Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia.

OBJECTIVE: To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). METHOD: Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. RESULTS: Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. CONCLUSION: These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.

Stigmatization of schizophrenia as perceived by nurses, medical doctors, medical students and patients.

Stigmatization of schizophrenia is widespread and its genetic explanation may potentially increase the stigma. The present study investigated whether seeing schizophrenia as a genetic or environmental disorder might influence perceived beliefs towards people with schizophrenia and whether social stigmatizing attitudes were differently perceived the 202 subjects who were recruited. Perceived social stigmatizing attitudes were compared among participants who read two vignettes depicting a person with schizophrenia. Then, the Standardized Stigmatization Questionnaire (SSQ) was administered. A genetic explanation of schizophrenia was more frequently associated with stigmatizing attitudes. Also, there were higher levels of perceived stigmatization in medical students and medical doctors than in other groups based on their social experience or background. However, the sample size was small and this was a non-experimental design; also the SSQ would benefit from more cross-validation. About half of the participants perceived stigmatizing social attitudes. Finally, considering schizophrenia as a genetic disorder influenced participants perception of other people's beliefs about dangerousness and unpredictability and people's desire for social distance.

Functional neuroimaging in obsessive-compulsive disorder.

BACKGROUND AND AIM: Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling psychiatric disorder that usually emerges during childhood or adolescence. This paper aims to review the literature on functional neuroimaging in OCD, analysing the reported dysfunctional connectivity in the corticostriatothalamocortical circuitry. METHOD: This study included papers published in peer-reviewed journals dealing with functional imaging in OCD. RESULTS: Striatal dysfunction, mainly of the caudate nucleus, leads to inefficient thalamic gating, resulting in hyperactivity within the orbitofrontal cortex (intrusive thoughts) and the anterior cingulate cortex (non-specific anxiety). Compulsions consist of ritualistic behaviours performed to recruit the inefficient striatum and neutralise unwanted thoughts and anxiety. Functional neuroimaging findings are discussed against the background of specific cognitive impairments, mainly regarding visuospatial processing, executive functioning and motor speed. Cognitive deficits are partial and specific, matching imaging data. CONCLUSIONS: Several studies have targeted brain regions hypothesised to be involved in the pathogenesis of OCD, showing the existence of dysfunctional connectivity in the corticostriatothalamocortical circuitry. Improvements in spatial resolution of neuroimaging techniques may contribute to a better understanding of the neurocircuitry of OCD and other anxiety disorders.

Affective temperaments are associated with higher hopelessness and perceived disability in patients with open-angle glaucoma.

AIM: The aims of the study were to study: (i) affective temperaments in open-angle glaucoma (OAG) patients with some degree of functional visual impairment; (ii) psychological well-being and perceived disability, and their associations with affective temperaments; and (iii) associations between visual impairment, affective temperaments and psychological well-being. METHOD: Participants were 91 outpatients (39 women, and 52 men) with open-angle glaucoma (OAG) who were assessed for Visual Field Index, Mean Defect and Pattern Standard Deviation. Patients were also administered the Beck Hopelessness Scale, the TEMPS-A (Rome), the Gotland Male Depression Scale, the Emotional Well-being Scale, the Perceived Disability Questionnaire and the Suicidal History Self-Rating Screening Scale. RESULTS: Open-angle glaucoma patients (compared with a non-clinical sample of university students) had higher scores on the TEMP-A dysthimic and hyperthimic traits and lower scores on cyclothimic, irritability and anxiety traits. Such temperament variability was not linked to differences in severity of glaucoma. We did not find strong evidence supporting the fact that measures of visual impairment were linked to emotional well-being and depression. However, logistic regression analysis revealed that patients may have different patterns related to their illness according to specific temperaments. CONCLUSION: Patients with OAG may have different temperament profiles than non-clinical individuals. Such categorisation may be useful for predicting how they face the illness, for providing better care as well as for early recognition of mood disorders symptoms.

Factor-structure of the Italian version of the Scale Of Prodromal Symptoms (SOPS): a comparison with the English version.

AIMS: The 19-item 'Scale Of Prodromal Symptoms' (SOPS) and its semi-structured interview, the Structured Interview for Prodromal Symptoms (SIPS), have been developed to assess prodromes of psychosis. We assessed psychometric properties of the Italian version of the instrument. METHODS: We collected socio-demographic and clinical data of 128 people seeking first-time psychiatric help in a large Roman area, either as outpatients at community facilities or as inpatients in psychiatric wards of two general hospitals. Participants were administered the Italian version of the SOPS and the 24-item Brief Psychiatric Rating Scale (BPRS). Data were analysed through Pearson's correlation and factorial analysis. RESULTS: The English and Italian SOPS versions showed similar psychometric properties and factorial structure. The best-fit model was trifactorial, explaining 90% of total variance, and roughly corresponding to the positive, negative, and general dimensions, with disorganisation spreading over the other dimensions. Compared with the BPRS, the Italian version of the SOPS showed construct validity and convergent validity. CONCLUSIONS: The factor-structure of the Italian version of the SOPS is similar to those of the English and Spanish versions, in that the factors emerged are the same (positive, negative, and general symptoms). The scale could be used to assess at-risk people in early intervention services.

Folie à deux: double case-report of shared delusions with a fatal outcome.

BACKGROUND: Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks. METHODS: We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years. RESULTS: The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up. CONCLUSIONS: Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives.

BACKGROUND: The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. METHOD: We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. RESULTS: Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. CONCLUSIONS: Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Burnout, hopelessness and suicide risk in medical doctors.

OBJECTIVES: The aim of the present study was to investigate the association between burnout and hopelessness in medical doctors. MATERIALS AND METHODS: We conducted an investigation of 133 medical doctors working either in a hospital setting or in general practice to explore the relationship between the level of burnout and hopelessness, a psychometric marker for suicide risk. The participants were administered the Oldenburg Burnout Inventory (OBI) and Beck's Hopelessness Scale (BHS). RESULTS: Burnout is an important issue in mediating the level of hopelessness. Doctors with high hopelessness had higher scores on the disengagement factor (2.61±0.47 vs 2.14±0.41; t131=-4.37; p<0.001; Cohen D=1.07), and on the exhaustion factor (2.68±0.65 vs 2.19±0.54; t131=-3.39; p<0.001; Cohen D=0.82) than doctors with low hopelessness. A multivariate regression analysis confirmed that disengagement and exhaustion are significant predictors of the BHS scores. CONCLUSIONS: People in charge of workers' health should pay particular attention to the level of burnout in doctors, intervene with changes in the work environment and evaluate the impact of such procedures.

White matter hyperintensities, suicide risk and late-onset affective disorders: an overview of the current literature.

White matter hyperintensities (WMHs) refer to areas of hyperintense signal on T2- or proton density-weighted brain magnetic resonance imaging. Although WMHs are a common finding in patients with bipolar disorder (BD), particularly with a later disease onset, some studies report a higher frequency of WMHs only in unipolar affective disorders. We reviewed the literature examining examining both the severity and presence of WMHs in late life and particularly in individuals with late-onset BD (LOBD). Studies investigating white matter lesions in LOBD were systematically retrieved and the reference lists of these studies were scanned for additional relevant studies of neuroimaging in LOBD. The majority of neuroimaging studies reported an association between older age and LOBD and the presence of WMHs in LOBD. Also, we found in a small sample of patients preliminary evidence of a significant relationship between older age with late-onset BD and WMHs having a higher prevalence of cardiovascular and cerebrovascular risk factors. In conclusion over 60 years older individuals with LOBD and WMHs might have a type of illness characterized by more neuropathological changes and biologically different compared to non LOBD. This is consistent with the hypothesis of vascular mania. WMHs could be a reliable biological risk marker for late onset mood disorders.

Suicide prevention among youths. Systematic review of available evidence-based interventions and implications for Italy.

Suicide completion is a leading cause of death for children, adolescents, and young adults. There is evidence that the suicide rate for those aged 15 to 24 years has tripled since 1950, and suicide is now the second or third leading cause of death in this age group. Recent studies indicate that the incidence of suicide attempts among adolescents may exceed 10% annually. The role of caregivers and schools (as well as colleges and universities) is important in the assessment, management, and prevention of suicidal behaviour in children and youth. Recognition of risk factors for suicide is of paramount importance for prevention. Furthermore, a number of educational programs have demonstrated possible key roles in implementing suicide prevention strategies. As suicide is a problem of concern among Italian youths, this paper overviews current official statistical evidence of the phenomenon and suggests a national suicide prevention strategy based on a number of tools already involved in this field, especially in the USA.

Duloxetine versus venlafaxine in the treatment of unipolar and bipolar depression.

OBJECTIVES: Both duloxetine and venlafaxine are efficacious in treating patients with Major Depressive Disorder (MDD), even though the advantages in treatment patients with bipolar disorder is unclear. This study aimed to evaluate the efficacy of duloxetine vs venlafaxine in the acute treatment of unipolar and bipolar depression. MATERIALS AND METHODS: The study was a non randomized controlled trial. The participants were 62 consecutive outpatients (41 men; 21 women) affected by unipolar and bipolar depression treated either with duloxetine and venlafaxine. RESULTS: More patients treated with duloxetine had a positive response to treatment and remission both for depression (HAMD17 response: 90.3% vs 0.0%; p < .001; HAM-D17 remission: 48.4% vs 0.0%; p < .001), and anxiety (HAM-A response: 90.3% vs 6.5%; p < .001; HAM-A remission: 71.0% vs 6.5%; p < .001) than controls. Patients treated with duloxetine were also more likely to show a decrease in HAM-D17 suicidality (100% vs 45.2%; p less than .001) and an increase in the quality of life (SF-36 percentage of improvement: 6.35 [SD=9.66 vs -2.58 [9.98]; p less than .001) than controls. CONCLUSIONS: Duloxetine is more effective in reducing anxiety and suicidal ideation. Both treatments were safe and tolerated, and both may be successfully used in unipolar and bipolar depression.

The effects of lithium and anticonvulsants on brain structure in bipolar disorder.

OBJECTIVE: To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). METHOD: A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. RESULTS: Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. CONCLUSION: Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing.

A woman lost in the cemetery: A case of time-limited amnesia.

A 43-year-old woman one day experienced a dissociative fugue which she could not recall. She was married, nulliparous, with no history of dissociative disorder or other psychiatric disorders. She had been sexually abused during late childhood-early adolescence. She was examined thoroughly from both psychiatric and medical standpoints to exclude organic causes for her condition. Magnetic Resonance Imaging showed only some non-specific abnormalities. On personality tests, a histrionic structure of personality emerged, with obsessive and narcissistic traits accompanied by rigidity and anxiety, dysphoria and high risk for depression; some impairment was found in executive function tests. Final diagnosis was one of dissociative fugue. In fact, organic traits were not sufficient to establish a diagnosis of Transient Global Amnesia.

Prospective, open study of long-acting injected risperidone versus oral antipsychotics in 88 chronically psychotic patients.

INTRODUCTION: A long-acting, injected, carbohydrate-microsphere preparation of risperidone (RLAI; Risperdal Consta ((R))) is reported to be safe and effective in chronic psychotic illnesses but, as its long-term and comparative efficacy remain unclear, this study compared clinical status during oral antipsychotic treatment versus conversion to RLAI. METHODS: Psychotic patients (n=88; initial BPRS=93+/-5) were treated for 6 months with clinically chosen oral medication and then converted to biweekly RLAI for the first 6 months (6-6 months matched mirror comparison) and then for another 18 months. Clinical status in the two treatment periods and in the 18 months of follow-up was compared with measures including BPRS improvement (primary outcome), CGI variants and SF-36 ratings. RESULTS: RLAI (at a mean dose of 47 mg/2 weeks at six and up to 23.1+/-3.3 months) was associated with major improvements in all outcome measures (p<0.001). Initial BPRS scores fell by an average of 50% within six months; hospitalizations declined from 19.8% to 0%, and rates of adverse events were reduced by 2.5- to 7.4-fold. Such benefits were sustained during 18 months of follow-up with RLAI-treatment. CONCLUSIONS: The findings are limited by the lack of a parallel control treatment, such as with oral risperidone or another antipsychotic, lack of blinded assessments, and a moderate number of subjects. Nevertheless, the findings add to indications that RLAI can be an effective and well-tolerated treatment-option for chronically psychotic patients.

[Predicting risk of suicide in bipolar and unipolar depression: correlation between temperament and personality]. / Prädiktion des Suizidrisikos bei bipolar und unipolar depressiven Patienten: Wechselwirkung von Temperament und Persönlichkeit.

OBJECTIVE: The aim of this study was to evaluate the roles of personality and affective temperament traits in the prediction of suicide risk in mood disorders. METHODS: The participants were 147 psychiatric inpatients with bipolar disorders I and II and major depressive disorder. Patients undertook the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness Scale. RESULTS: Sixty-four subjects were diagnosed with increased suicidal risk based on the Mini International Neuropsychiatric Interview (MINI). Logistic regression analysis resulted in two models predictive of MINI-based suicidal risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis further indicated that higher hyperthymic values are protective against hopelessness, while MINI-based suicidal intent is a predictor of hopelessness. CONCLUSIONS: Personality and affective temperament traits may have a role in the prediction of suicide.

Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats.

Spontaneously depressed flinders sensitive line (FSL) rats showed a reduced expression of mGlu2/3 metabotropic glutamate receptors in the hippocampus, as compared to "non-depressed" flinders resistant line (FRL) rats. No changes in mGlu2/3 receptor protein levels were found in other brain regions, including the amygdala, hypothalamus, and cerebral cortex. Biochemical analysis of receptor signalling supported the reduction of mGlu2/3 receptors in the hippocampus of FSL rats. Accordingly, the selective mGlu2/3 receptor agonist, LY379268 (1microM) reduced forskolin-stimulated cAMP formation by 56% and 32% in hippocampal slices from FRL and FSL rats, respectively. In addition, LY379268 enhanced 3,5-dihydroxyphenylglycine-stimulated inositol phospholipid hydrolysis from 65% to 215% in hippocampal slices from FRL rats, whereas it was inactive in slices from FRL rats. We also examined the behavioural response of FSL rats to systemic injection of LY379268 (0.5mg/kg, i.p., once a day for 1-21 days) by measuring the immobility time in the forced swim test, which is known to be increased in these rats. LY379268 was administered alone or combined with the classical antidepressant, chlorimipramine (10mg/kg, i.p.). LY379268 alone had no effect at any of the selected time-points, whereas chlorimipramine alone reduced the immobility time only after 21 days of treatment. In contrast, when combined with LY379268, chlorimipramine reduced the immobility time during the first 14 days of treatment. These data support the view that mGlu2/3 receptors might be involved in the pathophysiology of depressive disorders, and that pharmacological activation of these receptors may shorten the latency of antidepressant medication.

Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in vitro model for antidepressant drug-induced neurogenesis.

We examined the interaction between the selective serotonin reuptake inhibitor, fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor cells isolated from cultured cerebellar granule cells, considered as an in vitro model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3 receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R-APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the activation of 5-HT(1A) receptors. We found a strong synergism between fluoxetine and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The increased cell proliferation induced by fluoxetine+LY379268 was abrogated by the cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly, fluoxetine and LY379268 also acted synergistically in promoting neuronal differentiation when progenitor cells were incubated in the presence of serum. These data support the hypothesis that a combination between classical antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental treatment of depression.