Roberto Tatarelli

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures.This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients.

Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine

Recent studies have implicated brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression and the activity of antidepressant drugs. Serum BDNF levels are lower in depressed patients, and increase in response to antidepressant medication. However, how BDNF responds to different classes of antidepressant drugs is unknown. We assessed serum BDNF levels in 21 patients with major depressive episode treated with sertraline, escitalopram, or venlafaxine and 20 healthy controls. Serum samples were collected between 10 a.m. and 12 p.m. at baseline, 5 weeks, and 6 months of treatment. BDNF levels were measured via immunoassay. The severity of symptoms and response to treatment were assessed by the Hamilton rating scales for depression (HRSD). Baseline serum BDNF levels were significantly lower in depressed patients compared to controls. Sertraline increased BDNF levels after 5 weeks and 6 months of treatment. Venlafaxine increased BDNF levels only after 6 months. Escitalopram did not affect BDNF levels at either time point. A significant negative association was found between percentage increase in BDNF levels and percentage decreased in HRSD scores after 6 months of treatment. In conclusion, these results suggest that different antidepressant drugs have variable effects on serum BDNF levels. This is true even though the three different drugs were equally effective in relieving symptoms of depression and anxiety.

Suicidal behavior and alcohol abuse

Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns.

Psychiatric comorbidity in patients with chronic daily headache and migraine: a selective overview including personality traits and suicide risk

Studies on the prevalence and impact of psychiatric disorders among headache patients have yielded findings that have clarified the relationship between migraine and major affective disorders, anxiety, illicit drug abuse, nicotine dependence, and suicide attempts. Studies in both clinical and community-based settings have demonstrated an association between migraine and a number of specific psychiatric disorders. In large-scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. In longitudinal studies, the evidence supports a bidirectional relationship between migraine and depression, with each disorder increasing the risk of the other disorder. Although a strong association has been demonstrated consistently for migraine and major depression, especially for migraine with aura, there has been less systematic research on the links between migraine and bipolar disorder. This review will focus on the way in which psychiatric disorders decrease the quality of life and result in a worse prognosis, chronicity of the disease, and a worse response to treatment. Short-term pharmaceutical care intervention improves the patients’ mental health, but it does not significantly change the number and severity of headaches. The increase in self-efficacy and mental health associated with pharmaceutical care may be instrumental in improving the long-term pharmacotherapy of patients with migraine and headache.

Functional neuroimaging in obsessive-compulsive disorder.

Background and Aim: Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling psychiatric disorder that usually emerges during childhood or adolescence. This paper aims to review the literature on functional neuroimaging in OCD, analysing the reported dysfunctional connectivity in the corticostriatothalamocortical circuitry. Method: This study included papers published in peer-reviewed journals dealing with functional imaging in OCD. Results: Striatal dysfunction, mainly of the caudate nucleus, leads to inefficient thalamic gating, resulting in hyperactivity within the orbitofrontal cortex (intrusive thoughts) and the anterior cingulate cortex (non-specific anxiety). Compulsions consist of ritualistic behaviours performed to recruit the inefficient striatum and neutralise unwanted thoughts and anxiety. Functional neuroimaging findings are discussed against the background of specific cognitive impairments, mainly regarding visuospatial processing, executive functioning and motor speed. Cognitive deficits are partial and specific, matching imaging data. Conclusions: Several studies have targeted brain regions hypothesised to be involved in the pathogenesis of OCD, showing the existence of dysfunctional connectivity in the corticostriatothalamocortical circuitry. Improvements in spatial resolution of neuroimaging techniques may contribute to a better understanding of the neurocircuitry of OCD and other anxiety disorders.

Suicide in borderline personality disorder: A meta-analysis

Suicide is the major cause of death among patients with borderline personality disorder; however, the literature on completed suicides in such disorder is inconclusive, as suicide rates vary greatly among cohorts of patients. We searched MedLine, Excerpta Medica and PsycLit from 1980 to 2005 to identify papers dealing with suicide in borderline personality disorder. We also searched the World Health Statistics Annual to ascertain the suicide rate in the age groups for specific years and country. We selected eight studies comprising 1179 patients with a diagnosis of borderline personality disorder. Of these patients, 94 committed suicide. Results obtained for each study were processed together to calculate the mean figure for each year of suicides for 100,000 individuals suffering from borderline personality disorder. Our meta-analysis shows that suicide among patients with borderline personality disorder is more frequent when compared with the general population. All study analyses reported that patients with borderline personality disorder committed suicide more often than their counterparts in the general population. Suicide seems more alarming in the first phases of follow-up than during chronic phases of illness.

Anatomical and functional correlates in major depressive disorder: the contribution of neuroimaging studies.

Several studies suggested the neural networks modulating aspects of emotional behaviour to be implicated in the pathophysiology of mood disorders. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular, evidence from lesion analysis studies suggests that MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The aim of this paper is to review the contribution of the most relevant studies with single photon emission tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI) to the understanding of pathophysiology of major depressive disorder (MDD), with particular focus on the reversibility of functional correlates with treatment.

The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: A selective overview for the implications of suicide prevention.

Suicidal behavior and mood disorders are one of the world’s largest public health problems. The biological vulnerability for these problems includes genetic factors involved in the regulation of the serotonergic system and stress system. The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates the body’s response to stress and has complex interactions with brain serotonergic, noradrenergic and dopaminergic systems. Corticotropin-releasing hormone and vasopressin act synergistically to stimulate the secretion of ACTH that stimulates the biosynthesis of corticosteroids such as cortisol from cholesterol. Cortisol is a major stress hormone and has effects on many tissues, including on mineralocorticoid receptors and glucocorticoid receptors in the brain. Glucocorticoids produce behavioral changes, and one important target of glucocorticoids is the hypothalamus, which is a major controlling center of the HPA axis. Stress plays a major role in the various pathophysiological processes associated with mood disorders and suicidal behavior. Serotonergic dysfunction is a well-established substrate for mood disorders and suicidal behavior. Corticosteroids may play an important role in the relationship between stress, mood changes and perhaps suicidal behavior by interacting with 5-HT1A receptors. Abnormalities in the HPA axis in response to increased levels of stress are found to be associated with a dysregulation in the serotonergic system, both in subjects with mood disorders and those who engage in suicidal behavior. HPA over-activity may be a good predictor of mood disorders and perhaps suicidal behavior via abnormalities in the serotonergic system.

Temperament and Personality Dimensions in Suicidal and Nonsuicidal Psychiatric Inpatients

Background: Suicide is a serious public health problem. In the international literature there is evidence to support the notion that certain temperaments and personality traits are often associated with suicidal behavior. Sampling and Methods: In this study, 150 psychiatric inpatients were investigated using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego autoquestionnaire, the Minnesota Multiphasic Personality Inventory, 2nd edition (MMPI-2) and the Beck Hopelessness Scale and evaluated for suicide risk by means of the critical items of the Mini International Neuropsychiatric Interview. Results: Statistical analysis, including logistic regression analysis and multiple regression analysis, showed that suicide risk contributed to the prediction of hopelessness. Among the temperaments, only the hyperthymic temperament, as a protective factor, and the dysthymic/cyclothymic/anxious temperament contributed significantly to the prediction of hopelessness. Irritable temperament and social introversion were predictive factors for suicidal risk. Hopelessness and depression were associated with higher suicidal behavior and ideation, but, unexpectedly, depression as measured by the MMPI did not contribute significantly to the multiple regressions. Conclusions: The present study indicated that, although suicidal psychiatric patients have MMPI-2 profiles in the pathological range, they exhibit several differences from nonsuicidal patients. Patients at risk of suicide have specific temperaments as well as personality and defense mechanism profiles. They are more socially introverted, depressed and psychasthenic, and use hysterical and schizoid mechanisms more often. Generalizability of the findings was limited by the small sample size and the mix of bipolar disorder I, bipolar disorder II, major depressive disorder and psychotic disorder patients.

Life events as precipitants of suicide attempts among first-time suicide attempters, repeaters, and non-attempters

The aims of this study were to investigate risk factors for suicide attempts and propose a model explaining the associations among life events and suicide status. We assessed 263 subjects admitted following a suicide attempt to the Division of Psychiatry of the Department of Neurosciences of the University of Parma and compared them with 263 non-attempter clinical control subjects. Attempters reported significantly more adverse life events both in the last 6 months, and between the ages of 0-15 years than non-attempters. A multinomial logistic regression analysis with stepwise forward entry indicated that the best model to explain suicide status was one which included life events in the last 6 months, life events during age 0-15 years, and their interaction. First-time attempter status (vs. non-attempters) was more likely to be linked to life events in the last 6 months, the interaction between life events in the last 6 months and life events during age 0-15 years, and low social support. Those attempters with one or more prior attempts (repeat attempters) were more likely than non-attempters to be linked to the interaction between life events in the last 6 months and life events during age 0-15 years, and to higher rates of psychopharmacological treatment before the index admission. Guided by these findings, monitoring the impact of early-life and recent events in vulnerable individuals should be part of risk assessment and treatment.