The persisting sadness, an inclination to become emotional: the case of inspector Ricciardi gifted with the capacity to feel pain.

Through the analysis of "Luigi Alfredo Ricciardi" the main character of detective series by Maurizio De Giovanni, the structuring of a normal melancholic constitution, which we term the depression-prone style of personality, is reconstructed.

Bipolar Disorder and Frontotemporal Dementia: An Intriguing Association.

Bipolar disorder (BD) could represent a prodromal state of frontotemporal dementia (FTD). Two patients affected by lifelong BD with a progressive decline of cognitive functions, behavioral, and neurological signs, reached the early diagnosis of FTD before the age of 60. They were diagnosed as affected by primary progressive aphasia and FTD with parkinsonism, respectively. A diagnosis of FTD should therefore be taken into account, in case of unexpected cognitive and behavioral decline in patients with a long history of BD. Follow-up studies with genetic, neuropsychological, and neuroimaging markers of these BD/FTD patients could further explore some of the underlying association, opening new viable therapeutic options.

Gotan project: Tango, a dance to experience oneself.

The tango brings out the true essence of the individuals, it removes every mask and stops the lies you tells yourself, forcingthe contact with yourself even before with the others. This is the essence on which we relied to propose a course of psychotherapy with basic elements of tango, as a peculiar mode of experiencing oneself. In this paper we analyze how Tango could become an interesting instrument for the cure and the prevention of psychological and physical problems.

First-episode psychosis and migration in Italy (PEP-Ita migration): a study in the Italian mental health services.

BACKGROUND: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration. METHODS/DESIGN: The "Italian study on first-episode psychosis and migration (PEP-Ita)" is a prospective observational study over a two-year period (1 January 2012-31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose ("core") of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants. DISCUSSION: The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy.

The relationship between depression and cognitive deficits.

In the last years cognitive impairment in depression has been widely reported. It is clear that cognitive symptoms persist after remission of psychopathological symptoms but little is known about the pathophysiological events linking depression and cognitive impairment. Novel biological, structural and functional neuroimaging techniques have allowed a better definition of this relation. Depression and cognitive dysfunction share a common neuropathological platform in cortical and sub-cortical brain areas implicated in emotional and cognitive processing which may be under the control of genetic and environmental factors.

The lifetime prevalence of bipolar disorders and the use of antidepressant drugs in bipolar depression in Italy.

BACKGROUND: The prevalence of bipolar spectrum disorders in the community is under debate and the prescription of antidepressant drugs (ADs) in bipolar depression appears to be an underestimated problem. OBJECTIVES: To evaluate the prevalence of bipolar disorders by means of a screening instrument in seven communities within six regions of Italy and evaluate the appropriateness and number of prescriptions for ADs in bipolar depression. STUDY DESIGN: community survey. STUDY POPULATION: samples randomly drawn, after stratification from the adult population of municipal records. SAMPLE SIZE: 4999 people from seven communities within six regions of Italy. Tools: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Mood Disorder Questionnaire (MDQ). Training: interviewers were trained psychologists or medical doctors. STUDY LIMITATIONS: the population studied did not represent a nationally representative multistage clustered area probability sample of households. RESULTS: 3398 subjects were interviewed (68% of recruited sample). Positivity at MDQ (MDQ+) was higher in males (3.4% vs. 2.8%) but the difference was not significant (OR=1.2, P=0.37). The association between MDQ+ and Major Depressive Disorder (MDD) was statistically significant for both males (OR=14.9, P<0.0001) and females (OR=8.3, P<0.001); 30% of subjects with MDQ+ and MDD lifetime diagnosis were taking ADs. CONCLUSIONS: These overall rates of being MDQ+ are similar to community surveys conducted within USA and the use of ADs in people with MDQ+ and MDD diagnoses are.

Late life depression and late onset depression: are the same clinical and pathopsysiological picture?

Phenomenological differences between older patients with late- and early-onset depression may reflect differences in aetiology and neuropathological processes involved in these two types of depression. Early- onset depression has been mainly correlated to a family history of depression while late-onset depression has been principally correlated to vascular dysfunction. The same cortical and sub-cortical areas are involved in both types of depression. However, lesions in these brain areas and cognitive impairment are most pronounced in late-onset depression. Based on these observations we propose a common neuroanatomical substrate but different pathophysiological processes implicated in these two types of depression.

The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy.

BACKGROUND: The increased use of antidepressant drugs (ADs) improved the response to the needs of care although some community surveys have shown that subjects without lifetime psychiatric diagnosis (anxiety/depression) used ADs. OBJECTIVES: To evaluate the appropriateness and amount of prescription of psychotropic drugs in people with lifetime diagnosis of Major Depressive Disorder (MDD) by means of community survey with a semi-structured interview as a diagnostic instrument, administered by clinicians. STUDY DESIGN: community survey. STUDY POPULATION: samples randomly drawn, after stratification from the adult population of municipal records. SAMPLE SIZE: 4.999 people were drawn in 7 centres of 6 Italian regions. TOOLS: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview for DSM-IV modified (ANTAS); Training: interviewers were trained psychologists or medical doctors. RESULTS: 3.398 subjects were interviewed (68% of the recruited sample). The lifetime prevalence of DSM-IV MDD was 4.3% in males and 11.5% in females; antidepressant drugs were taken by 4.7% of subjects, 2.9% male and 5.9% female. 38% of males and 57% of females with lifetime diagnosis of MDD were taking ADs. CONCLUSIONS: Compared with studies using lay interviewers and structured tools the prevalence of the MDD was quite lower; ADs use was higher and tallied well with the data regarding antidepressant sales in Italy; the correspondence between lifetime diagnosis of MDD and ADs use was closer.

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Treatment with olanzapine is associated with modulation of the default mode network in patients with Schizophrenia.

Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.

Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia.

Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing, while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia.

Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia.

Dopamine D2 receptor signalling is strongly implicated in the aetiology of schizophrenia. We have recently characterized the function of three DRD2 SNPs: rs12364283 in the promoter affecting total D2 mRNA expression; rs2283265 and rs1076560, respectively in introns 5 and 6, shifting mRNA splicing to two functionally distinct isoforms, the short form of D2 (D2S) and the long form (D2L). These two isoforms differentially contribute to dopamine signalling in prefrontal cortex and in striatum. We performed a case-control study to determine association of these variants and of their main haplotypes with several schizophrenia-related phenotypes. We demonstrate that the minor allele in the intronic variants is associated with reduced expression of %D2S of total mRNA in post-mortem prefrontal cortex, and with impaired working memory behavioural performance, both in patients and controls. However, the fMRI results show opposite effects in patients compared with controls: enhanced engagement of prefronto-striatal pathways in controls and reduced activity in patients. Moreover, the promoter variant is also associated with working memory activity in prefrontal cortex and striatum of patients, and less robustly with negative symptoms scores. Main haplotypes formed by the three DRD2 variants showed significant associations with these phenotypes consistent with those of the individual SNPs. Our results indicate that the three functional DRD2 variants modulate schizophrenia phenotypes possibly by modifying D2S/D2L ratios in the context of different total D2 density.

Association of the SerCys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding.

A common nonsynonymous single nucleotide polymorphism leading to a serine-to-cysteine substitution at amino acid 704 (Ser(704)Cys) in the DISC1 protein sequence has been recently associated with schizophrenia and with specific hippocampal abnormalities. Here, we used multimodal neuroimaging to investigate in a large sample of healthy subjects the putative association of the Ser(704)Cys DISC1 polymorphism with in vivo brain phenotypes including hippocampal formation (HF) gray matter volume and function (as assessed with functional MRI) as well as HF functional coupling with the neural network engaged during encoding of recognition memory. Individuals homozygous for DISC1 Ser allele relative to carriers of the Cys allele showed greater gray matter volume in the HF. Further, Ser/Ser subjects exhibited greater engagement of the HF together with greater HF-dorsolateral prefrontal cortex functional coupling during memory encoding, in spite of similar behavioral performance. These findings consistently support the notion that Ser(704)Cys DISC1 polymorphism is physiologically relevant. Moreover, they support the hypothesis that genetic variation in DISC1 may affect the risk for schizophrenia by modifying hippocampal gray matter and function.

Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks.

BACKGROUND: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. METHODS: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. RESULTS: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. CONCLUSIONS: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

Activity in medial prefrontal cortex during cognitive evaluation of threatening stimuli as a function of personality style.

Cognitive evaluation of emotional stimuli involves a network of brain regions including the medial prefrontal cortex (mPFC). However, threatening stimuli may be perceived with differential salience in different individuals. The goal of our study was to evaluate how different personality styles are associated with differential modulation of brain activity during explicit recognition of fearful and angry facial expressions. Twenty-eight healthy subjects underwent fMRI. Based on a cognitivist model, subjects were categorized according to how they attribute salience to emotional stimuli and how they regulate their emotional activation. We compared 14 phobic prone (PP) subjects, whose identity is more centered on the inner experience ("inward") and around control of environmental threat, and 14 eating disorders prone (EDP) subjects, whose identity is more centered on external referential contexts ("outward") and much less around control of threatening stimuli. During fMRI subjects either matched the identity of one of two angry and fearful faces to that of a simultaneously presented target face or identified the expression of a target face by choosing one of two simultaneously presented linguistic labels. The fMRI results indicated that PP subjects had greater mPFC activation when compared with EDP subjects during cognitive labeling of threatening stimuli. Activity in the mPFC also correlated with personality style scores. These results demonstrate that PP subjects recruit greater neuronal resources in mPFC whose activity is associated with cognitive aspects that are closely intertwined with emotional processing. These findings are consistent with the contention that cognitive evaluation and salience of emotional stimuli are associated with different personality styles.

Clinical vs. structured interview on anxiety and affective disorders by primary care physicians. understanding diagnostic discordance.

AIMS: To assess in a national sample the ability of GPs to detect psychiatric disorders using a clinical vs. a standardized interview and to characterize the patients that were falsely diagnosed with an anxiety or affective disorder. METHODS: This is a national, cross-sectional, epidemiological survey, carried out by GPs on a random sample of their patients. The GPs were randomly divided into two groups. Apart from the routine clinical interview, the experimental group (group A) had to administer the Mini-International Neuropsychiatric Interview (MINI). RESULTS: Data was collected by 143 GPs. 17.2% of all patients had a clinical diagnosis of an affective disorder, and 25.4% a clinical diagnosis of an anxiety disorder. In group A, the number of clinical diagnoses was about twice that of MINI diagnoses for affective disorders and one and a half times that for anxiety disorders. The majority of clinical diagnoses were represented by MINI subsyndromal cases (52.3%). Females showed a higher OR of being over-detected by GPs with anxiety disorders or of not being diagnosed with an affective disorder. Being divorced/separated/widowed increased the OR of over-detection of affective and anxiety disorders. The OR of over-detection of an affective or an anxiety disorder was higher for individuals with a moderate to poor quality of life. CONCLUSIONS: In the primary care a gap exists between clinical and standardized interviews in the detection of affective and anxiety disorders. Some experiential and social factors can increase this tendency. The use of a psycho.

Preferential responses in amygdala and insula during presentation of facial contempt and disgust.

Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.

Prefrontal-hippocampal coupling during memory processing is modulated by COMT val158met genotype.

BACKGROUND: Studies in humans and in animals have demonstrated that a network of brain regions is involved in performance of declarative and recognition memory tasks. This network includes the hippocampal formation (HF) as well as the ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that the relationship between these brain regions is strongly modulated by dopamine. METHODS: Using fMRI in healthy humans matched for a series of demographic and genetic variables, we studied the effect of the COMT val158met polymorphism on function of HF and VLPFC as well as on their functional coupling during recognition memory. RESULTS: The COMT Val allele was associated with: relatively poorer performance at retrieval; reduced recruitment of neuronal resources in HF and increased recruitment in VLPFC during both encoding and retrieval; and unfavorable functional coupling between these two regions at retrieval. Moreover, functional coupling during retrieval was predictive of behavioral accuracy. CONCLUSIONS: These results shed new light on individual differences in responsivity and connectivity between HF and VLPFC related to genetic modulation of dopamine, a mechanism accounting at least in part for individual differences in recognition memory performance.