Anomalous self-experiences and their relationship with symptoms, neuro-cognition, and functioning in at-risk adolescents and young adults.

Empirical and theoretical studies support the notion that anomalous self-experience (ASE) may constitute a phenotypic aspect of vulnerability to schizophrenia, but there are no studies examining the relationship of ASE with other clinical risk factors in a sample of ultra-high risk (UHR) subjects. The aim of the present study was to explore the relationship between ASE, prodromal symptoms, neurocognition, and global functioning in a sample of 45 UHR adolescents and young adults (age range 15-25years) at first contact with Public Mental Health Services. Prodromal symptoms and global functioning were assessed through the SIPS interview. ASE was evaluated through the Examination of Anomalous Self-Experience (EASE); for neurocognition, we utilized a battery of tests examining seven cognitive domains as recommended by the Measurement And Treatment Research to Improve Cognition in Schizophrenia. In the UHR group, higher levels in two domains of the EASE (stream of consciousness and self-awareness) were found in comparison with help-seeking subjects. Correlational analysis corrected for possible confounding variables showed a strong association (p>0.001) between higher EASE scores and global functioning. A principal factor analysis with Varimax rotation yielded a two-factor solution, jointly accounting for 70.58% of the total variance in the UHR sample. The first factor was comprised of SOPS domains, while the second was comprised of EASE-total, EASE-10, and GAF variables. Our findings provide support for the notion that disorders of self-experience are present early in schizophrenia and are related to global functioning. As such, they may constitute a potential marker of risk supplementing the UHR approach.

Basic symptoms and psychotic symptoms: their relationships in the at risk mental states, first episode and multi-episode schizophrenia.

In the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.

Deep transcranial magnetic stimulation for treatment-resistant bipolar depression: a case report of acute and maintenance efficacy.

Deep Transcranial Magnetic Stimulation (dTMS) is currently being evaluated as a possible treatment for several neuropsychiatric disorders and has been demonstrated as a safe and effective procedure. This case presents a patient with bipolar depression that has been treated with 20 daily consecutive dTMS sessions and with one dTMS session every 2 weeks for the following 3 months. Depressive symptoms improved rapidly and response was maintained during the next 6 months; cognitive performances also improved. This report suggests that add-on dTMS may help overcoming drug-resistance in bipolar depression and protect from subsequent bipolar episodes of any polarity.

Neurodevelopment in schizophrenia: the role of the wnt pathways.

OBJECTIVES: To review the role of Wnt pathways in the neurodevelopment of schizophrenia. METHODS: SYSTEMATIC PUBMED SEARCH, USING AS KEYWORDS ALL THE TERMS RELATED TO THE WNT PATHWAYS AND CROSSING THEM WITH EACH OF THE FOLLOWING AREAS: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action. RESULTS: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established. CONCLUSIONS: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Epilepsy and brain injury: a case report of a dramatic neuropsychiatric vicious circle.

PRIMARY OBJECTIVE: Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery. DESIGN: Case description. A 51 years-old man had a history of putative petit mal seizures since adolescence and left frontotemporal lobectomy after a major traffic accident at age 17. He subsequently developed quickly generalizing partial complex seizures, associated with severe behavioural alterations and personality changes; the condition was left untreated. A further seizure-related loss of consciousness led to another traffic accident at age 47. METHODS AND PROCEDURES: The patient was administered 200 mg/day topiramate, 600 mg/day quetiapine, 1000 mg/day valproate, 1200 mg/day gabapentin and 800 mg/day carbamazepine. MAIN OUTCOMES AND RESULTS: The instituted anti-epileptic treatment reduced seizure frequency and severity, but did not affect psychiatric symptomatology, which even worsened. An association between anti-epileptic drugs with mood stabilizing properties and an atypical anti-psychotic dramatically improved psychiatric symptoms, but did not prevent the patient from needing long-term healthcare. CONCLUSIONS: Long-term untreated epilepsy may expose to accident proneness and further psychiatric deterioration. Early diagnosis and treatment of epilepsy may help in avoiding a potentially lethal vicious circle.

[Functional neuroimaging of the amygdala: the response to threatening and phobogenic stimuli]. / Neuroimaging funzionale dell'amigdala: la risposta a eventi minacciosi o fobigeni.

Recent functional neuroimaging studies show that the amygdala has a central role in threat evaluation, in response to conditioned and unconditioned stimuli, in fear learning and fear extinction. The amygdala is involved in the pathophysiology of phobias and anxiety. In this review we critically examine the main findings of functional neuroimaging studies reporting data on the amygdala. Findings suggest that the response of the amygdala to threatening stimuli is mainly modulated by the infralimbic and prefrontal cortices, which inhibit activation of the amygdala (top-down inhibition), and by the hippocampus, the function of which is related to stimulus learning. The activity of the amygdala is modulated by various factors, like stimulus type and origin, emotion triggered by stimulus perception, and attention. The neural network comprising the amygdala and the frontal cortex is involved not only in top-down inhibition, but also in the emotional perception of facial expressions. This network also includes the thalamic pulvinar, which is densely interconnected with the amygdala, directly or indirectly, and which is activated by emotional face recognition of scary fear. Both top-down inhibition mechanisms and emotional face recognition are altered in anxiety disorders, particularly in specific and social phobia, resulting in reduced amygdalar activity inhibition after anxiety - or fear - inducing stimulus perception. Future functional neuroimaging studies will be able to provide new insights of normal and altered neurophysiology of the amygdala.

The wnt pathway in mood disorders.

OBJECTIVES: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders. METHODS: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion. RESULTS: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders. CONCLUSIONS: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.

Insight and awareness as related to psychopathology and cognition.

BACKGROUND: Insight affects adherence and treatment outcome and relates to cognitive impairment and psychopathology. We investigated the relationship of insight with cognition in patients with major depression, schizophrenia and bipolar disorder in acute psychiatric care, long-term inpatient, and outpatient settings. METHODS: Eighty-one patients (women, 59.5%; age, 45.9 ± 13.5 years; 27 in each setting group; 33.3% with DSM-IV bipolar disorder, 39.5% with unipolar major depression, and 27.2% with schizophrenia) underwent the Wisconsin Card Sorting Test (WCST) to test flexibility, clinician-rated Scale to Assess Unawareness of Mental Disorder (SUMD), and self-rated Insight Scale (IS) to assess insight/awareness. RESULTS: Poor performance on the WCST correlated with higher SUMD scores such as current psychiatric illness unawareness, impaired symptom attribution, unawareness of medication effect, or of social consequences, but not with IS scores. The latter correlated with days on continuous treatment. Patients receiving psycho-education showed greater symptom awareness compared to patients treated with drugs alone. Cognitive flexibility and diagnostic category did not correlate. Poor insight corresponded with severe mental illness, particularly acute psychosis. CONCLUSIONS: Treatment setting specificity reflects psychopathology and severity. Insight is inversely proportional to illness severity and cognitive flexibility, which is also affected by psychopathology. Limitations comprise group heterogeneity, cross-sectional design, and limited sample size.

Successful and rapid response to electroconvulsive therapy of a suicidal patient with comorbid bipolar I disorder and histrionic personality disorder.

A woman with bipolar disorder I, histrionic personality disorder, and suicidal ideation with repeated suicide attempts, who had been treated for 2 years with mood stabilizers, antipsychotics, and benzodiazepines, received a total of 8 bitemporal-biparietal electroconvulsive therapy sessions. Her suicidal ideation and self-harm behavior disappeared immediately after the first session and her psychopathology soon after. This supports the existence of a relatively independent suicidal syndrome and confirms data on its immediate responsiveness to electroconvulsive therapy. Electroconvulsive therapy must not be long withheld from patients with such characteristics to reduce unnecessary sufferance and suicidality.

Electroconvulsive therapy in a physically restrained man with comorbid major depression, severe agoraphobia with panic disorder, and histrionic personality disorder.

A 36-year-old man with comorbid panic disorder with agoraphobia, major depression, and histrionic personality disorder since age 21 was resistant to combined drug and psychotherapy treatment. His conditions had progressively worsened with time, causing him to withdraw socially and to simultaneously require continuous physical restraint, which further worsened his functioning. He spent almost 3 consecutive years in restraint, until he consented to receive bilateral ECT treatment. He improved after 13 sessions in all areas (social and role functioning, and panic, depressive, and histrionic symptoms) and is well 3 months later with a lithium-atypical antipsychotic combination.

Duloxetine in the treatment of elderly people with major depressive disorder.

INTRODUCTION: The elderly population is more frequently subjected to depressive mood compared to the general population and show peculiarities affecting responsiveness; furthermore, aged people need also special care. Duloxetine is a relatively new antidepressant that proved to be effective in adult depression, but has received little attention in elderly population heretofore. AIM: To review the evidence of duloxetine in late-life major depressive disorder (MDD). METHOD: A systematic review of studies focusing on the use of duloxetine in MDD in the elderly has been carried out through the principal specialized databases, including PubMed, PsycLIT, and Embase. RESULTS: Only a handful of papers were specifically dedicated to this issue. Duloxetine was found to be effective and safe in old-age MDD, to be better than placebo on many clinical measures in all studies, and to better differentiate from placebo with respect to selective serotonin reuptake inhibitors. Compared to placebo, its side-effect profile is slightly unfavorable and its drop-out rate is slightly higher. Furthermore, when pain is present in old-age MDD, duloxetine is able to reduce it. CONCLUSIONS: The efficacy and safety of duloxetine in old-age depression are similar to those encountered in adult MDD. There is a relative lack of comparative studies other than with placebo. The special needs of elderly patients with MDD must be addressed with close patient contact to avoid the perils of inappropriate dosing.

Relationship between handedness and persistent emotional distress in adults experiencing an earthquake.

AIM: Post-traumatic emotional distress follows exposure to trauma and may be affected by atypical cerebral lateralisation. We aimed to explore the relationship between handedness and emotional dysfunction in people exposed to a nat-ural disaster. METHODS: About 22 months after an earthquake, 326 exposed adults completed the Edinburgh Handedness Inventory, the Impact of Events Scale-Revised, and the Insomnia Severity Index. RESULTS: Mixed-handed people, compared to right-handed, had a 3.3 fold increase in odds to have emotional distress. Consistent left-handers scored higher than consistent right- and mixed-handers on the ISI scale. CONCLUSIONS: Findings support that lateral preference is associated with emotion-al distress in people exposed to trauma.

Life-saving electroconvulsive therapy in a patient with near-lethal catatonia.

A young woman with bipolar I disorder and comorbid catatonia on enteral nutrition from several months, developed a form of near-lethal catatonia with weight loss, pressure sores, muscle atrophy, electrolyte imbalance, and depression of vital signs. A compulsory treatment was necessary, and informed consent was obtained from her mother for electroconvulsive therapy (ECT). After 7 ECT sessions, the patient recovered and resumed feeding. ECT may save the life of a patient with catatonia provided that legal obstacles are overcome. Clinicians should carefully evaluate patients with near-lethal catatonia, taking into account the risk of pulmonary embolism and other fatal events. The medical-legal issues, which vary across state regulations, should be addressed in detail to avoid unnecessary and potentially harmful delay in intervention.

Subjective disturbance of perception is related to facial affect recognition in schizophrenia.

To examine the relationship between facial affect recognition (FAR) and subjective perceptual disturbances (SPDs), we assessed SPDs in 82 patients with DSM-IV schizophrenia (44 with first-episode psychosis [FEP] and 38 with multiple episodes [ME]) using two subscales of the Frankfurt Complaint Questionnaire (FCQ), WAS (simple perception) and WAK (complex perception). Emotional judgment ability was assessed using Ekman and Friesen's FAR task. Impaired recognition of emotion correlated with scores on the WAS but not on the WAK. The association was significant in the entire group and in the ME group. FAR was more impaired in the ME than in the FEP group. Our findings suggest that there is a relationship between SPDs and FAR impairment in schizophrenia, particularly in multiple-episode patients.

Suicide in a large population of former psychiatric inpatients.

AIMS: The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM-IV diagnoses. METHODS: We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35-year period in a private hospital setting. We collected sociodemographic, clinical and temperamental data. RESULTS: Ninety-six patients from the sample committed suicide. There were no sex differences in suicide completion and no differences between major psychiatric disorders, but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression. Shorter-term treatment with lithium and anticonvulsants, longer-term treatment with antidepressants, history of suicide attempts, suicidal thinking, and single status positively predicted completed suicide. Suicide tended to occur after a mean period of about 14 years of duration of disease. Patients' symptoms during the period preceding suicide were assessed through interviewing patients' physicians or family members. Symptoms occurring in >10% of cases were, in decreasing order, inner tension, racing/crowded thoughts, aggressive behavior, guilt, psychomotor agitation, persecutory ideation, anxiety, and hallucinations. Surprisingly, cyclothymic temperament was less associated with completed suicide as compared to other temperaments. CONCLUSIONS: Suicide is likely to occur in a milieu of agitation, mixed anxiety and depression, and psychosis. Longer-term mood stabilizer treatment may reduce the rate of completed suicide.

Personality changes after Toscana virus (TOSV) encephalitis in a 49-year-old man: A case report.

Toscana virus (TOSV) infection may often cause symptomatic meningitides and encephalitides. These usually subside in few days and their sequelae do not last for more than few weeks. We here report the case of a 49-year-old man who developed encephalitis after being bitten by phlebotomi in a region near southern Tuscany, where TOSV is endemic, and who developed postencephalitic seizures and subsequently, persistent personality alterations, characterized by sexually dissolute behavior and aggressiveness. One year after infection, the patient needs a combination of an SSRI antidepressant and a mood stabilizer/anticonvulsant to obtain less than optimal symptom improvement. This points to the need of establishing better preventive measures in Tuscany and nearby regions.

Bipolar disorder presenting as stalking--a case report.

BACKGROUND: Stalking behaviour may find its roots in an individual's psychological development and culture-related factors that facilitate it. Psychiatric disorders may underlie some stalking cases, but no reports exist of the relationship of actual psychiatric status with the expression of stalking behaviour. CASE REPORT: A 22-year-old adoptive woman perpetrated stalking towards her gynaecologist, who took legal action to protect herself. She was admitted to a general hospital psychiatric department and diagnosed with bipolar disorder-I, manic phase, and personality disorder, not otherwise specified. She was prescribed lithium and valproate combination and followed-up as an outpatient. She underwent cognitive-behavioural therapy incorporating Bowlby's concepts. Stalking behaviour did not reemerge. CONCLUSION: Exacerbations of psychiatric episodes may trigger stalking behaviour. Drug treatment may prevent its clinical expression, but underlying ideation and affect may need long-term psychotherapy focusing on attachment.

Persistent interferon-ß-1b-induced psychosis in a patient with multiple sclerosis.

Interferon-ß is used in patients with multiple sclerosis to reduce autoimmunity; although other psychiatric side-effects are common, in contrast to interferon-alpha, psychosis has been reported only once. A patient with multiple sclerosis developed auditory hallucinations, paranoid delusions, and increased aggressiveness after 16 months of treatment with interferon-ß-1b, 250 mg every other day. He responded after about one month to antipsychotic treatment, but tended to relapse upon dose reduction, and after 2 years still needs antipsychotics to control his symptoms. Because there was no change in his magnetic resonance imaging between pre- and post-treatment with interferon, we concluded that psychosis was more related to interferon treatment than to the underlying disease.

Mixed Features in Depression: The Unmet Needs of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition introduced the specifier "with mixed features" including 3 or more nonoverlapping typical manic symptoms during a major depressive episode in bipolar disorder type I or II or unipolar major depressive disorder. Excluding overlapping excitatory symptoms, which are frequently observed in mixed depression, leaves many patients with mixed depression undiagnosed. As a consequence, alternative diagnostic criteria have been proposed, claiming for the inclusion in the rubric of mixed features the following symptoms: psychomotor agitation, mood lability, and aggressiveness. A deeper diagnostic reconsideration of mixed features in depression should be provided by the new nosologic classification systems.

Serum levels of risperidone and its metabolite, 9-hydroxyrisperidone: correlation between drug concentration and clinical response.

The aim of this study was to assess a method able to analyze serum levels of risperidone (RIS) and its metabolite, 9-hydroxyrisperidone (9-OH-RIS), and to investigate possible relationships between changes in serum concentrations of these drugs and clinical measures, so to identify early markers of treatment response. The authors developed a sensitive and specific liquid chromatography-tandem mass spectrometry method to measure RIS and its metabolite in serum. Fifteen RIS-naive patients were admitted to an acute psychiatric care unit and treated with 4-6 mg/d oral RIS. At days 7 and 21 of hospital stay, serum levels were measured; clinical scales and serum prolactin were assessed. RIS and its metabolite were analyzed by a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer in the multiple reaction-monitoring mode. Chromatographic separation was accomplished using a cyano column with an analytical run of 9 minutes. The calibration curve exhibited consistent linearity and reproducibility in the range 0-100 ng/mL for both analytes. Lower limit of quantification was 0.2 ng/mL; limit of detection, for a signal to noise ratio of 3, was 0.05 ng/mL for both analytes. Serum RIS and 9-OH-RIS levels increased at day 7, reaching a steady state, and remaining constant up to day 21. Scores on psychopathology rating scales decreased; serum prolactin and neurological rating scale for extrapyramidal effects rose at day 7 and remained stable thereafter. No correlation was found between serum concentration values, including sum and ratio of RIS and 9-OH-RIS, and any of the other clinical values (serum prolactin and clinical scales). These data indicate that clinical changes are related to the achievement of steady state levels of RIS and its metabolite and are maintained, but not continued, with continued RIS treatment. Therapeutic drug monitoring of RIS and its metabolites is not recommended as a routine procedure in patients with psychotic disorders.