Susana Alberich

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.

Poor Long-Term Prognosis in Mixed Bipolar Patients: 10-Year Outcomes in the Vitoria Prospective Naturalistic Study in Spain

OBJECTIVE There have been few prospective long-term naturalistic studies of patients with mixed episodes of bipolar disorder. The aim of this study was to examine 10-year outcomes in patients with at least 1 mixed episode. METHOD A naturalistic sample of bipolar I disorder patients (n = 120), representative of bipolar patients treated in a catchment area of Spain, was followed prospectively for up to 10 years. Outcomes including number (primary study outcome) and severity of episodes, hospitalizations, and suicide attempts were recorded at bimonthly visits. Bivariate and logistic regression models identified factors significantly associated with mixed episodes. The study was conducted from 1994 through 2004. RESULTS 37% of patients had mixed episodes. Mixed-episode patients had younger mean age at onset compared with the nonmixed group (25.3 vs 30.8 years; P = .025). After adjusting for age at onset, mixed-episode patients had an increased risk of hospitalization compared with the nonmixed group (OR = 2.86; 95% CI, 1.09-7.52; P = .033) and more episodes (OR = 1.21; 95% CI, 1.10-1.31; P < .001). Other differences between mixed and nonmixed patients, such as alcohol abuse, psychotic symptoms, and suicidality, were partially mediated by age at onset and were not significantly different after controlling for this variable. Mixed-episode patients with previous suicide attempts had a significantly shorter time to first suicide attempt during follow-up than those without history of suicide attempts (P = .014). CONCLUSIONS Although some factors associated with mixed episodes are mediated by a younger age at onset, the long-term prognosis of mixed-episode patients is worse than patients with nonmixed episodes.

Verbal memory as a mediator in the relationship between subthreshold depressive symptoms and functional outcome in bipolar disorder.

BACKGROUND Most studies on the factors involved in the functional outcome of patients with bipolar disorder have identified subsyndromal depressive symptoms and cognitive impairment as key players. However, most studies are cross-sectional and very few have analyzed the interaction between cognition and subclinical depression. The present study aimed to identify the role of cognition, and particularly verbal memory, and subthreshold depressive symptoms in the functional outcome of patients with bipolar I and II disorder at one year follow-up. METHOD A confirmatory analysis was performed using the path analysis. A total of 111 euthymic patients were included to test the role of verbal memory as a mediator in the relationship of subthreshold depressive symptoms and functional outcome at one year follow-up. Measures of verbal memory, subthreshold depressive symptoms and functioning (at baseline, at 6 months and at one year follow-up) were gathered through the use of a neuropsychological assessment and validated clinical scales. RESULTS The hypothesized mediation model displayed a good fit to data (Chi=0.393, df=2, p=0.625; RMSEA<0.001 with CI: 0.001-0.125 and CFI=1.00). Functional outcome at one year follow-up was predicted by the functional outcome at baseline, which in turn, was related to subthreshold depressive symptoms at baseline and to the verbal composite memory scores as a mediator variable. CONCLUSION The results of this study prospectively confirm previous findings on the disabling role of subthreshold depressive symptoms and verbal memory impairment on psychosocial functioning. However, these results come from a sample with moderate to severe functional impairment; hence, as a limitation, this may hinder the generalization of these results.

Different profile of substance abuse in relation to predominant polarity in bipolar disorder: The Vitoria long-term follow-up study

BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms, especially the course of comorbid alcohol/substance abuse. METHOD A naturalistic sample of bipolar I patients (n=120) was followed prospectively for up to 10years. At baseline, number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes, respectively. 25 patients were excluded from the analyses. Outcomes including episodes, hospitalisations and suicide attempts were recorded at bimonthly visits. Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients. RESULTS Of the 95 patients analyzed, 44 (46.3%) had predominantly manic episodes and 51 (53.7%) had predominantly depressive episodes. At baseline, the predominantly depressive group had more history of suicide attempts (45.1% vs. 20.5%; p=0.021) and more family history of affective disorders (64.7% vs. 38.6%; p=0.020), but they had fewer previous hospitalisations than the manic group (mean 0.38 vs. 0.50; p=0.025). During the 10-year follow-up, the predominantly depressive group was associated with more episodes (p=0.001), more hospitalisations (p=0.004) and more suicide attempts (p=0.002). At baseline, there were no differences between the manic and depressive groups in the frequency of alcohol abuse (43.2% and 35.3%, p=0.565) or other substance abuse (13.6% and 9.8%, p=0.794). During the 10-year follow-up, the frequency of alcohol and other substance abuse decreased significantly in the manic group only, after controlling by age at onset and civil (marital) status. CONCLUSION Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients, with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse. These differences should be considered when designing treatment approaches for bipolar patients with comorbid alcohol/substance abuse.

Predictors of pathological gambling severity taking gender differences into account.

Background: The current study aims to identify predictors of pathological gambling (PG) severity, taking gender differences into account, in an outpatient sample of pathological gamblers seeking treatment. Methods: The sample for this study consisted of 103 subjects (51 women and 52 men) meeting current DSM-IV-TR criteria for PG. Linear and logistic regression analyses were used to examine different risk factors (gender, age, impulsivity, sensation seeking, self-esteem) and risk markers (depression, anxiety, gambling-related thoughts, substance abuse) as predictors of PG severity. Results: Impulsivity, maladjustment in everyday life and age at gambling onset were the best predictors in the overall sample. When gender differences were taken into account, duration of gambling disorder in women and depression and impulsivity in men predicted PG severity. In turn, a high degree of severity in the South Oaks Gambling Screen score was related to older age and more familiy support in women and to low self-esteem and alcohol abuse in men. Female gamblers were older than male gamblers and started gambling later in life, but became dependent on gambling more quickly than men. Conclusions: Further research should examine these data to tailor treatment to specific patients’ needs according to sex and individual characteristics.

Relationship between negative symptoms and plasma levels of insulin-like growth factor 1 in first-episode schizophrenia and bipolar disorder patients.

Previous studies have suggested that insulin-like growth factor-1 (IGF-1) is altered in schizophrenia. The objective of this study was to investigate whether plasma IGF-1 levels were altered at the onset of psychiatric disorders such as schizophrenia or bipolar disorder. We focused at the first psychotic episode (FPE) and during 1-year follow-up. We also studied if IGF-1 levels were related to clinical symptoms. 50 patients and 43 healthy controls matched by age, gender and educational level were selected from the Basque Country catchment area in Spain. Plasma IGF-1 levels were measured at FPE and 1 month, 6 months and one year later. Patient symptoms were assessed at the same disease stages using the Positive and Negative Symptoms Scale (PANSS), the Global Assessment of Functioning (GAF), the Hamilton Depression Rating Scale (HDRS21) and the Young Mania Rating Scale (YMRS). A statistically significant increase in the plasma levels of IGF-1 was found in the whole cohort of patients one month after FPE compared to matched controls (219.84 ng/ml vs 164.15 ng/ml; p=0.014), as well as in schizophrenia patients alone at that stage (237.60 ng/ml vs 171.60 ng/ml; p=0.039). In turn, negative symptoms in both groups of patients were positively correlated with IGF-1 levels both at FPE (β=0.521; p<0.001) and after 1 year (β=0.659; p=0.001), being patients diagnosed with schizophrenia the main contributors to this relationship. These results indicate that there is a significant change in the plasma levels of IGF-1 at the initial stages of schizophrenia but not in bipolar disorder, and suggest that IGF-1 could have role in the pathophysiology of negative symptoms.

Validity and reliability of the Hamilton depression rating scale (5 items) for manic and mixed bipolar disorders.

Depressive symptoms during mania have prognostic value in bipolar disorder. For depressive symptoms, it has been proposed that shorter scales should be cost-effective and practical. To determine the usefulness of 5-item Hamilton Depression Rating Scale (HAMD-5) in manic and mixed bipolar disorder, we used a four-week follow-up prospective, observational study. Convergent and discriminant validity, internal consistency, and reliability were analyzed and compared with HAMD-21, HAMD-5, and HAMD-21 cut-off points were calculated versus CGI-BP. A total of 173 manic and mixed patients were evaluated. HAMD-5 showed appropriate convergent validity, discriminant validity, internal consistency, and test-retest reliability. Discriminant validity was higher for HAMD-5 than HAMD-21. Best cut-off point of remission was: HAMD-21 ≤5 and HAMD-5 ≤1. HAMD-5 presents appropriate validity and reliability estimates. It is comparable to HAMD-21 and focuses more specifically on depressive symptoms.

BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.

Validation and use of the functioning assessment short test in first psychotic episodes.

Numerous studies have documented high rates of functional impairment in patients with schizophrenia and bipolar disorder. However, this impairment appears early in the course of the illness. The purpose of the present study was to validate the Functioning Assessment Short Test (FAST) by comparing it with the Strauss-Carpenter Scale for use as an instrument to assess functional impairment in subjects with first psychotic episodes. The study was conducted on 53 patients admitted to Santiago Apostol Hospital because of a first psychotic episode. The FAST showed high internal consistency both at baseline and at 6 months as well as at 1 year. Concurrent validity showed a highly significant negative correlation at each time point. The FAST also showed good reliability and discriminant validity. The FAST showed strong psychometric properties and is a valid instrument for use in clinical practice, clinical trials, and research settings in subjects with first psychotic episodes.

Subclinical Depressive Symptoms and Continued Cannabis Use: Predictors of Negative Outcomes in First Episode Psychosis

Background Although depressive symptoms in first episode psychosis have been associated with cannabis abuse, their influence on the long-term functional course of FEP patients who abuse cannabis is unknown. The aims of the study were to examine the influence of subclinical depressive symptoms on the long-term outcome in first episode-psychosis patients who were cannabis users and to assess the influence of these subclinical depressive symptoms on the ability to quit cannabis use. Methods 64 FEP patients who were cannabis users at baseline were followed-up for 5 years. Two groups were defined: (a) patients with subclinical depressive symptoms at least once during follow-up (DPG), and (b) patients without subclinical depressive symptoms during follow-up (NDPG). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms using the Hamilton Depression Rating Scale (HDRS)-17, and psychosocial functioning was assessed using the Global Assessment of Functioning (GAF). A linear mixed-effects model was used to analyze the combined influence of cannabis use and subclinical depressive symptomatology on the clinical outcome. Results Subclinical depressive symptoms were associated with continued abuse of cannabis during follow-up (β= 4.45; 95% confidence interval [CI]: 1.78 to 11.17; P = .001) and with worse functioning (β = -5.50; 95% CI: -9.02 to -0.33; P = .009). Conclusions Subclinical depressive symptoms and continued cannabis abuse during follow-up could be predictors of negative outcomes in FEP patients.