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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain.

Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.

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.

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.

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.

Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style.

BACKGROUND: In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response. METHODS: We studied two groups (n=14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5' variable number tandem repeat (VNTR) polymorphism in the serotonin transporter. RESULTS: The fMRI results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups. CONCLUSIONS: The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information.

Functional lateralization of the sensorimotor cortex in patients with schizophrenia: effects of treatment with olanzapine.

BACKGROUND: Earlier cross-sectional studies with functional magnetic resonance imaging (fMRI) in treated patients with schizophrenia have reported abnormalities of cortical motor processing, including reduced lateralization of primary sensory motor cortex. The objective of the present longitudinal study was to evaluate whether such cortical abnormalities represent state or trait phenomena of the disorder. METHODS: Seventeen acutely ill, previously untreated patients were studied after 4 weeks and after 8 weeks of olanzapine therapy. Seventeen matched healthy subjects served as control subjects. All subjects underwent two fMRI scans 4 weeks apart during a visually paced motor task using a simple periodic block design. Functional magnetic resonance imaging data were analyzed in Statistical Parametric Mapping (SPM99). Region of interest analyses were used to determine a laterality quotient (an index of lateralization) of motor cortical regions. RESULTS: The fMRI data indicated that patients had reduced activation of the primary sensory motor cortex at 4 weeks but not at 8 weeks; however, the laterality quotient in the primary sensory motor cortex was reduced in patients at both time points. CONCLUSIONS: These results suggest that some cortical abnormalities during motor processing represent state phenomena, whereas reduced functional lateralization of the primary sensory motor cortex represents an enduring trait of schizophrenia.

Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder.

OBJECTIVE: The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits. METHOD: Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent (1)H-MRSI and were given the N-back working memory test. RESULTS: The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition. CONCLUSIONS: Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset.

Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.

OBJECTIVE: Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val(108/158)Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug. METHOD: Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks. RESULTS: There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.

Gabapentin in antipsychotic-induced tardive dyskinesia: results of 1-year follow-up.

BACKGROUND: In a previous study, improvement of antipsychotic-induced blefarospasm and involuntary oral-mandibulo movements were observed with the use of the anticonvulsant drug gabapentin among affectively ill patients who had been exposed to maintenance neuroleptics. The results reported in the present paper represent the sequel to the previous study. METHODS: The purported efficacy of gabapentin in the treatment of tardive dyskinesia has been assessed in an open design 1-year follow-up study, in which 30 schizoaffective, bipolar I and schizophrenic patients from seven Italian centres were evaluated by means of AIMS. The results showed a statistically significant time-related decrease in AIMS scores. The mean percentage of improvement at AIMS was 47.5+/-18.2%. An improvement of more than 35% after 1 year in 76% of the subjects who completed the trial (n=25) and in 63.3% of the entire sample admitted to the study was revealed. LIMITATION: Open trial. CONCLUSION: The introduction of new antipsychotic drugs has probably already limited the problems related to tardive dyskinesia. However, this type of side-effect is also observed during the course of treatment with atypical neuroleptics albeit with a lesser frequency. The fact that gabapentin treatment may have further improved clinical conditions of patients in whom therapeutic protocols had already been modified, appears to suggest exertion of a possible synergic action by the new neuroleptics on tardive dyskinesia.