Brain metabolic alterations in medication-free patients with bipolar disorder

BACKGROUND: Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings. OBJECTIVE: To investigate brain chemistry in medication-free individuals with BD. DESIGN: Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32 x 32, 1-cm(3) voxel matrix) acquired axially through the cingulate gyrus was used to quantify regional brain chemistry. SETTING: The Center for Anxiety and Depression at the University of Washington in Seattle and the Bipolar Research Programs at McLean Hospital and the Massachusetts General Hospital in Boston. PARTICIPANTS: Thirty-two medication-free outpatients with a diagnosis of BD type I (BDI) or BD type II (BDII), predominantly in a depressed or mixed-mood state, were compared with 26 age- and sex-matched healthy controls. MAIN OUTCOME MEASURES: Tissue type (white and gray) and regional analyses were performed to evaluate distribution of lactate; glutamate, glutamine, and gamma-aminobutyric acid (Glx); creatine and phosphocreatine (Cre); choline-containing compounds (Cho); N-acetyl aspartate; and myo-inositol. Chemical relationships for diagnosis and mood state were evaluated. RESULTS: Patients with BD exhibited elevated gray matter lactate (P =.005) and Glx (P =.007) levels; other gray and white matter chemical measures were not significantly different between diagnostic groups. Isolated regional chemical alterations were found. An inverse correlation between 17-item Hamilton Depression Rating Scale scores and white matter Cre levels was observed for BD patients. CONCLUSIONS: Gray matter lactate and Glx elevations in medication-free BD patients suggest a shift in energy redox state from oxidative phosphorylation toward glycolysis. The possibility of mitochondrial alterations underlying these findings is discussed and may provide a theoretical framework for future targeted treatment interventions.     

Barriers to the effective management of bipolar disorder: a survey of psychiatrists based in the UK and USA

Objective: To identify and prioritize barriers, challenges, and unmet needs in the management of patients with bipolar disorder, as perceived by their psychiatrists. Methods: A total of 500 US‐ or UK‐based psychiatrists were surveyed by telephone using a validated, semi‐structured questionnaire. Both preidentified and participant‐elicited barriers, challenges and unmet needs were ranked on a 0–6 point scale in four phases of management: I, entry into care; II, the manic/hypomanic phase; III, the depressive phase; and IV, the long‐term/maintenance phase. Results: Education and support for patients and families as well as earlier referral to specialist care were the highest ranked needs at entry into care. During treatment of acute episodes and long‐term management the highest ranked needs were for treatments with improved effectiveness and patient adherence, in addition to improved long‐term safety in the maintenance phase. Patients with comorbid alcohol and/or substance use disorders, followed by patients with a rapid‐cycling disease course, were rated as having the highest level of unmet need. Similarities were predominantly seen between the overall pattern of responses from UK‐ and US‐based psychiatrists. Conclusions: The highest priority items across the spectrum of treatment related to the need for clinically effective therapeutic agents with broad efficacy and favorable tolerability. At the time of initial diagnosis, patient education, family support, and earlier referral to specialist care were the highest priority needs.     

Barriers to the effective management of bipolar disorder: a survey of psychiatrists based in the UK and USA

Objective:  To identify and prioritize barriers, challenges, and unmet needs in the management of patients with bipolar disorder, as perceived by their psychiatrists.
Methods:  A total of 500 US- or UK-based psychiatrists were surveyed by telephone using a validated, semi-structured questionnaire. Both preidentified and participant-elicited barriers, challenges and unmet needs were ranked on a 0–6 point scale in four phases of management: I, entry into care; II, the manic/hypomanic phase; III, the depressive phase; and IV, the long-term/maintenance phase.
Results:  Education and support for patients and families as well as earlier referral to specialist care were the highest ranked needs at entry into care. During treatment of acute episodes and long-term management the highest ranked needs were for treatments with improved effectiveness and patient adherence, in addition to improved long-term safety in the maintenance phase. Patients with comorbid alcohol and/or substance use disorders, followed by patients with a rapid-cycling disease course, were rated as having the highest level of unmet need. Similarities were predominantly seen between the overall pattern of responses from UK- and US-based psychiatrists.
Conclusions:  The highest priority items across the spectrum of treatment related to the need for clinically effective therapeutic agents with broad efficacy and favorable tolerability. At the time of initial diagnosis, patient education, family support, and earlier referral to specialist care were the highest priority needs.     

Awareness of illness and subjective experience of cognitive complaints in patients with bipolar I and bipolar II disorder.

OBJECTIVE: The authors' goal was to investigate the awareness of illness and subjective cognitive complaints of patients with either bipolar I disorder or bipolar II disorder during a phase of clinical stabilization. METHOD: They used a structured clinical interview, the Frankfurt Complaints Questionnaire, to determine subjective cognitive complaints, and the Scale of Unawareness of Mental Disorder to assess 57 consecutively enrolled patients with bipolar I or bipolar II disorder. RESULTS: Patients with bipolar II disorder had significantly less insight and a higher level of subjective complaints of stimulus overload than patients with bipolar I disorder. CONCLUSIONS: These results suggest that a severe deficit in self-awareness may constitute a distinguishing psychopathological characteristic of patients with bipolar II disorder. Further studies are required to determine if there are associated neuropsychological dysfunctions.     

Age-specific prevalence of metabolic syndrome in Italian patients with bipolar disorder

Aim: Metabolic syndrome (MetS) is highly prevalent in patients with bipolar disorder (BD). Little research has evaluated the risk profile of MetS and cardiovascular disease in different gender and age groups in these patients. Our aim is to evaluate the prevalence of MetS in Italian patients with BD stratified by gender and age, and to determine the correlates of MetS. Methods: Subjects with BD were included and stratified by sex and age according to the following age groups: <30; 30–39; 40–49; 50–59; ≥60 years. Socio‐demographic and clinical characteristics, lifestyle information, and comorbidity for cardiovascular diseases and diabetes were collected. MetS was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. Results: MetS was evaluated in 200 patients, with a prevalence of 26.5%. Men had higher rates of hypertension and hypertriglyceridemia, women had more abdominal obesity. Women had a peak of prevalence in the ≥60 years group, while men displayed high rates even in the young age groups. In young patients, MetS was associated with Cluster B personality disorders and less physical exercise. Conclusion: Our paper highlights the importance of evaluating MetS even in young patients with bipolar disorder, especially males. The strong association with lack of physical exercise suggests that the implementation of healthy behaviors might be relevant in order to prevent MetS and future adverse cardiovascular outcomes.     

重性抑郁障碍与双相障碍患者躯体疾病共病调查

目的:了解重性抑郁障碍(MDD)与双相障碍(BD)患者躯体疾病共病情况。方法:对141例MDD和52例BD患者进行一般情况、躯体疾病调查及精神疾病评估。结果:MDD和BD患者躯体疾病的共病率分别为68.1%、46.2%,共病的躯体疾病以慢性病为主,依次为高血压、慢性胃炎、腰椎间盘突出、糖尿病。与非共病患者比较,共病患者年龄及起病年龄大,精神疾病复发次数多(P0.05或P0.01)。MDD共病患者自杀意念风险明显增加(P0.01)。结论:较高龄及较高龄起病的MDD、BD患者更易共病慢性躯体疾病。     

Awareness of illness in patients with bipolar I disorder with or without comorbid anxiety disorders

BACKGROUND: The present study examined whether specific types of comorbid anxiety disorders, namely panic disorder (PD), social phobia (SP) and obsessive-compulsive disorder (OCD) are differentially associated with course variables and insight into bipolar illness. METHOD: The sample consisted of 151 consecutively hospitalized patients with bipolar I disorder. They were assessed in the week prior to discharge using the Structured Clinical Interview for DSM-III-R (SCID-P), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF) and the Hopkins Symptom Checklist (HSCL-90). Level of insight was assessed with the Scale to assess Unawareness of Mental Disorders (SUMD). RESULTS: Of the 151 bipolar subjects, 92 had no PD, SP and OCD comorbidity, 35 had PD and 24 had SP and/or OCD. The three groups differed significantly on the current awareness of illness and treatment response scores and the retrospective awareness of illness and treatment response scores. Post-hoc analyses revealed that, compared with bipolar patients without PD/SD/OCD and those with comorbid PD, patients with comorbid SP and/or OCD had better insight on current awareness of illness, current awareness of treatment response, retrospective awareness of illness and retrospective awareness of treatment response. The regression analysis showed that the presence of no panic type anxiety comorbidity was a predictor of good insight. CONCLUSIONS: These data indicate the value of identifying comorbid anxiety disorders in patients with bipolar illness. The results could be interpreted as evidence of discrete disorders within the bipolar spectrum, one that is characterized by, among other things, SP and/or OCD with good insight, another characterized by PD with poor insight.     

Social anxiety disorder comorbidity in patients with bipolar disorder: a clinical replication

BACKGROUND: The authors investigated frequency, clinical correlates and onset temporal relationship of social anxiety disorder (SAD) in adult patients with a diagnosis of bipolar I disorder. METHODS: Subjects were 189 patients whose diagnoses were assessed by the Structured Clinical Interview for DSM-III-R-Patient Version. RESULTS: Twenty-four patients (12.7%) met DSM-III-R criteria for lifetime SAD; of these, 19 (10.1% of entire sample) had SAD within the last month. Significantly more bipolar patients with comorbid SAD also had substance use disorders compared to those without. On the HSCL-90, levels of interpersonal sensitivity, obsessiveness, phobic anxiety and paranoid ideation were significantly higher in bipolar patients with SAD than in those without. Bipolar patients with comorbid SAD recalled separation anxiety problems (school refusal) more frequently during childhood than those without. Lifetime SAD comorbidity was associated with an earlier age at onset of syndromal bipolar disorder. Pre-existing OCD tended to delay the onset of bipolarity. CONCLUSIONS: Social anxiety disorder comorbidity is not rare among patients with bipolar disorder and is likely to affect age of onset and phenomenology of bipolar disorder. These findings may influence treatment planning and the possibility of discovering a pathophysiological relationship between SAD and bipolarity.     

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.     

Health concerns in patients with obsessive-compulsive disorder

In the present study, individuals with obsessive-compulsive disorder (OCD) who also had excessive health concerns (n = 56) were compared with OCD individuals without such concerns (n = 343) regarding their OCD symptom severity, types of obsessions and compulsions, insight into the irrationality of their obsessions, and prevalence of generalized anxiety disorder. While the presence of health concerns did not affect the severity of OCD symptoms, the groups differed with respect to the types of symptoms displayed: those with health concerns had more somatic and harm obsessions, and checking compulsions: whereas those without such concerns had more contamination obsessions and washing compulsions. The insight of both groups ranged from poor to excellent, yet the number of individuals with poor insight was greater among those with health concerns than those without. Generalized anxiety disorder was also more prevalent among OCD individuals with excessive health concerns.     

The Maudsley bipolar disorder project. A survey of psychotropic prescribing patterns in bipolar I disorder

Objectives:  The outcome of Bipolar 1 Disorder (BD1) is greatly dependent on the adequacy and appropriateness of its treatment. As the treatment choices in BD1 disorder are increasing the aim of this study was to examine the current use of the pharmacological agents in BD1 patients and its association with clinical characteristics.
Methods:  Case note review of the pharmacotherapy of a sample of BD1 patients from a specified South London sector of a National Health Service Trust.
Results:  Half of the patients were on mood-stabilizers (usually lithium) and their use was associated with female gender and multiple admissions. Antipsychotics were more commonly used in patients with psychotic features and multiple manic episodes. Antidepressants were rarely prescribed alone and were not associated with increased number of manic episodes. Combination treatments were mostly used in patients in acute episodes and with multiple hospitalizations.
Conclusions:  In ordinary care, the treatment of BD1 is often driven by symptoms and falls short of the existing practice guidelines.     

Psychopharmacological treatment status in outpatients with bipolar disorder: a clinical survey in Germany

Objective

The objective of this epidemiological study was to evaluate the current treatment status as well as the acceptance of medication and satisfaction with life in outpatients with bipolar disorder in Germany.

Methods

Data for this cross-sectional epidemiologic survey was collected between February 15th, 2006 and May 31st, 2006. Three hundreds six bipolar euthymic outpatients under routine treatment conditions were included in the study. Forty one practicing psychiatrists used a clinical interview to evaluate the current treatment status, acceptance of current medication, and current life satisfaction.

Results

The majority of patients suffered from "pure" bipolar-II-disorder (50.6%), followed by 23.0% with "pure" bipolar-I-disorder. Apart from these patients, 12.9% of all participants had a history of mixed episodes and 5.6% a history of rapid cycling. Mean duration of bipolar disorder was 10.6 years. The majority of patients (54.3%) received psychopharmacological monotherapy. Combination therapy was administered in 45.9% of the patients, 39.3% receiving two agents, and 6.6% three agents. Antidepressants (64.1%) were the most common combination medications. Monotherapy was used preferably in bipolar-I- (62.7%) and bipolar-II-disorders (56.2%), combination therapy predominantly in patients with a history of mixed episodes (57.7%) and rapid cycling (55.0%). Half of the patients (49.2%) were able to hold an occupation. 84.2% of all patients were satisfied with their medication. Overall, patients evaluated their life satisfaction between "good" and "satisfactory" (2.69 according to German school grades where 1 is the highest and 6 the lowest mark). Patients receiving lithium, valproate or antidepressants as monotherapy rated above the mean, patients with combination therapy, carbamazepine monotherapy or medications summarized as "others" rated below the mean.

Conclusion

Most of the German outpatients received a pharmacotherapy that is recommended in the guidelines of bipolar disorder. The use of (atypical) antipsychotics was low. Conversely, the incidence of treatment with tricyclic antidepressants (not guideline compatible), was observed to be relatively high. Irrespective of their medication, in Germany patients with bipolar disorder show a high acceptance of their pharmacotherapy, and rate their life satisfaction as high. Nonetheless, half of the evaluated patients were not able to pursue a profession. Besides the disease age, gender and family life e.g., child care may also play a confounding role regarding the unemployment statistics.     

Decreased pituitary volume in patients with bipolar disorder.

BACKGROUND: Neuroendocrinologic investigations in bipolar disorder have suggested abnormalities in pituitary function. However, few imaging studies have evaluated possible anatomical differences in this brain structure in mood disorder patients. Our aim was to examine potential abnormalities in pituitary volume in patients with bipolar and in a comparison group of patients with unipolar disorder. METHODS: We measured the volumes of the pituitary gland in 23 patients with bipolar disorder (mean +/- s.d. = 34.3 +/- 9.9 years) and 13 patients with unipolar disorder (41.2 +/- 9.6 years), and 34 healthy control subjects (36.6 +/- 9.6 years) using 1.5 mm thick T1-weighted coronal 1.5 T MRI images. All measurements were done blindly by a trained rater. RESULTS: Patients with bipolar disorder had significantly smaller pituitary volumes than healthy control subjects (mean volume +/- s.d. = 0.55 +/- 0.15 ml and 0.68 +/- 0.20 ml, respectively; ANCOVA, F = 8.66, p = 0.005), and than patients with unipolar disorder (0.70 +/- 0.12 ml, F = 5.98, p = 0.02). No differences were found between patients with unipolar disorder and healthy control subjects (F = 0.01, p = 0.91). CONCLUSIONS: To our knowledge, this is the first study that reports smaller pituitary volumes in bipolar disorder. Our findings suggest that detectable abnormalities in pituitary size are present in patients with bipolar disorder, which may reflect a dysfunctional HPA axis.     

Improvements in metabolic abnormalities among overweight schizophrenia and bipolar disorder patients

PurposeAs weight-gain and metabolic abnormalities during treatment with psychotropic drugs are of great concern, we evaluated effects of psycho-education and medical monitoring on metabolic changes among severely mentally ill patients.Materials and methodsDuring repeated, systematic psycho-education about general health among 66 consecutive patients diagnosed with DSM-IV-TR schizophrenia (n = 33) or type-I bipolar disorder (n = 33), we evaluated (at intake 1, 2, 3, and 6 months) clinical psychiatric status, treatments and doses, recorded physiological parameters, and assessed attitudes about medication.ResultsAt intake, patients with schizophrenia vs bipolar disorder were receiving 3–7 times more psychotropic medication, with 14% higher initial body-mass index (BMI: 29.1 vs 25.6 kg/m2), 12 times more obesity, and significantly higher serum lipid concentrations. During 6-months follow-up, among bipolar disorder patients, polytherapy and serum lipid concentrations declined more than among schizophrenia patients (e.g., total cholesterol + triglycerides, by 3.21 vs 1.75%/month). BMI remained stable. Declining lipid levels were associated with older age, bipolar disorder, being unemployed, higher antipsychotic doses, and lower initial BPRS scores (all P ≤ 0.001).ConclusionsPsychotropic treatments were more complex, and metabolic measures more abnormal among bipolar disorder than schizophrenia patients. Intensive psycho-education, clinical monitoring, and encouragement of weight-control for six months were associated with improvements in metabolic measures (but not to BMI), and more realistic attitudes about medication.     

Medical monitoring in patients with bipolar disorder: a review of data

Patients with bipolar disorder have been found to have high rates of endocrine and cardiovascular disorders as well as obesity. Some health problems may be influenced by the psychiatric disorder itself, and, similarly, health problems may influence the course of bipolar disorder. Further, some pharmacologic treatments used for bipolar disorder have been associated with obesity, diabetes, hyperglycemia, dyslipidemia, metabolic syndrome, prolonged QTc, and thyroid dysfunction. To optimize care and achieve the best possible treatment outcomes, integrated psychiatric and medical care is needed.     

Serum lipids, metabolic syndrome and lifetime suicide attempts in patients with bipolar disorder

Obesity in children and adolescents is a worldwide health problem, characterized by various somatic, psychosocial and psychiatric complications, and is often associated with adult obesity and related complications. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding behavior, food intake regulation, energy metabolism and weight control. A common polymorphism of the BDNF genotype (Val66Met) has been associated with various forms of eating disorders, alterations in body mass index (BMI) values and obesity in adult populations. The aim of this study was to determine the association between the gene variants of the BDNF Val66Met polymorphism and obesity in 300 healthy Caucasian children and adolescents of the same ethnic background of Croatian origin, subdivided according to the BMI percentile, but without any form of eating disorders. The frequency of the Met/Met, Met/Val and Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met and Met/Val genotypes versus the homozygous Val/Val genotype) differed significantly between underweight, normal weight, overweight and obese children, and the presence of one or two Met alleles contributed to this significant effect. These results showed for the first time the significant association between the presence of one or two Met alleles and obesity in ethnically homogenous groups of healthy Caucasian children and adolescents. These data confirmed the major role of BDNF in energy metabolism, food regulation and BMI.     

Adult bipolar disorder is continuous with pediatric bipolar disorder.

Considerable debate exists regarding the continuity of bipolar disorder (BD) in children and adolescents. Do affected children continue to have BD as adults? Are pediatric forms of BD distinct from adult forms of the disorder? Here, I argue that, in fact, strictly defined BD I and II in children and adolescents is continuous with adult BD. First, if we take developmental differences into account, children and adults share similar symptoms, since they are both diagnosed according to DSM-IV criteria. Next, retrospective studies indicate that 50% to 66% of adults with BD had onset of their disorder before age 19 years. Early prospective data indicate that adolescents with BD progress to become young adults with BD. Further, family studies of pediatric BD probands find high rates of BD in adult relatives, and pediatric offspring of parents with BD have elevated rates of BD, compared with control subjects. Finally, biological characteristics of pediatric BD (such as treatment response, neurobiology, and genetics) are either shared with adults having BD or fit logically into developmental models of BD. Thus, while not conclusive, a preponderance of data support the hypothesis that pediatric BD is continuous with adult BD. Prospective studies incorporating phenomenological and biological assessment are needed to decisively address this issue.