White matter alterations associate with onset symptom dimension in obsessive-compulsive disorder.

AIM: The high heterogeneity of obsessive-compulsive disorder (OCD) is best described by a multidimensional model involving symptom dimensions. We aimed to investigate white matter alterations associated with OCD, focusing on the impact of long-lasting effect of symptom dimensions assessed at onset of illness. Furthermore, we investigated white matter alterations associated with this disorder, controlling for the impact of medications and for the prevailing current symptom dimension. METHODS: We studied 58 patients affected by OCD and 58 age- and sex-matched healthy controls. We divided patients according to symptom dimension at onset of illness, assessed with the five-factor model. T-tests were performed in order to investigate differences between subgroups. Similar analyses were performed considering the prevailing current symptom dimension. Analyses were conducted with tract-based spatial statistics on diffusion tensor imaging. RESULTS: Doubt/checking and rituals/superstition symptom dimensions at onset and symmetry/perfectionism current symptom dimensions were characterized by significant alterations in diffusion tensor imaging measures. An association of white matter alterations and symmetry/perfectionism current dimension was found only when controlling for the effect of doubt/checking dimension at onset. Finally, results pointed out that the observed differences between patients and healthy controls were carried by the effect of previous and current medications. CONCLUSION: Our findings evidenced that onset symptom dimensions are associated with enduring alterations of white matter microstructure. Onset symptom dimensions may reflect underlying endophenotypes. In addition, present results confirm the effect of medications on white matter in OCD, showing a large effect of current treatment on myelination.

Visual and audio emotion processing training for outpatients with schizophrenia: an integrated multisensory approach.

Deficits in emotion processing (EP) represent a target of rehabilitation in schizophrenia, as they have been related to poor personal and social functioning. To date neither the relationship between these deficits and the generalised cognitive impairment, nor the involvement of specific mechanisms of perception (visual or auditory) are fully comprehended. We developed two treatments targeting EP, through visual or auditory channels, with the aim of disentangling possible differences and/or interactions between the two modalities in schizophrenia-related impairments, also taking into account the role of cognition and social functioning. Thirty five outpatients with schizophrenia were assessed for neurocognition, social functioning and EP (visual and auditory channel) and participated in either visual or auditory EP training or in an active control group. Results showed a significant improvement in EP through the specific channel trained for both groups, with an extended effect also on vocal stimuli for the visual training group. Positive correlations were found between working memory, social functioning and EP. Our findings help to shed light on the possible different involvement of perceptual channels in schizophrenia, as well as supporting previous evidence that emotion recognition may be inter-related but does not overlap with neurocognition and can be specifically trained.

Right hemisphere neural activations in the recall of waking fantasies and of dreams.

The story-like organization of dreams is characterized by a pervasive bizarreness of events and actions that resembles psychotic thought, and largely exceeds that observed in normal waking fantasies. Little is known about the neural correlates of the confabulatory narrative construction of dreams. In this study, dreams, fantasies elicited by ambiguous pictorial stimuli, and non-imaginative first- and third-person narratives from healthy participants were recorded, and were then studied for brain blood oxygen level-dependent functional magnetic resonance imaging on a 3.0-Tesla scanner while listening to their own narrative reports and attempting a retrieval of the corresponding experience. In respect to non-bizarre reports of daytime activities, the script-driven recall of dreams and fantasies differentially activated a right hemisphere network including areas in the inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses were significantly greater for fantasies than for dreams in all regions, and inversely proportional to the degree of bizarreness observed in narrative reports. The inferior frontal gyrus, superior and middle temporal gyrus have been implicated in the semantic activation, integration and selection needed to build a coherent story representation and to resolve semantic ambiguities; in deductive and inferential reasoning; in self- and other-perspective taking, theory of mind, moral and autobiographical reasoning. Their degree of activation could parallel the level of logical robustness or inconsistency experienced when integrating information and mental representations in the process of building fantasy and dream narratives.

Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and Medication Load Influence White Matter Structure in Schizophrenia.

BACKGROUND: Diffusion tensor imaging (DTI) studies have shown a widespread disruption of white matter (WM) microstructure in schizophrenia. Furthermore, higher fractional anisotropy (FA) has been consistently correlated with the severity of psychotic symptoms. Antipsychotic drugs (APDs) affect lipid homeostasis. Gene polymorphisms in sterol regulatory element binding transcription factor (SREBF)-1 and SREBF-2 have been associated with schizophrenia. METHODS: In a sample of 65 patients affected by chronic schizophrenia, we investigated the effect of ongoing APD medication, SREBF-1 rs11868035 polymorphism and SREBF-2 rs1052717 polymorphism on the WM microstructure, using tract-based spatial statistics with threshold-free cluster enhancement. RESULTS: We reported increased FA associated with the risk rs11868035 G/G genotype in several WM tracts, mainly located in the left hemisphere, and opposite effects of the APD medication load, with reduced FA and generally increased diffusivity. These opposite effects overlapped in the forceps minor, cingulum, uncinate fasciculus, the superior and inferior longitudinal fasciculi, the corticospinal tract, inferior fronto-occipital fasciculus and the anterior thalamic radiation. CONCLUSION: We suggest that changes of WM structure could be an as yet poorly explored biomarker of the effects of APDs, to be further investigated in prospective studies correlating long-term clinical effects with changes of DTI measures in specific WM tracts contributing to the functional integrity of the brain. © 2015 S. Karger AG, Basel.

COMT and STH polymorphisms interaction on cognition in schizophrenia.

Catechol-O-methyltransferase (COMT) gene, a key regulator of prefrontal cortex (PFC) dopamine (DA) availability, has been extensively studied in relation to cognitive domains, mainly executive functions, that are impaired in schizophrenia, but results are still controversial. Since recent studies in patients affected by neurodegenerative and psychiatric disorders suggested a role of saitohin (STH) gene as a concurring factor in hypofrontality, we hypothesize that STH and COMT polymorphisms could have an additive effect on cognition in schizophrenia. Three forty three clinically stabilized patients with schizophrenia were assessed with a broad neuropsychological battery including the Brief Assessment of Cognition in Schizophrenia, the Wisconsin Card Sorting Test and the Continuous Performance Test and were genotyped for COMT Val108/158Met and STH Q7R polymorphisms. We observed the effects of COMT on speed of processing and executive functions, as well as a significant effect of STH on executive functions performances. Moreover, a significant interaction between COMT and STH polymorphisms was found on executive functions, with COMT Val/Val and STH R carriers performing worse. Our results showed a significant interaction effect of COMT and STH polymorphisms on cognitive performances, strengthening the involvement of STH in cognitive impairments, especially in the domains commonly impaired in schizophrenia.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

BACKGROUND: It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. METHODS: We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. RESULTS: Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. CONCLUSIONS: Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms.

The serotonin transporter genotype modulates the relationship between early stress and adult suicidality in bipolar disorder.

OBJECTIVE: Bipolar disorder (BD) is associated with a higher risk of suicide and with worse early life stress. A serotonin (5-hydroxytryptamine; 5-HT) transporter-linked polymorphic region (5-HTTLPR) has been shown to influence the relationship between stress and the risk of attempting suicide in the general population, but has not been investigated in BD. METHODS: We studied 136 inpatients (93 females, 43 males) with a major depressive episode in the course of BD. Early and recent stressful life events were scored on the Social Readjustment Rating Scale (SRRS). Regional gray matter (GM) volumes were analyzed, acquiring T1-weighted images on a 3.0 Tesla scanner. RESULTS: Homozygote l/l patients attempted suicide in a higher proportion than *s carriers. A separate-slopes logistic regression showed a significant effect of 5-HTTLPR on the relationship between stress, depression, and suicide among *s carriers, but not among l/l homozygotes, early stress associated with worse probability of attempting suicide and with earlier age at onset of BD. Exposure to early stress correlated with GM volumes in the right prefrontal cortex (Brodmann area 46) - again, in *s carriers only. CONCLUSIONS: 5-HTTLPR modulated the relationship between early life stress and the core features of bipolar illness. 5-HTTLPR*s carriers showed a higher sensitivity to the effects of stress; when exposed to low levels of early stress, they were protected against suicide in respect to l/l, but higher levels of stress progressively increased their risk of suicide and reduced the age at onset of illness.

Adverse childhood experiences and gender influence treatment seeking behaviors in obsessive-compulsive disorder.

BACKGROUND: Exposure to adverse childhood experiences (ACE) increases the risk of adult physical and mental health disorders, including obsessive-compulsive disorder (OCD), and influences adult brain structure and function. ACE could influence the use of psychotropic drugs in adulthood, and treatment seeking behaviors. METHODS: We assessed the severity of ACE in a sample of 31 healthy controls and 66 patients with OCD who were consecutively referred for hospitalization and were either drug-naïve or drug-treated. In addition, we explored the possible clinical relevance of ACE with two additional analyses: (a) a discriminant function analysis with sex and ACE as factors, and (b) a logistic regression with use of medication as dependent variable and ACE as factor. RESULTS: Despite comparable age, years at school, age at onset of illness, duration of illness, and severity of illness (Y-BOCS), adult drug-naïve patients reported lower exposure to ACE and later contacts with mental health professionals than drug-treated. This effect was particularly evident in female patients compared to males. CONCLUSIONS: The interaction of gender with factors linked with the early familial environment biased access to psychiatric care and use of medication, independent of OCD-associated factors such as severity of symptoms or duration of illness. The need for medications of patients could be higher in families where OCD symptomatology is associated with ACE.

Addiction and empathy: a preliminary analysis.

Addicted patients show impaired social functioning. Chronic drug consumption may lead to impairments in decoding empathic cues. The aim of the study is to explore empathy abilities in addicted patients and the hypothesis of a differential impairment between affective and cognitive empathy. 62 addicted patients and 40 healthy volunteers were evaluated using the empathy quotient (EQ) and its subscales cognitive empathy (factor 1), emotional empathy (factor 2), social skills (factor 3). Patients scored statistically significantly lower than controls in EQ total score, in particular in factor 2. No difference was found in factor 1 and in factor 3. Consistent with previous findings, our study suggests specific impairment in emotional empathy combined with preserved cognitive empathy. These findings show important clinical implication in the development of specific rehabilitative programmes for the empowerment of empathy abilities and interpersonal skills that constitute important components in the prevention of relapse.

Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.

BACKGROUND: The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. METHODS: Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. RESULTS: An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. DISCUSSION: This is the first study of the effect of rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by rs4680 COMT polymorphism.

Theory of Mind intervention for outpatients with schizophrenia.

Social disability is one of the critical areas known to be a predictor of daily functioning in schizophrenia. Recent studies showed that impairments in Theory of Mind (ToM) contribute to real-world social functioning and are more strongly associated with community outcomes than other neuropsychological domains of cognition. Several experiments revealed an improving potential of social cognition targeted training, particularly through introduction of verbalisation and explicit manipulation of information about others' mental states. Based on these data, we evaluated longitudinally, with a controlled trial, the feasibility and efficacy of ToM training and the possible influences of daily functioning and IQ on the enhancement of ToM abilities. Thirty outpatients with schizophrenia were recruited and randomly allocated to two groups: ToM Intervention (ToMI), based on verbalisation of selected comic strips representing ToM scenarios, or active control group (ACG). Results showed a significant improvement of ToM abilities among subjects allocated to ToMI compared to ACG, confirming the hypothesis of the enhancing potential of training methods targeting ToM functions. Moreover, we observed no influences of neuropsychological and functional variables on ToM improvement. Development of future studies should take into account possible effects of ToM training on functional outcome, according to the strong associations between ToM abilities and real-world social functioning.

Caudate gray matter volume in obsessive-compulsive disorder is influenced by adverse childhood experiences and ongoing drug treatment.

BACKGROUND: Exposure to adverse childhood experiences (ACE) increases the risk of adult physical and mental health disorders, including obsessive-compulsive disorder (OCD), and influences adult cortical neural responses and gray matter (GM) volumes. Robust neuroimaging findings associated OCD with corticostriatal dysfunction and with abnormal morphology and metabolism of cortical areas and basal ganglia. METHODS: We explored the GM correlates of ACE in 40 patients with OCD (15 drug-naive and 25 drug-treated patients) with magnetic resonance imaging voxel-based morphometry at 3.0 T. Regional GM volumes were the dependent variable, and drug treatment (naive vs treated) and breadth of exposure to ACE (high vs low) were the factors of interest. Sex, duration of illness, and handedness were considered as nuisance covariates. Whole brain statistical threshold was P < 0.05 familywise error corrected for multiple comparisons. RESULTS: Patients with higher levels of exposure to ACE showed increased GM volume in the head of the left caudate nucleus. Ongoing drug treatment was associated with reduced GM volume in the same area. Earlier age at onset of OCD, need for medication treatment, and mixed handedness were correlated with higher levels of ACE. CONCLUSIONS: Exposure to ACE increased, and ongoing drug treatment decreased, caudate GM in OCD. Increased volume and metabolism of the caudate nucleus have been consistently associated with OCD. Our findings suggest a detrimental effect of ACE on the brain underpinnings of OCD, with an opposite effect of medications.

An explorative study on metacognition in obsessive-compulsive disorder and panic disorder.

OBJECTIVE: To test the hypothesis that dysfunctional metacognitions might be a general vulnerability factor for anxiety disorder, metacognitive beliefs among patients with obsessive-compulsive disorder (OCD), patients with panic disorder (PD), and healthy subjects (HS) were studied. Correlations between metacognitive beliefs, OCD, and PD symptoms were also investigated. METHODS: Patients with OCD (n = 114), patients with PD (n = 119), and HS (n = 101) were assessed with the Metacognition Questionnaire (MCQ). RESULTS: Patients with OCD and those with PD scored significantly higher than HS on the MCQ in 2 dimensions: negative beliefs about worry concerning uncontrollability and danger as well as beliefs about the need to control thoughts dimensions. No difference in MCQ scores was observed between the OCD and PD groups. The former 2 MCQ dimensions were positively correlated with the degree of indecisiveness in patients with OCD, whereas the MCQ negative beliefs about worry positively correlated with the average intensity of anticipatory anxiety in patients with PD. CONCLUSIONS: The presence of dysfunctional metacognitions in both patients with OCD and those with PD suggests that such beliefs can represent not only generic vulnerability factors for anxiety disorders but also elements that contribute to maintaining the disorder, as evidenced by their associations with aspects of OCD and PD symptoms.

Alexithymia and anxiety sensitivity in populations at high risk for panic disorder.

OBJECTIVE: Populations at high risk for panic disorder (PD) probably share with subjects with PD an underlying vulnerability involving features like anxiety sensitivity (AS) and alexithymia. The present study would verify if PD relatives (R) and subjects who have experienced 1 or more panic attacks (PAs) show different levels of AS and alexithymia with respect to healthy controls (HC). METHODS: One hundred fifty-seven HCs, 30 subjects with PA, 64 R subjects, and 139 outpatients with PD were evaluated and compared on AS, alexithymia, and control variables. RESULTS: Subjects with PD show higher alexithymia and AS levels compared with HCs; R subjects do not differ on ASI total score; and R females show more alexithymic features. Subjects with PA are comparable with HCs both on AS and alexithymia. CONCLUSIONS: Results confirm an impairment in emotional and bodily sensations information processing in subjects with PD but partially disconfirm the expectation of a difference between R subjects and subjects with PA with respect to HCs on AS and alexithymia. Emotional and bodily sensation competencies could be protective factors for PD in high-risk populations.

Saitohin polymorphism and executive dysfunction in schizophrenia.

Saitohin (STH) is an intronless gene nested within the human tau gene, which contains a single nucleotide polymorphism (A/G), suggested to be involved in the physiopathology and clinical course of several neurodegenerative and neuropsychiatric diseases. Recently, an association between this polymorphism and frontal hypoperfusion and clinical prognosis in frontotemporal dementia was reported. The present study sought to evaluate the possible role of the STH polymorphism as a concurring factor of cognitive decline in schizophrenia, a disease sharing both early psychotic manifestations, a core deficit of executive functions and hypofrontality with frontotemporal lobe dementia. 220 clinically stabilized patients with schizophrenia were assessed with the Wisconsin Card Sorting Test (WCST) for evaluation of executive functions and compared for STH allele frequency with 48 patients affected by frontotemporal dementia and 47 healthy subjects. There was no significant difference in allelic distribution between the healthy controls and all other groups, while we observed a significantly greater frequency of G allele among both patients with frontotemporal dementia (p = 0.037) and schizophrenia patients with poor performances of WCST (p = 0.044), compared to schizophrenia patients with best WCST performances. Among the patients with schizophrenia, stratified for age and gender, the STH polymorphism resulted in a significant predictor of WCST performance (p = 0.007). These results suggest a possible contribution of STH gene products on the heterogeneity of core frontal executive functions deterioration, probably through complex interactions with mechanism involved in neurodevelopment and neurodegeneration.

Premorbid functioning and treatment response in recent-onset schizophrenia: prospective study with risperidone long-acting injectable.

Premorbid functioning may be associated with treatment response, but this is confounded by a lack of prospective longitudinal data and controls for medication compliance. This study tested the hypothesis that good premorbid functioning will be associated with better antipsychotic treatment response after controlling for drug adherence by using a long-acting injectable antipsychotic. This was a 6-month, open label, multicenter, phase IV trial in recent-onset schizophrenia treated with flexible doses of risperidone long-acting injectable (25-50 mg every 14 days). Premorbid functioning was assessed with the Premorbid Adjustment Scale (PAS)-Structured Interview; efficacy was evaluated with clinician-rated Positive and Negative Syndrome Scale, Clinical Global Impression scale of Severity of Illness, Clinical Global Impression scale of Change, Global Assessment of Functioning Scale, and trial participant completed SF-36. Analyses controlled for baseline scores and demographics. With the use of a priori PAS scoring criteria, the participants' premorbid functioning was categorized as stable-good (n = 142), stable-poor (n = 116), and deteriorating (n = 36). At baseline, the stable-good group had the best functioning on most efficacy measures. All groups showed significant improvement on efficacy measures with treatment. Improvement was significantly higher for the stable-good group. The PAS global assessment of highest level of functioning scale (excellent, n = 75; good, n = 117; fair, n = 78; and poor, n = 31) showed a strong association with baseline functioning and improvement and had a significant linear association with meeting Remission in Schizophrenia Working Group symptom criteria at baseline (P = 0.003) and attained and sustained remission for 3 months during study (47.7%, 49.3%, 29.6%, and 22.2%; P = 0.006). Good premorbid functioning corresponds with better treatment response in recent-onset psychosis as captured on both clinician and patient-reported measures.

Tract-specific white matter structural disruption in patients with bipolar disorder.

OBJECTIVES: A growing body of evidence suggests that, independent of localized brain lesions, mood disorders can be associated with dysfunction of brain networks involved in the modulation of emotional and cognitive behavior. We used diffusion tensor (DT) tractography to quantify the presence and extent of structural injury to the connections between the amygdala and other brain regions, which included the subgenual, the supragenual and posterior cingulate, the parahippocampal, the orbitofrontal and dorsolateral prefrontal cortices, as well as the insula. METHODS: Using a 3.0 Tesla scanner, conventional and DT magnetic resonance imaging sequences of the brain were acquired from 15 adult patients with major depressive disorder (MDD), 15 with bipolar disorder (BD), and 21 age-matched healthy controls. Using FSL software, diffusivity changes of the white matter (WM) fiber bundles belonging to the emotional network were measured. RESULTS: Compared to controls and MDD patients, BD patients had significantly decreased average fractional anisotropy, increased average mean diffusivity, and increased average axial and radial diffusivity values in the majority of the WM fiber bundles connecting structures of the anterior limbic network (p-values ranging from 0.002 to 0.040). Medication load did not influence the results with the exception of lithium, which was associated with normal diffusivity values in tracts connecting the amygdala with the subgenual cingulate cortex. CONCLUSIONS: We detected specific WM abnormalities, suggestive of disrupted integrity of fiber bundles in the brains of patients with BD. These abnormalities might contribute to understanding both mood dysregulation and cognitive disturbances in BD, and might provide an objective marker to monitor treatment efficacy in this condition.

Role of COMT, 5-HT(1A) , and SERT genetic polymorphisms on antidepressant response to Transcranial Magnetic Stimulation.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) is an effective technique in the treatment of depression, specifically in drug-resistant patients. However, there is little data available on the influence of genetic variables on TMS response. METHODS: We analyzed the role of three genetic polymorphisms that affected the antidepressant response: serotonin transporter promoter region (SERTPR) polymorphism, 5-HT(1A) serotonergic receptor promoter region polymorphism (rs6295), and the coding region of COMT gene polymorphism (rs4680). Ninety patients with a major depressive drug-resistant episode due to a Major Depressive Disorder or to a Bipolar Disorder were included in our study. Patients underwent high frequency TMS, focused on the left prefrontal cortex, for 2 weeks. At study completion, the response rate was 45.5%. Effects of gene polymorphisms on clinical improvement were analyzed with an analysis of variance with each gene (SERTPR, 5-HT(1A) , and COMT) as factors and the Hamilton Rating Scale for Depression variation from baseline to the end of the treatment as a dependent variable. RESULTS: We found a significant model in which three factors were not significant (diagnosis, COMT, and SERTPR), whereas factor 5-HT(1A) showed a significant influence on the outcome, with patients with C/C genotype showing a greater improvement than G/G and C/G and no difference between G/G and C/G. CONCLUSION: According to our data, 5-HT(1A) polymorphism may play a role in influencing TMS response. The effect of COMT and SERTPR did not reach statistical significance. The analysis of these and other candidate genes in larger samples could help explain genetic influence on TMS response.

Effect of 5-HT1A-receptor functional polymorphism on Theory of Mind performances in schizophrenia.

Theory of Mind (ToM) abilities are known to be impaired in schizophrenia and data from functional brain imaging studies showed that ToM deficit is correlated to prefrontal cortex (PFC) dysfunction. Moreover, several lines of evidence suggest a critical role for dopaminergic-serotoninergic interactions at the PFC level. In this view, we aimed to analyse the specific effect of the -1019C/G functional polymorphism of the serotonin 1A receptor (5-HT1A-R), involved in both serotonin and dopamine transmission regulation. A total of 118 clinically stabilised schizophrenia patients was assessed with a neuropsychological battery, including evaluation of IQ, verbal memory, attention and executive function and a ToM task; they also underwent 5-HT1A-R genotyping. We observed a significant effect of the 5-HT1A-R genotype on ToM performances, with the CC genotype performing significantly better. The finding suggests an effect of the 5-HT1A-R polymorphism on ToM cognitive performance in schizophrenia patients, probably through complex interactions between dopaminergic and serotoninergic systems, involved in mentalising.

Dysfunctional brain circuitry in obsessive-compulsive disorder: source and coherence analysis of EEG rhythms.

BACKGROUND: Morphological and functional studies suggested involvement of several cortical and subcortical circuitries in patients with obsessive-compulsive disorder (OCD). The aim of the present study was to investigate networks involved in OCD pathophysiology, using power (coupling of EEG bands, low-resolution electromagnetic tomography-LORETA) and coherence analysis in drug-naïve patients. METHOD: EEG was obtained from 37 drug-naïve patients with OCD and 37 age- and sex-matched controls. Resting EEG was recorded from 29 scalp channels. Coupling (ratio and correlation) between low and high frequencies was analyzed on Fz. For each frequency band, LORETA current density distribution, intra-hemispheric and inter-hemispheric coherence analysis were computed. RESULTS: OCD had increased current density for delta in the insula and for beta in frontal, parietal and limbic lobes. OCD also had decreased inter-hemispheric coherence and reduced coupling between delta and beta frequencies. CONCLUSIONS: In OCD, increased frontal beta is consistent with previous evidence of frontal dysfunction. Hyperactivity of insular delta sources, together with rhythms decoupling and reduced interhemispheric alpha coherence are consistent with additional involvement of cortico-subcortical functional connections. Combined use of power and coherence analysis may provide functional measures on different levels of involvement of cortico-subcortical circuits in neuropsychiatric disorders.