Cerebellar volume in schizophrenia and bipolar I disorder with and without psychotic features.

OBJECTIVE: There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder. METHOD: One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates. RESULTS: Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. CONCLUSION: Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.

Affect intensity measure in bipolar disorders: a multidimensional approach.

BACKGROUND: Emotional dysregulation, characterized by high levels of both arousal and intensity of emotional responses, is a core feature of bipolar disorders (BDs). In non-clinical populations, the 40-item Affect Intensity Measure (AIM) can be used to assess the different dimensions of emotional reactivity. METHODS: We analyzed the factor structure of the AIM in a sample of 310 euthymic patients with BD using Principal Component Analysis and examined associations between AIM sub-scale scores and demographic and illness characteristics. RESULTS: The French translation of the AIM demonstrated good reliability. A four-factor solution similar to that reported in non-clinical samples (Positive Affectivity, Unpeacefulness [lack of Serenity], Negative Reactivity, Negative Intensity), explained 47% of the total variance. Age and gender were associated with Unpeacefulness and Negative reactivity respectively. 'Unpeacefulness' was also positively associated with psychotic symptoms at onset (p=0.0006), but negatively associated with co-morbid substance misuse (p=0.008). Negative Intensity was positively associated with social phobia (p=0.0005). LIMITATIONS: We cannot definitively exclude a lack of statistical power to classify all AIM items. Euthymia was carefully defined, but a degree of 'contamination' of the self-reported levels of emotion reactivity may occur because of subsyndromal BD symptoms. It was not feasible to control for the possible impact of on-going treatments. CONCLUSIONS: The AIM scale appears to be a useful measure of emotional reactivity and intensity in a clinical sample of patients with BD, suggesting it can be used in addition to other markers of BD characteristics and sub-types.

Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder.

INTRODUCTION: Cytomegalovirus (CMV) is a member of the herpesviridae family that has a limbic and temporal gray matter tropism. It is usually latent in humans but has been associated with schizophrenia, bipolar disorder and cognitive deficits in some populations. Hippocampal decreased volume and dysfunction play a critical role in these cognitive deficits. We hypothesized that CMV seropositivity and serointensity would be associated with hippocampal volume and cognitive functioning in patients with schizophrenia or bipolar disorder. METHODS: 102 healthy controls, 118 patients with bipolar disorder and 69 patients with schizophrenia performed the California Verbal Learning Test (CVLT) and had blood samples drawn to assess CMV IgG levels. A subgroup of 52 healthy controls, 31 patients with bipolar disorder and 27 patients with schizophrenia underwent T1 MRI for hippocampal volumetry. We analyzed the association between CMV serointensity and seropositivity with hippocampal volume. We also explored the correlation between CMV serointensity and seropositivity and CVLT scores. RESULTS: In both patient groups but not in controls, higher CMV serointensity was significantly associated with smaller right hippocampal volume. Further, in the group of patients with schizophrenia but not bipolar disorder, CMV serointensity was negatively correlated with CVLT scores. CONCLUSION: CMV IgG titers are associated with decreased hippocampal volume and poorer episodic verbal memory in patients with schizophrenia or bipolar disorder. The mechanism of this association warrants further exploration.

[Emotional reactivity: a tool for diagnosis?]. / La réactivité émotionnelle: un outil diagnostic?

Emotional reactivity can be defined regarding the threshold needed to induce emotion and the amplitude of emotional response. In bipolar disorder, emotional dysregulations can be observed, sometimes related to mood. Description of emotional reactivity can contribute to the characterization of the different phases of bipolar disorder. During manic or mixed episodes, emotional reactivity is increased. Bipolar depression is a heterogeneous entity and emotional reactivity can help to characterize it and to define the most adequate therapeutic. Exploration of emotional reactivity can be helpful to understand pathophysiology of the different Thymic states observed in Bipolar disorder.

Preattentional processes and disorganization in schizophrenia: Influence of a 6-week risperidone treatment.

INTRODUCTION: Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls. METHODS: Ten unmedicated (nine naïve) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). RESULTS: At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost. CONCLUSION: Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia.

Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects.

OBJECTIVE: Only a few studies have examined specifically the neuropsychological performance of schizoaffective patients. METHOD: The sample consisted of 34 euthymic DSM-IV schizoaffective patients, who were compared with 41 euthymic bipolar patients without history of psychotic symptoms and 35 healthy controls. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. Patients were compared with several clinical, occupational, and neuropsychological variables such as executive function, attention, verbal and visual memory and the two groups were contrasted with 35 healthy controls on cognitive performance. The three groups were compared using mancova after checking the potential role of several co-variables. RESULTS: Schizoaffective patients showed greater impairment than controls and bipolar patients, in several domains, including verbal memory, executive function, and attentional measures. Bipolar patients without history of psychosis performed similar to the controls except for verbal fluency. CONCLUSION: Schizoaffective disorder carries more neurocognitive impairment than non-psychotic bipolar disorder and more occupational difficulties.

Functional outcome in bipolar disorder: the role of clinical and cognitive factors.

INTRODUCTION: Few studies have examined the clinical, neuropsychological and pharmacological factors involved in the functional outcome of bipolar disorder despite the gap between clinical and functional recovery. METHODS: A sample of 77 euthymic bipolar patients were included in the study. Using an a priori definition of low versus good functional outcome, based on the psychosocial items of the Global Assessment of Functioning (GAF, DSM-IV), and taking also into account their occupational adaptation, the patients were divided into two groups: good or low occupational functioning. Patients with high (n = 46) and low (n = 31) functioning were compared on several clinical, neuropsychological and pharmacological variables and the two patient groups were contrasted with healthy controls (n = 35) on cognitive performance. RESULTS: High- and low-functioning groups did not differ with respect to clinical variables. However, bipolar patients in general showed poorer cognitive performance than healthy controls. This was most evident in low-functioning patients and in particular on verbal memory and executive function measures. CONCLUSIONS: Low-functioning patients were cognitively more impaired than highly functioning patients on verbal recall and executive functions. The variable that best predicted psychosocial functioning in bipolar patients was verbal memory.

What really matters to bipolar patients' caregivers: sources of family burden.

BACKGROUND: Identifying and modifying burdensome aspects might reduce the level of burden and their negative effects both on caregivers and patients' outcome. Most studies evaluate acutely ill patients, whereas the most relevant problems may be related to subthreshold symptoms and long-term outcome. The aims of the present study were to assess caregiver's subjective burden, to analyse which were the most burdensome aspects for caregivers and to study which variables could explain the caregiver's subjective burden. METHODS: Caregivers of 86 euthymic bipolar patients completed the subjective burden subscale from an adapted version of the Social Behaviour Assessment Schedule. RESULTS: Caregivers showed a moderate level of subjective burden. The highest levels of distress were reported regarding the patient's behaviour; the most distressing behaviours were hyperactivity, irritability, sadness and withdrawal. Regarding the patient's role performance, the most worrying aspects were those associated with the patient's work or study and social relationships. Regarding adverse effects on others, caregivers were especially distressed by the way the illness had affected their emotional health and their life in general. Poorer social and occupational functioning, an episode in the last 2 years, history of rapid cycling and the caregiver being responsible for medication intake explained a quarter of the variance of the caregiver's subjective burden. LIMITATIONS: This was a cross-sectional study focused only on primary caregivers, there was no control group of non-bipolar patients. CONCLUSIONS: This study provides relevant data concerning the burden of caregivers of stable bipolar patients, pointing at potential targets for psychosocial interventions.

Clinical and therapeutic implications of predominant polarity in bipolar disorder.

BACKGROUND: To determine the clinical and therapeutic relevance of longitudinally predominant polarity for bipolar disorders long-term outcome. METHOD: Two hundred twenty-four patients (n=224) were enrolled for the study in the Bipolar Disorders Program of Barcelona, which provides integrated care for difficult-to-treat bipolar patients derived from all over Spain, but also provides clinical care to all bipolar patients coming from a specific catchment area (Eixample Esquerre) in Barcelona. Data collection regarding predominant polarity started on October 1994 and lasted for the following ten years. Patients were divided according to the predominance of depressive or manic/hypomanic episodes. The two groups were compared regarding clinical and sociodemographic variables. RESULTS: 135 patients (60.3%) were classified as Depressive Polarity, whilst 89 (39.7%) were considered as Manic Polarity. Manic Polarity was more prevalent amongst bipolar I patients than bipolar II. Depressive Polarity was strongly associated with depressive onset of bipolar disorder. Lifetime history of attempted suicide was strongly associated with Depressive Polarity, who also had a higher mean number of suicide attempts. As for therapeutic issues, acute and maintenance use of atypical antipsychotics and conventional neuroleptics were more common amongst Manic Polarity whilst antidepressants and lamotrigine use was highly prevalent amongst Depressive Polarity. CONCLUSIONS: Prevention of depression is crucial for the maintenance treatment of bipolar II patients, whilst prevention of mania and depression would be equally important in the case of bipolar I patients. Predominant polarity is a valid prognostic parameter with therapeutic implications.

Effects of lithium on saccadic eye movements in healthy subjects in a ten-day double-blind placebo-controlled cross-over pilot study.

INTRODUCTION: Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. METHODS: A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. RESULTS: There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. CONCLUSION: The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.

Hypothalamic-pituitary-adrenal axis and bipolar disorder.

There is robust evidence demonstrating abnormalities of the HPA axis in bipolar disorder. Hypercortisolism may be central to the pathogenesis of depressive symptoms and cognitive deficits, which may in turn result from neurocytotoxic effects of raised cortisol levels. Manic episodes may be preceded by increased ACTH and cortisol levels, leading to cognitive problems and functional impairments. Identification and effective treatment of mood and cognitive symptoms of mood disorders are clinical goals, but currently available treatments may fall short of this ideal. Manipulation of the HPA axis has been shown to have therapeutic effects in preclinical and clinical studies, and recent data suggest that direct antagonism of GRs maybe a future therapeutic strategy in the treatment of mood disorders.

Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome.

OBJECTIVE: Cognitive impairment in bipolar disorder may be a stable characteristic of the illness, although discrepancies have emerged with regard to what dysfunctions remain during remission periods. The aim of this study was to ascertain whether euthymic bipolar patients would show impairment in verbal learning and memory and in executive functions compared with healthy controls. Secondly, to establish if there was a relationship between clinical data and neuropsychological performance. METHODS: Forty euthymic bipolar patients were compared with 30 healthy controls through a battery of neuropsychological tests assessing estimated premorbid IQ, attention, verbal learning and memory, and frontal executive functioning. The effect of subsyndromal symptomatology was controlled. RESULTS: Remitted bipolar patients performed worse than controls in several measures of memory and executive function, after controlling for the effect of subclinical symptomatology, age and premorbid IQ. Verbal memory impairment was related to global assessment of function scores, as well as to a longer duration of illness, a higher number of manic episodes, and prior psychotic symptoms. CONCLUSIONS: Results provide evidence of neuropsychological impairment in euthymic bipolar patients, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions. Cognitive impairment seems to be related to a worse clinical course and poor functional outcome.

Impairment of predictive saccades in schizophrenia.

Using infrared oculography, we compared saccades toward predictable and pseudo-random visual targets in 19 neuroleptic-free patients with schizophrenia (including 13 neuroleptic-naïve patients) and in 29 age- and gender-matched healthy volunteers. Externally driven saccades were not different between patients and controls, whether or not the target was predictable. Anticipated saccades were specifically less accurate in the patients compared to the controls. The difference between primary gain of anticipated and non-anticipated saccades was markedly higher in the patients compared to controls (p=0.003). These results point to a deficit in the early step of internally driven oculomotor planning in schizophrenia.

[Immunity to measles, mumps and rubella in children vaccinated with triple viral vaccine]. / Inmunidad frente a sarampión, rubéola y parotiditis en niños vacunados con la triple vírica.

OBJECTIVE: To check up on measles-mumps-rubella immunity in children vaccinated with MMR vaccine. DESIGN: A descriptive cross-sectional study trough seroepidemiological survey. SETTING: Oliver-Miralbueno Health Centre, Zaragoza. PATIENTS: 92 healthy children of 5, 7 and 9 years of age who went for clinical preventive services. All of them vaccinated with MMR at the age of 15 to 18 months. None of them had suffered from measles, mumps or rubella. MEASUREMENTS AND MAIN RESULTS: 1) The percentage of seronegative children (title less than 1:8) was: 9.8% for measles, 8.7% for rubella, and 27.2% for mumps. 2) As to the time differences among seropositive and seronegative children. CONCLUSIONS: The study reveals that there is a high percentage of MMR vaccinated children showing minimal or undetectable levels of antibodies.