Patient-reported needs predict perceived psychosocial disability and quality of life beyond symptom severity in schizophrenia.

PURPOSE: We examined whether patient-rated or clinician-rated needs are more strongly associated with perceived psychosocial disability (PPD) and subjective quality of life (SQOL) of schizophrenia patients, beyond symptom severity. METHODS: Hierarchical regression analyses were computed to test patient and clinician-rated unmet and met needs (estimated by eighty-two patient-clinician pairs) as predictors of PPD and SQOL above and beyond demographics and psychopathology. Needs, symptomatology, PPD and SQOL were estimated using Camberwell Assessment of Need (CAN), PANSS, WHODAS 2.0 and WHOQOL-BREF respectively. RESULTS: Needs were significantly associated with all WHODAS 2.0 and WHOQOL-BREF domains above and beyond demographics and PANSS variables. Clinician-rated needs were better predictors of only one WHODAS 2.0 domain, while patient-rated needs were better predictors of all other WHODAS 2.0 and WHOQOL-BREF domains. Patient-rated unmet needs were more strongly than met needs associated with the most WHODAS 2.0 and WHOQOL-BREF subscores. CONCLUSION: This study offers the first evidence that patient-rated needs, especially unmet needs, are strongly associated, above and beyond symptomatology, with global and domain-specific PPD of schizophrenia patients. Accordingly, strong relations of patient-rated needs with SQOL emerged. Identifying and addressing patient-reported needs could facilitate PPD and SQOL improvement more effectively than interventions confined solely to symptom remission.IMPLICATIONS FOR REHABILITATIONSchizophrenia is associated with poor rehabilitation and recovery outcomes, i.e., perceived psychosocial disability (PPD) and subjective quality of life (SQOL).Assessment of patients' needs constitutes the basis of determining treatment goals and planning tailor-made interventions to achieve crucial rehabilitative outcomes.Higher levels of patient-reported unmet needs are associated with poorer SQOL and higher global and domain-specific PPD of schizophrenia patients, above and beyond symptom severity.Addressing patient-reported needs through personalized interventions can facilitate more effectively PPD and SQOL improvement, than treatment confined to symptomatic alleviation.

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

COVID-19 pandemic and the mental health care system.

The psychological impact of pandemics, which historically appear in the human species, is described in detail in Steven Taylor's excellent book "The Psychology of Pandemics",1 which was published in 2019, a few months before the outbreak of the Covid-19 pandemic. This pandemic shows similar characteristics in terms of mental health problems to the previous ones described in the book, according to the findings of epidemiological research, both internationally and in Greece.2-5 The results of these studies show a significant increase of the prevalence of common mental disorders, especially in vulnerable groups, particularly in persons with preexisting mental disorders. The necessary restrictive measures applied, especially in the first stages of the pandemic, had an impact in the accessibility of psychiatric patients to the mental health services, both in- and outpatient ones.6 This led to decreased outpatient appointments and admissions in inpatient wards, depriving a large number of these patients from necessary treatments and interventions, often resulting in worsening their mental state or relapse of acute episodes. The lack of accessibility to mental health services, had a greater impact on persons with social and financial problems, which deteriorated during the pandemic, leading to mental health problems.3 An additional problem is that persons suffering from severe mental disorders, such as chronic psychoses, face a greater risk of infection and death by Covid-19.7 These problems, arising during the pandemic (increased prevalence of mental disorders, increase of relapses of serious mental disorders, increased risk of infection and death by Covid-19, increased prevalence in those infected, especially those in the ICUs, problems of accessibility) underline the chronic insufficiencies of the mental health care system, which in many countries, especially in Greece, is fragmented and is not covering adequately the mental health needs of the population. A series of articles in prestigious mental health journals point out the problem and propose solutions, in order to correct insufficiencies and create a new strong mental health system through a series of activities.8-10 These articles underline the problems known for decades and propose the following solutions for enhancing the existing mental health system, not only to cover additional needs created by the pandemic, but leading to a new mental health system covering adequately the needs of the population: (1) Strengthening leadership and governance, with interventions to politicians and administrators, in order to understand mental health issues, and provide services in terms of inclusivity, equity and accountability. (2) Supporting financially evidence-based services, adopting policies to counteract the social determinants of mental health, as well as the additional needs created by the pandemic. (3) Promoting programmes targeting vulnerable groups, especially those related to social determinants, with the active participation of stakeholders, with emphasis in combating stigma and enhancing mental health literacy. (4) Strengthen mental health services in all three levels, with emphasis in community mental health services, treatment at home, special services for vulnerable groups, services for the Covid-infected and the relatives of the deceased from the infection, the staff of health services dealing with Covid-19, using "telehealth" services, adopting information systems to assist services and close collaboration with the services dealing with Covid-19. (5) Training the staff of primary health care in mental health by using the mhGAP programme of the World Health Organization (WHO) and linking them to the special mental health services. (6) Implementing programmes for mental health promotion and prevention of mental disorders, with the participation of stakeholders, NGOs and the civil society. (7) Improving mental health information systems and connecting them with parallel systems dealing with Covid-19. (8) Strengthen and finance research in mental health, from epidemiology and services research, to neurobiology, as well as research aiming to provide innovative solutions for improving the system of mental health services and the provision of services and interventions through the social media. (9) Protecting rights of mental patients aiming to provide high quality services by use of evaluation instruments such as WHOQualityRights of WHO.

Cognitive Rehabilitation in Schizophrenia-Associated Cognitive Impairment: A Review.

Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive rehabilitation-computerized or non-computerized-is widely known as an alternative way to enhance cognitive functioning in patients with schizophrenia. The aim of the present review was to examine the role of cognitive rehabilitation (both computerized and non-computerized) for the alleviation of cognitive impairment in schizophrenia patients. Fourteen relative studies were examined and included in the present review. The results revealed that both computerized and non-computerized cognitive rehabilitation could enhance cognitive functioning and more specifically memory, attention, executive functioning, processing speed and in a few cases, even non-cognitive impairments, such as other schizophrenia symptoms. The present results support the efficacy of cognitive rehabilitation in schizophrenia patients, regardless of whether it is computerized or non-computerized. As the randomized control trials (RCTs) are limited in number, there is urgent need for more RCTs and longitudinal studies combining different kinds of interventions, as well as systematic reviews and meta-analyses, in order to further investigate and confirm the current results.

Differentiation of 2 Obsessive-Compulsive Disorder Subgroups with Regard to Demographic and Phenomenological Characteristics Combining Multiple Correspondence and Latent Class Analysis.

INTRODUCTION: Classic factor analysis of obsessive-compulsive disorder (OCD) dimensions and attempts to identify valid subgroups have not yet produced definitive conclusions. OBJECTIVE AND METHODS: This study aims to examine possible homogeneous subgrouping of demographic and phenomenological characteristics in 134 treatment-seeking OCD patients. A combination of multiple correspondence analysis (MCA) and latent class analysis (LCA) was used. RESULTS: MCA showed 2 distinct subgroups of OCD patients and LCA confirmed this result by a two-class solution. Both analyses demonstrated (a) a clear subgroup of female patients with washing compulsions, obsessions related to contamination, and late age of onset and (b) a subgroup comprised mostly of male patients with earlier onset of OCD, checking rituals, and doubts or aggressive obsessions. Mental, ordering, hoarding compulsions, religious, or sexual obsessions and images appeared exclusively in this subgroup. CONCLUSIONS: Using 2 different analytic methods, we confirmed at least 2 subgroups in a clinical sample of Greek OCD patients. Future research combining dimensional and latent approaches could facilitate our understanding of the heterogeneous phenotype of OCD.

Depression and Its Relationship with Coping Strategies and Illness Perceptions during the COVID-19 Lockdown in Greece: A Cross-Sectional Survey of the Population.

OBJECTIVE: The COVID-19 epidemic has shown a more benign course in Greece possibly due to the early lockdown measures. Mental health consequences of the lockdown however are unknown. In addition, illness perceptions and relevant strategies to cope with the stress of the epidemic may have played a role in complying with the restrictions. We conducted a survey of the Greek population with the aim to investigate the prevalence of anxiety and depression during the lockdown, the emotional impact of the epidemic, and the effect of coping strategies and illness perceptions in mental health. METHODS: Adult persons were invited during the peak of the lockdown period through social media. Depressive and anxiety symptoms were assessed with the PHQ-9 and GAD-2 scales, respectively. Coping strategies were assessed with selected items of the Brief COPE questionnaire, while illness beliefs were assessed with items from the revised Illness Perception Questionnaire (IPQ-R). RESULTS: A total of 3379 individuals took part. A strong emotional impact of the epidemic was more often in women and in those with severe financial difficulties. Levels of depressive and anxiety symptoms were high but similar to past assessments. Participants showed high levels of personal control and used more often positive strategies to cope with the stress of the epidemic. Depressive symptoms were higher in the younger, in students, in those with a stronger emotional impact, in those isolated due to symptoms, and those overexposed to media for COVID-19-related news. Lower levels of depression were seen in those using positive coping strategies and showing high levels of personal and treatment control. CONCLUSIONS: The study shows that certain psychological and social determinants were associated with increased depressive symptoms during the lockdown warranting the development of public health guidelines to mitigate the effects of the epidemic to the mental health of the population.

Prevalence of Alcohol Use Disorders and Their Association with Sociodemographic Determinants and Depression/Anxiety Disorders in a Representative Sample of the Greek General Population.

BACKGROUND: Country-level epidemiological data about alcohol-related problems is useful for planning prevention and treatment services. Heavy Alcohol Consumption (HAC) and Alcohol Use Disorder (AUD) are two syndromes of alcohol-related problems that have been recognized worldwide. Study of the epidemiological determinants of HAC and AUD in different sociocultural contexts could inform hypotheses about the etiology or the consequences of alcohol-related problems. OBJECTIVES: We assessed the prevalence and associations of HAC and AUD with sociodemographic variables adjusting for common mental disorders in a representative sample of the general population of Greece (N = 4894 participants). The period of data collection just preceded the emergence of the financial crisis in Greece. RESULTS: The majority of the population did not report HAC, AUD or abstinence from alcohol. HAC was reported by 12.7% (95% CI: 11.8-13.6) of the population while 3.1% (95% CI: 2.7-3.6) met criteria for AUD. Younger age, divorce, lower educational level, living in an urban area, physical health problems, and smoking were associated with a higher prevalence of both conditions. Presence of severe financial difficulties and never married family status were associated with a higher prevalence of HAC but not AUD. HAC was associated with nonspecific psychiatric morbidity while AUD was associated with more specific psychiatric disorders. Conclusion/Importance. Both alcohol-related problems are frequent in the general population and have common and distinct determinants. The comparison between the findings of our study and those of similar studies during or after the period of financial austerity in Greece, would offer the opportunity to assess the possible effects of changes in the economical context in the determinants of alcohol-related problems.

Manualized single-session behavior treatment with self-help manual for panic disorder with or without agoraphobia.

Objective: We examined the clinical feasibility and utility of a single behavior treatment session, with 11 patients with Panic Disorder with or without Agoraphobia (PD+/-AG). Patients used an individualized, exposure based, homework manual, derived from their behavioral analysis. Treatment was implemented in an outpatient behavior treatment unit. Method: Patients presented with moderate to severe anxiety, avoidance behavior, functional impairment and depressive symptoms. Treatment was evaluated with a double-baseline case series/pre-post design with four follow-ups. Results: There was a significant and steady improvement in all self-rated outcome measures and participants were satisfied with the services provided. Nine out of 11 patients (82%) were free of PD+/-AG at 3 months and all patients at 1-year follow-up. The absence of a control group, the small sample and lack of blind assessments, limit the validity of the study. Conclusions: These case studies provide empirical evidence in support of both the feasibility and utility of a single-session behavior treatment (SSBT) plus self-help implemented in a public mental health unit. Further research with a control group is needed to assess the efficacy of the intervention in routine clinical practice.

Very Long-Term Outcome of Community-Dwelling Patients With Schizophrenia Spectrum Disorders in Rural Greece.

The objective of the present study was to measure the very long-term outcome in community-dwelling patients with a diagnosis of psychosis and to search for possible correlations of outcome with clinical factors. The sample included 55 psychotic patients with at least 15 years of disease duration (M = 32.1 years). For the estimation of the outcome, the Health of the Nations Outcome Scale and the Clinical Global Impression Scale were used. A total of 34.5% of the patients had a good outcome, whereas 27.3% had poor outcome. Outcome was found to be correlated to symptoms, and it was significantly worse in patients living with other severely mentally ill family members. In our study, outcome was good in more than a third of patients. Both symptoms and social functioning were associated with outcome. This study may have some implications for mental healthcare delivery.

Prevalence, comorbidity, quality of life and use of services of obsessive-compulsive disorder and subthreshold obsessive-compulsive symptoms in the general adult population of Greece.

Objective: We aimed to describe the epidemiology of obsessive-compulsive disorder (OCD) and related subthreshold symptoms in the general population of Greece and to assess the comorbidity, use of health services and impact on quality of life of these syndromes in the general population. Methods: This was a secondary analysis of the 2009-2010 general population Greek psychiatric morbidity survey (4902 participants living in private households, response rate 54%). Psychiatric disorders were assessed with the revised Clinical Interview Schedule (CIS-R). Quality of life was assessed with the EuroQoL EQ-5D. Results: 1.69% of the participants (95% confidence interval [CI]: 1.33%-2.05%) met criteria for current OCD while 2.79% met criteria for subthreshold obsessive-compulsive symptoms (95%CI: 2.33%-3.26%). In the adjusted analysis few sociodemographic associations remained statistically significant. Although the full-blown syndrome was more severe in terms of comorbidity and quality of life our results showed that even subthreshold obsessive-compulsive symptoms were associated with significant comorbidity and reductions in quality of life. Use of mental health services was small. Conclusions: OCD is an under-treated public health problem that needs more attention in Greece and elsewhere. Provision of specialised mental health services should be a priority for publicly funded national health systems. Keypoints OCD is common in the general population of Greece with few sociodemographic associations apart from subjective financial difficulties. The comorbidity pattern of the full-blown syndrome versus the subthreshold obsessive-compulsive symptoms is similar and differs in magnitude in the expected way. Quality of life in OCD is greatly reduced especially when there is chronicity and/or comorbidity with depression. Use of services is limited but comorbidity with depression may increase the chances of consultation with a mental health professional.

Mental Healthcare Delivery in Rural Greece: A 10-year Account of a Mobile Mental Health Unit.

INTRODUCTION: Patients living in rural and remote areas may have limited access to mental healthcare due to lack of facilities and socioeconomic reasons, and this is the case of rural areas in Eastern Europe countries. In Greece, community mental health service delivery in rural areas has been implemented through the development of the Mobile Mental Health Units (MMHUs). METHODS: We present a 10-year account of the operation of the MMHU of the prefectures of Ioannina and Thesprotia (MMHU I-T) and report on the impact of the service on mental health delivery in the catchment area. The MMHU I-T is a multidisciplinary community mental health team which delivers services in rural and mountainous areas of Northwest Greece. RESULTS: The MMHU I-T has become an integral part of the local primary care system and is well known to the population of the catchment area. By the end of 2016, the majority of patients (60%) were self-referred or family-referred, compared to 24% in the first 2 years. Currently, the number of active patients is 293 (mean age 63 years, 49.5% are older adults), and the mean caseload for each member of the team is 36.6. A significant proportion of patients (28%) receive care with regular domiciliary visits, and the provision of home-based care was correlated with the age of the patients. Within the first 2 years of operation of the MMHU I-T hospitalizations of treatment, engaged patients were reduced significantly by 30.4%, whereas the treatment engagement rates of patients with psychotic disorders were 67.2% in 5 years. CONCLUSIONS: The MMHU I-T and other similar units in Greece are a successful paradigm of a low-cost service which promotes mental health in rural, remote, and deprived areas. This model of care may be informative for clinical practice and health policy given the ongoing recession and health budget cuts. It suggests that rural mental healthcare may be effectively delivered by integrating generic community mental health mobile teams into the primary care system.

Changes in the cytokine profile in first-episode, drug-naïve patients with psychosis after short-term antipsychotic treatment.

An increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial. Our aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-ß2 (TGF-ß2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication. Thirty-nine first-episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-ß2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotics. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment. Serum levels of IL-2 were significantly increased six weeks after the initiation of antipsychotic treatment (p <0.001) while TGF-ß2 levels were decreased (p <0.001). IL-6 levels were overall increased (p <0.004), but this occurred in a non-linear way. These findings, although preliminary, provide further evidence that antipsychotic treatment in patients with psychosis may be correlated with immunological changes but further research is needed.

Determination of clozapine, and five antidepressants in human plasma, serum and whole blood by gas chromatography-mass spectrometry: A simple tool for clinical and postmortem toxicological analysis.

In this study, we describe a simple and rapid method for the determination of the antipsychotic drug clozapine and five commonly co-administered antidepressants - bupropion, mirtazapine, sertraline, clomipramine and citalopram - in serum, plasma and whole blood. Sample preparation includes solid phase extraction of analytes and determination of drug concentrations by gas chromatography-mass spectrometry without any derivatization steps. The method was fully validated according to international criteria and can be successfully applied for routine analyses. Correlation coefficients of calibration curves for the tested drugs in the three specimens were in the range 0.9977-0.9999. Intra-day and inter-day precisions ranged from 0.81-7.85% and 3.60-12.91% respectively for the studied analytes and matrices. Recoveries were satisfactory for different concentrations of each drug in each specimen allowing accurate determinations in the range from sub-therapeutic to toxic levels. The presented method shows acceptable sensitivity, linearity in wide concentration ranges (sub-therapeutic, therapeutic, supra-therapeutic/toxic levels), it is simple and rapid and it is applicable for qualitative and quantitative routine toxicological analyses of clinical and postmortem cases.

Elevated levels of Insulin-like Growth Factor-1 (IGF-1) in drug-naïve patients with psychosis.

Insulin-like growth factor 1 (IGF-1) plays an important role in neurogenesis and synaptogenesis and may be implicated in schizophrenia, although data so far have been inconclusive. The aim of our study was to compare levels of IGF-1 in drug-naïve patients with a first episode of schizophrenia and related disorders with matched healthy controls. Forty drug naïve first-episode patients with schizophrenia and related disorders and forty healthy subjects matched for age, gender, body mass index (BMI) and smoking status were enrolled in the study. Serum levels of IGF-1 for each sample were measured in duplicate by the enzyme-linked immunosorbent assay (ELISA) method using human IGF-1. The median IGF-1 levels were significantly higher in drug-naive patients with psychosis compared to healthy controls (109.66ng/ml vs. 86.96ng/ml, respectively p=0.039). Multiple regression analysis revealed that differences in serum IGF-1 values were independent of glucose metabolism (fasting glucose, fasting insulin, insulin resistance) and cortisol. These results show that IGF-1 may be implicated in the pathophysiology of psychosis but confirmation is needed from other studies.

Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders.

OBJECTIVE: Hyperprolactinaemia as a side effect of dopamine receptor blockers is common in patients with schizophrenia and other psychotic disorders and may lead to amenorrhoea, galactorrhoea, hypogonadism, subfertility and osteoporosis. The aim of our study was to determine whether hyperprolactinaemia occurs also in patients with schizophrenia and other psychotic disorders prior to any antipsychotic treatment. METHODS: Serum prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free tetraiodothyronine (FT4) and cortisol levels were measured in 40 newly diagnosed, drug naïve, patients with schizophrenia and other psychotic disorders and in 40 age and gender matched healthy subjects. RESULTS: The median prolactin value was 12.5 ng/ml (range: 2-38 ng/ml) for patients and 8.6 ng/ml (range: 4-17.6 ng/ml) for healthy subjects (p = 0.011). Patients had lower levels of T3 compared to healthy controls (mean: 1.08 ng/ml, SD: 0.16 vs. 1.18 ng/ml, 0.18, respectively; p = 0.008). Serum TSH, FT4 and cortisol levels were similar between the two groups. Multiple regression analysis revealed that the difference in serum prolactin values was independent of thyroid function (TSH, FT4, T3) and serum cortisol levels. CONCLUSIONS: A higher serum prolactin level was found in drug naïve, newly diagnosed patients with schizophrenia and other psychotic disorders compared to healthy controls, prior to starting any antipsychotic treatment.

Longitudinal association between different levels of alcohol consumption and a new onset of depression and generalized anxiety disorder: Results from an international study in primary care.

BACKGROUND: Several studies that have examined the full range of alcohol consumption have pointed to a possible non-linear association between alcohol use and the common mental disorders. Most of these studies are cross sectional and assessed psychiatric morbidity using non-specific instruments. Our aim was to investigate the longitudinal association between varying levels of alcohol consumption at baseline and the new-onset of depression and generalized anxiety disorder (GAD), in a large international primary care sample. METHODS: The sample consisted of 3201 primary care attenders from 14 countries in the context of WHO Collaborative Study of Psychological Problems in General Health Care. Alcohol use at baseline was assessed using AUDIT and the mental disorders were assessed with the Composite International Diagnostic Interview. RESULTS: Light to moderate alcohol consumption at baseline was associated with a lower incidence of depression and GAD compared to abstinence while excessive alcohol consumption was associated with a higher incidence of depression but not GAD. This non-linear association was not substantially affected after adjustment for a range of possible confounding variables. CONCLUSION: Any causal interpretation of this association is difficult in the context of an observational study and further combined and consistent evidence from different sources is needed.

A review of genetic alterations in the serotonin pathway and their correlation with psychotic diseases and response to atypical antipsychotics.

Serotonin is a neurotransmitter that plays a predominant role in mood regulation. The importance of the serotonin pathway in controlling behavior and mental status is well recognized. All the serotonin elements - serotonin receptors, serotonin transporter, tryptophan hydroxylase and monoamine oxidase proteins - can show alterations in terms of mRNA or protein levels and protein sequence, in schizophrenia and bipolar disorder. Additionally, when examining the genes sequences of all serotonin elements, several single nucleotide polymorphisms (SNPs) have been found to be more prevalent in schizophrenic or bipolar patients than in healthy individuals. Several of these alterations have been associated either with different phenotypes between patients and healthy individuals or with the response of psychiatric patients to the treatment with atypical antipsychotics. The complex pattern of genetic diversity within the serotonin pathway hampers efforts to identify the key variations contributing to an individual's susceptibility to the disease. In this review article, we summarize all genetic alterations found across the serotonin pathway, we provide information on whether and how they affect schizophrenia or bipolar disorder phenotypes, and, on the contribution of familial relationships on their detection frequencies. Furthermore, we provide evidence on whether and how specific gene polymorphisms affect the outcome of schizophrenic or bipolar patients of different ethnic groups, in response to treatment with atypical antipsychotics. All data are discussed thoroughly, providing prospective for future studies.

Long-term Benzodiazepine Treatment in Patients with Psychotic Disorders Attending a Mental Health Service in Rural Greece.

INTRODUCTION: Long-term benzodiazepine (BZD) treatment in patients with mental disorders is widespread in clinical practice, and this is also the case of patients with schizophrenia, although the evidence is weak and BZD prescription is discouraged by guidelines and medical authorities. Data on BZD prescription are usually derived from national or regional databases whereas information on the use of BZD by patients with schizophrenia and related psychoses in general population-based samples is limited. MATERIALS AND METHODS: Information for 77 patients with psychotic disorders who were regularly attending follow-up appointments with the multidisciplinary Mobile Mental Health Unit of the prefectures of Ioannina and Thesprotia, Northwest Greece, during 1-year period (2015) was obtained from our database. RESULTS: From the total of 77 engaged patients, 30 (39%) were regularly prescribed BZDs in the long term, as part of their treatment regimen. Prescribed BZDs were mostly diazepam and lorazepam, in 43.3% of cases each. The mean daily dose of these compounds was 13 mg and 3.77 mg, respectively. Statistical analysis showed a correlation of long-term BZD use with the history of alcohol/substance abuse. Most patients were receiving BZD continuously for several years, and the mean dose was steady within this interval. CONCLUSIONS: A large proportion of patients with psychotic disorders were regularly prescribed BZD in long term. It appears that when BZDs are prescribed for some period in the course of a psychotic disorder, their use commonly exceeds the recommended interval and then becomes a regular part of the chronic treatment regimen. Future research should address the factors that may be related to the long-term BZD use by patients with psychotic disorders. Interventions for the reduction of regular BZD prescription should target the primary care setting and all those who treat first episode patients.