The primary objective of this randomised, active–controlled, parallel group, double-blind study was to evaluate the tolerability of treatment with either amisulpride or risperidone in elderly patients with schizophrenia aged over 65 years; evaluation of efficacy was a secondary objective.

The study included patients of either sex aged 65 years or older fulfilling DSM IV-diagnostic criteria for psychotic disorders and who presented psychotic symptoms severe enough to require antipsychotic medication. Subjects were randomly allocated to a flexible dose of either amisulpride (100–400 mg/day) or risperidone (1–4 mg/day) for six weeks following a three- to six-day placebo wash-out period. Safety assessment involved adverse event reporting, physical examination, blood pressure, heart rate and ECG monitoring, and laboratory tests. Extrapyramidal symptoms were evaluated with the Simpson–Angus Scale, Barnes Akathisia Scale and the AIMS. Efficacy parameters were changes in score on the PANSS, BPRS, CDS and MMSE scores.

Thirty-eight patients were randomised, 25 to amisulpride and 13 to risperidone. A total of 26 adverse events were experienced by 10 patients in the amisulpride group and five patients in the risperidone group. One patient in each group discontinued the study due to the emergence of a movement disorder. Changes in scores on the three measures of extrapyramidal symptoms were similar in the two groups. The PANSS total score decreased by 27.8% in the amisulpride group and by 29% in the risperidone group between inclusion and study end.

Amisulpride and risperidone are generally well tolerated in elderly patients with schizophrenia. Both drugs appeared to be efficacious in this study population, with no differences in efficacy being observed. However, the sample size was too low to reveal potential inter-group differences. Both these atypical antipsychotics thus appear to be suitable for the treatment of schizophrenia in the elderly.

This Schizophrenia Outcome Survey compared medical costs, psychopathology and adverse events in outpatients for 2 years following hospitalisation for an acute schizophrenic episode.

Adults stabilised with haloperidol, olanzapine or risperidone entered this observational study ≤1 month after discharge and were assessed at baseline, 3, 6, 12, 18 and 24 months using Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Global Assessment of Functioning and adverse events reporting.

Among 323 patients (haloperidol 32, olanzapine 149, risperidone 142), baseline characteristics were similar in the olanzapine and risperidone groups, except for more first episodes in the risperidone group (p = 0.01). Haloperidol patients were more often single and institutionalised, less educated, had more residual schizophrenia, were longer hospitalised in the previous year, took more corrective and psychotropic drugs and had more extrapyramidal symptoms (EPS) and gynaecomastia (all significantly). Sixty-eight percent of patients completed a 2-year follow-up. In all groups, CGI and GAF improved during the first 3 months (both p < 0.0001) while BPRS deteriorated in the first year (all within group changes p < 0.05, between group changes NS) before it stabilised. There were no significant differences in hospitalisations and no change in social profile. At the last visit, 66% of haloperidol (p < 0.01), 35% of olanzapine (NS) and 39% (NS) of risperidone patients had ≥1 EPS; 69% (p < 0.013), 40 and 44%, respectively, had ≥1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p < 0.05) and 2.6 kg (p < 0.05), respectively.

In this naturalistic study, treatment allocation might have introduced a bias in the interpretation of efficiency results, but olanzapine and risperidone caused less EPS than haloperidol during 2 years of outpatient follow-up.

Our aim was to investigate bipolar patients in order to test the validity of various outcome measures and to identify prognostic predictors for pharmacological treatment.

One hundred patients were interviewed using a computerized life-charting program in a descriptive, retrospective analysis. The concept “Burden of illness” was defined as a combination of severity and duration of episodes. Response to treatment was defined as the difference in burden before and after treatment, a low burden during treatment, and freedom of episodes for at least 3 years after insertion of treatment.

The absence of mixed episodes and a high initial burden predicted a good response measured as the difference in burden. If remission for 3 years or a low burden during lithium treatment was used, the absence of rapid cycling and of mixed episodes were the most important predictors. The severity of illness before treatment had no impact.

We suggest the use of absolute measures of severity during treatment as the most appropriate measure of the outcome. Furthermore, our data provide corroboration that treatment with lithium ameliorates the prognosis of the illness, but that mixed episodes and rapid cycling predict a poorer response to lithium.

This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients.

In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1000–2400 mg/day) or divalproex (750–2000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were ≤12 for remission and ≥15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study.

Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p = 0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p < 0.01).

Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Cholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer’s disease (AD) and results are contradictory.

We performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.

Two of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p = 0.016; rs4900442: p = 0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p = 0.006). Haplotypes including both SNPs were calculated and haplotype G–C was identified to influence the risk of AD (p = 0.005). AD patients and non-demented controls, who were carriers of the G–C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p = 0.001) and cholesterol (p < 0.001).

Our results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.

Fyn tyrosine kinase is a member of the Scr family that phosphorylates the NR2A and NR2B subunits of the NMDA receptors reducing the inhibitory effects of ethanol and therefore may regulate the individual sensitivity to ethanol.

To investigate whether there is any relationship between the polymorphism at position −93 of the Fyn kinase gene and the susceptibility to develop alcoholism.

We studied the distribution of genotypes and alleles of the polymorphism −93A/G (137346 T/C) in the 5′ UTR region of the fyn gene in 207 male heavy drinkers (119 with alcohol dependence and 88 with alcohol abuse) and 100 control subjects from Castilla y León (Spain).

The frequency of G allele carriers was higher in alcohol dependents than in alcohol abusers (47.9% vs 30.6%; p = 0.015; OR = 2.077; 95% CI 1.165–3.704).

Our results show that the −93G allele of Fyn kinase gene is associated with higher risk to develop alcohol dependence in Spanish men.

As executive dysfunctions frequently accompany alcohol dependence, we suggest that reports of executive dysfunction in alcoholics are actually due, in some case to a maternal history of alcohol misuse (MHA+). A history of maternal alcohol dependence increases the risk for prenatal alcohol exposure to unborn children. These exposures likely contribute to executive dysfunction in adult alcoholics. To assess this problem, we propose a case-comparison study of alcohol-dependent subjects with and without a MHA.

Ten alcohol-dependent subjects, with a maternal history of alcoholism (MHA) and paternal history of alcoholism (PHA), were matched with 10 alcohol-dependent people with only a paternal history of alcoholism (PHA). Executive functions (cancellation, Stroop, and trail-making A and B tests) and the presence of a history of three mental disorders (attention deficit hyperactivity disorder, violent behavior while intoxicated, and suicidal behavior) were evaluated in both populations.

Alcohol-dependent subjects with MHA showed a significant alteration in executive functions and significantly more disorders related to these functions than PHA subjects. The major measures of executive functioning deficit are duration on task accomplishment in all tests. Rates of ADHD and suicidality were found to be higher in MHA patients compared to the controls.

A history of MHA, because of the high risk of PAE (in spite of the potential confounding factors such as environment) must be scrupulously documented when evaluating mental and cognitive disorders in a general population of alcoholics to ensure a better identification of these disorders. It would be helpful to replicate the study with more subjects.

To compare patterns of temperament and character and the prevalence of Obsessive-Compulsive Personality Disorder (OCPD) and OCPD traits in parents of children with OCD and parents of healthy controls.

TCI and SCID-II were administered to 63 parents of 32 children with OCD and 63 parents of age- and sex-matched controls with no psychiatric diagnosis. Interviewers were not blind to proband status. Personality dimension scores and frequencies of OCPD criteria in both groups were compared after excluding parents with a diagnosis of OCD. Relationships between TCI dimensions and OCPD symptoms in parents and the clinical characteristics of OCD children were also studied.

Parents of OCD children presented significantly higher scores in harm avoidance and lower scores in self-directedness, cooperativeness and reward dependence than parents of healthy children. A higher incidence of OCPD was found in parents of probands (p < 0.02). Hoarding, perfectionism and preoccupation with details were significantly more frequent in parents of OCD children. Counting, ordering and cleaning compulsions in OCD children predicted elevated odds of perfectionism and rigidity in their parents.

The existence of the dimensional personality profile associated with OCD in parents of children with OCD and the higher number of OCPD criteria in these parents in comparison to parents of healthy children highlight the importance of the role of personality factors in familial OCD.