Cobalamin deficiency resulting in a rare haematological disorder: a case report.

INTRODUCTION: We present the case of a patient with a cobalamin deficiency resulting in pancytopaenia, emphasizing the importance to define, diagnose and treat cobalamin deficiency. CASE PRESENTATION: A 52-year-old man from the Democratic Republic of Congo presented to the emergency department with shortness of breath and a sore tongue. Physical examination was unremarkable. His haemoglobin was low and the peripheral blood smear revealed pancytopaenia with a thrombotic microangiopathy. The findings were low cobalamin and folate levels, and high homocysteine and methylmalonate levels. Pernicious anaemia with chronic atrophic gastritis was confirmed by gastric biopsy and positive antiparietal cell and anti-intrinsic factor antibodies. Cobalamin with added folate was given. Six months later, the patient was asymptomatic. CONCLUSION: Cobalamin deficiency should always be ruled out in a patient with pancytopaenia. Our case report highlights a life-threatening cobalamin deficiency completely reversible after treatment.

Depressive disorder moderates the effect of the FTO gene on body mass index.

There is evidence that obesity-related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to body mass index (BMI) in two independent samples of major depressive disorder (MDD) cases and controls. We analysed 88 polymorphisms in the FTO gene in a clinically ascertained sample of 2442 MDD cases and 809 controls (Radiant Study). In all, 8 of the top 10 single-nucleotide polymorphisms (SNPs) showing the strongest associations with BMI were followed-up in a population-based cohort (PsyCoLaus Study) consisting of 1292 depression cases and 1690 controls. Linear regression analyses of the FTO variants and BMI yielded 10 SNPs significantly associated with increased BMI in the depressive group but not the control group in the Radiant sample. The same pattern was found in the PsyCoLaus sample. We found a significant interaction between genotype and affected status in relation to BMI for seven SNPs in Radiant (P<0.0057), with PsyCoLaus giving supportive evidence for five SNPs (P-values between 0.03 and 0.06), which increased in significance when the data were combined in a meta-analysis. This is the first study investigating FTO and BMI within the context of MDD, and the results indicate that having a history of depression moderates the effect of FTO on BMI. This finding suggests that FTO is involved in the mechanism underlying the association between mood disorders and obesity.

Anterior cingulate cortex pathology in schizophrenia and bipolar disorder.

To explore possible morphological abnormalities in the dorsal and subgenual parts of anterior cingulate cortex in mood disorders and schizophrenia, we performed a quantitative postmortem study of 44 schizophrenic patients, 21 patients with sporadic bipolar disorder, 20 patients with sporadic major depression, and 55 age- and sex-matched control cases. All individuals were drug naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Neuron densities and size were estimated on cresyl violet-stained sections using a stereological counting approach. The distribution and density of microtubule-associated (MAP2, MAP1b) and tau proteins were assessed by immunocytochemistry and quantitative immunodot assay. Mean total and laminar cortical thicknesses as well as mean pyramidal neuron size were significantly decreased in the dorsal and subgenual parts of areas 24 (24sg) in schizophrenic cases. Patients with bipolar disorder showed a substantial decrease in laminar thickness and neuron densities in layers III, V, and VI of the subgenual part of area 24, whereas patients with major depression were comparable to controls. Immunodot assay showed a significant decrease of both MAP2 and MAP1b proteins in bipolar patients but not in patients with schizophrenia and major depression. The neuroanatomical and functional significance of these findings are discussed in the light of current hypotheses regarding the role of areas 24 and 24sg in schizophrenia and bipolar disorder.

DSM-IV and DSM-5 alcohol use disorder among young Swiss men.

BACKGROUND AND AIMS: Previous studies suggest that the new DSM-5 criteria for alcohol use disorder (AUD) will increase the apparent prevalence of AUD. This study estimates the 12-month prevalence of AUD using both DSM-IV and DSM-5 criteria and compares the characteristics of men in a high risk sample who meet both, only one and neither sets of diagnostic criteria. DESIGN, SETTING AND PARTICIPANTS: 5943 Swiss men aged 18-25 years who participated in the Cohort Study on Substance Use Risk Factors (C-SURF), a population-based cohort study recruited from three of the six military recruitment centres in Switzerland (response rate = 79.2%). MEASUREMENTS: DSM-IV and DSM-5 criteria, alcohol use patterns, and other substance use were assessed. FINDINGS: Approximately 31.7% (30.5-32.8) of individuals met DSM-5 AUD criteria [21.2% mild (20.1-22.2); 10.5% moderate/severe (9.7-11.3)], which was less than the total rate when DSM-IV criteria for alcohol abuse (AA) and alcohol dependence (AD) were combined [36.8% overall (35.5-37.9); 26.6% AA (25.4-27.7); 10.2% AD (9.4-10.9)]. Of 2479 respondents meeting criteria for either diagnoses, 1585 (63.9%) met criteria for both. For those meeting DSM-IV criteria only (n = 598, 24.1%), hazardous use was most prevalent, whereas the criteria larger/longer use than intended and tolerance to alcohol were most prevalent for respondents meeting DSM-5 criteria only (n = 296, 11.9%). Two in five DSM-IV alcohol abuse cases and one-third of DSM-5 mild AUD individuals fulfilled the diagnostic criteria due to the hazardous use criterion. The addition of the craving and excluding of legal criterion, respectively, did not affect estimated AUD prevalence. CONCLUSIONS: In a high-risk sample of young Swiss males, prevalence of alcohol use disorder as diagnosed by DSM-5 was slightly lower than prevalence of DSM-IV diagnosis of dependence plus abuse; 63.9% of those who met either criterion met criteria for both.

The alpha1b-adrenergic receptor subtype: molecular properties and physiological implications.

The aim of this review is to summarize some of the main findings from our laboratory as well as from others concerning the biochemical, molecular, and functional properties of the alpha1b-adrenergic receptor. Experimental and computational mutagenesis of the alpha1b-adrenergic receptor have been instrumental in elucidating some of the molecular mechanisms underlying receptor activation and receptor coupling to Gq. The knockout mouse model lacking the alpha1b-adrenergic receptor has highlighted the potential implication of this receptor subtype in variety of functions including the regulation of blood pressure, glucose homeostasis, and the rewarding response to drugs of abuse.

Observer-rated Coping Associated with Borderline Personality Disorder: An Exploratory Study.

BACKGROUND: Little is known about coping specificities, as operationalization of the concept of affect regulation, in borderline personality disorder (BPD). It is most important to take into account methodological criticisms addressed to the self-report questionnaire approach and to compare BPD coping specificities to the ones of neighbouring diagnostic categories, such as bipolar disorder (BD). SAMPLING AND METHODS: The present exploratory study compared the coping profiles of N = 25 patients presenting BPD to those of N = 25 patients presenting BD and to those of N = 25 healthy controls. All participants underwent a clinical interview that was transcribed and rated using the Coping Patterns observer-rater system. RESULTS: Results partially confirmed study hypotheses and showed differences between BPD patients and healthy controls in all coping domains (competence, resources and autonomy), whereas the only coping domain presenting a BPD-specific lack of skills, compared with the BD patients, was autonomy, a set of coping strategies facing stress appraised as challenge. These coping processes were linked to general and BPD symptomatology. CONCLUSIONS: These results extend conclusions of earlier studies on affect regulation processes in BPD and bear important clinical implications, in the context of dialectical behavior therapy and other therapeutic approaches. Limitations of this exploratory study, such as the small sample size, are acknowledged. Copyright © 2012 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Coping can be reliably assessed in the narrative process in an non-structured interview frame. Patients with borderline personality disorder present with a specific lack of skills in affect regulation related to autonomy issues, compared to patients with bipolar disorder and healthy controls. Lack of skills in accommodation to distressing emotions in borderline personality disorder is related to symptom gravity and may be treated using radical acceptance strategies.

Cognitive errors assessed by observer ratings in bipolar affective disorder: relationship with symptoms and therapeutic alliance

The construct of cognitive errors is clinically relevant for cognitive therapy of mood disorders. Beck's universality hypothesis postulates the relevance of negative cognitions in all subtypes of mood disorders, as well as positive cognitions for manic states. This hypothesis has rarely been empirically addressed for patients presenting bipolar affective disorder (BD). In-patients (n = 30) presenting with BD were interviewed, as were 30 participants of a matched control group. Valid and reliable observer-rater methodology for cognitive errors was applied to the session transcripts. Overall, patients make more cognitive errors than controls. When manic and depressive patients were compared, parts of the universality hypothesis were confirmed. Manic symptoms are related to positive and negative cognitive errors. These results are discussed with regard to the main assumptions of the cognitive model for depression; thus adding an argument for extending it to the BD diagnostic group, taking into consideration specificities in terms of cognitive errors. Clinical implications for cognitive therapy of BD are suggested.

Physiological response to whole-body vibration in athletes and sedentary subjects.

Whole-body vibration (WBV) is a new exercise method, with good acceptance among sedentary subjects. The metabolic response to WBV has not been well documented. Three groups of male subjects, inactive (SED), endurance (END) and strength trained (SPRINT) underwent a session of side-alternating WBV composed of three 3-min exercises (isometric half-squat, dynamic squat, dynamic squat with added load), and repeated at three frequencies (20, 26 and 32 Hz). VO(2), heart rate and Borg scale were monitored. Twenty-seven healthy young subjects (10 SED, 8 SPRINT and 9 END) were included. When expressed in % of their maximal value recorded in a treadmill test, both the peak oxygen consumption (VO(2)) and heart rate (HR) attained during WBV were greatest in the SED, compared to the other two groups (VO(2): 59.3 % in SED vs 50.8 % in SPRINT and 48.0 % in END, p<0.01; HR 82.7 % in SED vs 80.4 % in SPRINT and 72.4 % in END, p<0.05). In conclusions, the heart rate and metabolic response to WBV differs according to fitness level and type, exercise type and vibration frequency. In SED, WBV can elicit sufficient cardiovascular response to benefit overall fitness and thus be a potentially useful modality for the reduction of cardiovascular risk.

Familiality and SNP heritability of age at onset and episodicity in major depressive disorder.

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Understanding Van Gogh's Night: bipolar disorder

Vincent Van Gogh (1853-1890) imparted in his art a deep essence of life, and in such a unique way that many would say it is possible to experience it vicariously by looking at his paintings even once. In 10 years, while exerting mental and physical efforts that may well have contributed to his premature death, he produced an impressive number of masterpieces. However, the specific neurological disorder Van Gogh suffered and how this may have influenced his art is still not clear. The combination of his eccentric personality, irascible temper, unstable moods and prolific creativity, makes the understanding of his illness a very complex endeavor and therefore poses a great challenge to those who investigate the relationships between the 'artistic mind', the brain and illness. In fact, most of the diagnoses (nearly 30) proposed for Van Gogh, during the last century, are not based on medical evidence but are ascertainable from analyses of his paintings and biographical data. Although no definitive diagnosis can be made based on such evidence, we conclude that according to DSM-IV criteria and findings extrapolated from his letters, Van Gogh is most likely to have suffered a bipolar disorder, affective or schizoaffective, which caused his death by suicide.