Insulin dysfunction and allostatic load in bipolar disorder

Bipolar disorder (BD) is associated with substantial morbidity, as well as premature mortality. Available evidence indicates that 'stress-sensitive' chronic medical disorders, such as cardiovascular disease, obesity and Type 2 diabetes mellitus, are critical mediators and/or moderators of BD. Changes in physiologic systems implicated in allostasis have been proposed to impact brain structures and neurocognition, as well as medical comorbidity in this population. For example, abnormalities in insulin physiology, for example, insulin resistance, hyperinsulinemia and central insulinopenia, are implicated as effectors of allostatic load in BD. Insulin's critical role in CNS physiological (e.g., neurotrophism and synaptic plasticity) and pathophysiological (e.g., neurocognitive deficits, pro-apoptosis and amyloid deposition) processes is amply documented. This article introduces the concept that insulin is a mediator of allostatic load in the BD and possibly a therapeutic target.     

Is it time to have another look at lithium maintenance therapy in bipolar disorder?

1. Bipolar disorder is typically a chronic disease entailing an episodes course, whereby psychiatric status alternates between periods of normal functioning and periods of illness. Lithium is well established and approved for the treatment of bipolar disorder. However, its efficacy in practice is not as great as expected. This retrospective record study was undertaken to determine the efficacy of lithium in bipolar disorders. 2. 48 patients who met DSM-III-R diagnostic criteria for bipolar I disorder and had been admitted once before lithium therapy and twice or more after that, were included in this study. 3. No significant difference in length between episode (frequency) was observed before and after lithium maintenance therapy. In addition, the percentages of manic episode after lithium therapy were much greater than before that. 4. The results indicate that it is worth re-examining the efficacy of lithium in bipolar disorders.     

Treating complexity: Collaborative care for multiple chronic conditions

Abstract

Individuals with co-morbid chronic medical illness and psychiatric illness are a costly and complex patient population, at high risk for poor outcomes. Health-risk behaviours (e.g. smoking, poor diet, and sedentary lifestyle), side effects from psychiatric medications, and poor quality medical care all contribute to poor outcomes. Individuals with major depression die, on average, 5 to 10 years before their age-matched counterparts. For individuals with severe mental illness such as bipolar disorder or schizophrenia, life expectancy may be up to 20 years shorter. As the majority of this premature mortality is due to cardiovascular disease, there is a critical need to engage these individuals around the care of chronic medical illness.     

Course and outcome of child and adolescent major depressive disorder

Major depressive disorder (MDD) is a familial recurrent illness that significantly interferes with the child's normal development and is associated with increased risk for suicidal behaviors and psychiatric and psychosocial morbidity. Although most children and adolescents recover from their first depressive episode, 30-70%, in particular those with familial history of MDD, comorbid psychiatric disorders, dysthymia, subsyndromal symptoms of depression, anxiety, negative cognitive style, and exposure to negative life events (e.g., family conflicts and abuse) will experience one or more depressive recurrences during their childhood, adolescence, and adulthood. Depressed youth who present with psychosis, psychomotor retardation, pharmacological induced hypomania/mania, and/or family history of bipolar disorder are at high risk to develop bipolar disorder.     

Is major depression a neurologic disorder with psychiatric symptoms?

In the last decade, multiple investigator groups have identified structural changes of various neuroanatomic structures in patients with idiopathic major depression and bipolar disorders. Using high-resolution MRI of the brain and functional neuroimaging studies (i.e., PET, SPECT), researchers have described decreases in the volume of hippocampal formation, amygdala, entorhinal cortex, various frontal lobe structures, and basal ganglia, in addition to abnormal cerebral blood flow and metabolic activity in these structures as well as in thalamic nuclei. Similar structural and functional changes have been identified in patients with depression associated with a variety of neurologic disorders (i.e., stroke, Parkinson's disease, epilepsy, Alzheimer's dementia). In addition, recent data have shown that depression is a risk factor for the development of several neurologic disorders, including epilepsy, stroke, and Parkinson's disease and bears a negative impact on the course and outcome of most neurologic disorders. This article reviews these data and provides evidence that major depressive and bipolar disorders may in fact be neurologic disorders with psychiatric symptoms.     

Children of parents with bipolar disorder. A population at high risk for major affective disorders

Children of parents who suffer from bipolar disorder are largely ignored by psychiatric services despite the fact that they constitute a population at very high risk for major depression and bipolar disorder in adulthood and a wide variety of disorders in childhood and adolescence. Major depression and bipolar disorder are chronic, recurrent disorders that seriously impair psychosocial functioning across the life-span. Evidence suggests that in this population bipolar disorder is preceded by externalizing disorders in childhood in many cases, and by depression in some cases. While heredity provides the vulnerability for the development of these characteristics, being raised by parents who model inappropriate coping skills, create a stressful family environment, and provide inadequate support and structure, contribute to consolidating these characteristics.     

New medication treatment options for bipolar disorders

OBJECTIVE: To assess new treatment options for bipolar disorders. METHOD: Controlled studies of new treatments for bipolar disorders were identified by computerized searches and reviews of scientific meeting proceedings, and were compiled by drug category. RESULTS: Two main categories of medications, newer anticonvulsants and newer antipsychotics, are yielding emerging new treatment options for bipolar disorders. Newer anticonvulsants have diverse psychotropic profiles, and although not generally effective for acute mania, may have utility for other aspects of bipolar disorders (e.g. lamotrigine for maintenance or acute bipolar depression), or for comorbid conditions (e.g. gabapentin for anxiety or pain, topiramate for obesity, bulimia, alcohol dependence, or migraine, and zonisamide for obesity). In contrast, newer antipsychotics generally appear effective for acute mania, and some may ultimately prove effective in acute depression (e.g. olanzapine combined with fluoxetine, quetiapine) and maintenance (e.g. olanzapine). CONCLUSION: Emerging research is yielding new treatment options for bipolar disorders and comorbid conditions.     

Spectrum of effectiveness of valproate in neuropsychiatry

Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.     

Functional adaptation skills training (FAST): a pilot psychosocial intervention study in middle-aged and older patients with chronic psychotic disorders.

OBJECTIVE: Developing behavioral interventions to improve functioning of older patients with schizophrenia and other chronic psychoses has the potential to significantly increase the patients' independence and quality of life. METHODS: The authors evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders (mean duration of illness: 21 years). Forty patients who resided in board-and-care facilities were randomly assigned to either a 24-session functional adaptation skills training (FAST) group therapy program targeting problem areas identified in previous work as being problematic for this population (e.g., using public transportation) or treatment-as-usual. Almost all the participants also received antipsychotics. RESULTS: Compared with the patients randomized to the treatment-as-usual condition, FAST-treated patients' performance on everyday living skills improved significantly immediately post-intervention and was still significantly better at a 3-month maintenance follow-up period. There was no significant change in psychopathology. CONCLUSION: Results suggest that older patients with longstanding psychotic disorders may benefit from participation in this skills-training program.     

Behavioral medicine in the prevention and treatment of cardiovascular disease

Cardiac behavioral medicine is the application of behavioral and psychosocial principles to the prevention and treatment of heart disease. Most biomedical cardiovascular risk factors (e.g., high blood lipids, high blood pressure, diabetes) require behavioral and medical interventions. Other risks, including obesity, high-fat eating pattern, smoking, and inactivity, clearly require lifestyle change. Behavioral medicine screening and intervention have been applied to psychosocial risk factors such as depression, hostility, and social isolation. Appropriate assessment of risk factors is essential because research has demonstrated successful prevention of heart disease and reduction of morbidity and mortality in patients with existing disease. Behavioral interventions have been beneficial in improving cardiac outcomes by enhancing compliance with medication taking and dietary/exercise recommendations. Future needs include the study of psychosocial factors in women and ethnic minorities with heart disease and the integration of behavioral medicine with newer medical technologies designed to detect subclinical biomarkers of heart disease.     

Détection et intervention précoce auprès des jeunes avec trouble bipolaire émergent : où en sommes-nous ?

Bipolar disorder (BD) is one of the most disabling chronic illness for which the delay in diagnosis and access to adequate care is about 10 years, with many consequences such as numerous comorbidities, greater illness severity and resistance to treatments. Building on advances in early intervention in psychosis, optimizing the detection of patients with BD and intervening early is essential to improve their prognosis. Identifying risk factors for BD would allow earlier detection of the target population with the aims of: (1) preventing the development of the disease, (2) delaying its onset and (3) improving the course through more timely treatment. We conducted a narrative review of the literature of the past 30 years on risk factors of BD and synthetising the concepts of at-risk of BD mental state, the staging model and associated interventions. These concepts are illustrated by a clinical case with and without early intervention highlighting the challenges of early intervention in BD and the scientific data currently available of use to the clinician (both general practitioners and psychiatrist). In addition to genetic and environmental risk factors (early trauma, substance use, etc.), vulnerability markers (cyclothymic or hyperthymic temperament, cluster B personality disorder) can guide the clinician towards the detection of at risk of BD mental state syndrome consisting of attenuated symptoms of hypomania, mood lability, early depressive episode with psychotic, severe or atypical characteristics. The delay in access to care attributable to the absence of “help-seeking”, to self-stigmatization, or to unrecognized diagnoses (misdiagnosis with personality disorders or substance use disorders) weighs down the prognosis leading, as episodes cumulate over time, to incomplete remission of episodes with residual symptoms and significant functional decline. The use of validated tools and careful coordination of the various actors are assets for the early identification of subjects at-risk of transition to BD. Following the staging model, targeted primary prevention interventions (e.g., promotion of good sleep hygiene, stress management strategies) for at-risk individuals should be offered by general practitioner or other front-line mental health professionals (e.g., psychologist, nurse); early secondary prevention (for stage 1) should be provided by general psychiatric or general medicine services. Although no official guidelines for early intervention for BD are available yet, experts opinions are multiplying and supporting an integrated approach that maximizes young patient engagement. These integrated approaches aiming at symptomatic and functional improvement combine effective psychopharmacology and psychosocial interventions, including cognitive- behavioral therapy, approaches based on social rhythm, psychoeducation, relapse prevention, social and vocational recovery and family interventions. The scarcity of studies on the early stages of bipolar disorder limits the predictive value of risk factors and at-risk syndromes which remain to be validated. Prospective controlled studies are warranted to improve the prevention efforts and effective early treatment of bipolar disorder.     

The neuropsychiatry of multiple sclerosis: Focus on disorders of mood,affect and behaviour

Neuropsychiatric symptoms are common in multiple sclerosis (MS). They include two broad categories of disturbances: abnormalities in cognition, and abnormalities of mood, affect and behaviour. The present review deals with the epidemiology, clinical features, etiology and treatment of disturbances included in the second category, i.e., major depression, fatigue and sleep disorders, bipolar disorder, euphoria, pathological laughing and crying, anxiety, psychosis and personality changes. Major depression is one of the most common neuropsychiatric disorders in MS with an approximate 50% lifetime prevalence rate. Early recognition and management of depression in MS is of major importance because it is a key predictor of morbidity, mortality, quality of life, possibly physical outcome and disease exacerbations, adherence to immunomodulatory treatments and suicide risk in MS patients, as well as of the caregiver's distress and quality of life. The etiopathogenesis of neuropsychiatric disorders in MS has been incompletely investigated. It is postulated that a complex interplay of biological, disease-related, behavioural and psychosocial factors contribute to the pathophysiology of most of them. Management of neuropsychiatric symptoms in MS is often effective, although commonly based on evidence provided by case studies and uncontrolled trials. A comprehensive biopsychosocial neuropsychiatric approach is essential for the optimal care of patients with MS.     

Chronic course and psychosocial disability caused by depressive illnesses in general practice patients during a one year period. Results of a study by the World Health Organization

As part of an international WHO study on psychological disorders in primary health care, patients were examined for mental disorders and especially depression and social disability in the course of 1 year. Depression is common in primary care (8.6%) and frequently associated with recurring or chronic courses (33.3%). Depression at baseline leads to a 100% increase of lost working days (3.2 per month) 1 year later as compared to patients without depression (1.7). The diagnosis of depression at baseline poses a greater risk for a relevant and lasting psychosocial disability (28.2%) than e.g. chronic somatic illnesses (8.6%). Even the diagnosis of a subthreshold depression leads comparatively to a higher degree of psychosocial disability (15.6% of patients) and days of absenteeism at work during the last month (2.9 days).     

Psychosocial issues near the end of life

End-of-life care has received increasing attention in the last decade; however, the focus continues to be on the physical aspects of suffering and care to the virtual exclusion of psychosocial areas. This paper provides an overview of the literature on the intra- and interpersonal aspects of dying, including the effects that psychosocial variables have on end-of-life decision-making; common diagnosable mental disorders (e.g., clinical depression, delirium); other types of personal considerations (e.g., autonomy/control, grief); and interpersonal/environmental issues (e.g., cultural factors, financial variables). Six roles that qualified mental health professionals can play (i.e., advocate, counselor, educator, evaluator, multidisciplinary team member, and researcher) are also outlined. Because psychosocial issues are ubiquitous and can have enormous impact near the end of life, properly trained mental health professionals can play vital roles in alleviating suffering and improving the quality of life of people who are dying.     

Relationships among psychosocial functioning, diagnostic comorbidity, and the recurrence of generalized anxiety disorder, panic disorder, and major depression

The present study examined the relationships among impaired psychosocial functioning, comorbidity, and the cumulative probability of future recurrence of anxiety disorders and major depression in recovered patients. Participants were part of the Harvard/Brown Anxiety Disorders Research Program (HARP), a naturalistic, prospective, longitudinal study of anxiety disorders in psychiatric outpatients. Using proportional hazards regressions, worsening psychosocial impairment in general and in specific areas was significantly associated with an increased risk of panic disorder, generalized anxiety disorder, and major depression recurring, even after controlling for diagnostic comorbidity. These results are consistent with and extend similar findings for patients with major depression [Leon, A., Solomon, D. A., Mueller, T. I., Endicott, J., Posternak, M., Judd, L. L., et al. (1999). The range of Impaired Functioning Tool (LIFE-RIFT): a brief measure of functional impairment. Psychological Medicine, 29, 869-878; Leon, A., Solomon, D. A., Mueller, T. I., Endicott, J., Posternak, M., Judd, L. L., et al. (2000). A brief assessment of psychosocial functioning of subjects with bipolar I disorder: The LIFE-RIFT. The Journal of Nervous and Mental Disease, 188, 805-812], and suggest that increased psychosocial impairment may be a risk factor for relapse.     

Bipolar affective and schizoaffective disorders of older age -- classification, symptoms and course

Bipolar affective and schizoaffective disorders of older age are underdiagnosed, although they are of growing importance for psychiatric services. In this review article, we present and discuss results concerning classification, psychopathology, epidemiology, course, prognosis, neuroimaging, family studies and therapy. Bipolar (schizo)affective disorders of older age are a diagnostic heterogeneous group, especially as secondary manias must be separated from "endogenous" bipolar disorders nosologically. Bipolar (schizo)affective disorders of older age show some peculiarities: Gender ratio, age at onset, mortality and comorbidity with neurological disease are amongst them. Nevertheless, in many other aspects bipolar (schizo)affective disorders of older age do not differ from bipolar disorders of younger patients. For the acute and maintenance treatment there is a dearth of controlled studies. Lithium is of great importance. Other substances, as well as psychoeducation and ECT may be used analogously as in younger patients, if age specific factors are taken into account (as for example the danger of falls).     

Hormonal Factors and Disturbances in Eating Disorders

This review summarizes the current state of the literature regarding hormonal correlates of, and etiologic influences on, eating pathology. Several hormones (e.g., ghrelin, CCK, GLP-1, PYY, leptin, oxytocin, cortisol) are disrupted during the ill state of eating disorders and likely contribute to the maintenance of core symptoms (e.g., dietary restriction, binge eating) and/or co-occurring features (e.g., mood symptoms, attentional biases). Some of these hormones (e.g., ghrelin, cortisol) may also be related to eating pathology via links with psychological stress. Despite these effects, the role of hormonal factors in the etiology of eating disorders remains unknown. The strongest evidence for etiologic effects has emerged for ovarian hormones, as changes in ovarian hormones predict changes in phenotypic and genetic influences on disordered eating. Future studies would benefit from utilizing etiologically informative designs (e.g., high risk, behavioral genetic) and continuing to explore factors (e.g., psychological, neural responsivity) that may impact hormonal influences on eating pathology.     

Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.     

Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders

There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.     

Stratégie de prise en charge de l’alcoolodépendance en ambulatoire : quel suivi et quelle durée de traitement ?

BackgroundAlcohol consumption with its addictive potential may lead to physical and psychological dependence as well as systemic toxicity all of which have serious detrimental health outcomes in terms of morbimortality. Despite the harmful potential of alcohol use disorders, the disease is often not properly managed, especially in ambulatory care. Psychiatric and general practitioners in ambulatory care are first in line to detect and manage patients with excessive alcohol consumption. However, this is still often regarded as an acute medical condition and its management is generally considered only over the short-term. On the contrary, alcohol dependence has been defined as a primary chronic disease of the brain reward, motivation, memory and related circuitry, involving the signalling pathway of neurotransmitters such as dopamine, opioid peptides, and gamma-aminobutyric acid. Thus, it should be regarded in terms of long-term management as are other chronic diseases.ObjectiveTo propose a standard pathway for the management of alcohol dependence in ambulatory care in terms of duration of treatment and follow-up.MethodsGiven the lack of official recommendations from health authorities which may help ambulatory care physicians in long-term management of patients with alcohol dependence, we performed a review and analysis of the most recent literature regarding the long-term management of other chronic diseases (diabetes, bipolar disorders, and depression) drawing a parallel with alcohol dependence.ResultsAlcohol dependence shares many characteristics with other chronic diseases, including a prolonged duration, intermittent acute and chronic exacerbations, and need for prolonged and often-lifelong care. In all cases, this requires sustained psychosocial changes from the patient. Patient motivation is also a major issue and should always be taken into consideration by psychiatric and general practitioners in ambulatory care. In chronic diseases, such as diabetes, bipolar disorders, or depression, psychosocial and motivational interventions have been effective to improve the patient's emotional functioning and to prevent or delay relapses. Such interventions help patients to accept their disease and to promote long-term therapeutic plans based on treatment adherence, behavioural changes, self-management and self-efficacy. The management of alcohol-dependence in ambulatory care should be addressed similarly. Therapeutic monitoring may be initiated to manage alcohol use disorders, including alcohol dependence, especially when the patient is unwilling or unready for alcohol withdrawal (i.e. using the strategy of reduction of alcohol consumption, which is considered a possible intermediate step toward abstinence).ConclusionAlcohol dependence needs long-term medical supervision, and the therapeutic success depends on the initiation of sustained monitoring at the time of diagnosis (initiating phase with several consultations over 2–4 weeks) with psychosocial and motivational interventions in order to address all the patient uncertainties, to involve him/her in a proactive disease management plan, and to insure adherence to treatment, behavioural changes and new lifestyle. A close monitoring (once a month during the first 6 months) during a consolidation phase is necessary. Finally, a regular monitoring should be maintained overtime after 6–12 months in order to insure that the patient maintains a minimal consumption during the first year, to consolidate the patient's motivation, to abstain in at risk situations, and to maintain a controlled consumption or abstinence.