The metabolic basis of psychosis in bipolar disorder: A positron emission tomography study.

OBJECTIVES: Psychotic symptoms are a common feature in bipolar disorder (BD), especially during manic phases, and are associated with a more severe course of illness. However, not all bipolar subjects experience psychosis during the course of their illness, and this difference often guides assessment and pharmacological treatment. The aim of the present study is to elucidate, for the first time, the FDG uptake dysfunctions associated with psychosis in BD patients with and without a history of past psychotic symptoms, through a positron emission tomography (PET) approach. METHODS: Fifty BD patients with lifetime psychotic symptoms, 40 BD patients without lifetime psychotic symptoms and 27 healthy controls (HC) were recruited and underwent an 18F-FDG-PET session. RESULTS: Compared to HC, BD subjects shared common FDG uptake deficits in several brain areas, including insula, inferior temporal gyrus and middle occipital gyrus. Moreover, we found that BD patients with a history of past psychotic symptoms had a unique FDG uptake alteration in the right fusiform gyrus compared to both BD patients without lifetime psychotic symptoms and HC (all P < 0.01, cFWE corrected). CONCLUSIONS: Overall, our results suggest that FDG uptake alterations in brain regions involved in emotion regulation are a key feature of BD, regardless the presence of past psychosis. Finally, we demonstrated that the FDG uptake reduction in fusiform gyrus is associated with the presence of past psychotic symptoms in BD, ultimately leading towards the idea that the fusiform gyrus might be considered a putative biomarker of psychosis.

Psychotic versus non-psychotic bipolar disorder: Socio-demographic and clinical profiles in an Italian nationwide study.

OBJECTIVE: Psychotic versus non-psychotic patients with bipolar disorder have been traditionally associated with different unfavorable clinical features. In this study on bipolar Italian patients, we aimed to compare clinical and demographic differences between psychotic and non-psychotic individuals, exploring clinical factors that may favor early diagnosis and personalized treatment. METHODS: A total of 1671 patients (males: n = 712 and females: n = 959; bipolar type 1: n = 1038 and bipolar type 2: n = 633) from different psychiatric departments were compared according to the lifetime presence of psychotic symptoms in terms of socio-demographic and clinical variables. Chi-square tests for qualitative variables and Student's t-tests for quantitative variables were performed for group comparison, and a multivariable logistic regression was performed, considering the lifetime psychotic symptoms as dependent variables and socio-demographic/clinical characteristics as independent variables. RESULTS: Psychotic versus non-psychotic bipolar subjects resulted to: be more frequently unemployed (p < 0.01) and never married/partnered (p < 0.01); have an earlier age at onset (p < 0.01); more frequently receive a first diagnosis different from a mood disorder (p < 0.01); have a shorter duration of untreated illness (p < 0.01); have a more frequently hypomanic/manic prevalent polarity (p < 0.01) and a prevalent manic-depressive type of cycling (p < 0.01); present a lower lifetime number of depressive episodes (p < 0.01), but have more manic episodes (p < 0.01); and less insight (p < 0.01) and more hospitalizations in the last year (p < 0.01). Multivariable regression analysis showed that psychotic versus non-psychotic bipolar patients received more frequently a first diagnosis different from bipolar disorder (odds ratio = 0.64, 95% confidence interval = [0.46, 0.90], p = 0.02) or major depressive disorder (odds ratio = 0.66, 95% confidence interval = [0.48, 0.91], p = 0.02), had more frequently a prevalent manic polarity (odds ratio = 1.84, 95% confidence interval = [1.14, 2.98], p < 0.01) and had a higher number of lifetime manic episodes (more than six) (odds ratio = 8.79, 95% confidence interval = [5.93, 13.05], p < 0.01). CONCLUSION: Lifetime psychotic symptoms in bipolar disorder are associated with unfavorable socio-demographic and clinical features as well as with a more frequent initial misdiagnosis.

Structural and metabolic cerebral alterations between elderly bipolar disorder and behavioural variant frontotemporal dementia: A combined MRI-PET study.

BACKGROUND: Elderly bipolar disorder (BD) and behavioural variant of frontotemporal dementia (bvFTD) may exhibit similar symptoms and both disorders are characterized by selective abnormalities in cortical and subcortical regions that are associated with cognitive and emotional impairments. We aimed to investigate common and distinct neural substrates of BD and bvFTD by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques. METHODS: 3-Tesla MRI and 18 fluorodeoxyglucose-PET scans were acquired for 16 elderly BD patients, 23 bvFTD patients with mild cognitive impairments and 68 healthy controls (48 for PET and 20 for MRI analyses). RESULTS: BD and bvFTD patients exhibit a different localization of grey matter reductions in the lateral prefrontal cortex, with the first group showing grey matter decrease in the ventrolateral prefrontal cortex and the latter group showing grey matter reductions in the dorsolateral prefrontal cortex as well as unique grey matter and metabolic alterations within the orbitofrontal cortex. The bvFTD group also displayed unique volumetric shrinkage in regions within the temporo-parietal network together with greater metabolic impairments within the temporal cortex and more extensive volumetric and metabolic abnormalities within the limbic lobe. Finally, while the BD group showed greater grey matter volumes in caudate nucleus, bvFTD subjects displayed lower metabolism. CONCLUSION: This MRI-PET study explored, for the first time to the best of our knowledge, structural and functional abnormalities in bvFTD and elderly BD patients, with the final aim of identifying the specific biological signature of these disorders, which might have important implications not only in prevention but also in differential diagnosis and treatment.

Research Review: The role of obstetric and neonatal complications in childhood attention deficit and hyperactivity disorder - a systematic review.

BACKGROUND: Attention deficit and hyperactivity disorder (ADHD) is a developmental disorder characterized by an inability to sustain attention, activity levels and impulse control, and, according to the latest studies, the prevalence is about 8% and in some countries less than 1%. Currently, it is well-known that complications during the perinatal period have significant implications on child's physical and mental health. Purpose of the present paper is to review the literature about the association between perinatal complications and future risk of an ADHD diagnosis. METHODS: A research in the main database sources has been conducted to obtain a systematic review on the perinatal risk factors of ADHD. RESULTS: Among perinatal complications, available data indicate low birth weight (LBW) (Cohen's d effect size range: 0.31-1.64-small effect size) and preterm birth (PB) (range d: 0.41-0.68) as the most important factors associated with a future diagnosis of ADHD. CONCLUSIONS: PB and LBW children should be carefully monitored for an early diagnosis of ADHD limiting the impact of the disease in life span. A systematic review focusing on these risk factors have not been published until now, in the next future preventive strategies should be developed in order to minimize ADHD onset.

Potential Gender-Related Aging Processes Occur Earlier and Faster in the Vermis of Patients with Bipolar Disorder: An MRI Study.

BACKGROUND: In the last decades, there has been increasing interest in investigating the role of the vermis in bipolar disorder (BD), especially because of its involvement in cognitive processes. The main aims of this study were to explore the integrity of the vermis and elucidate the role of demographic and clinical variables on vermis volumes in BD patients, stratified according to gender. METHODS: T1-weighted images were obtained for 38 BD patients and 38 healthy controls using a 1.5-T MRI scanner. Images were analyzed with a PC workstation with BRAINS2 software on a Linux system. Anatomical regions were traced manually from a blinded operator, with respect to subject identity and other clinical variables. RESULTS: The direct comparison between the 2 groups showed no significant gray matter differences in vermis volumes. Interestingly, vermis volumes were significantly inversely associated with chronological age and age of BD onset, particularly in male subjects. CONCLUSIONS: Our study provides evidence of the impact of aging on the vermis in BD, potentially related to earlier and faster gender-related neurodegenerative phenomena occurring during the progression of the disease.

Pharmacological Management of Psychiatric Symptoms in Frontotemporal Dementia: A Systematic Review.

Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical management of these patients. Purpose of the present article is to present and discuss available data about the pharmacological treatment of psychiatric symptoms in patients with FTD. A research in the main database sources has been conducted to obtain an overview of the pharmacological management of psychiatric symptoms in patients with FTD. The search strategy included the following terms-"FTD and psychiatry," "FTD and behavioural disturbances," and "FTD and treatment". Pathophysiology of psychiatric symptoms in FTD is different from other types of dementia. Although drugs for Alzheimer disease appear to be ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence supports a possible usefulness of serotonergic antidepressants for these patients. Data are too scanty to draw definitive conclusions, but antidepressant treatment, particularly with serotonergic compounds, may improve psychiatric symptoms in patients with FTD. Large observational studies are needed to confirm this preliminary evidence, and a lot of effort and collaboration between neurologists and psychiatrists will be definitely crucial for future research of effective treatments for FTD.

Sexual dimorphism of the planum temporale in schizophrenia: A MRI study.

OBJECTIVE: Anatomical alterations in the superior temporal gyrus have been consistently reported in patients with schizophrenia, and they have mostly been linked to positive symptoms, including hallucinations and thought disorders. The superior temporal gyrus is considered one of the most asymmetric and lateralized structure of the human brain, and the process of lateralization seems to vary according to gender in the normal population. However, although it has been consistently suggested that patients with schizophrenia did not show normal brain lateralization in several regions, only few studies investigated it in the superior temporal gyrus and its sub-regions considering the effects of gender. In this context, the aim of this study was to evaluate sexual dimorphism in superior temporal gyrus volumes in a sample of patients with schizophrenia compared to age- and gender-matched healthy controls. METHODS: A total of 72 right/left-handed males (40 schizophrenia patients and 32 healthy controls) and 45 right/left-handed females (18 schizophrenia patients and 27 healthy controls) underwent clinical evaluation and a 1.5T magnetic resonance imaging scan. Gray and white matter volumes of regions of interest within the superior temporal gyrus were manually detected, including the Heschl's gyrus and the planum temporale. RESULTS: Female patients with schizophrenia presented a reduction in left planum temporale gray matter volumes ( F = 4.58, p = 0.03) and a lack of the normal planum temporale asymmetry index ( t = 0.27; p = 0.79) compared to female controls ( t = 5.47; p = 0.001). No differences were found between males for any volumes or laterality indices. Finally, in female patients with schizophrenia, Heschl's gyrus gray and white matter volumes negatively correlated with positive symptoms ( r = -0.56, p = 0.01). CONCLUSION: Our results showed that sexual dimorphism plays a key role on planum temporale in schizophrenia, underlining the importance of gender as a modulator of brain morphology and lateralization of schizophrenia.

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

Psychiatric Conditions in Parkinson Disease: A Comparison With Classical Psychiatric Disorders.

Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD.

Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.

BACKGROUND: The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness-intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs. METHODS: 101 SKZ or SSD patients were assessed with respect to DUI and related variables through clinical interview and questionnaire. RESULTS: Patients with SKZ showed earlier ages of onset, first diagnosis and first antipsychotic treatment compared with patients with other SSDs (F = 11.02, p < 0.001; F = 12.68, p < 0.001; F = 13.74, p < 0.001, respectively) who showed an earlier access to benzodiazepines than SKZ patients (F = 6.547; p < 0.05). Dividing the total sample by the epoch of onset (before 1978; between 1978-2000; after 2000) showed a significantly later age of onset in patients with onset within the two most recent epochs (F = 7.46; p < 0.001) and a reduced DUI across epochs (from 144 to 41 to 20 months, on average; F = 11.78, p < 0.001). CONCLUSION: Schizophrenic patients showed earlier onset and longer DUI compared with patients with other SSDs. Data on the total sample showed a later age of onset and a reduced DUI across epochs.

Duloxetine in elderly major depression disorder: effectiveness and drug plasma level evaluation.

OBJECTIVE: The aim of this open-label naturalistic study was to assess clinical outcomes and the predictive value of duloxetine plasma levels in major depressive disorder in the elderly. METHODS: This naturalistic, open-label design involved 35 outpatients aged between 65 and 87 years. Duloxetine plasma levels were collected in 24 patients after the first month. Patients were evaluated using 21-item Hamilton Rating Scales for Depression, Hamilton Rating Scales for Anxiety, the Clinical Global Impression Severity, Mini Mental State Examination, Cumulative Illness Rating Scale, Barthel Index and Beck's Depression Inventory. RESULTS: Duloxetine plasma levels at T2 ranged from 4.9 to 201.9 ng/mL without a significant correlation between duloxetine dose and plasma levels. A significant improvement in mean 21-item Hamilton Rating Scales for Depression total scores at T2,T3, T4, T9 and T12 and a progressive significantly decrease of the mean Hamilton Rating Scales for Anxiety scores from T3 to T12 were observed. CONCLUSIONS: The levels of duloxetine in plasma do not correlate with a greater clinical improvement, indeed appear to adversely affect the improvement of the Beck Depression Inventory and Hamilton Rating Scales for Anxiety. This could be explained by an increase in side effects that may aggravate the discomfort felt by the patient. Copyright © 2016 John Wiley & Sons, Ltd.

Normative data of the Magical Ideation Scale from childhood to adulthood in an Italian cohort.

The assessment of schizotypy allows to identify people at risk to develop psychosis. For this purpose, psychometric tools have been developed, such as the Magical Ideation Scale (MIS). This scale investigates attenuated forms of thought transmission experiences, thought withdrawal and aberrant beliefs, related to positive schizotypy. This study aims at providing an Italian version of the MIS and its normative data in the general population from childhood to adulthood, being the first study evaluating subjects under 17year-old. The Italian MIS version was translated by three independent operators and administered to 1378 non-clinical participants, stratified into four age groups (i.e., 8-13, 14-17, 18-24 and 25-34). The unidimensionality of the scale was supported, and its internal consistency was satisfactory (i.e., ordinal Cronbach's αs ranging from 0.86 to 0.90 in different age groups), as well as test-retest reliability (i.e., 1-month ICC of 0.82 in a retested sub-sample). Normative data for the age groups were provided. Specific gender and age-related differences in MIS score were found, i.e. females scored higher than males in the 25-34 age group, which in general, as a group, scored lower than all the other age groups. This study provided evidence of reliability for the Italian version of the MIS in childhood and adolescence, for the first time, as well as in adulthood, showing specific gender and age effects in the early adult cohort.

Is duration of illness really influencing outcome in major psychoses?

BACKGROUND: An increasing number of studies identifies the duration of illness (DI) as an important predictor of outcome in patients affected by major psychoses (MP). The aim of the present paper was to revise medical literature about DI and its effects on MP, focusing in particular on the relationship between DI and outcome with particular reference to treatment response, suicidal risk, cognitive impairment and social functioning. METHODS: A search in the main database sources has been performed to obtain a comprehensive overview. Studies with different methodologies (open and double-blinded) have been included, while papers considering other variables such as duration of untreated episode/illness were excluded. MP included the diagnoses of schizophrenia, bipolar disorder and major depressive disorder. RESULTS: Available data show that DI influences treatment response, suicidal risk and loss of social functioning in schizophrenic patients, while results are more controversial with regard to cognitive impairment. In bipolar disorder, a long DI has been associated with less treatment response, more suicidal risk and cognitive impairment, but more data are needed to draw definitive conclusions. Finally, studies, regarding DI of illness and its predictive value of outcome in major depressive disorder show contradictory results. CONCLUSIONS: DI appears a negative outcome factor particularly for schizophrenia, while with regard to mood disorders, more data are needed to draw definitive sound conclusions.

Comorbidity in obsessive-compulsive disorder (OCD): a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

BACKGROUND: Obsessive-compulsive disorder (OCD) is often associated with significant psychiatric comorbidity. Comorbid disorders include mood and anxiety disorders as well as obsessive-compulsive spectrum disorders (OCSDs). This paper aims to investigate comorbidity of DSM Axis I-disorders, including OCSDs, in patients with OCD from 10 centers affiliated with the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). METHODS: This is a cross-sectional study of comorbidity of Axis I disorders including OCSDs in 457 outpatients with primary OCD (37% male; 63% female), with ages ranging from 12 to 88years (mean: 39.8±13). Treating clinicians assessed Axis I disorders using the Mini International Neuropsychiatric Interview and assessed OCSDs using the Structured Clinical Interview for OCD related/spectrum disorders (SCID-OCSD). RESULTS: In terms of the OCSDs, highest comorbidity rates were found for tic disorder (12.5%), BDD (8.71%) and self-injurious behavior (7.43%). In terms of the other Axis I-disorders, major depressive disorder (MDD; 15%), social anxiety disorder (SAD; 14%), generalized anxiety disorder (GAD; 13%) and dysthymic disorder (13%) were most prevalent. DISCUSSION: High comorbidity of some OCSDs in OCD supports the formal recognition of these conditions in a separate chapter of the nosology. Rates of other Axis I disorders are high in both the general population and in OCSDs, indicating that these may often also need to be the focus of intervention in OCD.

Long-term efficacy after acute augmentative repetitive transcranial magnetic stimulation in bipolar depression: a 1-year follow-up study.

BACKGROUND: : The efficacy of repetitive transcranial magnetic stimulation (rTMS) has been poorly investigated in the long-term. The present follow-up study was aimed to assess the long-term efficacy and the discontinuation effects of rTMS in a sample of depressed bipolar patients. METHODS: : After the completion of an acute trial with augmentative, low-frequency, navigated rTMS, 11 drug-resistant depressed bipolar subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [Text Revision] criteria) entered a naturalistic follow-up with monthly evaluations through the Hamilton Depression Rating Scale and the Young Mania Rating Scale. RESULTS: : After 1 year of follow-up, results showed that the achievement of remission after acute rTMS was predictive of maintenance of response at 1 year. On the other hand, the absence of acute rTMS response predicted the absence of subsequent response in the long-term. CONCLUSIONS: : This first report on the long-term discontinuation effects after acute rTMS suggests that immediate remission is predictive of sustained benefit after 1 year. Larger controlled studies are needed to confirm present preliminary findings.

Which factors delay treatment in bipolar disorder? A nationwide study focussed on duration of untreated illness.

AIM: The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD). METHOD: A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one-way analyses of variance or Kruskal-Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another. RESULTS: An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = -.52, P < .001). DUI resulted to be longer in patients with: at least one lifetime marriage/partnership (P = .009), a first psychiatric diagnosis of major depressive disorder or substance abuse (P < .001), a depressive polarity of first episode (P < .001), no lifetime psychotic symptoms (P < .001), BD type 2 (P < .001), more lifetime depressive/hypomanic episodes (P < .001), less lifetime manic episodes (P < .001), presence of suicide attempts (P = .004), depressive episodes (P < .001), hypomanic episodes (P = .004), hospitalizations (P = .011) in the last year. CONCLUSIONS: Different factors resulted to increase the length of DUI in a nationwide sample of bipolar patients. In addition, the DUI was found to show a negative long-term effect in terms of more suicidal behaviour, more probability of hospitalization and depressive/hypomanic episodes.

Neuropsychobiological aspects, comorbidity patterns and dimensional models in borderline personality disorder.

Borderline personality disorder (BPD) is a comorbid and disabling condition with high prevalence in psychiatric settings. The pathogenesis of BPD involves complex interactions among genetic, neurobiological and environmental factors, resulting in multiple core symptom domains such as emotional dysregulation, impulse dyscontrol, aggression, cognitive dysfunctions and dissociative states. Neurobiological studies show that symptoms and behaviors of BPD are partly associated with alterations in glutamatergic, dopaminergic and serotonergic systems. In addition, neuroimaging studies in BPD patients indicate differences in the volume and activity of specific brain regions related to emotion and impulse control, such as the prefrontal and cingulate cortex, amygdala and hippocampus. Neurobiological alterations are related to cognitive disturbances in patients with BPD and neuropsychological tests have shown abnormalities of memory, attention, language, and executive functions. The aim of the present review is to provide an updated overview of the main neuropsychobiological aspects of BPD and their relation to clinical symptoms, comorbidity patterns and dimensional models.

Symptom dimensions as predictors of clinical outcome, duration of hospitalization, and aggressive behaviours in acutely hospitalized patients with psychotic exacerbation.

In the present study we extract clusters of symptoms in acute hospitalized psychotic patients during a re-exacerbation phase, using factor analysis of BPRS-E. We aim to investigate the relative contribution of each symptom dimension in predicting the severity of symptoms at discharge, the length of acute hospitalization, and the occurrence of aggressive behaviours during acute hospitalization. The data are drawn from a prospective, naturalistic, observational study of 183 patients with Psychotic Disorders consecutively admitted to a psychiatric ward, during a re-exacerbation phase. General symptomatology has been measured through BPRS-E at admission and at discharge. Statistical analyses include principal component analysis and multiple linear regression.We found symptoms of acute psychosis disorder to cluster together in four distinct domains, labelled "Excitement/Activation", "Positive symptoms", and "Negative symptoms", and "Depression/Anxiety". Excitement/activation was the dimension most associated with occurrence of aggressive behaviours and severity of psychopathological symptoms at discharge. The negative symptoms dimension, also, predicted the severity of symptoms at discharge. Positive and negative symptoms dimensions were both predictors of duration of hospitalization. The depressive dimension was significantly associated only to self-aggression. These data indicate that during acute hospitalization due to re-exacerbation of psychosis each symptom dimension has a specific impact on distinct measures of outcome.