4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/205476 doi: bioRxiv preprint first posted online Oct. 18, 2017; Zanão et al, 3 ABSTRACTObjective: to investigate abnormal functional connectivity in the resting-state default mode network (DMN) and its relation to memory impairments in patients with temporal lobe epilepsy with and without hippocampal sclerosis (HS) Method: we enrolled 122 MTLE patients divided into right-HS (n=42), left-HS (n=49), MRI-negative MTLE (n=31) and controls (n=69). All underwent resting-state seedbased connectivity fMRI, with a seed placed at the posterior cingulate cortex, an essential node for the DMN. In addition, patients and 41 controls were tested for verbal and visual memory, estimated intelligence coefficient and delayed recall.Results: Both right-HS and MRI-negative group presented the poorest visual memory scores, and right-HS and left-HS had a worse performance in verbal memory compared to controls and MRI-negative groups. As expected, hippocampus was less connected than controls in all groups of patients. Although EEGs indicated that 64.5% of MRInegative patients were lateralized to the left, this group showed activations similar to the right-HS. Conclusion:Our data suggest that there is a disruption of the normal pattern of DMN in MTLE. Patients with left and right-HS presented similar, increased and decreased connectivity in the ipsilateral hemisphere; however, left-HS had abnormal decreased connectivity in the contralateral hemisphere. Per neuropsychological examination, the presence of HS in the left hemisphere had more impact on verbal memory, which was not found when the seizure focus is in the left hemisphere in the absence of HS. The absence of hippocampal atrophy seems to yield a less prominent disruption in both functional connectivity and neuropsychological performance.

BackgroundIn recent years the goal of the treatment of patients with schizophrenia has shifted from symptom remission to the improvement in health as a whole. In this context, concepts such as quality of life (QoL), social and occupational functioning gained interest. The aim of this study is to investigate changes in QoL of chronic schizophrenia patients in the long-term follow-up and their associations with symptoms and level of community functioning.MethodsWe will contact 85 patients with schizophrenia, considered clinically stable in the previous year, who participated in a study about the deficit syndrome of schizophrenia in 2009/2010. Back then, they were recruited in two sites: an outpatient service of a university general hospital (49 patients) and a community-based service (36 patients). Patients will be assessed with the same instruments adopted in the first study: SAPS, SANS, Calgary Depression Scale and Quality of Life Scale (QLS), plus the Personal and Social Performance Scale (PSP), not used at baseline. We started recruitment by the patients originally treated in the outpatient clinic.ResultsUntil now, of the 49 patients, 2 dropped out treatment, 8 had been transferred to other services, 5 refused to participate, 1 had the diagnostic changed to bipolar disorder and 3 had died precociously. Of the deaths, 1 was due to complications secondary to the use of clozapine, 1 due to suicide and 1 patient was murdered by another patient during a psychiatric hospitalization. Up to now, 20 patients completed reassessment, mean age at baseline was 36.9 ± 8.9 years, mean duration of mental illness was 16 ± 10.1 years, and 75% were men. They had in mean, 10.7 ± 3.3 years of education, only 4 had any work activity and 55% had a low socioeconomic position. Assessment interval was 6.9 years ± 0.5. Some demographic aspects slightly worsened: only 15% had an occupation at follow-up, and 60% fell in the lower socioeconomic position. Between assessments, 8 (40%) patients have had periods of noncompliance to medication, 5 had psychiatric hospitalizations, three of them involuntarily. At follow-up 70% of the patients were using clozapine and, despite that, some presented residual positive symptoms (SAPS 6.2 ± 4.8); Calgary mean score was low (2.2 ± 2.2) and, except for the patient who died, there was no new suicide attempts between assessments. Negative symptoms severity was moderate in general (mean SANS 14.8 ± 7.2). Patients as a group had no significant change in QLS scores (61.5 ± 28.2 versus 60.1 ± 28.2 at follow-up). However, 15% of patients had an improvement greater than 20% in their QLS scores, and 30% had a worsening of their scores greater than 20%. Baseline scores on SANS (p=0.005), SAPS (p=0.03) and number of hospitalizations (p=0.03) were negatively correlated with follow-up QLS scores; and years of schooling at baseline was positively correlated (p=0.2). Baseline QLS scores were strongly associated with current QLS scores, as well as with PSP scores (both with P <0.000) at follow-up. Regarding PSP o...

BackgroundNegative symptoms of schizophrenia are admittedly associated with a poorer outcome regarding aspects such as functionality, quality of life and cognitive performance. Patients with prominent, persistent and primary negative symptoms have been considered to manifest a putative subtype called “Deficit schizophrenia” (DS). However, the boundaries of deficit and nondeficit forms were put in question since the publication of a study that considered separately a group of patients with persistent negative symptoms whose primary nature could not be asserted, the “ambiguous nondeficit” group, who would be otherwise categorized as nondefict according to the gold standard instrument: the Schedule for the Assessment of the Deficit Syndrome (SDS). Those patients presented psychopathological features, quality of life, insight and cognitive function quite different from the nondeficit group, and closer to the deficit group. The objectives of the present study are to investigate the stability of the categorization regarding the presence of DS in three groups: “deficit”(DS), “nondeficit” (ND) and “ambiguous nondeficit” (SND) over a long term follow-up and to evaluate clinical outcomes in the different groups.MethodsWe will contact 85 patients with schizophrenia, considered clinically stable in the previous year, who participated in a study about the DS in 2009/2010. Back then, they were recruited in two sites: an outpatient service of a university general hospital (49 patients) and a community-based mental health service (36 patients). Patients will be assessed with the same instruments adopted in the first study: a questionnaire for clinical and demographic information; BPRS, SAPS, SANS, Calgary Depression Scale, the SDS, QLS, and a battery of neurocognitive tests. We started the recruitment by the patients originally treated in the outpatient clinic.ResultsHere we present partial results. Of the 49 patients, 5 refused to participate in the follow-up study, 3 died prematurely, and 1 had the diagnostic changed for bipolar disorder. Assessment interval was 6.9 years ± 0.5 Among the 20 reassessed patients, mean age at baseline was 36.9 ± 8.9 years, mean duration of mental illness was 16 ± 10.1 years, and 75% were men. They had in mean, 10.7 ± 3.3 years of education, only 20% had any work activity, 15% were married and 55% had a low socioeconomic position. These demographic aspects slightly worsened: only 15% had an occupation at follow-up, and 60% fell in the lower socioeconomic position. Regarding the SDS classification, 4 of 9 ND patients at the baseline were reclassified as DS; 1 of 7 DS was reclassified as ND, the other 6 remained DS; from the AND, 3 were considered DS and 1 ND, from a total of 4. At the end, there were 13 DS and 7 ND, while at the baseline they were: 7 DS, 9 ND and 4 AND. Concerning psychopathology, 80% of the patients had an increase in SANS and the most expressive increase was in nondeficit group (an average of 5.4 points), although the average in DS group remained the higher (18.9 points)....

BackgroundCognitive deficits are prevalent among patients with schizophrenia and are robustly associated with functioning and outcome. Although cognitive deficits are known to be present at the prodromal phase and to worsen at the onset of the disease, the long-term course of cognitive impairments are less well established. Many studies have focused on first episode psychosis with relatively short lengths of follow-up. Thus, the aim of this study is to investigate changes in cognitive performance of chronic schizophrenia patients in a variety of neurocognitive tests over a seven-year test-retest period.MethodsWe will contact 85 patients with schizophrenia (as defined by the DSM-IV-TR), considered clinically stable in the previous year, who participated in a study about the deficit syndrome of schizophrenia carried out in 2009 and 2010. Back then, they were recruited in two sites: an outpatient psychiatric service of a university general hospital (49 patients) and a community-based mental health service for patients with severe mental illness (36 patients), both in Campinas, Sao Paulo, Brazil. Patients will be assessed with the same instruments adopted in the first study: a questionnaire for clinical and demographic information; SAPS, SANS, Calgary Depression Scale and a battery of neurocognitive tests comprising: Digit Span Forward (DSF), Digit Span Backward (DSB), Rey Complex Figure Copy (RCFC), Rey Complex Figure Memory (RCFM), Digit symbol-coding (DSC), Picture Completion (PC), Matrix Reasoning (MR), Vocabulary (V), Trail Test A (TTA), Trail Test B (TTB), Phonological Fluency (PF) and Semantic Fluency (SF). To test differences in neurocognitive performance, and in symptoms severity at base and at follow-up we used the Wilcoxon Test.ResultsWe present in this poster partial results. Among the 20 reassessed patients the mean age at baseline was 36.9 ± 8.9 years, mean duration of mental illness was 16 ± 10.1 years, 75% were men. They had, in mean, 10.7 ± 3.3 years of education, only 20% had any work activity, and 15% were married. Mean length of test-retest interval was 6.9 years (minimum 6 and maximum 7.7). At follow-up, 4 patients had improved their education, but only 3 (15%) had any work activity. Up to now 19 patients completed the cognitive reassessment. Severity of positive and of depressive symptoms was low at base line (mean score on SAPS 5.5 ± 4.8; mean score on Calgary 1.5 ± 1.9) and remained low at follow-up (SAPS 6.2 ± 4.4, Calgary 2.2 ± 2.2), with no significant change. Patients, as a group, had moderate negative symptoms were at baseline (mean SANS score 10.5 ± 6.9) and had their negative symptoms worsened at follow-up (SANS 14.8 ± 7.1), p=0.005. Patients had a worse performance at follow-up in 4 out of 12 tests: DSF (3.8 ± 1.5 at follow-up versus 10.1 ± 2.8 at baseline, p < 0.000), DSB (3.4 ± 1.9 at follow-up versus 4.3 ± 2.2, p=0.005), RCFC (14.8 ± 9.4 versus 30.2 ± 8.6, p < 0.000) and RCFM (5.9 ± 6.5 versus 13.9 ± 9.8, p < 0.000). In the remaining 8 tests: DSC, PC, MR, V, TTA, TTB, PF and...

Dedico esta dissertação à dona Izabel, pois, como canta Milton Nascimento: Minha voz vem da mulher, minha voz veio de lá, de quem me gerou. Quem explica o cantor, quem entende essa voz, sem as vozes que ele traz do interior? (A voz feminina do cantor -Milton Nascimento) AGRADECIMENTOS [...] todos nascemos filhos de mil pais e de mais mil mães, e a solidão é sobretudo a incapacidade de ver qualquer pessoa como nos pertencendo, para que nos pertença de verdade e se gere um cuidado mútuo. Como se nossos mil pais e nossas mil mães coincidissem em parte, como se fôssemos por aí irmãos, irmãs uns dos outros. Somos resultado de tanta gente, de tanta história, tão grandes sonhos que vão passando de pessoa a pessoa, que nunca estamos sós.