Maria J. Portella

Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression

Deep brain stimulation (DBS) is currently tested as an experimental therapy for patients with treatment-resistant depression (TRD). Here we report on the short- and long-term (1 yr) clinical outcomes and tolerance of DBS in eight TRD patients. Electrodes were implanted bilaterally in the subgenual cingulate gyrus (SCG; Broadman areas 24-25), and stimulated at 135 Hz (90-μs pulsewidth). Voltage and active electrode contacts were adjusted to maximize short-term responses. Clinical assessments included the 17-item Hamilton Depression Rating Scale (HAMD17; primary measure), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) Scale. In the first week after surgery, response and remission (HAMD ⩽7) rates were, respectively 87.5% and 50%. These early responses were followed by an overall worsening, with a response and remission rates of 37.5% (3/8) at 1 month. From then onwards, patients showed a progressive improvement, with response and remission rates of 87.5% and 37.5%, respectively, at 6 months. The corresponding figures at 1 yr were 62.5% and 50%, respectively. Clinical effects were seen in all HAMD subscales without a significant incidence of side-effects. Surgical procedure and post-operative period were well-tolerated for all patients. This is the second independent study on the use of DBS of the SCG to treat chronic depression resistant to current therapeutic strategies. DBS fully remitted 50% of the patients at 1 yr, supporting its validity as a new therapeutic strategy for TRD.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study

BACKGROUND Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Influence of Clinical and Neuropsychological Variables on the Psychosocial and Occupational Outcome of Remitted Bipolar Patients

Objective: To measure the impact of the clinical course, the residual mood symptoms and the cognitive variables on the psychosocial and occupational functioning in bipolar disorder patients in remission. Method: Forty-four euthymic DSM-IV-TR bipolar lithium-treated outpatients were assessed with a clinical interview and neuropsychological testing. To assess psychosocial function, some psychometric scales were administered (Global Assessment of Functioning Scale and World Health Organization Disability Assessment Schedule), and to evaluate occupational function, the sample was divided according to the current work status (active vs. inactive). Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Measures of psychosocial functioning were significantly correlated with cognition (processing speed, p = 0.004), clinical severity (p = 0.03) and residual depressive symptoms (p = 0.05). Occupational functioning showed a significant effect with a cognitive domain (visual memory, p = 0.006) and a clinical variable (chronicity, p = 0.04) but not with residual mood symptoms (p > 0.2). Conclusions: Remission in bipolar disorder is not synonymous with recovering in psychosocial and occupational functioning. Cognitive deficits, clinical course and persistent subsyndromal symptoms may compromise psychosocial functioning, and neurocognitive symptoms and chronicity may particularly affect occupational functioning.

Health-related quality of life in inflammatory bowel disease patients: The role of psychopathology and personality

Background: The present study aimed at assessing whether psychological factors, specifically psychopathology and personality, together with clinical and sociodemographic factors, were independent predictors of quality of life (QoL) in patients with inflammatory bowel disease (IBD). Methods: A cohort of 147 outpatients with IBD was enrolled in the study. Clinical and sociodemographic variables were recorded. QoL was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ); personality traits were assessed by means of the Temperament and Character Inventory; and psychopathology was evaluated by the Hospital Anxiety and Depression Scale. To explore the relation of variables on the QoL, univariate analyses were performed for each variable. Factors statistically significant at these analyses were included in a multiple linear regression analysis with dimensional and global IBDQ scores as dependent variables. Results: Some clinical and psychological factors were related with QoL, but regression analysis showed that disease activity and psychological distress were the strongest predictors of QoL impairment. Personality traits do not play a significant role in QoL. Conclusions: The presence of psychological distress in IBD patients contributes to poor QoL, along with IBD clinical activity. Controlling and minimizing the symptoms of the disease, along with identification and treatment of psychopathology, should become integral aspects of IBD care to improve QoL of these patients.

Life events and inflammatory bowel disease relapse: a prospective study of patients enrolled in remission.

OBJECTIVES:The impact of life events in recurrence of inflammatory bowel disease (IBD) is unclear. We sought to determine whether stressful life events or the emotional impact of these events are associated with IBD relapses, hypothesizing that the exposure of life events among patients with inactive disease will increase the risk of subsequent relapses.METHODS:In this prospective study, 163 patients with inactive IBD, who had had at least one relapse in a 2-yr period before entry into the study, were enrolled. The Spanish version of the Social Readjustment Rating Scale (SRRS) (measuring life events), a measure of the emotional impact of these life events, and an IBD activity index were completed monthly up to the end of the study (maximum 11 months) or up to a relapse. Biological factors associated with an increased risk of relapse were identified in patients who relapsed.RESULTS:Fifty-one patients relapsed (32.9%), 104 remained in remission, and 8 dropped out. Multivariate Cox regression analysis with time dependent variables showed that the number of life events was not associated with the rate of relapse after adjustment for significant covariates on the subsequent month (hazard ratio = 0.88, 95% CI = 0.68–1.13, p= 0.33) or in the time-lagged analysis. The emotional impact of stressful events was also not associated with the risk of relapse. When patients who suffered a biological risk factor for relapsing were excluded in subsequent statistical analyses, similar results were obtained.CONCLUSIONS:Our results suggest that stressful life events do not trigger exacerbations in patients suffering from IBD.

Effects of the dialectical behavioral therapy-mindfulness module on attention in patients with borderline personality disorder.

It is known that patients with borderline personality disorder (BPD) show attention deficits and impulsivity. The main aim of this study was to explore the effects of Dialectical Behavioral Therapy-Mindfulness training (DBT-M), used as an adjunct to general psychiatric management (GPM), on attention variables in patients diagnosed with BPD. A second objective was to assess the relation of mindfulness formal practice on clinical variables. A sample of 60 patients with BPD was recruited. Forty of them were allocated to GPM + DBT-M treatment and the other 20 received GPM alone. At the termination of the mindfulness training, DBT-M + GPM group showed a significant improvement on commissions, hit reaction time, detectability scores from the CPT-II neuropsychological test, and also on the composite scores of inattention and impulsivity. Further, the more minutes of mindfulness practice were correlated to greater improvement in general psychiatric symptoms and affective symptomatology, but not in CPT-II measures. This is probably the first study so far assessing the effects of this single DBT module in patients with BPD. The results suggest a positive effect of such intervention on attention and impulsivity variables.

Single-blind comparison of venlafaxine and nortriptyline in elderly major depression

The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.

The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.

Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (β = -0.47, p < 0.0001), Executive Index (β = 0.62, p < 0.0001) and Visual Memory Index (β = 0.44, p = 0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.

Physiological Responses Induced by Emotion-Eliciting Films

Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear.

Microstructural white-matter abnormalities associated with treatment resistance, severity and duration of illness in major depression

BACKGROUND Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established. METHOD The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate. RESULTS Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered. CONCLUSIONS Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.