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.

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.

Self-reported attenuated psychotic-like experiences in help-seeking adolescents and their association with age, functioning and psychopathology.

OBJECTIVE: Self-rated attenuated psychotic-like experiences (APLEs) are increasingly used to screen for ultra-high-risk (UHR) across all ages. However, self-rated psychotic-like experiences (PLEs), in particular perception-related ones, were more frequent in children and adolescents, in which they possessed less clinical significance. We therefore explored the prevalence of different factors of APLEs in help-seeking adolescents, and their relationship with age, functioning and psychopathology. METHOD: As a part of the "Liberiamo il Futuro" project, help-seeking adolescents (N=171; 11-18 years, 53% male) were screened with the 92-item Prodromal Questionnaire (PQ-92). A factor analysis was performed on the PQ-92 positive items (i.e., APLEs) to identify different APLE-factors. These were assessed for their association with age, functioning and psychopathology using regression analyses. RESULTS: APLEs were very common in help-seeking adolescents, and formed four factors: "Conceptual Disorganization and Suspiciousness", "Perceptual Abnormalities", "Bizarre Experiences", and "Magical Ideation". Associations with age and functioning but not psychopathology were found for "Perceptual Abnormalities" that was significantly more severe in 11-12-year-olds, while "Conceptual Disorganization and Suspiciousness" was significantly related to psychopathology. CONCLUSION: In line with findings on PLEs, prevalence and clinical significance of APLEs, especially perception-related ones, might depend on age and thus neurodevelopmental stage, and may fall within the normal spectrum of experience during childhood. This should be considered when screening for UHR status in younger age groups.

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.

[Basic symptoms and neurocognition: preliminary comparison of first-episode psychosis vs multi-episode long-term illness]. / Sintomi base e neurocognizione: confronto preliminare dell'esordio psicotico vs malattia di lunga durata.

BACKGROUND: Schizophrenia is preceded by basic symptoms which may persist after long time and include subjective cognitive impairment. Furthermore, it is characterised by cognitive deficits that may deteriorate with the progression of illness. To examine the relationship between neurocognition and basic symptoms along the course of schizophrenia, we compared the cognitive performance and the basic symptoms of one population with first episode psychosis (FEP) and one with a chronic, multi-episode course (MEP). METHODS: We tested 8 FEP (5 male) and 7 MEP (7 male) in- and outpatients, for basic symptoms with the Schizophrenia Proneness Instrument-Adult version (SPI-A) and for neurocognition with Raven's Color Progressive Matrices (CPM), Rey-Osterrieth's complex figure (Rey), Corsi's and Buschke-Fuld tests, the Wisconsin Card Sorting Test (WCST), the Stroop test, and the Trail Making Test (TMT). RESULTS: FEP patients did not differ from MEP patients as for SPI-A scores. MEP patients were significantly more impaired on several subtests of Buschke-Fuld, the Rey, and the WCST with respect to FEP. Impairment on the cognitive subscale of the SPI-A correlated with non-perseverative WCST errors, and on the self subscale of the SPI-A with impaired performance on the Buschke-Fuld. Further, in MEP, impairment on the body subscale of the SPI-A correlated inversely with number of categories completed of the WCST. CONCLUSIONS: Basic symptoms persist throughout the phases of schizophrenia and are relatively independent of cognitive performance. A chronic, multi-episode course is associated with increased cognitive impairment in 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.

[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.

Risperidone-induced leukopenia: a case report and brief review of literature.

A Caucasian, male, young adult with recurrent agitated depression and suicidal ideation received lithium and oral olanzapine. His white blood cell count was normal at that time. Due to unsatisfactory response, he received 4 mg/day risperidone. While symptoms improved, leukopenia emerged, specifically directed towards neutrophils. Upon risperidone discontinuation, white blood cell count returned to reference values within 1 week. As symptom control was satisfactory, we attempted no risperidone rechallenge. Accurate blood testing must accompany atypical antipsychotic drug administration since blood dyscrasias are always possible with these drugs.

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.

Mental disorders diagnosed in childhood and at-risk mental state in a help-seeking population.

AIM: Disorders usually first diagnosed in infancy, childhood or adolescence (DUFD-ICA) may have preceded the onset of psychosis by several years and share some co-morbidity with psychotic disorders, but only a few studies have investigated this aspect. We looked for past or current DUFD-ICA in a sample of first adult psychiatric service users assessed for the presence of an at-risk mental state with the Structured Interview for Psychosis-risk Syndromes (SIPS). METHODS: We interviewed with the SIPS 159 first-time help seekers (age range 13-30 years) at adult psychiatric services who volunteered to participate in the study. For psychiatric diagnoses, we used the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition-Text Revision. We also assessed retrospectively the presence of DUFD-ICA and administered the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning. The sample has been subdivided diagnostically into first-episode psychosis, multiple episode psychosis, ultra-high risk (UHR) and other diagnoses. RESULTS: The risk for having one of first-episode psychosis, multiple episode psychosis or UHR was over 3.45 higher in the DUFD-ICA-positive history group than in the non-DUFD-ICA. Grouping the UHR with the not full-blown psychosis cases resulted in a further increase of the risk to 4.71. DUFD-ICA-positive participants scored higher than non-DUFD-ICA on the Positive, Negative and Disorganization scales of the SIPS and on several core-psychotic BPRS items. CONCLUSIONS: A positive history of DUFD-ICA increases the risk of a diagnosis of prodromal or current psychosis at help seeking. Impaired neurodevelopment may be shared among the psychoses and DUFD-ICA.

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.

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.

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.

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.

The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence.

Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies cast doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer's disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder.

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.

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.

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.