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What is mood? Despite its crucial place in psychiatric nosography and cognitive science, it is still difficult to delimit its conceptual ground. The distinction between emotion and mood is ambiguous: mood is often presented as an affective state that is more prolonged and less intense than emotion, or as an affective polarity distinguishing high and low mood swinging around a baseline. However, these definitions do not match the clinical reality of mood disorders such as unipolar depression and bipolar disorder, and do not allow us to understand the effect of mood on behaviour, perception and cognition. In this paper, we propose a multidimensional and computational theory of mood inspired by contemporary hypotheses in theoretical neuroscience and philosophy of emotion. After suggesting an operational distinction between emotion and mood, we show how a succession of emotions can cumulatively generate congruent mood over time, making mood an emerging state from emotion. We then present how mood determines mental and behavioral states when interacting with the environment, constituting a dispositional state of emotion, perception, belief, and action. Using this theoretical framework, we propose a computational representation of the emerging and dispositional dimensions of mood by formalizing mood as a layer of third-order Bayesian beliefs encoding the precision of emotion, and regulated by prediction errors associated with interoceptive predictions. Finally, we show how this theoretical framework sheds light on the processes involved in mood disorders, the emergence of mood congruent beliefs, or the mechanisms of antidepressant treatments in clinical psychiatry., (Copyright © 2022 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The objective of this paper is to verify if traits and symptoms defined as pathological and maladjusted in certain contexts may produce adaptive effects in other contexts, especially if they occur in sub-threshold forms., Methods: A historical examination of how the symptoms of depression have changed in front of great social changes and an analysis of Sardinian migrants' thymic profiles toward several metropolises., Results and Conclusions: Mood disorders have been increasing since the "English malady" in the 17th century, and we suppose that some forms of mood disorders might have an adaptive advantage. Otherwise, the increase of such an epidemic would have been self-limited. From a sociobiological point of view, it is highly probable that the environment of a rapidly evolving society can select people who are explorers and able to support accelerated biorhythms and that the condition of social change stimulates psychological and psychopathologic changes. It is also possible that hyperthymic persons modulate and create the new environment. If this model can explain the epidemic of mood disorders, its verification should guide future research., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects., Case Report: A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction. On June 5th 2012, it was decided to administrate 600mg per day of quetiapine in combination with tropatepine consequent to an episode of agitation and aggressiveness. On June 14th 2012, while the patient was receiving diazepam and valproic acid, loxapine oral solution was introduced. On June 23th, the patient started mentioning digestive disorders, such as diffuse abdominal pain with constipation but continued to pass gaz. On June 25th, at 6:30 am, he declared abdominal pain, which worsened at 8:15 am despite administration of analgesics, followed by malaise and onset of vomiting. His laboratory tests showed leukocytosis 11.2G/L with neutrophils 7.7G/L. The abdomen's radiograph without preparation showed small bowel and colonic air-fluid levels. The result of the CT scan confirmed an occlusive syndrome affecting the whole small gut and colon. At 1 pm, the patient's condition worsened. He received an intramuscular injection of 100mg of loxapine and an opioid treatment, including tramadol and morphine. At 2:30 pm, the clinical condition further deteriorated with an onset of generalized abdominal contracture, the absence of abdominal breathing, sweating, tachycardia at 104 beats per minute, and hypothermia of 34.5°C. He was transferred to an intensive care unit. Laboratory tests showed metabolic acidosis, elevated liver enzymes and acute renal failure. He received volume expansion and was treated by renal replacement therapy and antibiotics. He was intubated and transferred to the operating room. At laparotomy, both colonic necrosis with perforation and necrosis of the small bowel were seen. The patient underwent total colectomy with small bowel resection, distal ileostomy and closure of the rectal stump. The onset of septic and hemorrhagic state required further surgery on June 26th. The evolution was characterized by multi-organ failure with acute anuric renal failure, multiple cardiac arrests, and systemic bacterial and fungal infection. On July 24th, this unfavorable outcome lead to death. In summary, the patient had an occlusive syndrome due to neuroleptics and complications, including mesenteric ischemia with necrotizing colitis., Discussion/conclusion: Quetiapine, like all antipsychotics, has anticholinergic effects, including cardiac, psychiatric and digestive disorders. The combination of anticholinergic drugs decreases intestinal peristalsis. Without any prompt management, this decrease can result in a colonic ischemia or necrosis. In patients treated with neuroleptics, the onset of constipation must alert medical staff. Systematic monitoring of bowel movements should be performed in any patient receiving anticholinergic drugs., (Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Bipolar disorders (BD) are frequent mood disorders associated with a poor prognosis mainly due to a high relapse rate. Depressive relapses may follow a seasonal cyclicality, and bright-light therapy (BLT) has been established as the treatment of choice for seasonal affective disorder (SAD). The use of BLT for seasonal unipolar depression is well known, but the scientific literature is much poorer on the management of seasonal depressive episodes in BD. In addition, some specificities related to BD must be taken into account., Methods: We conducted a comprehensive review using Medline and Google Scholar databases up to August 2014 using the following keywords combination: "bipolar disorder" and "light therapy" or "phototherapy". Papers were included in the review if (a) they were published in an English or French-language peer-reviewed journal; (b) the study enrolled patients with BD and SAD; and (c) the diagnosis was made according to the DSM or ICD criteria., Results: BLT was considered among the first-line treatments for SAD with a size effect similar to antidepressants. Most of the studies did not distinguish between patients with unipolar and bipolar disorders. However, it has been demonstrated that the most significant risk of BLT in patients with BD is the mood shift. Thus, the most important therapeutic adaptation corresponds to the use of an effective mood stabilizer, as with any antidepressant. Another therapeutic adaptation in first intention is that the times of exposure to light should be shifted from morning to midday. This review also includes therapeutic guidelines regarding the management of BLT in seasonal bipolar depressive episodes., Discussion: There are very few specific data on seasonal bipolar depressive episodes. This literature review has highlighted that BLT should be handled as a regular antidepressant treatment in patients suffering from seasonal bipolar depressive episodes., (Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Bipolar disorder (BD) is a life course illness; and there is increasing awareness of the many personal, social and economic consequences of the illness in older adults. However, it is important to emphasize that BD usually begins in late adolescence or early adulthood and 75 % cases have a first episode in this age period. This early onset and the associated level of disability mean that BD is the 4th leading cause of global disease burden in adolescents and young adults. Internationally, mental health services are increasingly striving to diagnose and treat BD as early as possible to try to prevent poor outcomes. In addition, researchers are using methods employed previously in psychosis studies as these may help us to recognise the earliest manifestations of BD. If it is possible to identify sub-threshold and 'ultra high risk' syndromes for BD, this might lead to new interventions that could target the prevention of first episodes of mania. One approach to understanding these risk syndromes is to examine prospective community cohort studies and BD offspring studies., Methods: This paper reviews prospective cohort studies that identify robust risk factors in early illness onset, which was defined as age at onset of BD between 15-25 years., Results: We found that although > 50 % of individuals who developed BD had developed a putative BD prodrome prior to 14 years of age, this usually began with non-specific symptoms that overlap with similar presentations for those who later develop psychosis or severe depression. However, there are some features that seem to better identify groups with a BD "at-risk" syndrome. This syndrome is frequently composed of several factors such as mood lability, depressive episodes, prior anxiety, sleep and/or conduct disorders, attention and concentration impairment, altered energy patterns, and a family history of mania and/or depression. The course of these early predictors suggests the precursor syndromes are composed of mini-clusters of symptoms many of which are episodic and change over time. During the early phases of BD, most of the affective disturbances reported were depressive in polarity and started during adolescence, there were few manic or mixed or psychotic episodes with an onset before puberty. The pathogenesis of BD demonstrates a gradual progression from non-specific to more specific symptoms and then to frank BD features., Conclusion: Prospective community and offspring BD cohort studies are approaches that together can help us understand the evolution of BD and allow us to define the developmental pathways. Further, identifying subjects with BD "at-risk" syndrome using a clinical staging model may allow benign interventions to be used as first-line treatment - such as neuroprotective agents like essential fatty acids; second line treatments, with a less benign risk to benefit ratio should be reserved for severe or resistant cases., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Bipolar disorder is a complex disease which requires multiple healthcare resources and complex medical care programs including pharmacological and non pharmacological treatment. If mood stabilizers remain the corner stone for bipolar disorder treatment, the development of atypical antipsychotics and their use as mood stabilizers has significantly modified therapeutic care. At the present time, psychiatrists have a large variety of psychotropic drugs for bipolar disorder: mood stabilizers, atypical antipsychotics, antidepressants, anxiolytics… However, despite the publication of guidelines on pharmacological treatment, with a high degree of consensus, everyday clinical practices remain heterogeneous. Moreover, there are few longitudinal studies to describe therapeutic management of bipolar disorder, whatever the phase of the disease is. Indeed, most of the studies are carried out on a specific phase of the disease or treatment. And there is no study comparing French and European practices., Objectives: In this paper, we aim to present the comparison of the management of pharmacological treatments of bipolar disorder between France and Europe, using the data of the observational Wide AmbispectiVE study of the clinical management and burden of bipolar disorder (WAVE-bd study)., Methods: The WAVE-bd study is a multinational, multicentre and non-interventional cohort study of patients diagnosed with BD type I or type II, according to DSM IV-TR criteria, in any phase of the disorder, who have experienced at least one mood event during the 12 months before enrolment. In total, 2507 patients have been included across 8 countries of Europe (480 in France). Data collection was retrospective (from 3 to 12 months), but also prospective (from 9 to 15 months) for a total study length of 12 to 27 months. Main outcome measures were the healthcare resource use and pharmacological treatments., Results: Our results show differences in the therapeutic management of bipolar disorder between France and other European countries. Regarding healthcare resource use, our results show that French patients consult more frequently a psychiatrist or a psychologist and less frequently a general practitioner or the emergency ward in comparison with patients from other European countries. In the whole European population, including France, atypical antipsychotics are widely used. Only 25% of the patients receive lithium and more than 50% of the patients receive antidepressants, while their use in bipolar disorder remains controversial. Most of the patients receive polymedication. Considering all phases of the disease pooled, less lithium and less atypical antipsychotics are prescribed to French patients, whereas they receive more antidepressants and more benzodiazepines than patients from other European countries. On the over hand, prescription of anticonvulsants and electroconvulsive therapy are equal. Moreover, data analyses by polarity of the episodes globally confirm these trends. There are a few exceptions: mixed states, in which lithium is twice more prescribed in France in comparison to other countries; depressive states, in which antidepressants are even more prescribed in other countries than in France; and less prescription of anticonvulsants in manic, mixed and euthymic phases in France., Conclusion: The WAVE-bd study is the first observational study conducted on a large sample of bipolar I and II patients that compares therapeutic management between France and other European countries. The differences observed in therapeutic care across the different phases of the disease show that treatments differ depending on the countries studied, but also according to the preventive or curative phases, polarity of the bipolar disorder, comorbidities, impact of guidelines, and care organization. Although French patients have been treated by less lithium and less atypical antipsychotics than other European patients, they receive more antidepressants and more benzodiazepines. Finally, patients generally receive polymedication and the diversity in prescriptions shows how bipolar disorder is a complex disorder., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Mixed states present nosologic and diagnostic challenges with a relative paucity of evidence to guide treatment. Mixed bipolar states are difficult to treat and are associated with a high neuropsychiatric morbidity, a high risk of suicide and a poor outcome. In DSM- 5, the definition of mixed episode has been removed (in DSM- IV TR: "juxtaposed full manic and depressive episodes"). Mixed symptoms are captured under a broader concept called "mixed features" that is applied to mania and depression. The classification of mixed states as defined in DSM- 5 is less restrictive than in DSM- IV TR and challenges us at methodological and therapeutic levels., Objective: The aim of this paper was to conduct an overview of the literature to ascertain the efficacy of pharmacotherapy of mixed states., Method: A systematic review of the literature was conducted using PubMed., Results: Manic symptoms of mixed episodes seem to show a good response to second generation antipsychotics and to divalproate. There is no evidence of differential efficacy for second generation of antipsychotics (SGAs). Lithium and carbamazepine may be effective in mixed states in monotherapy and perhaps benefit in combination with SGAs as second line. Combination pharmacological treatment of SGAs and moodstabilizers are common in mixed states. This pattern has the best literature evidence., Conclusions: There is a few evidence to help us to choose the right treatment for patients with mixed state. In light with the DSM 5, more drugs specifically designed to treat mixed state are needed., (Copyright © 2013 Sociedade Brasileira de Farmacognosia. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Fasting during the Ramadan month is a cornerstone of Islam. Several disorders of the chronobiological rhythms occur during this month and impact on mood. Through this paper the authors provide a literature review of the impact of fasting on patients with bipolar disorders., Materials and Subjects: A literature review using Mesh keywords through Medline database. From 1970 to 2011, articles in French and English were selected., Results: Circadian rhythm refers to the approximately 24-hour cycles that are generated by an organism. Most physiological systems demonstrate circadian variations. Many hormones and other metabolisms, such as gastric pH, insulin, glucose, calcium and plasmatic gastrine, have been shown to exhibit circadian oscillation. The role of social rhythm in behaviors and its influence on circadian rhythms in humans is now obvious. It has been shown that the lack of concentration and irritability increased continuously during Ramadan month and reached its peak at the end of the month. Mood and vigilance are significantly decreased during the fasting month. Several authors have stated that the course of bipolar illness may be affected by the changes in social rhythm that occur during Ramadan (fasting month). Studies which have been devoted to this topic are sparse. Kadri et al., in 2000, studied 20 bipolar patients during the fasting month of Ramadan of 1417 (Hegirian calendar, corresponding to January 1997). Diagnosis of bipolar disorder was made according to ICD-10 criteria. Patients were assessed during the week before Ramadan, the second and the fourth weeks of the fasting month and the first week after its end, with the Hamilton Depression and Bech-Rafaelsen scales. The plasma concentration of lithium was also assessed. The main finding of the study was that 45% of the patients relapsed, 70% during the second week, and the remaining patients at the end of Ramadan. These relapses were not related to plasma concentration of lithium. Most of the relapses were manic (71,4%). Patients who did not relapse had more insomnia and anxiety during the second and third weeks of the study. The side effects of lithium increased and were seen in 48% of the sample, mostly dryness of the mouth with thirst and tremor. However, Farooq et al. in 2006 studied 62 bipolar patients during the fasting month of Ramadan 1427 (from 25 September to 24 October 2006). Serum lithium, electrolytes, Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were assessed, one week before Ramadan, mid Ramadan and one week after Ramadan. The side effects and toxicity were measured by symptoms and signs checklist. There was no significant difference in mean serum lithium levels at three time points. The scores on HDRS and YMRS showed significant decrease during Ramadan (F=34,12, P=0,00, for HDRS and F=15,6, P=0,000 for YMRS). Also the side effects and toxicity did not differ significantly at the three point's assessment., Conclusion: All physiologic parameters are influenced by the circadian rhythm, which is influenced in its turn by the food rhythm. So far, the results of these two main studies, with opposite results, do not help us advise bipolar patients to fast or not to fast. Other studies in this field are badly needed., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Bipolar disorder is a chronic and recurring disorder associated with significant psychosocial impairment. A number of psychosocial interventions have been developed to address impairment. The consensus makes mood stabilizer the treatment of bipolar disorder. However, numerous patients are not in complete remission despite a controlled observance. Every patient can follow a psycho educational program. What this paper adds. The review identifies that a range of interventions have demonstrated efficacy in extended periods of euthymia, improved social and occupational functioning and alleviation of subsyndromal symptoms. Adjunctive, short-term psychotherapies have been shown to offer fairly consistent benefits to bipolar disorder patients. Cognitive-behavioural therapy, family-focused therapy, and psychoeducation offer the most robust efficacy in regard to relapse prevention. The most complex situations including comorbidities can be helped by behavioral and cognitive therapy for bipolar disorder. Evaluations emphasize positive impact. The psychosocial interventions reviewed provide mental health nurses with evidence-based approaches to improving mental health care for patients with bipolar disorder. There is a need for mental health nurses to conduct high quality trials of the clinical effectiveness of these interventions., (Copyright © 2012 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Assertive Community Treatment (ACT) is known to have a positive impact on the number and length of inpatient stays. Yet, research is needed in order to help understand how ACT programs may ease off families' burden, e.g. in terms of economic expenditures. Indeed, many families with siblings suffering from chronic mental illness, who disengaged from psychiatric services, report needs related to ACT. This paper aims to describe the impact of a new ACT program in Geneva on patients and their families' burden., Methods: Out of 91 patients consecutively treated by the ACT program for at least 3 months, 55 consented to participate in the research. Twenty-one allowed us to contact their families (out of 37 who had relatives in the area). Data were gathered on patients and families before and after a 6-month-follow-up., Results: For the patients, after adjustment for the time spent during follow-up, most of the studied variables evolved favorably, particularly for their symptoms. At baseline, most of the family members felt overburdened by the financial cost (59.1%) related to their relatives with severe mental disorder and experienced inconvenience at having to give them assistance in daily life (68.2%) and to supervise them in daily activities (54.5%). Several variables evolved favorably during follow-up. Notably the best changes were observed for the inconvenience relating to assistance in daily life and relatives' emotional distress. Families of patients with delusional disorder featured less or no improvement during the ACT follow-up. The best correlate of improvement in familial burdens was improvement in patient's positives symptoms. Among those patients, being a female and suffering from a schizo-affective disorder was known to have had a higher impact on the number of interventions provided by families., Discussion: ACT should be recommended for patients who feature a poor outcome when treated in other settings. In addition, our results suggest that their families can also improve considerably, particularly those confronted with patients with persistent and enduring disturbing behaviors related to positive symptoms which do not, however, warrant hospitalization. Clinicians should pay particular attention to patients suffering from delusional disorder and their families, as this disorder does not appear to be associated with improvement in family burdens. These data do not allow definitely disentangling whether the improvement of families' burden is directly related to ACT interventions with them, to the implementation of support by other structures (such as peer support groups) or to an indirect effect related to patients' improvement. To our knowledge no similar study on the effect of ACT on family burden exists. Hence, such research needs to be replicated in other areas with different clinical and cultural backgrounds., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Management of bipolar disorder has undergone many revisions in recent years as new agents and treatments have been developed and studied with variable success. In conjunction with the advent of novel therapies and indications, there has been an increase in the understanding of the phenomenology and neurobiology of bipolar disorder that has made the classification and management of the illness necessarily more sophisticated. However, there remains a significant delay of 8 years in detecting and diagnosing bipolar disorder, and a further need to improve treatments. However, this paper has emphasized the need to be aware of recent advances and the emerging uses of new pharmacological treatments in the management of bipolar disorder. It has also highlighted the need for tailoring management to the individual. In particular, the successful treatment of bipolar disorder requires achieving prophylaxis and preventing relapse. In this regard, maintenance therapy is of paramount importance, and thus the tolerability of agents needs to be considered throughout treatment and should be factored into all management decisions. At the centre is the individual with bipolar disorder and the need to maintain a healthy therapeutic relationship. However, it is important to note that the evidence synthesized in this paper serves only as a guide to the management of bipolar disorder and that, in clinical practice, all treatment recommendations require contextual interpretation, the consideration of local factors and the consultation of additional resources., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

While early intervention strategies have been developed for psychotic disorders, affective psychoses and bipolar disorders have been neglected by this movement. However, when considering that outcome of bipolar disorders is often not as favorable as previously thought and that delay between illness onset and introduction of an adequate treatment is often very long, such developments seem clearly justified. In this paper we briefly review arguments supporting early intervention in bipolar disorders, the practical and theoretical obstacles that still need to be overcome, the strategies that may already now contribute to decrease treatment delay, and we describe current state of research regarding identification of the prodromal phase of bipolar disorders., (Copyright © 2010 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: The commercial introduction of atypical antipsychotics, called second-generation antipsychotics (SGAs), a few years ago, has led to a world-wide reappraisal of the established treatment strategies for people with psychotic or bipolar disorders. They permitted improvements in the pharmacologic management of psychiatric diseases. As compared to conventional neuroleptics or first-generation antipsychotics (FGAs), they promised better efficacy especially on negative symptoms and cognitive impairments of psychiatric diseases and, at the same time, better tolerance on neurological side effects. Now, they have shown other side effects and they have a higher acquisition cost than FGAs., Objectives and Methods: The aim of this paper is to describe and analyse the prescribing practices of antipsychotic drugs in French psychiatric hospitals for adult inpatients and to compare them with other surveys and guidelines. In June 2004, we conducted a one-day, cross-sectional, observational and naturalistic study in 13 hospitals, members of the PIC network., Results: Two thousand one hundred and ninety-two prescriptions with antipsychotic treatment were collected. One thousand one hundred and fifty-four prescriptions (52.6%) included a SGA, but the FGAs were the most prescribed (65.8%; n=2259), principally cyamemazine (24.7%). There was one antipsychotic in 50.7% of prescriptions, two antipsychotics in 42.2%, but the second neuroleptic used was a sedative (82.6%), principally cyamemazine. Multiple antipsychotics were present in 1081 prescriptions (49.3%), with an average number of 1.57 antipsychotics. A mood stabiliser, an antidepressant, an anxiolytic and a hypnotic were coprescribed in respectively 37, 30.5, 65.1 and 41.6%. There were 2.48 psychotropic drugs associated with the principal antipsychotic; in total, with correctors of side-effects of the antipsychotics, there were 3.38 drugs per prescription. The SGAs aimed more often for psychotic (F20-F29) patients (61.9% versus 43.3% with FGAs), who were males (61.4% versus 68%), younger (42.6 years versus 44.1 years; p<0.02), with higher average daily doses, more associated with other neuroleptics (p<0.0004) and less associated with anticholinergic antiparkinsonian agents (p<10(-4)) than FGAs. Compared to other surveys, these results showed that the SGAs have become the first-line treatment for psychiatric disorders. The highest average daily doses corresponded to treatments of psychotic patients and, hence, the values might largely exceed the authorized maximum doses. Furthermore, in more than half of the cases, an FGA, generally a sedative, was associated with an SGA that did not comply with the principle of monotherapy established by the national and international guidelines; that also annulled the expected benefit of the SGAs on the awakening, cognition and the neurological tolerability of the treatment. The coprescriptions of the other psychotropic drugs to neuroleptics also remained the rule in psychiatry, showing all the complexity of pharmacological psychiatric medications. Prescriptions also included treatments for side effects of antipsychotics; even on the prescriptions including the SGAs, there was the coprescription of anticholinergic antiparkinsonian drugs, the deleterious character of which one knows on cognition. This resulted in a difficulty of understanding the prescription for the patient, associated with reduced compliance and increased risks of pharmacological side effects. The heterogeneity of the situations of crisis in psychiatric hospitals could make the strict application of guidelines' recommendations difficult. Nevertheless, the educational interventions in psychopharmacology for patients and the training campaigns for psychiatrists and nurses are necessary to improve the therapeutic management of the patient and ensure him/her optimal quality of life., Conclusion: This kind of survey, far too rare, was very important because it showed the routine clinical settings in which these new drugs were really used. The results showed that SGAs appeared to take the place of the FGAs used in the treatment of psychoses, particularly schizophrenia, but also in the treatment of mood disorders and they reflected actual clinical practices. Other surveys must be conducted to see whether our study confirms the general trend concerning the use of these drugs and, therefore, to reassess these prescribing practices.

The number of structural neuroimaging studies of bipolar disorder have increased during recent years, expanding the literature on the nature of cerebral abnormalities underlying this disorder. The purpose of this paper is to provide a selective review on the main issues concerning this literature. Consistent findings are higher rate of periventricular and deep subcortical white matter hyperintensites seen on MRI. Although there is strong evidence for links between hyper-intense lesions and age or cardio-vascular risk factors, some authors have observed the presence of these abnormalities early in the course of the illness. There are also frequent reports on ventricular enlargement, which has been described as mild and predominant in the right lateral ventricle. Total cerebral volume appears to be preserved. Whereas changes in total grey matter volume are uncertain, evidence suggests that reduced white matter volume reflects genetic factors predisposing to the disorder. Recent studies have reported volume changes in several cortical areas including the subgenual cingular, frontal and temporal cortices. Additionally, a number of reports described morphometric abnormalities in various subcortical structures, such as amygdala, basal ganglia and thalamus. Part of the variability in the morphometric abnormalities might be attributable to differences in clinical status and demographic characteristics of patient groups. Despite some inconsistencies across the studies, it emerges that abnormalities are asymmetrically distributed throughout the two cerebral hemispheres. When increase in volume is reported, it is preferentially localised in the left cerebral hemi-sphere and more specifically in prefrontal and temporal cortices and in amygdala. By contrast, when structural abnormalities concern the right cerebral hemisphere, they are identified as deficits. These latter results are in direct line with those of studies of mania following brain injuries, which report that these secondary mania result mainly from right cerebral lesions. It is also important to notice that most of the abnormalities concern both the cortical and subcortical level, ie frontal, striatal, thalamic and limbic regions. These abnormalities highlight the role in the pathophysiology of bipolar disorder of the loops involved in emotional information processing. The particular role of fronto-limbic loops in the phenomenology of bipolar disorder have been emphasised by recent data from functional neuroimaging studies.

After a previous paper discussing the possible association between beta-thalassemias and bipolar disorder, this article considers a possible association between alpha-thalassemia and the bipolar disorder. We report the case of a 36 year old woman with bipolar disorder and alpha-thalassemia. The patient, native of Reunion Island, has a family history of bipolar disorder (both parents, one brother, and a paternal uncle). The severity of the bipolar disorder type I in her family, is illustrated by the suicides of both parents, one brother and the paternal uncle, in intervals of only a few years. After a Medline review (1980-2004) we found only two studies suggesting a possible relationship between bipolar disorders and alpha-thalassemias, but without clinical case report information. Some genetic studies described the existence of possible genetic susceptibility for bipolar disorder on the short arm of chromosome 16, close to the gene involved in certain alpha-thalassemias, on the region 16p13.3. An interesting finding is that the sequencing of 258 kb of the chromosome region 16p13.3 not only allowed the identification of genes involved in the alpha-thalassemia and in the vulnerability to bipolar disorders, but also the identification of genes implicated in tuberous sclerosis, in polycystic kidney disease, in cataract with microophtalmia, and in vulnerability genetic factors for ATR-16 syndrome, asthma, epilepsy, certain forms of autism and mental retardation. Numerous clinical descriptions and some familial studies on linkage suggested a possible relationship between tuberous sclerosis, polycystic kidney disease, cataract with microophtalmia, ATR-16 syndrome, asthma, epilepsy, certain forms of autism, mental retardation and bipolar disorder, given the closeness of these vulnerability genes on the short arm of the chromosome 16. A vulnerability gene of alcohol dependence was also identified on this same chromosome region (16p13.3), by a study concerning 105 families. Taking into account the methodological difficulties due to the clinical and genetic heterogeneity of bipolar disorder, we suggest that linkage techniques should be used to confirm the presence of susceptibility genetic factor for bipolar disorders on chromosome 16. Thus a known genetic disease (alpha-thalassemia) could contribute to confirming the presence on the short arm of chromosome 16 of a susceptibility genetic factor for bipolar disorders. Linkage studies should be performed in families with a strong association for both diseases. Thanks to linkage techniques, one could hope for an improvement in understanding the physiopathology of bipolar disorder, with possible implications at a therapeutic level.

This paper presents the definite data from a French multi-center study (EPIDEP). The aim of EPIDEP was to show the feasibility of validating the spectrum of soft bipolar disorders by practicing clinicians. In this report we focus on data concerning the frequency of BP-II disorder and the key characteristics of BP-II by systematic comparison versus Unipolar depression. EPIDEP involved training 48 french psychiatrists in 15 sites; it is based on a common protocol following the DSM IV criteria (Semi-Structured Interview for Hypomania and Major Depression), and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal). Comorbidity and family history (Research Diagnostic Criteria) were also obtained; EPIDEP was globally scheduled in two phases: Phase 1 devoted to recruiting major depressives, and phase 2 involved in more sophisticated assessment of soft bipolarity and administrating related measures. Results are presented on the total of 537 patients included at "visit 1" and 493 assessed for soft bipolarity at "visit 2". The BP-II global rate which was 21.7% at initial evaluation, nearly doubled (39.8%) by systematic evaluation of hypomania. Intergroup comparison versus unipolar depressives showed the following key characteristics of BP-II disorder: 1) distinct clinical presentation at index depressive episode despite uniformity in global intensity of depression (overrepresentation in BP-II of "suicidal thoughts", "guilt feelings", "depersonalisation-derealisation", "hypersomnia" "and weight gain"; and of "psychic anxiety" and "initial insomnia" in UP); 2) different course of illness with younger age of onset of first depression, higher rate of suicidal attempts, recurrency and hospitalisations; 3) more difficulties for recognition of the correct diagnosis; 4) more complex temperamental dysregulations (mixture of cyclothymic, hyperthymic and irritable traits which are highly represented in BP-II group); 5) higher rate in family history of mental disorders, especially bipolar disorders. Finally, EPIDEP data confirmed the diagnostic reliability of self-rating of hypomania and cyclothymia. With a systematic search of hypomania, almost 40% of major depressive episodes seen in psychiatric settings were classified as BP-II, of which only half were recognized by the clinicians at study inclusion. The BP-II validity as a distinct disorder from Unipolars was confirmed. Moreover, EPIDEP emphasized the reliability of self-rating in assessing soft-bipolarity (hypomania and cyclothymia). In total, EPIDEP data indicated that recognition of BP-II is feasible in diverse practice settings and proposed for clinicians some adapted clinical tools for assessing soft bipolarity.

Antipsychotic drugs are widely used in the long term treatment of bipolar and schizoaffective disorders. Nevertheless clinical trials devoted to the specific assessment of the mood stabilizing effect of these drugs are quite rare. Among recent studies only those by S. McElroy on olanzapine and by R. Bowden on divalproex have included mood symptoms as inclusion and outcome criteria. This paper reviews the different methodological proposals both in term of protocol designs (retrospective, naturalistic, longitudinal and prospective studies) and of efficacy criteria (time to relapse, reasons for drop outs, treatment switch, functional status).

From 1899 to 1913, Emil Kraepelin (1856-1926) creates and elaborates the nosographical group of the "manic-depressive insanity". In the 50-60s, Leonhard splits off this homogeneous group and describes unipolar psychosis, bipolar psychosis and cycloïd psychosis (anxiety-elation psychosis, motility psychosis and confusion psychosis). Recent nosographical orientations seem to announce a come-back to Kraepelin's conception of "mood disorders". This paper presents the essential of Kraepelin's "manic-depressive insanity" theory-temperamental basis, integration of mixed states, epidemiological datas- and highlights its dialectical relations with today's theory of bipolarity.

Rapid cyclers are defined by the occurrence of four or more mood episodes during the previous 12 months. Clinical, epidemiological and population characteristics of these patients are presented as well as studies that validate them. Hypotheses and theoretical models allowing their analysis are reviewed. The last part of the paper deals with treatments.

In this paper results of a prospective follow-up study from 1959 to 1975 are presented. 159 unipolar depressive and 95 bipolar manic-depressive patients were subdivided into: --early onset patients (EO) less than 40 years, and--late onset patients (LO): greater than 40 years. These two groups are compared with each other. The common features predominate: they do not differ in the sex ratio, and the periodicity of the disorder. However, they differ in the length of episode of unipolar depression, recovery rate, and chronification.

Despite our extensive knowledge regarding the biochemical and physiological actions of lithium, we have so far been unsuccessful in linking this information to the clinical actions of lithium in a unified model. It may be that a psychological/behavioural approach may allow us to achieve this objective. The present paper presents an outline of some studies on the behavioural actions of lithium in rats and mice and suggests how the data from such work can lead to a model of lithium action and of manic-depressive disorder couched in terms of information-processing mechanisms. Recent work in manic-depressive patients, using a signal detection task, is also described: the results are broadly confirmatory of the information-processing model of lithium effects.