Association of intracortical myelin and cognitive function in bipolar I disorder.

OBJECTIVE: Although cognitive dysfunction persists through affective and euthymic states in bipolar disorder (BD), its neurobiological correlates remain undetermined. We explore whole-cortex intracortical myelin (ICM) and cognition in BD-I and controls. METHODS: T1 -weighted images (3T) optimized for ICM measurement were analyzed using a surface-based approach. MRI signal was sampled at cortical mid-depth. Cognitive performance was measured via standardized computerized battery and paper-and-pencil Trails B. RESULTS: ICM was associated with verbal memory (VM) in BD throughout a cortical network identified with pertinence to VM function, with strongest effects in left caudal middle temporal cortex and left dorsolateral prefrontal cortex (Pcorrected  < 0.05). Subanalyses revealed specific association with correct word recognition, without delay. Processing speed, executive function, and reaction time were also predicted by ICM in BD, but not controls, although this did not survive Bonferroni correction. CONCLUSION: This is the first study to show VM association with ICM in BD. ICM has been implicated in the integrity of neural connections and neural synchrony. VM dysfunction is one of the most replicated cognitive abnormalities in BD. Therefore, these results provide a novel mechanism for understanding cognitive dysfunction in BD, which can aid in the development of targeted therapeutics to improve cognitive outcomes in BD.

The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study.

OBJECTIVE: We examined the relationship between biological rhythms and severity of depressive symptoms in subjects with bipolar disorder and the effects of biological rhythms alterations on functional impairment. METHOD: Bipolar patients (n = 260) and healthy controls (n = 191) were recruited from mood disorders programs in three sites (Spain, Brazil, and Canada). Parameters of biological rhythms were measured using the Biological Rhythms Assessment in Neuropsychiatry (BRIAN), an interviewer administered questionnaire that assesses disruptions in sleep, eating patterns, social rhythms, and general activity. RESULTS: Multivariate analyses of covariance showed significant intergroup differences after controlling for potential confounders (Pillai's F = 49.367; df = 2, P < 0.001). Depressed patients had the greatest biological rhythms disturbance, followed by patients with subsyndromal symptoms, euthymic patients, and healthy controls. Biological rhythms and HAMD scores were independent predictors of poor functioning (F = 12.841, df = 6, P < 0.001, R2  = 0.443). CONCLUSION: Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning.

Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder.

Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

Obsessive-compulsive symptoms in adults with history of rheumatic fever, Sydenham's chorea and type I diabetes mellitus: preliminary results.

OBJECTIVE: Rheumatic fever (RF) associated with Sydenham's chorea (a neurological variant of RF), but not RF without chorea, has been acutely related to obsessive-compulsive symptomatology/disorder (OCS/OCD). This study investigated the presence of OCS in adults who had RF with or without chorea in childhood. METHOD: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate OCS in 38 adults with history of RF (13 with chorea; 25 without chorea) or diabetes (controls; n = 19). RESULTS: The OCS was similar in both groups, although the intensity of symptoms was not clinically relevant. Moreover, subjects with RF with or without chorea did not score differently in the Y-BOCS. CONCLUSION: The similar occurrence of OCS in patients with history of RF and diabetes suggests that the development of this symptomatology, triggered by group A beta-haemolytic streptococcus infections, is restricted to the RF acute phase, occurred during infancy, and did not seem to predispose the appearance of OCS in adulthood.

Corpus callosum signal intensity in patients with bipolar and unipolar disorder.

BACKGROUND: Anatomical abnormalities in the corpus callosum have been reported in magnetic resonance imaging (MRI) studies in patients with bipolar but not unipolar disorder. MRI signal intensity can be used as a putative index of corpus callosum myelination. OBJECTIVES: To measure MRI signal intensity in patients with bipolar and unipolar disorder to investigate abnormalities of corpus callosum myelination. METHODS: The study involved 29 DSM-IV bipolar patients (mean (SD) age, 35 (11) years; 16 male, 13 female), 23 DSM-IV unipolar patients (41 (10) years; 4 male, 19 female), and 36 healthy controls (37 (10) years; 23 male, 13 female). A 1.5T GE Signa magnet was employed, with a fast spin echo sequence. Corpus callosum signal intensity was obtained blindly using the semiautomated software NIH Image 1.62. RESULTS: Bipolar patients had lower corpus callosum signal intensity for all callosal subregions (genu, anterior and posterior body, isthmus, splenium) than healthy controls (ANCOVA, age and sex as covariates, p<0.05). No significant differences were found between unipolar and healthy subjects (ANCOVA, age and sex as covariates, p>0.05). CONCLUSIONS: The findings suggest abnormalities in corpus callosum white matter in bipolar but not unipolar patients, possibly because of altered myelination. Such abnormalities could lead to impaired interhemispheric communication in bipolar disorder. Longitudinal MRI studies involving first episode and early onset bipolar patients will be necessary for a better understanding of the potential role of abnormalities of corpus callosum myelination in the pathophysiology of bipolar disorder.

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.

Zipf's law organizes a psychiatric ward.

We developed a simple mathematical model based on power law fitting for describing the interactions among patients from a psychiatric ward. First we defined a protocol in order to evaluate in a quantative way the state of the patient, measuring sociability/restlessness through a daily analysis of the behavior and attributing a grade for both parameters, per patient. The grades were checked by two different specialists and a table of incidence was constructed. This table generated power laws for the grades and their variations. We concluded that power laws, like Zipf's law, may be good to explain the data, showing a self-organizing process that indicates a strong interaction component determining the whole behavior. We would like to see more data being collected, in other centers and among normal populations, trying to quantify complex collective behavioral phenomena using self-organizing criticality laws.