Alcohol use and bipolar disorders: Risk factors associated with their co-occurrence and sequence of onsets.

BACKGROUND: Little is known about the sequence of onsets in patients affected by comorbid alcohol use and bipolar disorder. This study examines the risk factors associated with their co-occurrence and order of onset. METHOD: The demographic, clinical, and temperament characteristics as well as the course of illness were analyzed within our sample of 1090 DSM-IV bipolar I manic patients. Our sample was categorized according to the presence of comorbid alcohol use disorder and the sequence of onsets of bipolar and alcohol use disorders i.e., alcohol first (AUD-BD) and bipolar first (BD-AUD). RESULTS: Regression analyses revealed that alcohol use disorder (52.5%) was associated with the male gender, additional substance use disorders, as well as an irritable and a hyperthymic temperament. The AUD-BD group (6.6%) was older than the BD-AUD group (45.8%) and showed higher rates of comorbid sedative use, organic, and anxiety disorders with higher levels of irritable temperament, and a bipolar subtype characterized by depressive polarity at onset. The BD-AUD group had high levels of hyperthymic temperament with higher rates of comorbid stimulant use disorder and a manic polarity at onset. CONCLUSIONS: In the AUD-BD group, alcohol might have been used to reduce stress and tension caused by the presence of an irritable temperament as well as anxious and organic disorders, leading to first depressive episode. In the BD-AUD group, stimulant use might have triggered the first manic episode, and alcohol abuse result from mania severity.

Relationship of suicide rates with climate and economic variables in Europe during 2000-2012.

BACKGROUND: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. METHODS: Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. RESULTS: The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. DISCUSSION: The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Pharmacological treatment of schizophrenia with comorbid substance use disorder.

INTRODUCTION: While antipsychotics remain the cornerstone of treatment for schizophrenic patients with comorbid substance use disorder (SUD), such treatment is nonetheless complicated by frequent medical comorbidity and poor adherence to medication. AREAS COVERED: Randomised controlled trials (RCTs) on the efficacy of antipsychotics for the treatment of schizophrenic patients with comorbid SUD are reviewed and analysed on the basis of a systematic literature search (PubMed) ranging from 1985 to 2015. On the same basis, findings from RCTs on the efficacy of psychotropic and other medications used for primary SUD are summarised, and the main issues liable to influence treatment choice are discussed, including pharmacodynamic as well as pharmacokinetic interactions, adherence, medical comorbidity and the impact on brain structure. EXPERT OPINION: As far as the treatment of schizophrenic patients with SUD is concerned, direct and indirect evidence tends to stand in favour of the use of second-generation antipsychotics (SGAs), and particularly those with lower metabolic, cardiovascular and extrapyramidal side effects, as well as those with a depot formulation. A few of the usual medications for the treatment of primary SUD, such as naltrexone and disulfiram for alcohol use and bupropion for tobacco cessation, can also be safely and efficiently administered to schizophrenic patients with SUD.

Lithium might be associated with better decision-making performance in euthymic bipolar patients.

Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p<0.001) by lithium dose, level of education and no family history of bipolar disorder (all p≤0.01). Because medication was not randomized, it was not possible to discriminate the effect of different medications. Lithium medication might be associated with better decision-making in remitted bipolar patients. A randomized trial is required to test for the hypothesis that lithium, but not other mood stabilizers, may specifically improve decision-making abilities in bipolar disorder.

Age-at-onset and comorbidity may separate depressive disorder subtypes along a descending gradient of bipolar propensity.

Depressive illnesses with subthreshold bipolar features are still misdiagnosed as unipolar. The goal of this study was to identify depressive disorder subtypes at risk for bipolarity. Four hundred ninety three major depressive patients were submitted to a cluster analysis on the basis of affective illness history and symptoms of the current episode. Seven clusters were identified which were regrouped into three age-at-onset subgroups; subgroups were further differentiated into subtypes according to predominant comorbidities. The latter were found to precede the occurrence of the related depressive disorder subtypes, decrease their age-at-onset, and increase their risk of belonging to the bipolar spectrum: the earlier the comorbidity, the higher the bipolar propensity was. This is likely to have implications for the diagnosis, natural history, as well as prophylaxis of bipolar disorders.

Frequency and characteristics of individuals with seasonal pattern among depressive patients attending primary care in France.

OBJECTIVE: High rates of bipolar disorder (BD) have been found among major depressives with seasonal pattern (SP) consulting in psychiatric departments, as well as among patients seeking primary care. As SP was reported to be common in the latter, the current study was designed to assess (a) the frequency and characteristics of SP among major depressives attending primary care and (b) the prevalence and aspects of BD in this population. METHODS: Among 400 patients who consulted French general practitioners (GPs) for major depression between February and December 2010, 390 could be included in the study: 167 (42.8%) met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for seasonal pattern [SP(+)], whereas 223 (57.2%) did not meet these criteria [SP(-)]. The two groups were compared on demographic, clinical, family history and temperamental characteristics. RESULTS: Compared to SP(-), SP(+) patients were more frequently female, married and with a later age at first depressive episode, and showed more atypical vegetative symptoms, comorbid bulimia and stimulant abuse. They also exhibited more lifetime depressive episodes, were more often diagnosed as having BD II and met more often bipolarity specifier criteria, with higher rates of bipolar temperaments and a higher BD family loading. Among SP(+) patients, 68.9% met the bipolarity specifier criteria, whereas 31.1% did not. Seasonality was not influenced by climatic conditions. The following independent variables were associated with SP: BD according to bipolarity specifier, female gender, comorbid bulimia nervosa, hypersomnia, number of depressive episodes and family history of substance abuse. CONCLUSIONS: Seasonal pattern is frequent among depressive patients attending primary care in France and may be indicative of hidden bipolarity. Given the risks associated with both SP and bipolarity, GPs are likely to have a major role in regard to prevention.

Relationship of suicide rates to economic variables in Europe: 2000-2011.

BACKGROUND: It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS: The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD: Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS: There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS: Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Gender differences in a cohort of major depressive patients: further evidence for the male depression syndrome hypothesis.

BACKGROUND: Previous studies have shown that major depressive patients may differ in several features according to gender, but the existence of a specific male depressive syndrome remains controversial. METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 125 (27.7%) were of male gender, whereas 317 (72.3%) were female, after exclusion of bipolar I patients. RESULTS: Compared to women, men were more often married, had more associated mixed features, with more bipolar disorder NOS, more hyperthymic temperaments, and less depressive temperaments. Women had an earlier age at onset of depression, more depressive episodes and suicide attempts. A higher family loading was shown in men for bipolar disorder, alcohol use disorder, impulse control disorders and suicide, whereas their family loading for major depressive disorder was lower. Men displayed more comorbidities with alcohol use, impulse control, and cardiovascular disorders, with lower comorbidities with eating, anxiety and endocrine/metabolic disorders. The following independent variables were associated with male gender: hyperthymic temperament (+), alcohol use disorder (+), impulse control disorders (+), and depressive temperament (-). LIMITATIONS: The retrospective design and the lack of specific tools to assess the male depressive syndrome. CONCLUSION: Study findings may lend support to the male depression syndrome concept and draw attention to the role of hyperthymic temperament, soft bipolarity as well as comorbidities as determinants of this syndrome. The latter could help recognize an entity which is probably underdiagnosed, but conveys a high risk of suicide and cardiovascular morbidity.

Negative Symptoms in Schizophrenia: Where We have been and Where We are Heading.

This review traces the history of negative symptom profiles in neuropsychiatry from their earliest emergence in the 19th century to the current psychiatric concepts and therapeutic approaches. Recent investigations performing exploratory and confirmatory factor analysis have suggested that negative symptoms are multidimensional, including evidence for at least two distinct negative symptom subdomains: diminished expression and amotivation. Preliminary studies have demonstrated the clinical validity of this distinction. Several potential pathophysiological validating factors based on brain imaging analysis of emotional experiences and expressions in individuals with schizophrenia are examined. Finally, the potential of different treatment strategies, including medications and various psychotherapeutic techniques, to most favorably treat each of these subdomains is discussed.

Effectiveness of methylphenidate as augmentation therapy after failure of adjunctive neuromodulation for patients with treatment-refractory bipolar depression: a case report.

Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar, geriatric, or bipolar depression, and depression secondary to medical illness. We present a case of bipolar depression in which the patient responded significantly to augmentation with methylphenidate, without any side effects, after failure of adjunctive repetitive transcranial magnetic stimulation and electroconvulsive therapy. Mr U, a 56-year-old man with bipolar I disorder, had melancholic symptoms during his sixth episode of bipolar depression. After failure of repetitive transcranial magnetic stimulation and electroconvulsive therapy, he was treated with fluoxetine 80 mg/day, duloxetine 360 mg/day, mirtazapine 60 mg/day, and sodium valproate 1,000 mg/day, with no improvement. We added methylphenidate at a dose of 10 mg/day for one week, which resulted in mild clinical improvement, and then methylphenidate extended-release 20 mg/day for one week, with significant clinical improvement. He tolerated his medications well. His clinical recovery was stable over one year. The patient's antidepressants and methylphenidate were gradually tapered and finally discontinued after one year with no withdrawal syndrome. To date, he remains well on sodium valproate as monotherapy and is being followed up at our bipolar department. This case suggests that methylphenidate augmentation might be a therapeutic option when treating highly treatment-resistant patients with bipolar depression, even if they had not responded to adjunctive neuromodulation. In these clinical situations, physicians might be interested in prescribing methylphenidate because of its efficacy and safety.

[Ketamine in acute and severe major depressive disorder]. / La kétamine dans le traitement du trouble dépressif aigu sévère.

CONTEXT: Depression is a frequent, severe and expensive illness. Approximately 20% of depressive episodes are resistant to classic antidepressants. Glutamatergic antagonists, in particular ketamine, established a new, rapid and robust therapeutic approach in resistant depression. RESULTS: The main results in the literature show a rapid and robust antidepressant effect of ketamine, with infra-anesthesic posology (0.5mg/kg) administered in intravenous way. Positive effects are observed on depressive symptoms, suicidal thoughts, and there is a potential synergic action when used in the induction of anesthesia for electroconvulsive therapy. However, effects only last shortly. Side effects are mostly reversible and of mild intensity, no severe consequences were reported. LIMITS: Limits are the lack of power of the included studies, due to small sample sizes, and the scarcity of studies. Misuse of ketamine is an important issue to be taken into account, and few data about ketamine addiction potential and its long-term effects are published at the moment.

Risks associated with gender differences in bipolar I disorder.

BACKGROUND: Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial. METHODS: The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender. RESULTS: Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (-), excessive alcohol use (+), cyclothymic temperament (-), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+). LIMITATIONS: The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations. CONCLUSIONS: Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.

Characteristics and profiles of bipolar I patients according to age-at-onset: findings from an admixture analysis.

BACKGROUND: Many studies have used admixture analysis to separate age-at-onset (AAO) subgroups in bipolar patients, but few have looked at the phenomenological characteristics of these subgroups, in order to find out phenotypic markers. METHODS: Admixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 1082 consecutive DSM-IV bipolar I manic inpatients who were assessed for demographic, clinical, course of illness, comorbidity, and temperamental characteristics. RESULTS: The model best fitting the observed distribution of AAO was a mixture of three Gaussian distributions. We could identify three AAO subgroups: early, intermediate, and late age-at-onset (EAO, IAO, and LAO, respectively). Patients in the EAO subgroup were more often single young males exhibiting severe mania with psychotic features, a subcontinuous course of illness with substance use and panic comorbidity, more suicide attempts, and temperamental components sharing hypomanic features. Patients with LAO showed a less severe picture with more depressive temperamental components, alcohol use and comorbid general medical conditions. A less typical phenotype was present in IAO patients. LIMITATIONS: The following are the limitations of this study: retrospective design, and bias toward preferential enrollment of patients with manic predominant polarity. CONCLUSIONS: This study confirms that bipolar I disorder can be subdivided into three subgroups based on AAO distribution and shows that patients from these subgroups differ in phenotypes.

[Psychostimulants in the treatment of depression]. / Psychostimulants dans le traitement de la dépression.

Psychostimulants promote alertness and reduce fatigues that have suggested their use in the treatment of depressive disorders in the early part of the 20th century. Overall, data support the use of psychostimulants in depression particularly in cases of drug resistance, when there is a severe physical illness or when short-term efficiency is needed, especially in the elderly. Psychostimulants are relatively better tolerated than conventional antidepressants, side effects concern less than 20% of patients. Nevertheless, they have to be prescribed carefully in front of the increased cases of misuse described by the literature and the French national committee of narcotics and psychotropics. Larger randomized, controlled trials with longer follow-up periods are needed to clarify a profile of response to psychostimulants, and assess the risk of developing tolerance or dependence on these substances.

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

BACKGROUND: Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. OBJECTIVE: This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). METHODS: 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. RESULTS: Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. CONCLUSIONS: These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group.

Self-assessment and characteristics of mixed depression in the French national EPIDEP study.

BACKGROUND: Studies on mixed depression have been conducted so far on the basis of DSM-IV manic symptoms, i.e., a list of 7 symptoms which may provide limited information on the subsyndromal features associated with a full depressive episode. METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 102 (23.8%) were classified as mixed depressives (≥3 hypomanic symptoms), and 146 (34%) as pure depressives (0 hypomanic symptom), after exclusion of bipolar I patients; hypomanic symptoms were assessed with the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self assessment format. A narrower definition of mixed depression, resting on those MVAS-BP items referring to DSM-IV hypomanic symptoms was also tested, as a sensitivity analysis. RESULTS: Compared to pure depressives, mixed depressive patients had more psychotic symptoms, atypical features and suicide attempts during their index episode; their illness course was characterized by early age at onset, frequent episodes, rapid cycling, and comorbidities. Mixed depressive patients were more frequently bipolar with a family history of bipolar disorder, alcohol abuse, and suicide. A dose-response relationship was found between intradepression hypomania and several clinical features, including temperament measures. The following independent variables were associated with mixed depression: hyperthymic temperament, cyclothymic temperament, irritable temperament, and alcohol abuse. Using the narrower definition of mixed depression missed risk factors such as suicidality and comorbidities. LIMITATIONS: The following are the limitations of this study: retrospective design, recall bias, lack of sample homogeneity, no cross-validation of findings by hetero-evaluation of hypomanic symptoms. CONCLUSIONS: EPIDEP data showed the feasibility and face validity of self-assessment of intradepressive hypomania. They replicated previous findings on the severity and high suicidal risk of mixed depression profile. They confirmed, for mixed depression, that mixed states occur when mood episodes are superimposed upon temperaments of opposite polarity. They finally suggested that a definition of mixed depression only based on DSM-IV-TR hypomanic symptoms may not allow to identify the most unstable subforms of the entity.

Insight in schizophrenia: from conceptualization to neuroscience.

Lack of insight into illness is a prevalent and distinguishing feature of schizophrenia, which has a complex history and has been given a variety of definitions. Currently, insight is measured and treated as a multidimensional phenomenon, because it is believed to result from psychological, neuropsychological and organic factors. Thus, schizophrenia patients may display dramatic disorders including demoralization, depression and a higher risk of suicide, all of which are directly or indirectly related to a lack of insight into their illness, and make the treatment difficult. To improve the treatment of people with schizophrenia, it is thus crucial to advance research on insight into their illness. Insight is studied in a variety of ways. Studies may focus on the relationship between insight and psychopathology, may view behavioral outcomes or look discretely at the cognitive dysfunction versus anatomy level of insight. All have merit but they are dispersed across a wide body of literature and rarely are the findings integrated and synthesized in a meaningful way. The aim of this study was to synthesize findings across the large body of literature dealing with insight, to highlight its multidimensional nature, measurement, neuropsychology and social impact in schizophrenia. The extensive literature on the cognitive consequences of lack of insight and the contribution of neuroimaging techniques to elucidating neurological etiology of insight deficits, is also reviewed.

Investigation of impulsivity in a sample of treatment-seeking pathological gamblers: a multidimensional perspective.

Numerous studies have shown that problem gambling is characterised by lack of impulse control. However, they have often been conducted without considering the multifaceted nature of impulsivity and related psychological mechanisms. The current study aims to disentangle which impulsivity facets are altered in pathological gambling. Twenty treatment-seeking pathological gamblers (PGs) and 20 matched control participants completed a self-reported questionnaire measuring the various facets of impulsive behaviours (UPPS Impulsive Behaviour Scale), as well as two laboratory tasks assessing inhibitory control (the go-stop task) and tolerance for delayed rewards (single key impulsivity paradigm). Compared with matched controls, PGs exhibited higher urgency, lower premeditation, impairment in prepotent inhibition, and lower tolerance towards delayed rewards. Nevertheless, complementary profile analyses showed that impulsivity-related deficits found in PGs are highly heterogeneous, and that some PGs are neither impulsive in the impulsivity facets assessed nor impaired in the cognitive mechanisms measured. These findings underscore (1) the necessity to disentangle the construct of impulsivity into lower-order components and (2) that further studies should take into account, in addition to impulsivity-related mechanisms, other psychological factors potentially involved in pathological gambling.

Lithium toxicity profile: a systematic review and meta-analysis.

BACKGROUND: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium. METHODS: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity. FINDINGS: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders. INTERPRETATION: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment. FUNDING: National Institute for Health Research Programme Grant for Applied Research.

Quality of life among caregivers of individuals with affective disorders.

OBJECTIVE: The aims of this study were as follows: 1. to assess the quality of life (QoL) of caregivers of individuals with affective disorders (major depressive disorder and bipolar disorder); 2. to compare QoL levels with those observed in caregivers of individuals with schizophrenia and in the general population; 3. to determine the impact of sociodemographic and clinical factors on the caregivers' QoL. METHODS: Data were collected from the psychiatric departments of a French public teaching hospital. QoL was measured with the SF-36 questionnaire. The QoL of 232 caregivers of individuals with affective disorders was compared with 246 caregivers of individuals with schizophrenia and 232 French age-sex-matched controls. RESULTS: Caregivers of individuals with affective disorders experienced lower QoL levels than French age-sex-matched controls. The most severe impairment concerned psychological distress, social and role disability due to emotional problems (SF36-mental composite score=38.2). In contrast, caregivers of individuals with affective disorders reported higher SF36 dimension scores than caregivers of individuals with schizophrenia. Among caregivers of individuals with affective disorders, women (p=0.010), parents/family or spouse (p=0.017), caregivers living in the same home (p=0.003) and caregivers of individuals with MDD (p=0.005) were significantly associated with a lower SF36-mental composite score. CONCLUSION: The QoL of caregivers of individuals with affective disorders is seriously impaired, mainly because of an altered psychological or mental well-being and social life. QoL adds interesting and complementary information to information that has been traditionally collected (burden, stress, perceived stigma) and facilitates the identification of specific needs that should be addressed in support groups for caregivers.