Iñaki Zorrilla

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.

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.

Adherence to Antipsychotic Medication in Bipolar Disorder and Schizophrenic Patients: A Systematic Review

Abstract Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients.

Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study

The objective of the study is to examine the association of baseline total antioxidant status (TAS) and glutathione (GSH) levels with short- and long-term cognitive functioning in patients with early onset first-episode psychosis, comparing affective and non-affective psychoses. We analysed 105 patients with an early onset-first episode psychosis (age 9-17 years) and 97 healthy controls. Blood samples were taken at admission for measurement of TAS and GSH, and cognitive performance was assessed at baseline and at 2years of follow-up. Regression analysis was used to assess the relationship between TAS/GSH levels at baseline and cognitive performance at both time points, controlling for confounders. Baseline TAS and GSH levels were significantly lower in patients than healthy controls. In patients, baseline TAS was positively associated with the global cognition score at baseline (p=0.048) and two years later (p=0.005), while TAS was not associated with cognitive functioning in healthy controls. Further, baseline TAS in patients was specifically associated with the memory domain at baseline and with the memory and attention domains two years later. Stratifying by affective and non-affective psychoses, significant associations were only found between TAS and cognition in the non-affective psychosis group. Baseline GSH levels were not associated with cognitive functioning at either time point in either group. The antioxidant defence capacity in early onset first-episode psychotic patients is directly correlated with global cognition at baseline and at 2years of follow-up, especially in non-affective psychosis.

Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain

Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.

Prognostic Value of Affective Symptoms in First-Admission Psychotic Patients

Background: Very little research has been conducted in patients with first-episode psychosis using a dimensional approach. Affective dimensional representations might be useful to predict the clinical course and treatment needs in such patients. Methods: Weincluded 112 patients with first-episode psychosis in a longitudinal-prospective study with a five-year follow-up (N = 82). Logistic analyses were performed to determine the predictive factors associated with depressive, manic, activation, and dysphoric dimensions. Results: High scores on the depressive dimension were associated with the best prognosis. On the other hand, high scores on the activation dimension and the manic dimension were associated with a poorer prognosis in terms of relapses. Only the dysphoric dimension was not associated with syndromic or functional prognosis. Conclusion: Ourresults suggest that the pattern of baseline affective symptoms helps to predict the course of psychotic illness. Therefore, the systematic assessment of affective symptoms would enable us to draw important conclusions regarding patients’ prognosis. Interventions for patients with high scores on manic or activation dimensions could be beneficial in decreasing relapses in first-episode psychosis.

Psychometric properties and validation of a four-item version of the Strauss–Carpenter scale in bipolar disorder

BackgroundBipolar disorder is a chronic illness that impairs functioning and affects the quality of life of patients. The onset of this illness usually occurs at an early age, and the risk of relapse remains high for decades. Thus, due to the great clinical relevance of identifying long-term predictors of functioning in bipolar disorder, Strauss and Carpenter developed a scale composed of items known to have prognostic value.Methods To determine the clinical usefulness of the four-item Strauss–Carpenter scale in bipolar disorder, a 1-year prospective follow-up study was carried out. The internal consistency, convergent and discriminant validity, and test–retest reliability of the scale were assessed. We also compared the Strauss–Carpenter scale with the reference scales Global Assessment Functioning (GAF), Clinical Global Impression for Bipolar Disorder, the Modified Version (CGI-BIP-M) and the Sheehan Disability Scale (Sheehan). Additionally, a cut-off point for remission was established.ResultsThe total sample was composed of 98 patients with a diagnosis of bipolar disorder. The four-item version of the Strauss–Carpenter scale showed to have appropriate psychometric properties, comparable to those of reference scales. The best cut-off point for remission was 14.ConclusionsThe four-item version of the Strauss–Carpenter scale has suitable validity and reliability for the assessment of functioning in patients with bipolar disorder.

Smoking does not impact social and non-social cognition in patients with first episode psychosis

BACKGROUND Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. METHODS A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. RESULTS Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F=13.45; p≤0.001) and working memory domains (F=4.30; p=0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F=19.60; p≤0.001). No significant differences were revealed in the comparison between the patient groups. CONCLUSIONS This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.

Eficacia y seguridad de la ketamina en depresión bipolar: una revisión sistemática

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects.

Erratum to: Online information seeking by patients with bipolar disorder: results from an international multisite survey (Int J Bipolar Disord, (2016), 4, (1), 10.1186/s40345-016-0058-0)

Online information seeking by patients with bipolar disorder: results from an international multisite survey (Int J Bipolar Disord, (2016), 4, (1), 10.1186/s40345-0160058-0) Conell, Jörn; Bauer, Rita; Glenn, Tasha; Alda, Martin; Ardau, Raffaella; Baune, Bernhard T.; Berk, Michael; Bersudsky, Yuly; Bilderbeck, Amy; Bocchetta, Alberto; Bossini, Letizia; Paredes Castro, Angela Marianne; Cheung, Eric Yat Wo; Chillotti, Caterina; Choppin, Sabine; Del Zompo, Maria; Dias, Rodrigo; Dodd, Seetal; Duffy, Anne; Etain, Bruno; Fagiolini, Andrea; Garnham, Julie; Geddes, John; Gildebro, Jonas; Gonzalez-Pinto, Ana; Goodwin, Guy M.; Grof, Paul; Harima, Hirohiko; Hassel, Stefanie; Henry, Chantal; Hidalgo-Mazzei, Diego; Kapur, Vaisnvy; Kunigiri, Girish; Lafer, Beny; Lam, Chun; Larsen, Erik Roj; Lewitzka, Ute; Licht, Rasmus W.; Lund, Anne Hvenegaard; Misiak, Blazej; Piotrowski, Patryk; Monteith, Scott; Munoz, Rodrigo; Nakanotani, Takako; Nielsen, René E.; O’Donovan, Claire; Okamura, Yasushi; Osher, Yamima; Reif, Andreas; Ritter, Philipp; Rybakowski, Janusz K.; Sagduyu, Kemal; Sawchuk, Brett; Schwartz, Elon; Scippa, Ângela Miranda; Slaney, Claire; Sulaiman, Ahmad Hatim; Suominen, Kirsi; Suwalska, Aleksandra; Tam, Peter; Tatebayashi, Yoshitaka; Tondo, Leonardo; Vieta, Eduard; Vinberg, Maj; Viswanath, Biju; Volkert, Julia; Zetin, Mark; Zorrilla, Iñaki; Whybrow, Peter C.; Bauer, Michael