Detecting syntactic and semantic anomalies in schizophrenia.

One of the major challenges in the study of language in schizophrenia is to identify specific levels of the linguistic structure that might be selectively impaired. While historically a main semantic deficit has been widely claimed, results are mixed, with also evidence of syntactic impairment. This might be due to heterogeneity in materials and paradigms across studies, which often do not allow to tap into single linguistic components. Moreover, the interaction between linguistic and neurocognitive deficits is still unclear. In this study, we concentrated on syntactic and semantic knowledge. We employed an anomaly detection task including short and long sentences with either syntactic errors violating the principles of Universal Grammar, or a novel form of semantic errors, resulting from a contradiction in the computation of the whole sentence meaning. Fifty-eight patients with diagnosis of schizophrenia were compared to 30 healthy subjects. Results showed that, in patients, only the ability to identify syntactic anomaly, both in short and long sentences, was impaired. This result cannot be explained by working memory abilities or psychopathological features. These findings suggest the presence of an impairment of syntactic knowledge in schizophrenia, at least partially independent of the cognitive and psychopathological profile. On the contrary, we cannot conclude that there is a semantic impairment, at least in terms of compositional semantics abilities.

Effects of CLOCK gene variants and early stress on hopelessness and suicide in bipolar depression.

BACKGROUND: Patients with mood disorders show a high dependence of behavior on the molecular characteristics of the biological clock. CLOCK rs1801260 gene polymorphism influences circadian behavior in bipolar disorder (BD), with *C carriers showing a delayed sleep onset and worse insomnia. Sleep phase delay and insomnia associate with suicide in the general population. METHODS: We investigated the effects of rs1801260, and of exposure to stressful life events, on current suicidal ideation and history of suicide attempts in 87 depressed patients with BD. RESULTS: rs1801260*C carriers currently showed worse Hamilton Depression Rating Scale scores for suicide and worse ratings for depressive cognitive distortions. Previous history of attempted suicide associated with exposure to higher stressful events in the early life, with rs1801260*C carriers showing a higher dependency of the modeled probability of attempting suicide on the severity of exposure to early stress. DISCUSSION: CLOCK rs1801260 modulated the relationship between early stress, adult history of attempted suicide and current suicide ideation. Factors affecting the biological clock can influence "non-clock" core psychopathological features of mood disorders.

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.

Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression.

BACKGROUND: One third of patients with bipolar disorder attempt suicide. Depression in bipolar disorder is associated with drug resistance. The efficacy of antidepressants on suicidality has been questioned. Total sleep deprivation and light therapy prompt a rapid and stable antidepressant response in bipolar disorder. METHOD: We studied 143 consecutively admitted inpatients (December 2006-August 2012) with a major depressive episode in the course of bipolar disorder (DSM-IV criteria). Among the 141 study completers, 23% had a positive history of attempted suicide and 83% had a positive history of drug resistance. During 1 week, patients were administered 3 consecutive total sleep deprivation cycles (each composed of a period of 36 hours awake followed by recovery sleep) combined with bright light therapy in the morning for 2 weeks. At admission, patients who had been taking lithium continued it, and those who had not been taking lithium started it. Severity of depression was rated according to the Hamilton Depression Rating Scale (HDRS) (primary outcome measure) and Beck Depression Inventory (BDI). RESULTS: Two patients switched polarity. Among the 141 who completed the treatment, 70% achieved a 50% reduction in HDRS score in 1 week, which persisted 1 month after in 55%. The amelioration involved an immediate and persistent decrease in suicide scores soon after the first total sleep deprivation cycle (F3,411 = 42.78, P < .00001). A positive history of suicide attempts was associated with worse early life stress and with worse suicide scores at baseline, but it did not influence response. Patients with current suicidal thinking or planning responded equally well (F3,42 = 20.70, P < .000001). Remarkably, however, nonresponders achieved a benefit, with significantly decreased final scores also including suicidality ratings (F3,120 = 6.55, P = .0004). Self-ratings showed the same pattern of change. Previous history of drug resistance did not hamper response. During the following month, 78 of 99 responders continued to stay well and were discharged from the hospital on lithium therapy alone. CONCLUSIONS: The combination of total sleep deprivation, light therapy, and lithium is able to rapidly decrease depressive suicidality and prompt antidepressant response in drug-resistant major depression in the course of bipolar disorder.

Patterns of evidence integration in schizophrenia and delusion.

Previous studies documented a bias against disconfirmatory evidence (BADE) in patients affected by schizophrenia spectrum disorders, with some discrepant findings on its relationship with delusions. In order to further investigate the patterns of evidence integration in schizophrenia and delusion, we recruited 40 deluded and non-deluded patients with schizophrenia and 40 healthy control subjects. Participants were administered the BADE test, which consisted of 30 delusion-neutral scenarios, each one progressively described by three subsequent disambiguating statements and providing four types of interpretation to rate for plausibility; at every additional evidence presentation, participants were asked to adjust their ratings. In contrast to previous works, patients displayed both a BADE and a bias against confirmatory evidence (BACE) relative to healthy subjects, as they reduced plausibility ratings on incorrect interpretations and increased plausibility ratings on correct interpretation significantly less over trial progress. Moreover, BACE and BADE measures showed to discriminate differentially control from schizophrenia participants and delusional from non-delusional patients.

Theory of mind and emotion processing training for patients with schizophrenia: preliminary findings.

Impairments in social cognition are critical predictors of social functioning in patients with schizophrenia. Emotion processing (EP) and theory of mind (ToM) are hypothesized to influence real-world behavior more directly than basic cognition and represent important targets of intervention. The use of video scenes depicting human interactions could constitute an appropriate tool to enhance understanding of the characters' behavior and stimulate inferences on mental states. The aim of our pilot study was to evaluate longitudinally, with a controlled trial, the feasibility and the efficacy of a single-paradigm emotion recognition and ToM training designed for outpatients affected by schizophrenia, with the goal to create an ecological treatment, overcoming artificial laboratory biases, by the use of specific videotaped material. Fifty-two outpatients were randomly assigned to an EP and ToM video-based training (n=27) or to a standard social cognitive rehabilitation treatment (n=24). They were assessed before and after 12 weeks of intervention and compared to a time-matched control group (n=24). Our results show a statistically significant improvement in ToM abilities, confirming the hypothesis of the enhancing potential of social cognitive interventions, but no changes with respect to EP; despite the need for a deeper examination, these data support further development of this treatment approach.

Self-awareness of cognitive functioning in schizophrenia: patients and their relatives.

Cognitive impairment has been recognized since the earliest descriptions of schizophrenia as a core feature of the illness and different programmes have been developed to remediate these deficits. In all likelihood it is important for compliance and adherence to treatment that not only the patients but also their relatives be aware of the patients; cognitive deficits. Sixty-two patients with a diagnosis of schizophrenia and, for each one of them, one family member and an informant from the medical staff, were recruited and administered the Schizophrenia Cognition Rating Scale (SCoRS) ratings. Patients were tested for cognitive deficits with a neuropsychological battery and their performance was compared to the ratings of cognitive functioning provided by the patient himself, his family member and the informant. Results show no significant association between cognitive performance and SCoRS ratings in patients; only for executive functions the patient's performance was found to be predictive of the respective judgment on the SCoRS that was given by the relative. This is the first study to investigate awareness of the patients' cognitive deficits, both in the patients themselves and in their first degree relatives, through a direct comparison between subjective clinical ratings and objective measures of cognitive performances. When both patients and relatives are unaware of the patients' cognitive deficits, this could affect adherence to remediation treatment and need to be specifically addressed in future rehabilitation strategies.

Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia.

BACKGROUND: Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. METHODS: Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. RESULTS: Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe (encompassing BA 22-42), in smaller clusters in left temporo-parietal junction and temporal pole (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. CONCLUSIONS: Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia.