Feasibility and effectiveness of cognitive remediation in the treatment of borderline personality disorder.

Several studies have demonstrated that borderline personality disorder (BPD) is associated with neuropsychological deficits and there is evidence that the neurocognitive profile of patients with BPD may be related to the outcome of this disorder. The aim of this study was to investigate the feasibility and the effectiveness of a cognitive remediation intervention in patients with BPD. Thirty patients with a DSM-IV-TR diagnosis of BPD were assessed on clinical, neuropsychological and functional outcome measures at baseline and after 16 weeks of a computer-assisted cognitive remediation (CACR) intervention or treatment as usual (TAU). Patients who received CACR showed a greater improvement in working memory and psychosocial functioning measures than patients treated with TAU. Symptom severity was not significantly affected by CACR treatment. The findings of this pilot study suggest the feasibility and potential effectiveness on specific cognitive domains, but modest clinical usefulness of a computerised modality of cognitive remediation in the treatment of BPD.

Effects of cognitive remediation therapy on neurocognition and negative symptoms in schizophrenia: an Italian naturalistic study.

INTRODUCTION: Cognitive remediation therapy (CRT) has been reported to positively affect neurocognitive processes among patients with schizophrenia; however, the degree to which changes in cognition is linked to improved clinical symptoms, remains poorly understood. The current study aimed to investigate whether cognitive gains were associated to improvements in negative symptoms' severity in patients with schizophrenia living in two Italian psychiatric facilities. METHODS: Patients with a diagnosis of schizophrenia were consecutively assigned to CRT (n = 33) and compared with an historical control group (n = 28). Assessments were performed at baseline and post-treatment using a neuropsychological battery (Trail Making Test A and B, Self-Ordered Pointing Task, California Verbal Learning Test), along with clinical and functioning measures. RESULTS: Visual attention (TMT-A score change) was found as the only significant predictor of improvement in negative symptoms subscale of the Positive and Negative Syndrome Scale. Furthermore, a mediation path analysis confirmed that better performance in visual attention acts as mediator of the positive association between CRT intervention and lower post-treatment negative symptoms score. CONCLUSIONS: CRT can have a positive impact on a measure of visual attention in patients with schizophrenia and on negative symptoms reduction that is mediated by this significant intervention effect.

Case Report: Long-Acting Oral Cariprazine.

Introduction: Cariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1-2 days and 2-3 weeks, respectively. Case Report: Here we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72-96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing. Discussion: Reported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a "oral long-acting" seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.

Antipsychotics, antidepressants, anticonvulsants, and placebo on the symptom dimensions of borderline personality disorder: a meta-analysis of randomized controlled and open-label trials.

The aim of this study was to quantitatively review randomized controlled trials (RCTs) and open-label trials analyzing the efficacy of antidepressants, mood stabilizers, and antipsychotics for the treatment of the core symptoms of borderline personality disorder (BPD). Using a similar meta-analytic approach, the efficacy of placebo on the same core symptoms of BPD was evaluated. The risk of discontinuation of each of the medication classes reported in the studies was also analyzed to establish the major causes of discontinuation. MEDLINE (1966 to June 2010) and EMBASE (1980 to June 2010) databases were systematically searched to identify relevant RCTs and open studies. The primary outcome was improvement in the specific core symptoms of the disorder: affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual symptoms. Evidence from RCTs and open studies suggests that drug treatment, especially with mood stabilizers and antipsychotics, may be effective for treating affective dysregulation and impulsive-behavioral dyscontrol. Antipsychotics were also effective in reducing cognitive-perceptual symptoms. Antidepressants failed to show efficacy in treating BPD symptom dimensions other than affective dysregulation. Our analyses of the placebo arm of RCTs showed a significant improvement of symptomatology in these patients also. There were no significant differences in overall dropout rates between patients on medications and those on placebo. In conclusion, the efficacy of pharmacological treatment on the symptom dimensions of BPD has been shown by various independent meta-analyses, with a positive effect of drug treatment on the core symptoms of BPD and some documentable differences in terms of efficacy between different drug classes in each of the symptom domains.

Strucutural brain imaging at the onset of schizophrenia:What have we learned and what have we missed.

Over the past 50 years, the application of structural neuroimaging techniques to schizophrenia research has added relevant information about the pathophysiology of the disorder. Several lines of investigation gave strong evidence that schizophrenia is associated with multiple subtle brain abnormalities that involve both cerebral grey and white matter volumes and structure. The time of onset and longitudinal course of brain morphological abnormalities support the notion that brain pathology of schizophrenia has a neurodevelopmental component and a progressive course, although several confounders of brain changes should be carefully taken into account. Brain anomalies detected before and close to the onset of schizophrenia are likely to be unrelated to confounders of brain changes such as antipsychotic drug treatment, duration of illness or illicit substance abuse, i.e. they related to the pathological process of the disorder per se. Nonetheless, clinically useful diagnostic or prognostic biomarkers have not derived from neuroimaging studies and this is likely related to the neurobiological heterogeneity of the disorder. Thus, there is the compelling need to set new methodological standards for developing innovative hypothesis-driven studies to overcome what we have missed to date in neuroimaging research in schizophrenia.

Are Schizophrenic disorders with or without early cannabis use neurobiologically distinct disease entities? A meta-analysis of magnetic resonance imaging studies.

Cannabis use is considered an important risk factor for the development of psychotic illness and is associated with worse outcomes of the disorder. This study aimed to determine through a meta-analytic approach whether patients at the onset of schizophrenia with comorbid cannabis use (SCH CU+) show a different pattern of brain abnormalities as compared to patients with no comorbid cannabis use (SCH CU-). Ten Magnetic Resonance Imaging (MRI) studies were identified as suitable for analysis leading to the inclusion of n= 465 patients with schizophrenia (n= 227 SCH CU+ and n= 238 SCH CU-) and n= 366 healthy controls. Compared to healthy controls, both SCH CU+ and SCH CU- patients showed reduction of whole brain, total grey matter and hippocampal volumes. The direct comparison of SCH CU+ and SCH CU- patients, including up to 5 independent studies, did not demonstrate significant differences of brain volumes between the two groups even though total and regional grey matter volume deficits were more prominent in SCH CU+ patients. The available literature data indicate that, essentially, there is an overlap of brain abnormalities in SCH CU+ and SCH CU- patients at the onset of schizophrenia. The common vs specific trajectories of brain pathomorphology in SCH CU+ and SCH CU- patients are discussed.

Gray matter, white matter, brain, and intracranial volumes in first-episode bipolar disorder: a meta-analysis of magnetic resonance imaging studies.

OBJECTIVES: To perform a comprehensive quantitative analysis of the existing magnetic resonance imaging (MRI) studies of the brain conducted on patients with first-episode bipolar disorder (BD). METHODS: A systematic search was performed of MRI studies that reported quantitative measurements of brain volumes of first-episode bipolar patients and healthy controls. Four meta-analyses were performed for four cerebral regions. RESULTS: Significant overall effect sizes were demonstrated, with a reduction detected in patients with BD for total intracranial and white matter volumes, but not for gray matter and whole brain volumes. CONCLUSIONS: The available MRI literature indicates that specific structural brain abnormalities are already present in first-episode bipolar patients. These do not overlap with those emerging from previous meta-analyses performed in patients with chronic BD. These findings support the hypothesis of different patterns of changes in brain morphology over the time course of bipolar disorder.

Variation in brain structure volumes in schizophrenia: A commentary.

Recently, Kuo and Pogue-Geile (2019) quantitatively reviewed Magnetic Resonance Imaging (MRI) findings in patients with schizophrenia demonstrating, besides altered volume of several brain structures significantly greater structural variability in patients relative to controls as for intracranial, lateral and third ventricles volumes. We believe that additional points could be usefully included in the discussion of the conceptual meaning of these findings. In this commentary, first we highlight the role of potential confounding factors such as antipsychotic medication intake and duration of illness when interpreting MRI data in schizophrenia. Second, we discuss the finding of greater variability of cerebral structure volumes in the broader context of the pathophysiology and time course of brain abnormalities in the disease.

Patterns of structural MRI abnormalities in deficit and nondeficit schizophrenia.

Negative symptoms of schizophrenia have generally been found in association with ventricular enlargement and prefrontal abnormalities. These relationships, however, have not been observed consistently, most probably because negative symptoms are heterogeneous and result from different pathophysiological mechanisms. The concept of deficit schizophrenia (DS) was introduced by Carpenter et al to identify a clinically homogeneous subgroup of patients characterized by the presence of primary and enduring negative symptoms. Findings of brain structural abnormalities reported by magnetic resonance imaging (MRI) studies focusing on DS have been mixed. The present study included 34 patients with DS, 32 with nondeficit schizophrenia (NDS), and 31 healthy comparison subjects, providing the largest set of MRI findings in DS published so far. The Schedule for the Deficit Syndrome was used to categorize patients as DS or NDS patients. The 2 patient groups were matched on age and gender and did not differ on clinical variables, except for higher scores on the negative dimension and more impaired interpersonal relationships in DS than in NDS subjects. Lateral ventricles were larger in NDS than in control subjects but were not enlarged in patients with DS. The cingulate gyri volume was smaller in NDS but not in DS patients as compared with healthy subjects. Both groups had smaller dorsolateral prefrontal cortex and temporal lobes than healthy subjects, but DS patients had significantly less right temporal lobe volume as compared with NDS patients. These findings do not support the hypothesis that DS is the extreme end of a severity continuum within schizophrenia.

Lithium in drinking water and suicide prevention: a review of the evidence.

Suicide is a serious public health problem worldwide, and many nations are committed to developing prevention programmes to reduce the incidence of suicide. To date, several strategies have been proposed for suicide prevention, both at the population and at the individual level, some of which may be pharmacological. In particular, a substantial amount of data show that lithium significantly reduces mortality in patients with mood disorders. Initiating from this evidence, some recent studies have investigated whether a relationship might exist between levels of lithium in drinking water and mortality rates for suicide in the general population. We have systematically reviewed all the articles published on this issue to date. The available literature indicates that higher lithium levels in drinking water may be associated with reduced risk of suicide in the general population.

The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies.

BACKGROUND: Deficits in cortical gray matter (GM) have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the role of potential moderators of such changes, in particular of the amount and type of antipsychotic medication intake. METHODS: Longitudinal magnetic resonance imaging studies comparing changes in the volume of cortical GM over time between patients with schizophrenia and healthy control subjects published between January 1, 1983, and March 31, 2014, were analyzed. Hedges' g was calculated for each study and volume changes from baseline to follow-up were analyzed. Meta-regression statistics were applied to investigate the role of potential moderators of the effect sizes. RESULTS: Eighteen studies involving 1155 patients with schizophrenia and 911 healthy control subjects were included. Over time, patients with schizophrenia showed a significantly higher loss of total cortical GM volume. This was related to cumulative antipsychotic intake during the interval between scans in the whole study sample. Subgroup meta-analyses of studies on patients treated with second-generation antipsychotics and first-generation antipsychotics revealed a different and contrasting moderating role of medication intake on cortical GM changes: more progressive GM loss correlated with higher mean daily antipsychotic intake in patients treated with at least one first-generation antipsychotic and less progressive GM loss with higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics. CONCLUSIONS: These findings add useful information to the controversial debate on the brain structural effects of antipsychotic medication and may have both clinical relevance and theoretical implications.

Efficacy and tolerability of asenapine for acute mania in bipolar I disorder: meta-analyses of randomized-controlled trials.

The aim of this study was to quantitatively review, using a meta-analytic approach, randomized-controlled trials analyzing the efficacy and safety profiles of asenapine in the treatment of bipolar disorder (BD). MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012) databases were systematically searched to identify relevant papers. Data from four randomized-controlled trials were analyzed. For continuous data (Young Mania Rating Scale, Clinical Global Impression Scale for Bipolar Disorder, and Montgomery-Asberg Depression Rating Scale scores), the Hedges g was adopted as a measure of the effect size; for dichotomous outcome measures (discontinuation and rates of adverse events), the risk ratio was calculated. In short-term trials, asenapine was found to be significantly superior to placebo in the treatment of manic symptoms of BD. There is also evidence of the positive effects of asenapine compared with placebo on depressive symptoms in mixed bipolar states. In the medium-term and long-term studies, asenapine showed comparable efficacy with the well-established comparator olanzapine in the treatment of manic and depressive symptoms of BD. Adverse events such as somnolence, weight gain, and extrapyramidal symptom, which have an impact on treatment adherence, are scarcely or moderately elicited by asenapine, which shows a better profile than olanzapine on metabolic parameters. On the basis of these results, asenapine can be considered as an effective and tolerable treatment for manic and mixed episodes of BD.

Cognitive remediation in schizophrenia: current status and future perspectives.

Objectives. This study is aimed to review the current scientific literature on cognitive remediation in schizophrenia. In particular, the main structured protocols of cognitive remediation developed for schizophrenia are presented and the main results reported in recent meta-analyses are summarized. Possible benefits of cognitive remediation in the early course of schizophrenia and in subjects at risk for psychosis are also discussed. Methods. Electronic search of the relevant studies which appeared in the PubMed database until April 2013 has been performed and all the meta-analyses and review articles on cognitive remediation in schizophrenia have been also taken into account. Results. Numerous intervention programs have been designed, applied, and evaluated, with the objective of improving cognition and social functioning in schizophrenia. Several quantitative reviews have established that cognitive remediation is effective in reducing cognitive deficits and in improving functional outcome of the disorder. Furthermore, the studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and even in subjects at risk of the disease. Conclusions. Cognitive remediation is a promising approach to improve real-world functioning in schizophrenia and should be considered a key strategy for early intervention in the psychoses.

Interview-based assessment of cognition in schizophrenia: applicability of the Schizophrenia Cognition Rating Scale (SCoRS) in different phases of illness and settings of care.

INTRODUCTION: The Schizophrenia Cognition Rating Scale (SCoRS), an interview-based assessment of cognition, has proved to be a valid measure of cognitive performance in patients with schizophrenia. OBJECTIVE: The aims of this study were to analyze the validity of this scale in a naturalistic setting representative of the Italian system of psychiatric care, and to test whether the SCoRS could be appropriately used in different phases of illness and contexts of care. METHODS: Eighty-six patients with schizophrenia (DSM-IV-TR criteria) (N = 59 clinically stabilized patients; N = 27 recently hospitalized patients) were administered the SCoRS. The reliability of SCoRS was assessed and global ratings were correlated with neurocognitive, clinical, and psychosocial functioning measures. RESULTS: SCoRS inter-rater and test-retest reliability were high. In clinically stabilized patients, SCoRS global ratings were significantly correlated with composite scores of cognitive performance (global cognitive index: r = -0.570, P<0.001), symptoms (Positive and Negative Syndrome Scale (PANSS) total score: r = 0.602, P < 0.001), and psychosocial functioning (Global Assessment of Functioning (GAF): r = -0.532, P<0.001; Health of the Nation Outcome Scale (HoNOS): r = 0.433, P < 0.001). On the other hand, no such correlations were found in recently hospitalized patients. Correlations with neuropsychological and functional measures were less significant as the severity of the patients' symptoms, especially positive symptoms, increased. CONCLUSION: The SCoRS is a valid measure of cognitive performance and is related to psychosocial functioning, especially in clinically stable patients with schizophrenia. The usefulness of the SCoRS in patients recently admitted to hospital for an acute phase of illness is uncertain.

Predictors of cognitive and functional improvement and normalization after cognitive remediation in patients with schizophrenia.

OBJECTIVE: Although the efficacy of cognitive remediation interventions has been demonstrated in several experimental studies on schizophrenia, few studies have investigated the predictors of response to such interventions. We were interested in determining what factors contribute to a positive outcome after cognitive rehabilitation and whether different factors are associated with different degrees of improvement in cognitive and real-world functioning in individual patients after cognitive remediation. METHODS: The study sample consisted of 56 patients with schizophrenia who had completed a 6-month cognitive remediation intervention and showed different cognitive and functional outcomes. Measures of cognitive and functional amelioration after cognitive remediation were analyzed in relation to patients' clinical, neuropsychological and functional variables at baseline using logistic regression analysis. RESULTS: Lower antipsychotic intake at baseline predicted cognitive improvement, whereas lower antipsychotic intake, severity of specific symptoms, and higher neurocognitive functioning (particularly executive functions and verbal memory) at baseline were associated with cognitive normalization after remediation treatment. Functional improvement was predicted by lower patient age and type of cognitive remediation intervention, whereas functional normalization was related to lower baseline antipsychotic intake and, at a trend level, to higher executive functioning and type of cognitive remediation intervention. CONCLUSION: Cognitive remediation could be more effective in younger, less disorganized, and cognitively less impaired patients, who take a smaller amount of antipsychotics. The predictive role of lower antipsychotic dosage on cognitive and functional outcome after remediation suggests either that patients with less severe illness could gain better advantage from cognitive remediation interventions or that high dose or complex antipsychotic therapy may limit the effectiveness of such interventions.