Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study.

BACKGROUND: Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). METHODS: Twenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. RESULTS: Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. CONCLUSIONS: These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression. OBJECTIVE: To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment. METHODS: This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome. RESULTS: After 5 days of treatment, BDI and HDRS scores decreased significantly (29%±36%, 18%±9%, respectively, P<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (ß=4.92, P<0.01) and multivariate (ß=5.8, P<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (ß=-4.7, P=0.02). A similar trend was observed for tricyclics (ß=-4, P=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs. CONCLUSION: tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.

Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients.

Transcranial direct current stimulation (tDCS) is a selective, painless, brain stimulation technique that allows the electric stimulation of specific cortical regions. TDCS has been recently used as investigational intervention for major depression and treatment resistant depression (TRD) with encouraging results. The present study was aimed to investigate the efficacy and tolerability of tDCS in major depressives with poor response to pharmacological treatment. Twenty-three depressed patients, with a diagnosis of major depressive disorder or bipolar disorder, were treated with augmentative tDCS for 5 days, two sessions per day in a blind-rater trial. The course of depressive symptoms was analyzed using repeated measures ANOVA for HAM-D and MADRS total scores. A qualitative analysis on the basis of the HAM-D response was performed as well. Both analyses were conducted at three time-points: T0 (baseline), T1 (endpoint tDCS) and T2 (end of the first week of follow-up). All patients completed the trial without relevant side-effects. A significant reduction of HAM-D and MADRS total scores was observed during the study (P<0.0001). Treatment response (endpoint HAM-D reduction ≥50%) was obtained by four patients (17.4%) at T1 and by seven patients (30.4%) at T2 and remission (endpoint HAM-D<8) by three patients (13.0%) at T1 and by four subjects (17.4%) at T2. Present findings support the efficacy and good tolerability of tDCS in the acute treatment of patients with TRD with clinical benefit being progressive and extended to the first week of follow-up. Further sham-controlled trials with longer follow-up are needed to confirm present results.

Nimodipine in human alcohol withdrawal syndrome--an open study.

The aim of this study was to evaluate the efficacy and tolerability of the DHP Ca2+ antagonist nimodipine in human AWS and post-AWS. Ten hospitalized alcoholics of both sexes with a diagnosis of AWS according to the DSM-III criteria were treated for 3 weeks in monotherapy with nimodipine p.o. at flexible daily dosages. Evaluation of AWS symptoms was performed at baseline and after 3, 5, 7, 10, 14 and 21 days. A statistically significant improvement of AWS was seen at evaluation on day 3, particularly in neurovegetative and psychopathological symptoms, and lasted up to the end of the study. The treatment was well tolerated and no side effects were observed or reported. In this pilot, open study nimodipine proved effective in the treatment of mild-to-moderate AWS. If these data are confirmed in a double-blind study nimodipine could be a rational alternative to benzodiazepines in the treatment of AWS.

Ritanserin versus lorazepam: a double-blind, cross-over study of reaction times in healthy volunteers.

Ritanserin, a benzydrilen-piperidine derivative, with a potent, selective and long-lasting antagonist activity on serotonin type 2 receptors, has shown anxyolitic properties and a lesser sedative profile than benzodiazepines. Ritanserin and lorazepam at therapeutical doses, were compared in eight healthy volunteers in a double-blind, cross-over study in order to detect possible different impairments of performances. Before and during the treatment, all subjects were daily submitted to a test of rapidity and regularity of response to acoustic and visual stimuli by means of an electronic device. A visual analogue scale for the self-assessment of the drowsiness degree was also administered. Ritanserin did not modify reaction times, while lorazepam significantly prolonged them. The analysis of data within treatments significantly favoured ritanserin, while between treatments there was only a trend in favour of ritanserin. The analogical scale for concentration showed a significant reduction with lorazepam, whereas for drowsiness no alteration occurred with either drug.

Hyperbaric oxygen induced experimental epilepsy: the age factor.

Two methods of inducing convulsions were used in male Swiss albino mice of different ages: exposure to hyperbaric oxygen and pentylenetetrazole treatment. Hyperbaric oxygen proved to be a valid model of experimental epilepsy with an age-dependent trend. The youngest mice presented a much longer convulsion latency time than the adult mice but the curve of distribution of latency time versus age showed progressively increasing sensitivity. Pentylenetetrazole induced convulsions, apart from the youngest subgroup, without variations by age. Hyperbaric oxygen convulsions provide an interesting model for the study not only of the neurochemistry of convulsions but also of the membrane changes that occur in the course of cerebral maturation and aging.

Therapeutic attempts with lithium in young drug addicts.

On the hypothesis that drug addiction may be due to "masked depression", lithium was administered to 20 opiate addicts. Only nine patients took the lithium carbonate tablets for more than a few weeks; during this period they seemed to abstain from taking opiates. After 1 year, all the patients were off lithium and most of them again took opiates. Due to lack of cooperation on the part of the patients, the observations can neither confirm nor refute our hypothesis. The study shows that psychological and socio-environmental factors make trials on drug treatment of opiate addicts almost impossible to carry out.