Marianna Mazza

Clinical features, response to treatment and functional outcome of bipolar disorder patients with and without co-occurring substance use disorder: 1-year follow-up

INTRODUCTION Bipolar disorder patients (BP) with comorbid Substance Use Disorder (SUD) may present clinical features that could compromise adherence and response to pharmacological treatment. The purpose of this study was to examine clinical and psychopathological features of BP with and without comorbid SUD in a real-world setting. METHODS The sample was composed by 131 affective patients. Sixty-five patients were affected by Bipolar Disorder I (BP-I, 49.2%), 29 by Bipolar Disorder II (BP-II, 22.3%) and 37 by Cyclothymic Disorder (CtD, 28.5%), according to DSM-IV. Sixty-six patients were diagnosed for a comorbid SUD. All patients have been submitted to psychometric assessment with Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Young Mania Rating Scale (YMRS), Global Assessment Scale (GAS), Social Adjustment Self-reported Scale (SASS), Quality of Life Scale (QoL), at baseline and repeated follow-up periods (1, 3, 6, 12 months). RESULTS BP comorbid for SUD were more likely diagnosed as BP-II and CtD and were less likely to present a moderate-severe manic symptomatology. Furthermore, personality disorders were more frequent in SUD patients than in non-comorbid BP. BP with SUD were not different for primary outcome measure (HDRS, HARS, YMRS, GAS) from non-comorbid BP; however, BP with SUD were significantly more impaired in social functioning (SASS) at any stage of the follow-up and poor functioning increased the risk of relapse in substance use during treatment. Finally, SUD comorbidity did not represent a risk factor for treatment drop-out, while in our sample young age, low treatment dosage and BP-I diagnosis were significantly associated with drop-out. DISCUSSION The primary finding of this work is that BP with comorbid SUD are significantly more compromised in social functioning. Second, these patients were less likely to be diagnosed for BP-I and to present a severe manic symptomatology. Finally, we found that the diagnosis of SUD, but young age, low treatment dosage and BP-I diagnosis to be risk factors for treatment drop-out. Physicians should be alert to these differences in their clinical practice.

Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150—450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

Behavioural addictions in bipolar disorder patients: Role of impulsivity and personality dimensions

BACKGROUND Behavioural addictions (BAs) can be understood as disorders characterized by repetitive occurrence of impulsive and uncontrolled behaviours. Very few studies have investigated their association with mood disorders. The present study was undertaken to determine the prevalence of the main behavioural addictions in a sample of bipolar outpatients in euthymic phase or stabilised by medications and to investigate the role of impulsivity and temperamental and character dimensions. METHODS One-hundred-fifty-eight Bipolar Disorder (BD) (DSM-IV) outpatients were assessed with tests designed to screen the main behavioural addictions: pathological gambling (SOGS), compulsive shopping (CBS), sexual (SAST), Internet (IAD), work (WART) and physical exercise (EAI) addictions. TCI-R and BIS-11 were administered to investigate impulsivity and personality dimensions mainly associated with BAs. The clinical sample has been compared with 200 matched healthy control subjects. RESULTS In bipolar patients, 33% presented at least one BA respect to the 13% of controls. Significantly higher scores at the scales for pathological gambling (p<.001), compulsive buying (p<.05), sexual (p<.001) and work addictions (p<.05) have been found. Self-Directness (p=.007) and Cooperativeness (p=.014) scores were significantly lower while impulsivity level was significantly higher (p=.007) in bipolar patients with BA than those without BA. CONCLUSIONS To our knowledge, this is the first study investigating the prevalence of behavioural addictions in BD showing a significant association of these disorders. BAs are more frequent in bipolar patients than in healthy controls and are related to higher impulsivity levels and character immaturity.

Primary Cerebral Blood Flow Deficiency and Alzheimer's Disease: Shadows and Lights

Alzheimers disease (AD) is a degenerative disorder characterized by a decreased regional cerebral blood flow (CBF). It is most likely that a reduction in CBF could displace a pathway leading to AD genesis, in so far neuron death explains a sustained reduction in the supply of oxygen, glucose, and nutrients. Nevertheless, the concept of secondary CBF deficiency cannot explain the critical stages of early memory loss while, on the other hand, the picture of progressive ischemia due to primary CBF decline sheds light on the course of AD in a most persuasive manner. The concept of primary CBF deficiency is even more strengthened by the lack of correlation between degree of dementia and amount of CBF. Vascular abnormalities, frequently observed to co-occur with AD, might play a critical role in the initiation and aggravation of AD pathology given that the elimination of amyloid-β (Aβ) through a vascular route is an important brain Aβ clearance mechanism and its failure leads to formation of vascular amyloidosis and dense-core plaques. The goal of this review is to provide scientists comprehensive knowledge of the state-of the art influence vascular damage and reduced perfusion have on the final development of AD and to hopefully stimulate more research in this area of neuroscience.

Selective serotonin reuptake inhibitors provide significant lower re-hospitalization rates in patients recovering from acute coronary syndromes: evidence from a meta-analysis

Depression is an independent negative prognostic factor in patients with acute coronary syndromes (ACS), yet it is unclear if its treatment is beneficial after ACS. We sought to compare, through a meta-analytic process, antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs) versus control treatment in patients with recent ACS. BioMedCentral, CENTRAL, ISI Web of Science, PsycInfo, and PubMed were searched for pertinent studies (November 2008). We selected studies with randomized allocation to antidepressant drug versus control in patients with acute or recent ACS reported as intention-to-treat. Exclusion criteria were: duplicate publication, regimen of antidepressant drug <4 weeks, follow-up <6 weeks or incomplete follow up, or a lack of clear/reproducible results. Changes from the baseline to the follow-up in depression score, major adverse cardiac events (MACE — including death, myocardial infarction, and repeat revascularization), and hospitalizations were pooled with random or fixed-effect methods. Five randomized trials (801 patients) were included. Fifteen studies were excluded because they were unpublished, ongoing, or duplicates. Subjects treated with antidepressant medications did not show, after a median of six months, a significant improvement in depression symptoms, although there was a trend for a reduction in depression scores. Besides, subjects treated with antidepressant medications showed a significantly lower rate of re-hospitalizations from all causes (risk difference (RD) = 14% (95% confidence interval: 5—23%), p = 0.001). Therapy with antidepressants was notably safe, with similar rates of adverse events, including MACE, death, myocardial infarction, or repeat revascularization (all p > 0.05). Treatment with SSRIs in patients recovering from ACS is associated with significant lower re-hospitalization rates. These data suggest that antidepressant therapy with SSRIs, given its efficacy and safety, should be routinely considered in patients with a recent ACS and depression symptoms.

Oxcarbazepine improves mood in patients with epilepsy.

This study prospectively examined whether continued add-on treatment with oxcarbazepine (OXC) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy. Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale (HDRS), the Cornell Dysthymia Rating Scale (CDRS), the Beck Depression Inventory (BDI), and the Hamilton Anxiety Rating Scale (HARS). Forty controls (patients with epilepsy treated with antiepileptic drugs other than OXC) and 40 OXC-treated patients were enrolled and completed the study. In our study, a significant improvement in affect, as measured by the CDRS, was demonstrated during the course of OXC treatment for 3 months. HDRS and BDI scores also declined in the OXC-treated group, but these decreases did not reach statistical significance. In addition, 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry (score > or =20) demonstrated affective improvement consistent with a treatment-related antidepressant effect (score <20). Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant, the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood.

Bipolar Disorder and Epilepsy: A Bidirectional Relation? Neurobiological Underpinnings, Current Hypotheses, and Future Research Directions

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. In bipolar patients, changes in second-messenger systems, such as G-proteins, phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate, or calcium activity have been described, along with changes in c-fos expression. Common mechanisms at the level of ion channels might include the antikindling and the calcium-antagonistic and potassium outward current-modulating properties of antiepileptic drugs. All these lines of research appear to be converging on a richer understanding of neurobiological underpinnings between bipolar disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders. NEUROSCIENTIST 13(4):392—404, 2007. DOI: 10.1177/1073858407301117

Pregabalin in outpatient detoxification of subjects with mild-to-moderate alcohol withdrawal syndrome.

In this open, prospective study we aimed to investigate the efficacy, medical safety and practicability of pregabalin in outpatient detoxification of alcohol‐dependent patients with mild‐to‐moderate alcohol withdrawal syndrome (AWS). Craving reduction, improvement of psychiatric symptoms and quality of life were the secondary endpoints.

Microstructure of sleep in depressed patients according to the cyclic alternating pattern

BACKGROUND The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Harm avoidance moderates the influence of serotonin transporter gene variants on treatment outcome in bipolar patients

Response to pharmacological treatments is moderated by both genetic and environmental factors. The contribution of such factors is relatively small and complex interactions are likely to be involved. Serotonin transporter gene (SLC6A4) is a major candidate gene associated to response to antidepressant treatment. Moreover, the 5-HTTLPR polymorphism has been associated with anxiety-related traits such as neuroticism and harm avoidance (HA), which are known to influence the risk to develop mood disorders and response to treatments. In the present study we aimed to investigate the interaction between 3 SLC6A4 variants and HA on medium term antidepressant response in a sample of depressed bipolar-spectrum patients followed for 12 months. Contrary to expectations, SLC6A4 variants did significantly influence neither the course of depressive symptoms nor HA scores. However, a significant interaction was observed between HA and 5-HTTLPR genotype. Indeed, a high HA impaired outcome in patients carrying the L(G)/S or the S/S genotype more than in L(A)/L(A) patients. Though a number of limitations characterize the present study, our results indicate HA as a potential moderator of the effect of 5-HTTLPR on the outcome of depression. Given that many factors may influence response to pharmacological treatments, studies that consider personality and other individual characteristics are warranted also in pharmacogenetic investigations.