Paolo Girardi

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

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.

Psychotic-like experiences and correlation with distress and depressive symptoms in a community sample of adolescents and young adults

OBJECTIVE Studies conducted in community samples indicate that psychotic-like experiences (PLEs) are common in the general population; it has been suggested that such experiences are either variations in normal personality or different expressions of vulnerability to psychotic disorders. The aim of this study was to determine whether different subtypes of PLEs could be identified in a community sample of adolescents and young adults, and to investigate whether particular subtypes of PLEs were more likely to be associated with psychosocial difficulties, i.e. distress, depression and poor functioning, than other subtypes. METHOD 1882 students from high schools and universities participated in a cross-sectional multisite survey that measured i) PLEs using the Positive Scale of the Community Assessment of Psychic Experiences (CAPE), ii) depression and distress using the CAPE Depression and Distress Subscales, and iii) functioning using the General Health Questionnaire-12. Factor analysis was conducted to identify any subtypes of PLEs. RESULTS Four subtypes of PLEs were identified: bizarre experiences (BE), perceptual abnormalities (PA), persecutory ideas (PI) and grandiosity (GR). Intermittent, infrequent psychotic experiences were common, whereas frequent experiences were not. BE and PI were strongly associated with distress, depression and poor functioning. PA and GR were associated with these variables to a lesser degree. CONCLUSIONS Different subtypes of PLEs were identified in this large sample, confirming the findings of our previous studies. These subtypes seem to have different psychopathological meaning and may therefore indicate different levels of risk of severe psychiatric disorders, which suggests it is misleading to define PLEs as a homogenous entity.

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.

Epidemiology of suicide in bipolar disorders: a systematic review of the literature.

Suicidal behavior is a major public health problem worldwide, and its prediction and prevention represent a challenge for everyone, including clinicians. The aim of the present paper is to provide a systematic review of the existing literature on the epidemiology of completed suicides in adult patients with bipolar disorder (BD).

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.

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.