The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.

There is convincing evidence that schizophrenia is characterized by abnormalities in brain volume. At the Department of Psychiatry of the University Medical Centre Utrecht, Netherlands, we have been carrying out neuroimaging studies in schizophrenia since 1995. We focused our research on three main questions. First, are brain volume abnormalities static or progressive in nature? Secondly, can brain volume abnormalities in schizophrenia be explained (in part) by genetic influences? Finally, what environmental factors are associated with the brain volume abnormalities in schizophrenia?

Based on our findings we suggest that schizophrenia is a progressive brain disease. We showed different age-related trajectories of brain tissue loss suggesting that brain maturation that occurs in the third and fourth decade of life is abnormal in schizophrenia. Moreover, brain volume has been shown to be a useful phenotype for studying schizophrenia. Brain volume is highly heritable and twin and family studies show that unaffected relatives show abnormalities that are similar, but usually present to a lesser extent, to those found in the patients. However, also environmental factors play a role. Medication intake is indeed a confounding factor when interpreting brain volume (change) abnormalities, while independent of antipsychotic medication intake brain volume abnormalities appear influenced by the outcome of the illness.

In conclusion, schizophrenia can be considered as a progressive brain disease with brain volume abnormalities that are for a large part influenced by genetic factors. Whether the progressive volume change is also mediated by genes awaits the results of longitudinal twin analyses. One of the main challenges for the coming years, however, will be the search for gene-by-environment interactions on the progressive brain changes in schizophrenia.

The florid positive symptoms of schizophrenia (hallucinations, delusions, grossly disordered thinking) are often obvious. By comparison, negative symptoms (flattened affect, impoverished speech, apathy, avolition, anhedonia) are subtler and more difficult to recognize and diagnose. However, there is increasing recognition of the importance of negative symptoms in patients with schizophrenia. Secondary negative symptoms attributable to such factors as unrelieved positive symptoms, the adverse effects of antipsychotic pharmacotherapy, or social isolation may subside with resolution of such factors. In contrast, primary negative symptoms are an intrinsic aspect of schizophrenia; they are persistent and have been associated with poorer clinical outcomes. Although the lack of a reliably effective treatment for negative symptoms is a serious unmet need in this patient population, accurate diagnosis is still important. Assessment of suspected negative symptoms, using validated rating scales, can help to rule out comorbid affective or cognitive disorders that may mimic negative symptoms and to distinguish primary negative symptoms from potentially reversible secondary negative symptoms. This article reviews the definitions and classification of negative symptoms, compares the tools available for their assessment, and offers practical clinical algorithms for sorting through the differential diagnosis.

The poorly understood aetiology of schizophrenia is known to involve a major genetic contribution even though the genetic factors remain elusive. Most genetic studies are based on Mendelian rules and focus on the nuclear genome, but current studies indicate that other genetic mechanisms are probably involved. This review focuses on mitochondrial DNA (mtDNA), a maternally inherited, 16.6-Kb molecule crucial for energy production that is implicated in numerous human traits and disorders. The aim of this review is to summarise the studies that have explored mtDNA in schizophrenia patients and those which provide evidence for its implication in this illness. Alterations in mitochondrial morphometry, brain energy metabolism, and enzymatic activity in the mitochondrial respiratory chain suggest a mitochondrial dysfunction in schizophrenia that could be related to the genetic characteristics of mtDNA. Moreover, evidence of maternal inheritance and the presence of schizophrenia symptoms in patients suffering from a mitochondrial disorder related to an mtDNA mutation suggest that mtDNA is involved in schizophrenia. The association of specific variants has been reported at the molecular level; however, additional studies are needed to determine whether the mitochondrial genome is involved in schizophrenia.

Nicotine has been proposed to provide anxiety relief, oral gratification and self-medication of psychotic symptoms in psychiatric patients. In order to investigate the relations between psychopathology and tobacco use we measured the concentration of cotinine, the major metabolite of nicotine, in the saliva of psychiatric patients and healthy volunteers. In a sample of 42 schizophrenic patients we correlated smoking status, cotinine levels, symptom profiles (PANSS), and neuroleptic side effects (Simpson–Angus). Despite reporting the same amount of cigarettes consumed per day the saliva concentration of cotinine was significantly higher in patients with schizophrenia than in the controls. There were no significant differences in clinical characteristics between smoking and non-smoking schizophrenic patients, but smokers tended to be on higher drug doses. High cotinine concentrations correlated significantly with the negative symptoms Passive withdrawal and Social avoidance. The results indicate that the schizophrenic patients smoke cigarettes more intensely than other patients and healthy subjects. The correlation between high cotinine levels and negative symptomatology may reflect an attempt by schizophrenic patients to overcome the emotional withdrawal and thus the results may lend support to a self-medication hypothesis.

Until now, the instruments for the clinical evaluation of impulsivity have relied essentially on either personality inventories or to a lesser extent on specific questionnaires. Therefore this paper presents the preliminary results of a new rating scale: the Impulsivity Rating Scale (IRS). This is a 7-item hetero-evaluation of impulsivity based on the behaviour of the patient in usual life situations. The administration of the scale is easy and short: 15 minutes. The IRS was tested in five different population samples: 31 impulsive inpatients, 36 adults with major depressive episode, 15 healthy control subjects, 56 smokers before and after one week of tobacco withdrawal, and 47 adolescent depressed inpatients before and four weeks after antidepressant treatment. The results show good construct validity, good concurrent validity, good inter-rater reliability and sensitivity to change. A threshold of 8 for the total score (range 0 to 21) gives good specificity and sensitivity. The principal component analysis shows the existence of a main factor composed of all items, with lower correlation for two items which may belong to a second factor needing further investigations.

Persistent psychotic symptoms represent a major challenge for psychiatric care. Basic research has shown that psychotic symptoms are associated with cognitive biases. Metacognitive training (MCT) aims at helping patients to become aware of these biases and to improve problem-solving. Fifty-two participants fulfilling diagnostic criteria of schizophrenia or schizoaffective disorders and persistent delusions and stabilized antipsychotic medication were enrolled in this study. Following baseline assessment patients were randomized either to treatment as usual (TAU) conditions or TAU + MCT. The intervention consisted of eight weekly 1-hour sessions (maximum: 8 hours). Participants were assessed at 8 weeks and 6-months later by blind assessors. Participants were assessed with the Psychotic Symptoms Rating Scales (PSYRATS) and the positive subscale of the PANSS. Between-group differences in post- and pre-test values were significant at a medium effect size in favor of the MCT for the PSYRATS delusion scale and the positive scale of the PANSS both at post and follow-up. The results of this study indicate that MCT training has a surplus antipsychotic effect for patients suffering from schizophrenia-related disorders who demonstrate only a partial response to antipsychotic treatment and that the effect of the intervention persists for at least 6 months after the intervention.

Insight is a complex phenomenon that can be interpreted according to a dimensional model. Given the controversial data of insight in obsessive–compulsive disorder (OCD), our study aimed to investigate insight in an Italian sample of patients with OCD by means of the specific item on the Yale–Brown obsessive–compulsive scale (Y-BOCS) and to explore the possible correlations between it and clinical features. One hundred and seventeen out-patients with a DSM-IV diagnosis of OCD and different comorbid psychiatric disorders were included in the study and assessed by means of the Y-BOCS, Hamilton rating scale for depression (HRSD) and the global clinical impression. The results showed that almost 50% of the patients had an excellent level of insight and 15% had a little or no insight. No correlation between levels of insight and clinical features was observed, except for a negative trend with the presence of somatic obsessions. In addition, a trend towards a lower level of insight was observed in those bipolar patients with a positive history of repeated manic or hypomanic episodes. Further studies seem to be necessary in order to establish whether or not OCD patients with poor insight represent a distinct sub-group of patients.

Objective. It is widely known that the risk of suicide is higher in cases of major depressive disorders in comparison to the general population. The purpose of this study was to examine which psychopathologic symptoms during the index episode are predictors for an increased risk of suicide in the further course of major depression. Method. Mortality data were determined from a prospective study of 280 patients with major depression (DSM-III-R, single episode or recurrent) during a follow-up period of 5 years. The predictive power of different depressive symptoms including psychotic symptoms for suicide risk was investigated. Results. Patients who committed suicide (N = 16) during the follow-up period had reported significantly more often hypochondriacal preoccupations or delusions (but not delusions or preoccupations of impoverishment, guilt or sin), suicidal thoughts and suicide attempts as well as feelings of severe hopelessness during the index episode than still living patients or patients who had died from natural causes. Conclusion. These symptoms seem to be helpful early predictors for the risk of suicide during the further course of illness. This should be taken into account for suicide prevention in the course of major depression.

Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.

Psychiatric disorders, especially depression, are frequent in patients with multiple sclerosis (MS). They are attributed both to the psychosocial impact of a chronic, usually progressive, disabling illness and to cerebral demyelination. Besides, drugs such as corticosteroids and possibly interferon (IFN) may also have depressogenic effects. Major depressive disorders and/or suicidal ideation are a major concern and efforts to identify and minimize these reactions are of much importance. Psychiatric side effects, particularly depression, are widely reported with IFN-α and have been suspected with IFN-β but are not yet fully established. Our review of the literature revealed that most studies discard an association between IFN-β and depression or suicide. However, few patients, especially those with a history of depression, might be at higher risk for depression when treated with IFN-β. Overall, considering the uncertainty of a link between IFN-β and depression and/or suicide, as well as the complete remission of psychiatric complications after IFN discontinuation and/or antidepressant treatment, physicians should closely monitor the psychiatric status of patients, but should not refrain from including them in IFN-β treatment programs, even when they have past or present depression.

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of ≥ 20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), ≥ 7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), ≥ 4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and ≤17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline demonstrated greater efficacy than clomipramine in the intent-to-treat patient group: mean baseline to final visit changes were 50.8% (Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y-BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P < 0.05). The number of patients withdrawing because of adverse events was substantially greater for clomipramine (26%) than sertraline (11%) (P < 0.05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.

Beck and collaborators have proposed a distinction between clinical insight and cognitive insight and have developed a tool for the assessment of the latter, namely the Beck Cognitive Insight Scale (BCIS). The present study explored in 51 patients with a first episode of psychosis the neurocognitive correlates of cognitive insight as assessed with the BCIS. Global measures for seven domains of cognition including verbal learning and memory, visual learning and memory, working memory, speed of processing, reasoning and problem solving, attention, and social cognition were examined. Secondly, we examined whether two clinical insight measures, the Scale to assess Unawareness of Mental Disorder (SUMD) and the insight item from the Positive and Negative Symptoms Scale (PANSS), could produce similar or different patterns of association with neurocognitive functions as those identified with the BCIS. Correlational analyses revealed significant associations between the BCIS Composite Index and the verbal learning and memory. No significant associations were observed between any of the neurocognitive domains and the PANSS or SUMD clinical insight measures, despite high inter-correlations among the three insight measures. These results suggest that cognitive insight, but not clinical insight, may rely on memory processes whereby current experiences are appraised based on previous ones.