Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Suicide and Schizophrenia: an Interplay of Factors.

PURPOSE OF REVIEW: The main purpose of this review is to elucidate the interplay of various factors in the relationship between suicide and schizophrenia. Suicide and schizophrenia have been interlinked as a symptom, factor in recovery and prognosis, outcome measure and response to psychotic symptoms in patients with schizophrenia. Many biomarkers have been identified in relation to the two phenomena. RECENT FINDINGS: The analysis of the papers of the last 5 years (2015-2019) and till date has revealed studies looking at outcomes in relation to suicide, biological markers to determine the protection from and occurrence of suicide in schizophrenia and demographic factors that play a role in the occurrence of suicide in patients with schizophrenia. Suicide is a common occurrence in patients with schizophrenia and must be studied further in diverse populations of the disorder to help determine exact relationships between these two variables that will aid in clinical recovery, better outcome and improve prognosis.

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study.

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

Resilience as a Psychopathological Construct for Psychiatric Disorders.

Understanding of the psychopathology of various psychiatric disorders is evolving, with newer avenues of research enlightening us from genetics, epigenetics, functional neurobiology, neural circuits, hormones and social/environmental determinants. We are now aware that neurobiological factors are contributing to the development of psychiatric illnesses coupled with their interaction with psychosocial factors. Resilience is defined as the ability to bounce back after an adversity or life event that was traumatic and life-changing. It is a factor that is a unique psychopathological construct as it is a biopsychosocial factor which determines an individual's response to an illness and recovery from the same. Resilience is a human capacity to adapt swiftly and successfully to stress and to revert to a positive state. There has been now a paradigm shift in the understanding of resilience with respect to stress risk vulnerability and such dimensions of psychopathology. Resilience is a factor that must be evaluated in every patient and that shall help us determine the outcome of psychiatric disorders and will also be a determinant in the occurrence of relapses. Early identification of vulnerable patients shall lead to the implementation of resilience-based interventions in these populations and shall prevent against future occurrence of these disorders. In this chapter, we posit the construct of resilience as a psychopathological construct for mental disorders.

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.

Predicting suicidality among psychiatric patients.

In a sample of 50 psychiatric patients, suicidality as measured by a 54-item scale was associated with scores on scales to assess the presence of comorbidities, family history, medical factors, clinical ratings of psychiatric diagnosis, psychosocial/environmental factors, and protective factors (multiple R2 = .66).

Telepsychiatry and Telepsychotherapy: Critical Issues Faced by Indian Patients and Psychiatrists.

Telepsychiatry and telepsychotherapy are new treatment modalities that have been used more than ever during the COVID-19 pandemic. There are many challenges that are faced with the use of this modality for both patients and psychiatrists alike. There are critical issues faced with regard to the development of rapport, managing the entire teleconsultation set up, privacy and issues related to fees, issues related to prescribing and monitoring, and issues while handling emergencies. The challenges faced are discussed and some solutions if possible are laid out.

Mental Hospitals in India: Reforms for the future.

Mental hospitals are an integral part of mental health services in India. It is an interesting story how mental hospitals have responded to the challenges of contemporary period they were built in. It is beyond doubt that it is a progressive journey along with advances in mental health both in India and internationally. As in other countries, mental hospitals in India have responded to the social challenges, disparities, and poor resources of workforce and fiscal investment. Historically, there have been changes and three major reforms are needed, namely attempt to facilitate discharge and placing patients back into the family, introducing teaching and research in mental hospitals, and accountability to civil rights as per the requirements of the National Human Rights Commission. In this review, we explore the brief history of mental hospitals in India and examine the reforms in the clinical, administrative, and psychosocial areas of these hospitals and progress in teaching and research. We finally summarize and conclude the necessity and the relevance of mental hospitals in India akin to modern psychiatric practice. We believe that mental hospitals have an important and perhaps a central role in mental health services in India. Its modernization to address issues of long-term stay, burden on caregivers, stigma, research and teaching including undergraduate and postgraduate training, new curriculum, and training for nonpsychiatric professionals and primary care physicians are necessary components of the role of mental hospitals and responsibilities of both government and nongovernmental sectors. Last but not the least, it is obligatory for mental hospitals to ensure that evidence-based treatments are implemented and that the standard of care and respect of civil and human rights of the patients and families are provided while involving the people's participation in its functioning.

Serum cholesterol and Suicide in first episode psychosis: A preliminary study.

BACKGROUND: Low levels of cholesterol have been described in suicide behavior including among those individuals who have an increased tendency for impulsivity. Violent suicide attempters show significantly lower cholesterol levels than nonviolent suicide attempters. The suicide rate is particularly high in the prodromal and early phase of schizophrenia. It is unclear if there is a psychopathological relationship between early psychosis, suicide, and cholesterol levels. The present study examines levels of cholesterol and suicide behavior in a cohort of early psychosis. METHODOLOGY: Sixty admitted patients with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of nonaffective schizophrenia spectrum disorder (early psychosis) were assessed in a naturalistic cross-sectional, cohort study. Psychopathology was assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS), Hamilton Depression Rating Scale, and Scale for Impact of Suicidality-Management, Assessment and Planning of Care (SIS-MAP). Serum levels of cholesterol were estimated in the cohort as well. The findings were analyzed for a clinical correlation of cholesterol levels, suicidal attempters, and psychopathology. RESULTS: Out of 60 patients, 13 patients had a suicide attempt in the recent past. No serum cholesterol abnormality (3.7 ± 1.2 mmol/L) was observed in patients as a group and those with low suicidality (SIS-MAP <17, serum cholesterol: 4.1 ± 1.3 mmol/L). However, low levels of cholesterol were observed in a subgroup with severe suicidality (SIS-MAP >33; serum cholesterol: 3.5 ± 1.4 mmol/L). Females with moderate suicidality showed statistically significant lower cholesterol levels than males (P = 0.047). CONCLUSIONS: The study suggests lower levels of cholesterol in patients of psychosis with severe suicidal thoughts and depression in early psychosis. More research is required in this field to determine the neurochemistry of suicide behavior in psychosis and its significance in the prediction of suicidal behavior.

Child sexual abuse and the development of psychiatric disorders: a neurobiological trajectory of pathogenesis.

Child sexual abuse (CSA) is an important public health problem with long-standing neurobiological, developmental, and psychiatric abnormalities. The present review analyzes the long-term effects of CSA from a developmental, psychiatric morbidity, neurochemical and neurobiological perspective and then tries to posit a developmental neurobiological trajectory from CSA to the genesis of psychopathology in later life. The role of various neurotransmitters such as serotonin and dopamine affected by CSA are discussed. Serotonin abnormalities have been reported in various studies among participants exposed to CSA. Structures such as the prefrontal cortex, superior temporal gyrus, corpus callosum, parietal lobes, hippocampus, and cerebellum all demonstrate volumetric and structural changes in response to the trauma of CSA. Neurocognitive studies demonstrate memory and spatial awareness as well as decrements in general cognitive performance and memory when compared to normal individuals. The hypothalamic-pituitary-adrenal axis has also been implicated in CSA, and there is an alteration in corticotropin-releasing hormone response due to the continuous cumulative trauma of CSA. This paper also reviews a section on the role of genetic and epigenetic factors in the development of psychiatric disorders as a result of exposure to episodes of CSA where studies have demonstrated changes in DNA methylation in response to CSA. This review tries to hypothesize a developmental trajectory framework which is individual for every case where exposure to CSA may lead to psychopathology and psychiatric morbidity later in life. Rapid and emerging fields such as developmental traumatology in relation to CSA are also discussed.

Resilience: A psychobiological construct for psychiatric disorders.

Understanding of psychopathology of mental disorder is evolving, particularly with availability of newer insight from the field of genetics, epigenetics, social, and environmental pathology. It is now becoming clear how biological factors are contributing to development of an illness in the face of a number of psychosocial factors. Resilience is a psychobiological factor which determines individual's response to adverse life events. Resilience is a human capacity to adapt swiftly and successfully to stressful/traumatic events and manage to revert to a positive state. It is fundamental for growth of positive psychology which deals with satisfaction, adaptability, contentment, and optimism in people's life. Of late, there has been a paradigm shift in the understanding of resilience in context of stress risk vulnerability dimension. It is a neurobiological construct with significant neurobehavioral and emotional features which plays important role in deconstructing mechanism of biopsychosocial model of mental disorders. Resilience is a protective factor against development of mental disorder and a risk factor for a number of clinical conditions, e.g. suicide. Available information from scientific studies points out that resilience is modifiable factor which opens up avenues for a number of newer psychosocial as well as biological therapies. Early identification of vulnerable candidates and effectiveness of resilience-based intervention may offer more clarity in possibility of prevention. Future research may be crucial for preventive psychiatry. In this study, we aim to examine whether resilience is a psychopathological construct for mental disorder.

Brain-Derived Neurotrophic Factor and Suicide in Schizophrenia: Critical Role of Neuroprotective Mechanisms as an Emerging Hypothesis.

Suicide is a common occurrence in psychiatric disorders and is a cause of increased healthcare utilization worldwide. Schizophrenia is one of the most common psychiatric disorders worldwide and posited to be seen in 1% of the population worldwide. Suicide is a common occurrence in schizophrenia with 25%-30% patients with schizophrenia attempting suicide and 8%-10% completing it. There is a need for valid biological markers to help clinicians identify patients with schizophrenia that may be at a risk of suicide and thus help in them receiving better care and interventions at the earliest even before a suicide attempt occurring. There are clear neurobiological changes at a genetic, neuroimaging, and neurochemical level that occurs in patients with schizophrenia that attempt suicide. There is a new theory that postulates neuronal plasticity and neuroprotection to have a role in the biological changes that ensue when suicidal thoughts and feelings occur in patients with schizophrenia. Neurotrophic growth factors like brain-derived neurotrophic factor (BDNF) have been documented to play a role in the protection of neurons and in the prevention of neurobiological changes that may lead to suicide both in schizophrenia and depression. The present paper presents a commentary that looks at the role of BDNF as a protective factor and neurobiological marker for suicide in schizophrenia.

Suicide in hospitalized early psychosis patients at the time of discharge from hospital: An exploratory study of attempters and nonattempters.

BACKGROUND: Early intervention programs for psychosis are gateways for suicide prevention. These programs offer an excellent opportunity for prevention due to easy access, early identification, and provisions for continuity of care. These programs have been found effective in reducing rates of suicide after discharge to communities. The objective of this study was to examine suicide risk level among early psychosis patients admitted with and without previous suicide attempts. We hypothesized that all patients admitted with early psychosis would be at high risk of suicide, regardless of a previous suicide attempt. METHODOLOGY: Suicide risk was compared between patients admitted with a suicide attempt (n = 30) and patients admitted without a suicide attempt (n = 30). The primary outcome measure of interest was suicide risk which was measured with the Scale for Impact of Suicidality-Management, Assessment and Planning of Care clinical interview. All patients met DSM-IV TR criteria for schizophrenia. Psychopathology was assessed using the Brief Psychiatric Rating Scale and level of depression was assessed using the Hamilton Depression Rating Scale. The data were statistically analyzed. RESULTS: Patients admitted with a previous attempt (mean = 29.5, standard deviation [SD] =12.0) did not differ significantly in suicide risk from those admitted without a previous attempt (mean = 27.5, SD = 12.5), (t[58] =0.63, P = 0.53). Patients admitted without a suicide attempt scored higher in depressive symptoms (t[58] =10.62, P < 0.001) than that of admitted with a suicide attempt. There were no significant differences between patients admitted with and without suicide attempts on any comorbidity, other than a trend toward a higher prevalence of personality disorder in patients with no suicide attempt. Attempters and nonattempters did not differ on any demographic variables either. CONCLUSIONS: Of those admitted without a previous suicide attempt, our findings suggest that it is critical that all patients discharged from an acute psychiatric unit must receive comprehensive community care. The identification of risk, and subsequent intervention for suicidal and self-harm behaviors, should be a central part of treatment for all mental disorders.

Pathways to psychosis in cannabis abuse.

Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

Suicide prevention competencies among urban Indian physicians: A needs assessment.

INTRODUCTION: India accounts for the highest estimated number of suicides in the World. In 2012, more than 258,000 of the 804,000 suicide deaths worldwide occurred in India. Early identification and effective management of suicidal ideation and behavior are paramount to saving lives. However, mental health resources are often scarce and limited. Throughout India, there is a severe shortage in mental health professions trained, which results in a treatment gap of about 90%. A comprehensive needs assessment was undertaken to identify the nature of the deficits in suicide prevention training for physicians in three Indian cities: Mumbai, Ahmedabad, and Mysore. MATERIALS AND METHODS: The study was carried out in several concurrent phases and used a mixed-method approach of converging quantitative and qualitative methodologies. Data were collected using survey questionnaires, focus groups, consultations, and environmental scans. A total of 46 physicians completed the questionnaire. Focus groups were conducted in Mumbai and Ahmedabad with 40 physicians. Consultations were carried out with psychiatrists and psychiatric residents from hospitals and clinics in Mumbai, Ahmedabad, and Mysore. RESULTS: Training gaps in suicide prevention exist across the health care professions. Existing training lacks in both quality and quantity and result in critical deficits in core competencies needed to detect and treat patients presenting with suicidal ideation and behavior. Only 43% of the surveyed physicians felt they were competent to treat suicidal patients. The majority of surveyed physicians believed they would greatly benefit from additional training to enhance their suicide risk assessment and intervention skills. CONCLUSIONS: There is a dire need for medical schools to incorporate suicide prevention training as a core component in their medical curricula and for continuing medical education training programs for physicians to enhance competencies in early detection and management of suicidal behavior.

Cannabis and psychosis: Neurobiology.

Cannabis is a known risk factor for schizophrenia, although the exact neurobiological process through which the effects on psychosis occur is not well-understood. In this review, we attempt to develop and discuss a possible pathway for the development of psychosis. We examine the neurobiological changes due to cannabis to see if these changes are similar to those seen in schizophrenic patients the findings show similarities; however, these mere similarities cannot establish a 'cause-effect' relationship as a number of people with similar changes do not develop schizophrenia. Therefore, the 'transition-to-psychosis' due to cannabis, despite being a strong risk factor, remains uncertain based upon neurobiological changes. It appears that other multiple factors might be involved in these processes which are beyond neurobiological factors. Major advances have been made in understanding the underpinning of marijuana dependence, and the role of the cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions is of now, it is clear that some of the similarities in the neurobiology of cannabis and schizophrenia may indicate a mechanism for the development of psychosis, but its trajectories are undetermined.

Clozapine response and pre-treatment EEG-is there some kind of relationship.

BACKGROUND: Clozapine has been used widely in the management of treatment-resistant schizophrenia. The present study aims at determining whether pre-treatment electroencephalography (EEG) abnormalities would serve as a marker for response to clozapine treatment. SUBJECTS AND METHODS: This was a cross-sectional study done in a tertiary care center in Mumbai where patients diagnosed with schizophrenia using DSM-IV criteria and resistant schizophrenia using Kane criteria were assessed using EEG prior to starting clozapine treatment. They were rated for symptomatic improvement using the Positive and Negative Syndrome Scale (PANSS) along with Clinical Global Improvement for Severity (CGI-S). The results were statistically analysed and presented. RESULTS: 55 out of the 80 patients in the study showed baseline EEG abnormalities. The mean duration of illness in the patients were 2.65 years. Slow wave and background EEG abnormalities were common in pre-treatment EEG. 36.4% patients in the study showed clinical response. Patients with negative symptoms and baseline EEG abnormalities showed better response. CONCLUSIONS: The study was circumscribed and had many limitations due to a small sample size. The relation between pre-treatment EEG abnormalities and clozapine response could not be statistically correlated and it could not be ascertained to be a marker for response to clozapine therapy.

Dimensions of suicidality: analyzing the domains of the SIS-MAP Suicide Risk Assessment Instrument and the development of a brief screener.

This study aimed at validating the domains of suicidality assessed by the Scale for Impact of Suicidality-Management, Assessment and Planning of Care (SIS-MAP) and creating a brief screener based on the full scale. A total of 50 individuals with suicidal ideation were given the SIS-MAP interview. Support was found for these domains of suicide risk; in particular, the subscales of ideation and protective factors for suicide risk were highly reliable. For each domain of suicidality, items most predictive of total risk index scores were selected to create a brief screener aimed at expediting the assessment process. The screener was reliable, predicted overall suicide risk index scores, and approached significance in predicting subsequent suicide attempts.

Polypharmacy in psychiatry: a review.

Psychiatric polypharmacy refers to the prescription of two or more psychiatric medications concurrently to a patient. It can be categorised as same-class, multi-class, adjunctive, augmentation and total polypharmacy. Despite advances in psychopharmacology and a better understanding of the principles of therapeutics, its practice is increasing rapidly. The prevalence of polypharmacy in psychiatry varies between 13%-90%. There are various clinical and pharmaco-economic factors associated with it. Dealing with polypharmacy requires an understanding of its associated factors. Education, guidelines and algorithms for the appropriate management of various conditions are effective ways to avoid irrational polypharmacy.