderly patients with psychiatric comorbidities.
Conclusions
Irrespective of age, eszopiclone appeared safe as administered in this study for 24 weeks. Eszopiclone improved sleep variables in insomnia patients with and without psychiatric disorders and health-related quality of life in those with psychiatric disorders.
Trial registration
ClinicalTrials.gov #NCT00770692; http://clinicaltrials.gov/ct2/show/NCT00770692.
doi:10.1186/1744-859X-11-15
PMCID: PMC3430596  PMID: 22731653
Elderly; Long-term; Eszopiclone; Insomnia; Psychiatric disorder; Quality of life; Japanese
19.  Development of the Global Disability Scale (Glo.Di.S): preliminary results 
Background
The assessment of functioning and disability is an important part of the clinical evaluation, since it measures disease burden and reflects the effectiveness of therapeutic planning and interventions. The aim of the current study was to develop such a self-report instrument on the basis of a review of the literature, and compatible with the WHO approach.
Material and methods
The review of the literature led to the development of the Global Disability Scale (Glo.Di.S) with 25 items assessing different aspects of disability. The study sample included 728 persons from vulnerable populations (homeless, jobless, very low income, single parent families etc.; (29.12% males and 70.88% females; aged 55.96 ± 15.22 years). The protocol included also the STAI and the CES-D. The statistical analysis included factor analysis item analysis and ANCOVA.
Results
The factor analysis revealed the presence of 4 factors explaining 71% of total variance (Everyday functioning, Social and interpersonal functioning, Severity and Mental disability). Chronbach’s alpha for the whole scale was 0.95 and for subscales were 0.74–0.94.
Discussion
The results of the current study suggest that the Glo.Di.S. has the potential to serve as a reliable and valid tool for assessing functioning and disability. Further research is needed to prove that it could be useful across countries, populations and diseases, and whether it provides data that are culturally meaningful and comparable. It can be used in surveys and in clinical research settings and it can generate information of use in evaluating health needs and the effectiveness of interventions to reduce disability and improve health.
doi:10.1186/1744-859X-11-14
PMCID: PMC3434028  PMID: 22594786
Disability; Burden; Functioning; ICF; Development; Impairment
20.  Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study 
Background
About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect.
Methods
A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire.
Results
In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups.
Conclusions
Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients.
Trial Registration
Clinicaltrials.gov identifier: NCT00564096.
doi:10.1186/1744-859X-11-13
PMCID: PMC3355036  PMID: 22559192
21.  Treatment of refractory catatonic schizophrenia with low dose aripiprazole 
This case is of 54-year-old female with catatonic schizophrenia, characterized by treatment resistance to the pharmacotherapy with olanzapine, risperidone, flunitrazepam, and ECT. Olanzapine and risperidone and flunitrazepam did not improve her catatonic and psychotic symptoms, and induced the extrapyramidal symptoms. The effects of ECT did not continue even for a month. However, the treatment with low-dose aripiprazole dramatically improved the patient’s psychotic symptoms and extrapyramidal symptoms. The mechanisms underlying the effects of low-dose aripiprazole in this case remain unclear, but unlike other antipsychotics, aripiprazole is a dopamine D2 partial agonist. In this regard, our results suggest that aripiprazole has numerous advantages, especially in cases of stuporous catatonia and a defective general status.
doi:10.1186/1744-859X-11-12
PMCID: PMC3473267  PMID: 22553911
22.  Body composition in patients with schizophrenia: Comparison with healthy controls 
Background
Recently, a relationship between obesity and schizophrenia has been reported. Although fat- mass and fat free mass have been shown to be more predictive of health risk than body mass index, there are limited findings about body composition among patients suffering from schizophrenia. The aim of this study is to compare the body composition of schizophrenia patients with that of healthy subjects in Japan.
Methods
We recruited patients (n = 204), aged 41.3 ± 13.8 (mean ± SD) years old with the DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospital using a cross-sectional design. Subjects' anthropometric measurements including weight, height, body mass index (BMI), and medications were also collected. Body fat, percent (%) body fat, fat- free mass, muscle mass, and body water were measured using the bioelectrical impedance analysis (BIA) method. Comparative analysis was performed with schizophrenic subjects and 204 healthy control individuals.
Results
In a multiple regression model with age, body mass index, and dose in chlorpromazine equivalents, schizophrenia was a significantly linked with more body fat, higher % body fat, lower fat- free mass, lower muscle mass, and lower body water among males. In females, schizophrenia had a significant association with lower % body fat, higher fat- free mass, higher muscle mass, and higher body water.
Conclusions
Our data demonstrate gender differences with regard to changes in body composition in association with schizophrenia. These results indicate that intervention programs designed to fight obesity among schizophrenic patients should be individualized according to gender.
doi:10.1186/1744-859X-11-11
PMCID: PMC3494526  PMID: 22554352
Body composition; Bioelectrical impedance; Schizophrenia; Japanese
23.  Treatment received, satisfaction with health care services, and psychiatric symptoms 3 months after hospitalization for self-poisoning 
Background
Patients who self-poison have high repetition and high mortality rates. Therefore, appropriate follow-up is important. The aims of the present work were to study treatment received, satisfaction with health care services, and psychiatric symptoms after hospitalization for self-poisoning.
Methods
A cohort of patients who self-poisoned (n = 867) over a period of 1 year received a questionnaire 3 months after discharge. The Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and Generalized Self-Efficacy Scale (GSE) were used. The participation rate was 28% (n = 242); mean age, 41 years; 66% females.
Results
Although only 14% of patients were registered without follow-up referrals at discharge, 41% reported no such measures. Overall, satisfaction with treatment was fairly good, although 29% of patients waited more than 3 weeks for their first appointment. A total of 22% reported repeated self-poisoning and 17% cutting. The mean BDI and BHS scores were 23.3 and 10.1, respectively (both moderate to severe). The GSE score was 25.2. BDI score was 25.6 among patients with suicide attempts, 24.9 for appeals, and 20.1 for substance-use-related poisonings.
Conclusions
Despite plans for follow-up, many patients reported that they did not receive any. The reported frequency of psychiatric symptoms and self-harm behavior indicate that a more active follow-up is needed.
doi:10.1186/1744-859X-11-10
PMCID: PMC3347980  PMID: 22520705
Follow up; depression; psychiatric symptoms; self-poisoning; suicide attempt; treatment; satisfaction
24.  The role of cytokines and hot flashes in perimenopausal depression 
Background
An imbalance in the production of proinflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of perimenopausal depression. The aim of this study was to examine serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNFα), and the anti-inflammatory cytokine IL-10, in perimenopausal women suffering from depression. Furthermore, to assess whether serum cytokine levels are associated with the presence of hot flashes or the use of selective serotonin reuptake inhibitors (SSRIs). We also evaluated the possible association of hot flashes and perimenopausal depression.
Methods
Serum samples from 65 perimenopausal women, 41 with depression and 24 without depression, were assessed for serum IL-6, TNFα and IL-10 by conventional enzyme-linked immunosorbent assays. Depression was evaluated by the 17-item Hamilton Depression Rating Scale (HAM-D 17) and a psychiatric interview. The presence and severity of hot flashes were examined using the Menopause Rating Scale (MRS).
Results
Serum levels cytokines did not differ between depressed women and normal controls. Serum levels of cytokines did not change significantly in depressed women with hot flashes or in depressed women treated with SSRIs. Hot flashes were strongly associated (P < 0.0001) with perimenopausal depression.
Conclusion
The study supports the hypothesis that perimenopausal depression is not characterized by increased proinflammatory cytokines and decreased anti-inflammatory cytokines. Women with perimenopausal depression suffer from more severe and more frequent hot flashes than women without perimenopausal depression.
doi:10.1186/1744-859X-11-9
PMCID: PMC3348044  PMID: 22490187
antidepressants; cytokines; depression; hot flashes; interleukin 6 (IL-6); interleukin 10 (IL-10); perimenopause; tumor necrosis factor α (TNFα)
25.  Caregiving in severe mental illness: the psychometric properties of the Involvement Evaluation Questionnaire in Portugal 
Background
Despite the achievements of previous research, caregiving assessments in severe mental illness should be crossculturally validated in order to define risk groups or to evaluate family work. This study reports on the psychometric properties of the European version of the Involvement Evaluation Questionnaire (IEQ-EU) in Portugal.
Methods
A Portuguese translation of the IEQ-EU was developed according to the 'European Psychiatric Services: Inputs Linked to Outcome Domains and Needs' (EPSILON) group guidelines. We then studied 194 caregivers who were related to patients with schizophrenia spectrum disorders in psychiatric outpatient services. All relatives were assessed using the IEQ-EU. In order to describe the corresponding patients' sample, the majority (n = 162) was evaluated with the World Health Organization Disability Assessment Schedule (WHO-DAS II); 108 patients were also assessed with the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF).
Results
The factor structure of the Portuguese version of the questionnaire was similar to the original; internal consistency was good, with Cronbach's α ranging from 0.71 to 0.87 in the IEQ-EU scales (total score and domains: tension, supervision, worrying, urging); test-retest reliability yielded intraclass correlation coefficients (ICCs) from 0.80 to 0.94, concerning the same scores. Ecological validity was confirmed. Most caregiving consequences were reported on the worrying domain of the IEQ-EU.
Conclusions
Validity and reliability of the Portuguese IEQ-EU translation were established. Specifically the four IEQ-EU subscale domains seem to be valid in Portugal.
doi:10.1186/1744-859X-11-8
PMCID: PMC3364850  PMID: 22455541
Caregiver; crosscultural psychiatry; family member; measurement validation; questionnaires; schizophrenia

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