Miguel Gutiérrez

Cannabis and First-Episode Psychosis: Different Long-term Outcomes Depending on Continued or Discontinued Use

Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. Methods: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI] = 0.65 to 1.86) for functional outcome and −0.72 (95% CI = −1.27 to −0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

Principal components of mania

OBJECTIVE An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS Patients of the sample were all medicated inpatients. CONCLUSIONS Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.

First episode in bipolar disorder: misdiagnosis and psychotic symptoms

BACKGROUND This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis.

Psychoeducation and cognitive-behavioral therapy in bipolar disorder: an update

Objective:  To review the available literature on psychoeducation and cognitive‐behavioral therapy (CBT) in bipolar disorder (BD) and to give an integral view of these therapies.

Hierarchical structure of the cognitive processes in schizophrenia: the fundamental role of processing speed

OBJECTIVE Decreased processing speed (PS) is a key feature of schizophrenia with respect to cognition, functional outcome and clinical symptoms. Our objective was to test whether PS slowing mediates other neuropsychological deficits among patients with chronic schizophrenia. METHOD One hundred patients with schizophrenia and 53 healthy adults completed a series of neuropsychological measures that assess six cognitive domains. In addition to PS these included attention, verbal memory, visual memory, working memory, and executive functioning. Confirmatory factor analysis (CFA) was used to evaluate the fit of the 6-factor model. The cognitive performances of both groups were compared before and after controlling for the effect of PS, but also after controlling for the effect of each cognitive factor at a time. Finally, the PS-related variance was removed and the effect of the other cognitive factors was tested again. RESULTS CFA supported the hypothesized 6-factor cognitive structure. As expected, the patients and controls differed on all cognitive measures. However, after controlling for the effects of PS, group differences on the other five cognitive factors decreased substantially. Controlling for other factors produced smaller attenuation of group differences, and these effects were also partially accounted for by decreased PS. CONCLUSIONS PS deficits account for most of the differences in cognition between patients with schizophrenia and healthy controls. PS slowing appears to be a core feature of schizophrenia, one that underlies impairments of working memory, executive functioning, and other abilities.

Safety and effectiveness of olanzapine versus conventional antipsychotics in the acute treatment of first-episode schizophrenic inpatients.

OBJECTIVE To assess the safety and effectiveness of olanzapine compared to typical antipsychotics in the treatment of first-episode schizophrenics in acute psychiatric inpatient wards. METHODS Data were collected from a prospective, comparative, nonrandomized, open, observational study of 904 inpatients with schizophrenia. One hundred and fifty-eight patients fulfilled the criteria for first-episode schizophrenia, defined as (1) the International Classification of Diseases: Mental and Behavioral Disorders, 10th ed. (ICD-10) diagnosis of schizophrenia, (2) antipsychotic nai;ve, and (3) a course of illness of less than 5 years. Eighty-nine (56.3%) of these patients were assigned to the olanzapine treatment group (OLZ) and 69 (43.7%) to the control group that received treatment with conventional antipsychotics (CON). Safety was evaluated in terms of the spontaneous adverse events reported and a specific questionnaire for extrapyramidal symptoms (EPS). Clinical status was measured by means of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Severity (CGI-S). Clinical response was defined as the baseline-endpoint decrease in BPRS>40% plus an endpoint BPRS<18 or an endpoint CGI</=3. RESULTS The rate of clinical response to treatment in the OLZ was 76.7%, compared to 54.4% in the CON (chi(2)=8.48; P=.003). Olanzapine was significantly more effective than conventional antipsychotics in lowering the total BPRS score (P=.0003), as well as each of the following BPRS subscales: positive symptoms (P=.0019), negative symptoms (P<.0001), depression (P=.018), and agitation (P=.007), even after mean scores were adjusted for their baseline value and disease duration. Olanzapine also proved to be significantly superior to conventional antipsychotics in lowering mean CGI scores (P=.013). The frequency with which new EPS appeared, or previously existing ones worsened, was significantly greater in the CON than in the OLZ (55.1% vs. 13.5%; P<.001). Anticholinergics were needed more frequently in the CON than in the OLZ (58.0% vs. 6.7%; P<.0001). CONCLUSIONS The results of this observational, naturalistic study show that olanzapine is safe and effective in a nonselected sample of acute, first-episode schizophrenic inpatients.

Treatment of bipolar I rapid cycling patients during dysphoric mania with olanzapine

The simultaneous presentation of manic and depressive symptoms in the same patient is fairly common. The terms dysphoric, mixed, and depressive mania have been used as equivalents to mixed states. Pharmacotherapy is less effective in this group of patients. The aim of this study is to determine the effectiveness and safety of olanzapine as an add-on therapy in patients with bipolar disorder with a rapid cycling course during a dysphoric mania episode. Thirteen patients treated with mood stabilizers for at least 1 year and diagnosed with a mixed episode were included in an open trial. All had at least 4 episodes in the last year. Patients with organic diseases, including altered thyroid function, were excluded from the research. Patients were evaluated at inclusion and at day 28. Response was defined as a decrease of 50% in the Young Mania Rating Scale and the Hamilton Rating Scale for Depression concomitant with a Clinical Global Impression improvement of 1 or 2. All patients completed the study. The doses of olanzapine were 16.15 ± 5.82 mg/day. There was a reduction in the manic and depressive symptoms in all patients. Ten of the 13 patients were considered to have responded to the treatment according to the response definition. Adverse effects included somnolence (23.08%) and weight gain (0.81 ± 1.96 kg in women, 2.20 ± 2.28 kg in men). Our results suggest that olanzapine combined with mood stabilizers is safe and effective in the treatment of the manic and the depressive symptoms of dysphoric mania with a rapid cycling course.

Age-dependence of Schneiderian psychotic symptoms in bipolar patients.

Psychotic symptoms frequently occur in bipolar disorder, especially in younger patients. However, whether the association with younger age also extends to psychotic symptoms that have traditionally been associated with schizophrenia, such as Schneiderian first-rank symptoms (FRSs), is unclear. This study examined FRSs in bipolar I patients and their relationship to age and gender. The sample comprised 103 consecutive inpatients who met DSM IV criteria for bipolar disorder, manic or mixed. FRSs were rated with the Scale for the Assessment of Positive Symptoms (SAPS). Interaction between FRSs and gender and FRSs and age was assessed using logistic regression. A high rate of FRSs in manic and mixed patients was found with a higher frequency in men (31%) than in women (14%; P=0.038). A monotonic increase in the association between FRSs and younger age was apparent (odds ratios (OR) over five levels: 1.42; 1.00-2.01). These results confirm previous findings that FRSs are not specific to schizophrenia and suggest in addition that a dimension of nuclear psychotic experiences of developmental origin extends across categorically defined psychotic disorders.

Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis

The relationship of neurocognitive course with clinical and functional outcomes in psychosis is not well known, especially in the long term. The aim of the study was to examine the clinical and neuropsychological course of first-episode psychosis patients at 5-year follow-up and analyze the relationship of cognitive performance with clinical and functional outcome. The 5-year follow-up was conducted with 26 first-episode psychosis patients. Psychotic symptoms were measured by the Positive and Negative Syndrome Scale, manic and depressive symptoms by the Young Mania Rating Scale and Hamilton Depression Rating Scale respectively, and psychosocial functioning by the Functioning Assessment Short Test. The cognitive domains were assessed by the Wechsler Adult Intelligence Scale, the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test, the Stroop Colour-Word Test and the Wechsler Memory Scale. Patients showed symptomatic improvement in the follow-up except in negative psychotic symptoms. There was also improvement in most cognitive domains except in working memory and processing speed in the follow-up. Working memory impairment was associated to negative psychotic symptoms and poor functional outcomes. Negative symptoms mediated the relationship between working memory and outcome. Therefore, negative symptoms should be a primary target of treatment to improve functional outcomes.

Verbal fluency in schizophrenia: does cognitive performance reflect the same underlying mechanisms in patients and healthy controls?

Verbal fluency is impaired in patients with schizophrenia, but the association with other cognitive domains remains unclear. Forty-seven patients with schizophrenia (DSM-IV) and 47 controls matched by age, gender, years of education, and vocabulary (Wechsler Adult Intelligence Scale-III) were assessed in terms of sociodemographic, clinical, and cognitive variables. Healthy controls performed significantly better than patients with schizophrenia in all cognitive measures. However, the way these cognitive domains were related differed across groups. Semantic fluency (SF) and phonological fluency (PF) were predicted by working memory (WM) in patients with schizophrenia, whereas the predictor in the healthy controls was processing speed (PS). Moreover, after dividing the sample of patients according to their performance on fluency tests, we found that a worse performance on SF or PF was predicted by WM. However, for patients with a better performance on fluency, the pattern was similar to that of healthy controls. Cognition may show a different pattern of interaction in schizophrenia, with less impaired patients showing a closer pattern to healthy controls. Therefore, we suggest that, depending on the severity of cognitive deficits, performance on neuropsychological tests may not reflect the same underlying mechanisms.