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.

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.

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.

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.

Intracranial meningiomas in the 9th decade of life: a retrospective study of 17 surgical cases.

The general availability of cerebral computed tomographic and magnetic resonance imaging scans makes the observation of symptomatic intracranial meningiomas in very elderly patients (aged 80 yr or more) relatively frequent. A few authors have reported on patients who have undergone surgery for intracranial meningiomas in their 9th decade of life, without providing indications regarding the surgical criteria and the prognostic factors. We report on a series of 17 patients who have received surgery for intracranial meningiomas in their 9th decade of life, with the goal of determining some surgical criteria for general physicians and neurosurgeons. Patients with severe systemic disease and definite functional limitations (American Society of Anesthesiology Class III) had a major postoperative morbidity (P = 0.020) and mortality (P = 0.005), especially if they scored low (< 70) on the preoperative Karnofsky Rating Scale (P = 0.010). The risk of postoperative morbidity was higher when the maximum diameter of the tumor was > 5 cm (P = 0.031).

Peduncular hallucinosis following a transoral odontoidectomy for cranio-vertebral junction malformation. A case report.

This is a case report of a sixty-two years old man suffering from a cranio-vertebral malformation whose dens epistrophei was removed through a transoral approach. During the postoperative course, he experienced a transient peduncular hallucinosis probably caused by surgical trauma on his brainstem. The possible physiopathological, etiopathological, clinical, and therapeutic aspects of this rare phenomenon are discussed.

Drugs and human interactions.

Some reflections and hypotheses on drugs and human interactions are presented from a psychiatric-psychotherapeutic point of view. Considering the drug both as an agent and a relational mediator, an attempt is made to systematize the interactive whole of the intraindividual and interindividual effects activated by drugs. The hypothesis is presented that pharmacological effects on mind are prevalently due to an energic action and that this action is status-specific, in other words relative to a mental-relational good order of the individual in that particular moment of his history. Concerning the extra-pharmacological effects in therapeutic relations, the values assumed from the drug during the course of the interaction are different and variable, depending in the same individual (patient or therapist) on superimposition of several experiential and semantic orders. Finally some elements of drug relational psychology are introduced.

[Psychiatric approach to the clinical aspects of drug dependence: psychiatric comorbidity in drug addicts]. / L'approccio psichiatrico alla clinica delle tossicodipendenze: la comorbidità psichiatrica nel paziente tossicodipendente.

The authors analyze the most important theoretical models in the field of drug addiction: the moral, the medical, the psychodynamic and the psychiatric model, with particular reference to the concepts of comorbidity and dual diagnosis. It is pointed out as these approaches invariably lead to a dichotomy between the "defect/process" model and the "conflict/development" model. The proposed hypothesis is an attempt to reconcile the opposite points of view in an unitary vision: on the basis of the fundamental psychopathological elements (drive dyscontrol and dependence), the addicts are so distributed into three areas, different for nosography and treatment.

[Target symptoms in the utilization of antidepressants]. / Les symptômes-cibles dans l'utilisation des antidépresseurs.

The authors intend to bring their contribution to the controversial question of target symptoms in the use of antidepressants. An extensive literature is analyzed, and, for comparative purposes, only works in double blind are chosen that use a specific rating scale (H.D.R.S.) in such a way as to obtain results referable to homogeneous symptoms on the phenomenal level and therefore qualitatively comparable among themselves. Each item of the H.D.R.S. is compared to the target symptom only if the relative score shows a statistically significant decrease, not only in comparison to the length of treatment, but above all in comparison with other antidepressants. On the grounds of the data obtained from this methodology, it is postulated that the relation between the action of a drug and the positive response to treatment is not to be placed in comparison with phenomenal traits, but in comparison with psychopathological processes that would make up the effective targets of the action of a drug.

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.

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.

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.