Cristóbal Gastó

Cognitive dysfunctions in bipolar disorder: evidence of neuropsychological disturbances.

Although cognitive dysfunctions in psychosis have classically been associated with schizophrenia, there is clinical evidence that some bipolar patients show cognitive disturbances either during acute phases or in remission periods. The authors critically review the data on cognitive impairment in bipolar disorder. The main computerized databases (Medline, Psychological Abstracts, Current Contents) have been consulted crossing the terms ‘cognitive deficits’, ‘neuropsychology’, ‘intellectual impairment’, ‘mania’, ‘depression’ and ‘bipolar disorder’. Changes in the fluency of thought and speech, learning and memory impairment, and disturbances in associational patterns and attentional processes are as fundamental to depression and mania as are changes in mood and behavior. Moreover, a significant number of bipolar patients show persistent cognitive deficits during remission from affective symptoms. However, there are several methodological pitfalls in most studies such as unclear remission criteria, diagnostic heterogeneity, small sample sizes, absence of longitudinal assessment, practice effect and poor control of the influence of pharmacological treatment. Most studies point at the presence of diffuse cognitive dysfunction during the acute phases of bipolar illness. Most of these deficits seem to remit during periods of euthymia, but some of them may persist in approximately one third of bipolar patients. Methodological limitations warrant further research in order to clear up the relationship between neuropsychological functioning and clinical, demographic and treatment variables in bipolar disorder.

Psychiatric Morbidity and Impact on Hospital Length of Stay Among Hematologic Cancer Patients Receiving Stem-Cell Transplantation

PURPOSE To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation (SCT) and to estimate their impact on hospital length of stay (LOS). PATIENTS AND METHODS In a prospective inpatient study conducted from July 1994 to August 1997, 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution. Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death, yielding a total of 1,062 psychiatric interviews performed. Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Univariate and multivariate linear regression analyses were used to identify variables associated with LOS. RESULTS Overall psychiatric disorder prevalence was 44.1%; an adjustment disorder was diagnosed in 22.7% of patients, a mood disorder in 14.1%, an anxiety disorder in 8.2%, and delirium in 7.3%. After adjusting for admission and in-hospital risk factors, diagnosis of any mood, anxiety, or adjustment disorder (P =.022), chronic myelogenous leukemia (P =.003), Karnofsky performance score less than 90 at hospital admission (P =.025), and higher regimen-related toxicity (P <.001) were associated with a longer LOS. Acute lymphoblastic leukemia (P =.009), non-Hodgkins lymphoma (P =.04), use of peripheral-blood stem cells (P <.001), second year of study (P <.001), and third year of study (P <.001) were associated with a shorter LOS. CONCLUSION Our data indicate high psychiatric morbidity and an association with longer LOS, underscoring the need for early recognition and effective treatment.

Differential features between bipolar I and bipolar II disorder.

Although bipolar II disorder is generally viewed as a mild form of classic manic-depressive illness, recent investigations suggest that it could be a valid diagnostic category different from bipolar I in genetic, biological, clinical, and pharmacological aspects. Twenty-two patients fulfilling Research Diagnostic Criteria for the diagnosis of bipolar II disorder and 38 bipolar I patients were evaluated with the Schedule for Affective Disorders and Schizophrenia by two independent interviewers and compared. Bipolar II patients had significantly more previous episodes (P = .001), including both depressive (P = .003) and hypomanic (P = .006) switches, but had been hospitalized (P = .001) and presented psychotic symptoms (P < .001) less frequently. These results suggest that bipolar II disorder is less severe than bipolar I with regard to symptom intensity, but is more severe with respect to episode frequency.

Executive Function in Patients with Remitted Bipolar Disorder and Schizophrenia and Its Relationship with Functional Outcome

Background: Recent studies have reported that differences in cognitive performance between schizophrenic and bipolar patients seem to be smaller than expected. Patients with schizophrenia have consistently shown frontal executive dysfunctions, but studies regarding executive abilities in bipolar patients are scarce and discrepant. As executive function has been associated with psychosocial functioning in schizophrenia, we wanted to investigate if such a relationship is also present in bipolar disorder and the differences between the two groups. Methods: Executive function was assessed in 49 euthymic (at least 6 months in remission, Hamilton Depression Rating Scale ≤8 and Young Mania Rating Scale ≤6) bipolar and in 49 schizophrenic, residual-type (with at least 1 year without acute exacerbation and predominant negative symptomatology) patients, by the Wisconsin Card Sorting Test (WCST), FAS Test (COWAT) and Trail Making Test. Baseline clinical and psychosocial variables were controlled and psychopathology evaluated by means of the Positive and Negative Syndrome Scale (PANSS). Results: The two groups showed a similar pattern of cognitive deficits in tests of executive function, except for the number of categories achieved in the WCST, which was significantly lower in the schizophrenic group (F = 7.26; p = 0.009). Functional outcome was predicted by the negative syndrome (PANSSN) and perseverative errors (WCST) in schizophrenic patients, and general psychopathology (PANSSG) was the best predictor of functional outcome in the bipolar group. Conclusion: Executive function was a good predictor of functional outcome in the schizophrenic group, whereas clinical variables were more predictive of the bipolar one. Patterns of cognitive disturbances in tasks of executive function are similar in both groups but quantitatively more marked in schizophrenia.

5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study.

In the context of a long term follow-up study, we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram. The sample consisted of 131 patients, all of Spanish origin, diagnosed according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale (HDRS) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week, respectively. Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week (χ2 = 8.7, P = 0.013). Moreover, homozygous for the allele S presented three times more risk for non reaching remission of depressive episode after citalopram treatment than patients with any other 5-HTTLPR genotype combination (χ2: 7.29, P = 0.006; OR = 3.23 [95%CI: 1.24–8.5]). In conclusion, our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment.

Executive function and nonverbal memory in obsessive-compulsive disorder

It has been suggested that memory impairments found in obsessive-compulsive disorder (OCD) are mediated by organizational problems in encoding that are caused by primary executive dysfunction. Performance on different nonverbal memory and executive skills was tested in 68 subjects (35 non-depressed OCD sufferers and 33 healthy controls). Multiple regression models were performed to analyze the role of different cognitive variables, especially organizational encoding strategies in nonverbal memory. OCD patients performed significantly worse than controls in immediate nonverbal memory [Rey-Osterrieth Complex Figure Test (RCFT)] and on all the executive functions such as interference control (Stroop test), mental set shifting (Trail-Making Test), and organizational strategies (copy organization). As no differences were found in the memory of faces, where organizational strategies are minimal, it is possible to speculate that immediate nonverbal memory problems in OCD appear only when organizational strategies mediate the recalling process. Thus, memory deficits appear to have less to do with memory, per se, and more to do with the degree of organization necessary to effectively complete the task. Statistical analyses of mediation models showed the highest explanatory power for the organizational approach and demonstrated the mediation effect of organizational strategies in nonverbal impairment.

Role of Depression As a Predictor of Mortality Among Cancer Patients After Stem-Cell Transplantation

PURPOSE To determine the association between depression and survival among cancer patients at 1, 3, and 5 years after stem-cell transplantation (SCT). PATIENTS AND METHODS This was a prospective cohort study of 199 hematologic cancer patients who survived longer than 90 days after SCT and who were recruited in a University-based hospital between July 1994 and August 1997. Patients received a psychiatric assessment at four consecutive time points during hospitalization for SCT, yielding a total of 781 interviews. Depression diagnoses were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS Eighteen (9.0%) and 17 patients (8.5%) met criteria for major and minor depression, respectively. Multivariate Cox regression models found major depression to be predictive of higher 1-year (hazard ratio [HR], 2.59; 95% CI, 1.21 to 5.53; P = .014) and 3-year mortality (HR, 2.04; 95% CI, 1.03 to 4.02; P = .041) but not 5-year mortality (HR, 1.48; 95% CI, 0.76 to 2.87; P = .249). Minor depression had no effect on any mortality outcome. Other multivariate significant predictors of higher mortality were higher regimen toxicity in the 1-, 3-, and 5-year models; older age and acute lymphoblastic leukemia in the 3- and 5-year models; chronic myelogenous leukemia in the 3-year model; and lower functional status and intermediate/higher risk status in the 5-year model. Use of peripheral-blood stem cells predicted lower mortality in the 5-year model. CONCLUSION After adjusting for multiple factors, major depression predicted higher 1- and 3-year mortality among cancer patients after SCT, underscoring the importance of adequate diagnosis and treatment of major depression.

Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging.

It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.

Cognitive Remediation Therapy for outpatients with chronic schizophrenia: A controlled and randomized study

Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.

Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study

BACKGROUND Cognitive remediation therapy positively affects cognition and daily functioning in patients with schizophrenia. However, studies on the underlying neurobiological mechanisms of this treatment are scarce. The aim of the current study was to investigate functional and structural connectivity brain changes in schizophrenia patients after cognitive remediation therapy using a whole-brain approach that combined functional magnetic resonance imaging and diffusion tensor imaging. METHODS A randomized controlled trial with 30 schizophrenia outpatients and 15 healthy volunteers. A strategy-learning-based treatment was used as a cognitive remediation therapy. A social skills training that provides useful information about illness management was used as an active control. We investigated changes in the pattern of functional connectivity assessed during an n-back task by tensorial independent component analysis as implemented in the multivariate exploratory linear decomposition into independent components and in the fractional anisotropy index of white matter integrity using tract-based spatial statistics. RESULTS Brain networks activation pattern significantly changed in patients exposed to the cognitive treatment in the sense of normalizing toward the patterns observed in healthy control subjects. Additionally, in white matter, they showed an increase in fractional anisotropy index in the anterior part of the genu of the corpus callosum. Cognitive improvement, functional, and also structural changes showed statistically significant correlations. CONCLUSIONS Improvement in brain functioning detected after cognitive remediation therapy in schizophrenia patients might be based on an increase of the interhemispheric information transfer between the bilateral prefrontal cortexes via the corpus callosum.