Functional Neuroimaging in Psychopathy.

BACKGROUND AND AIM: Psychopathy is associated with cognitive and affective deficits causing disruptive, harmful and selfish behaviour. These have considerable societal costs due to recurrent crime and property damage. A better understanding of the neurobiological bases of psychopathy could improve therapeutic interventions, reducing the related social costs. To analyse the major functional neural correlates of psychopathy, we reviewed functional neuroimaging studies conducted on persons with this condition. METHODS: We searched the PubMed database for papers dealing with functional neuroimaging and psychopathy, with a specific focus on how neural functional changes may correlate with task performances and human behaviour. RESULTS: Psychopathy-related behavioural disorders consistently correlated with dysfunctions in brain areas of the orbitofrontal-limbic (emotional processing and somatic reaction to emotions; behavioural planning and responsibility taking), anterior cingulate-orbitofrontal (correct assignment of emotional valence to social stimuli; violent/aggressive behaviour and challenging attitude) and prefrontal-temporal-limbic (emotional stimuli processing/response) networks. Dysfunctional areas more consistently included the inferior frontal, orbitofrontal, dorsolateral prefrontal, ventromedial prefrontal, temporal (mainly the superior temporal sulcus) and cingulated cortices, the insula, amygdala, ventral striatum and other basal ganglia. CONCLUSIONS: Emotional processing and learning, and several social and affective decision-making functions are impaired in psychopathy, which correlates with specific changes in neural functions.

Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature.

OBJECTIVE: The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. DESIGN: The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. RESULTS: Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors. CONCLUSIONS: Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive-compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact.

Relationships between psychopathological variables and insight in psychosis risk syndrome and first-episode and multiepisode schizophrenia.

Insight may vary across psychosis risk syndrome (PRS), first-episode schizophrenia (FES), or multiepisode schizophrenia (MES). We aimed to compare insight domains (awareness, relabeling, and compliance) in PRS, FES, and MES groups and to correlate scores with psychopathological measures. Insight was assessed in 48 (14 PRS, 16 FES, and 18 MES) patients using the Schedule for the Assessment of Insight-Expanded Version. We conducted psychopathological assessment through the Brief Psychiatric Rating Scale (BPRS). In the whole group, the BPRS psychosis factor correlated with all insight domains. In the MES group, the more severe the anxiety/depression, the higher the insight score in the symptom relabeling domain. Insight did not differ significantly between the PRS, FES, and MES groups. Our results suggest that, across different phases of the illness, lack of insight behaves like a trait and is modulated by positive symptom severity. Anxiety and depression may be associated with increased insight in patients with chronic schizophrenia.

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.

Electroconvulsive therapy in a man with comorbid severe obesity, binge eating disorder, and bipolar disorder.

A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.

Effectiveness of electroconvulsive therapy in a patient with a treatment-resistant major depressive episode and comorbid body dysmorphic disorder.

A 24-year-old man experiencing comorbid body dysmorphic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms improved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may improve symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

Structural neuroimaging in patients with panic disorder: findings and limitations of recent studies.

BACKGROUND: Panic disorder, a relatively common anxiety disorder, is often associated to agoraphobia and may be disabling. Its neurobiological underpinnings are unknown, despite the proliferation of models and hypotheses concerning it; investigating its correlates could provide the means for better understanding its pathophysiology. Recent structural neuroimaging techniques may contribute to the identification of possible brain morphological alterations that could be possibly related to the clinical expression of panic disorder. METHODS: Through careful major database searches, using terms keen to panic, agoraphobia, structural magnetic neuroimaging and the like, we identified papers published in peer-review journals and reporting data on the brain structure of patients with panic disorder. Included papers were used comparatively to speculate about the nature of reported brain structural alterations. RESULTS: Anxiety, which is the core feature of the disorder, correlates with the function of the amygdala, which showed a smaller volume in patients, as compared to healthy subjects. Data also showed a volumetric decrease of the anterior cingulate along with increased fractional anisotropy, and increase of some brainstem nuclei, particularly of the rostral pons. Other structures with reported volumetric correlates of panic disorder are the hippocampus and the parahippocampal cortices, the insula, the putamen, and the pituitary gland. Volumetric changes in the anterior cingulate, frontal, orbitofrontal, insular, and temporal cortices have also been described in structural neuroimaging studies. Major methodological limitations are considered in context. CONCLUSIONS: Several data point to the existence of structural neuroanatomical alterations in panic disorder, consisting in significant volumetric reductions or increases in different brain areas. White matter alterations were shown also in the only diffusion tensor imaging study performed to date. Available data do not allow us to conclude about the possible progression of these alterations.

[Olanzapine in manic/mixed patients with or without substance abuse]. / Olanzapina in pazienti maniacali o misti con o senza abuso di sostanze.

AIM: To evaluate the efficacy of olanzapine in patients in their manic/mixed phase with or without comorbidity with substance abuse/dependence disorder. METHODS: In this observational, controlled, prospective study, 60 patients with a DSM-IV-TR diagnosis of bipolar disorder, manic/mixed episode (30 patients with and 30 patient without comorbidity with a substance abuse/dependence disorder) were treated with olanzapine, evaluated at discharge, and followed-up for 8 weeks. Efficacy of olanzapine was assessed by comparing the proportion of responders (an at least 50% drop in Young Mania Rating Scale [YMRS] score from baseline) and remitters (YMRS ≤ 12 and Hamilton Depression Rating Scale [HAM-D] ≤ 8) in both groups. Craving and days of abuse/use were assessed with Visual Analogue Scale (VAS) and Time-line Follow-Back (TLFB), respectively. RESULTS: Differences in response and remission percentages were statistically not significant at discharge and during follow-up. A reduction of days of abuse has been observed in the drug-abuse group, while craving was only slightly decreased. DISCUSSION: These results suggest that olanzapine is effective in both groups and its efficacy in reducing the days of abuse appears to be independent from its action on craving.

[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.

Functional neuroimaging in specific phobia.

Specific phobias (SPs) are common, with lifetime prevalence estimates of 10%. Our current understanding of their pathophysiology owes much to neuroimaging studies, which enabled us to construct increasingly efficient models of the underlying neurocircuitry. We provide an updated, comprehensive review and analyze the relevant literature of functional neuroimaging studies in specific phobias. Findings are presented according to the functional neuroanatomy of patients with SPs. We performed a careful search of the major medical and psychological databases by crossing SP with each neuroimaging technique. Functional neuroimaging, mostly using symptom provocation paradigms, showed abnormal activations in brain areas involved in emotional perception and early amplification, mainly the amygdala, anterior cingulate cortex, thalamus, and insula. The insula, thalamus and other limbic/paralimbic structures are particularly involved in SPs with prominent autonomic arousal. Emotional modulation is also impaired after exposure to phobic stimuli, with abnormal activations reported for the prefrontal, orbitofrontal and visual cortices. Other cortices and the cerebellum also appear to be involved in the pathophysiology of this disorder. Functional neuroimaging identified neural substrates that differentiate SPs from other anxiety disorders and separate SP subtypes from one another; the results support current Diagnostic and Statistical Manual of Mental Disorders, 4th edition-Text Revision (DSM-IV-TR) diagnostic subtyping of SPs. Functional neuroimaging shows promise as a means of identifying treatment-response predictors. Improvement in these techniques may help in clarifying the neurocircuitry underlying SP, for both research and clinical-therapeutic purposes.

Competence to consent to sexual activity in bipolar disorder and schizophrenic spectrum disorders.

Little is known about the ability of persons with severe mental disorders to give consent to sexual activity. A possible reason for this shortcoming is the absence of specific criteria and tools to measure sexual consent in psychiatric clinical settings. We developed a clinician oriented semi-structured interview, the Sexual Consent Assessment Scale (SCAS), and investigated sexual consent capacity in a sample of hospitalized patients with bipolar disorder (n = 54, M (age) = 38.1 years, 48% males) and schizophrenic spectrum disorders (n = 31, M (age) = 38.4 years, 29% males). The SCAS items were derived from the criteria proposed by Kennedy and Niederbuhl (Am J Ment Retard, 106:503-510, 2001). The full scale and a shorter scale comprising 10 items (SCAS-10) achieved good initial validity. Patients with schizophrenic spectrum disorders had worse sexual consent capacity than patients with bipolar disorder. This difference was unexpectedly independent from patients' symptomatology, as measured by the Brief Psychiatric Rating Scale. Conversely, poor cognitive functioning measured by the Raven's Standard Progressive matrices was associated with reduced capacity to give sexual consent in both groups. Subjects in the schizophrenic spectrum disorders group were more frequently judged incapable in basic knowledge of birth control methods and in domains underlying metacognitive abilities. Principal component analysis revealed two SCAS-10 interpretable factors: "appropriateness-recognition" and "consequences-metacognition." Our study suggests that patients with severe psychiatric disorders, especially those with cognitive dysfunction, might be at risk of incapacity to give valid sexual consent.

Neurocognition, psychopathology, and subjective disturbances in schizophrenia: a comparison between short-term and remitted patients.

Patients with schizophrenia present deficits in multiple domains of cognition. The study of the relationship between cognitive performance and symptoms of schizophrenia has yielded heterogeneous results. The purposes of this study were to examine the extent of the relationship between psychopathologic symptoms, cognitive function, and subjective disturbances in a group of patients affected by schizophrenia spectrum disorders and to compare short-term with remitted patients. Seventy-nine patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia, schizophreniform disorder, and schizoaffective disorder were assessed through the Positive and Negative Syndrome Scale, the Frankfurt Complaint Questionnaire, and a neuropsychologic battery exploring the 7 Measurement and Treatment Research to improve Cognition in Schizophrenia cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) plus executive control. Neuropsychologic and psychopathologic variables were compared and correlated. Treatment groups did not differ in neuropsychologic and psychopathologic measures. The cognitive factor of the Positive and Negative Syndrome Scale correlated with worse performance on cognitive tasks and with higher scores on the Frankfurt Complaint Questionnaire 24 in the short-term, remitted, and combined groups. Subjective disturbances correlated with impaired executive control, reasoning and problem solving, and social cognition but not during the short-term phase. Both "objective" and subjective psychopathology are intertwined with cognitive function, suggesting some common underlying neural bases. The condition of being in a short-term or a remitted phase of the illness influences this interrelationship, regardless of the type of antipsychotic medication taken.

Temperaments mediate suicide risk and psychopathology among patients with bipolar disorders.

BACKGROUND: Several studies have demonstrated that bipolar II (BD-II) disorder represents a quite common, distinct form of major mood disorders that should be separated from bipolar I (BD-I) disorder. The aims of this cross-sectional study were to assess temperament and clinical differences between patients with BD-I and BD-II disorders and to assess whether temperament traits are good predictors of hopelessness in patients with bipolar disorder, a variable highly associated with suicidal behavior and ideation. METHOD: Participants were 216 consecutive inpatients (97 men and 119 women) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), BD who were admitted to the Sant'Andrea Hospital's psychiatric ward in Rome (Italy). Patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego--Autoquestionnaire, the Beck Hopelessness Scale (BHS), the Mini International Neuropsychiatric Interview (MINI), and the Gotland Scale of Male Depression. RESULTS: Patients with BD-II had higher scores on the BHS (9.78 ± 5.37 vs 6.87 ± 4.69; t(143.59) = -3.94; P < .001) than patients with BD-I. Hopelessness was associated with the individual pattern of temperament traits (ie, the relative balance of hyperthymic vs cyclothymic-irritable-anxious-dysthmic). Furthermore, patients with higher hopelessness (compared with those with lower levels of hopelessness) reported more frequently moderate to severe depression (87.1% vs 38.9%; P < .001) and higher MINI suicidal risk. CONCLUSION: Temperaments are important predictors both of suicide risk and psychopathology and may be used in clinical practice for better delivery of appropriate care to patients with bipolar 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.

Suicide attempts in acute psychiatric referrals with substance use disorders.

AIMS: The aim of the present study was to investigate suicidal risk in psychiatric referrals admitted to a University Hospital Emergency Department (ED) who had a substance use disorder. METHODS: The participants were 135 psychiatric referrals (84 men and 51 women) admitted to the ED of the Sant' Andrea Hospital of Rome (Italy) between January 2006 and February 2007. The data were collected for the purpose of this research via electronic medical records of ED patients. RESULTS: Attempters with substance use disorders were more likely to have higher burden of major affective disorders, and psychiatric history than substance use disorder referrals without recent suicide attempt; and they were at higher risk of suicide (higher rates of suicidal ideation reported during the psychiatric interview). CONCLUSIONS: When evaluating suicide attempters with substance use disorders, health professionals working in the ED settings have to assess not only somatic emergencies that can undermine patient's life but also the chance of repetition of suicidal behavior.

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.