Vanessa Sánchez-Gistau

Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study.

OBJECTIVE To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort. METHOD 110 subjects in their first episode of psychosis aged between 9 and 17 years were assessed by using the DSM-IV diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and a battery of clinical instruments at baseline and at 12 and 24 months. Patients were enrolled in the study from March 2003 through November 2005. Suicide attempts and level of suicidality at each assessment were evaluated by using the Clinical Global Impression for Severity of Suicidality and the Hamilton Depression Rating Scale. Subjects were classified as being at high, low, or no risk of suicide, depending on their scores on certain items of these scales. Clinical associations between the outcome measures high risk for suicide during acute episode and suicide attempts during follow-up were investigated by 2 sets of logistic regression analyses. RESULTS The 24-month prevalence of suicide attempters was 12.4%. History of suicide attempts prior to psychotic episode (OR = 20.13; 95% CI, 1.83-220.55; P = .01), severe depressive symptoms (OR = 8.78; 95% CI, 1.15-67.11; P = .003), and antidepressant treatment (OR = 15.56; 95% CI, 2.66-90.86; P = .002) were associated with being classified as high suicide risk at baseline. The categorization of high suicide risk at baseline predicted suicide attempts during follow-up (OR = 81.66; 95% CI, 11.61-574.35; P = .000). CONCLUSIONS Suicide is a major concern in early-onset first-episode psychosis. Suicidal behavior and depressive symptoms at psychosis onset are important signs to be aware of to prevent suicide attempts during the early period after first-episode psychosis.

Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study.

We aim to investigate whether temporal origin of epilepsy increases the risk of developing a psychiatric disorder and more specifically a major depressive disorder. The lack of standardized diagnostic instruments and the methodologic differences between studies highlight the fact that this issue warrants further, systematic, study. Three‐hundred eight patients with complex partial seizures were classified according to temporal or extratemporal origin, following the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE), 1989 localization‐related concept. All patients were assessed using the Structured Interview for DSM‐IV axis I psychiatric disorders (SCID‐I). Lifetime and previous‐year prevalence of psychiatric disorders were compared in temporal and extratemporal subgroups, using multivariate analysis. Previous‐year major depression was significantly associated with temporal lobe origin. Our results do not support the hypothesis that patients with temporal lobe epilepsy (TLE) have more psychiatric illness in general, although they do suggest a specific connection between TLE and major depression.

Is major depressive disorder specifically associated with mesial temporal sclerosis

Purpose:  Whether a specific lesion such as mesial temporal sclerosis (MTS) increases the risk for a mood disorder in epilepsy remains subject to debate. Despite evidence of limbic system involvement in the genesis of emotional symptoms, recent studies fail to support an association between depression and MTS. We aimed to clarify this controversial issue by overcoming prior methodologic limitations, hypothesizing that rates of major depressive disorder (MDD) would be higher in patients with MTS.

Neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder

BACKGROUND Bipolar disorder (BD) is a severe mental disorder with a strong genetic component. The assessment of child and adolescent offspring of patients diagnosed with BD (BDoff) provides an opportunity to investigate vulnerability factors and the first abnormalities associated with the disorder. Previous literature in child and adolescent BDoff is scarce and controversial. However, some studies concur in identifying significant impairment in executive functions, memory and attention. The present study aims to compare global neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder with a group of offspring of parentswith no history of psychotic disorder, and to assess the influence of psychopathology on neuropsychological performance. METHODS This research was part of The Bipolar and Schizophrenia Young Offspring Study (BASYS). A group of BDoff (N= 90) and a group of offspring of parents with no history of psychotic disorder (CC) (N = 107) were assessed with a complete neuropsychological battery. Intellectual quotient, working memory, processing speed, verbal memory and learning, visual memory, attention and executive functions were included in the cognitive assessment. RESULTS BDoff showed significantly worse performance in processing speed and immediate recall of visual memory relative to CC. When the presence of any lifetime psychopathology was analysed, the results showed that belonging to the BDoff group was the main explicative factor for the scores obtained in both processing speed and visual memory immediate recall, regardless of the presence of psychopathology. CONCLUSIONS These findings suggest that processing speed and visualmemory should be taken into consideration in future research on vulnerability markers of BD.

Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls

Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7–19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

The affective dimension of early‐onset psychosis and its relationship with suicide

BACKGROUND The affective dimension has scarcely been studied in early-onset psychosis. Our aims were to investigate the prevalence and type of affective symptoms in the prodromal and acute phases of early-onset psychosis and to examine their relationship with suicide. We also sought to establish whether the presence of premorbid antecedents or the presence of affective symptoms during the prodromal and acute phase might predict a later diagnosis of bipolar disorder (BP) or schizophrenia (SZ). METHOD Participants were 95 youths, aged 9-17 years, experiencing a first episode of a psychotic disorder (FEP) according to DSM-IV criteria. Prodromal affective symptoms in the year prior to the onset of full-blown psychosis were assessed by means of the K-SADS. Affective symptoms during the acute episode were evaluated using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Suicidality was assessed during the acute episode and at 6 and 12 months. RESULTS Half of the patients experienced affective symptoms during the prodrome, with depressive symptoms being the most frequently reported. During the acute episode, 23.2% presented depressive, 41.4% mixed and 18.9% manic symptoms. After logistic regression analysis, only the presence of depressive symptoms was significantly associated with suicidality during the 12 months following the FEP. Neither early premorbid antecedents nor the prevalence or type of affective symptoms during the FEP predicted a diagnosis of BP or SZ at 12 months. However, both depressive and manic prodromal symptoms were associated with a later diagnosis of BP. CONCLUSIONS The FEP of both SZ and BP is preceded by an identifiable prodromal phase. Early detection programs should target young people at clinical risk for the extended psychosis phenotype. The high prevalence of affective symptoms during the early phases of psychosis may encourage clinicians to identify and treat them in order to prevent suicide behaviour.

Clinical, Cognitive, and Neuroimaging Evidence of a Neurodevelopmental Continuum in Offspring of Probands With Schizophrenia and Bipolar Disorder

Background Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders. Aims To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth. Methods One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6-17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders. Results Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders. Conclusions Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.

Association of CACNA1C and SYNE1 in offspring of patients with psychiatric disorders

Schizophrenia (SZ) and bipolar disorder (BD) are severe mental diseases associated with cognitive impairment, mood disturbance, and psychosis. Both disorders are highly heritable and share a common genetic background. The present study assesses, for the first time, differences in genotype frequencies of polymorphisms located in genes involved in neurodevelopment and synaptic plasticity between genetic high-risk individuals (offspring of patients with SZ or BD; N=100: 31 and 69, respectively) and control subjects (offspring of community controls; N=96). Individuals from both groups had similar ages, around 12 years. A higher percentage of men were included in the genetic high-risk group (58%) compared with the control group (40.6%). A total of 244 validated SNPs located in 35 candidate gene regions were analyzed in 196 participants. Multivariate methods based on logistic regression analysis were performed to assess differences in genotype frequencies. Bonferroni correction was applied for the multiple comparisons performed. Two polymorphisms, CACNA1C rs10848683 and SYNE1 rs214950, showed significant differences. The frequency of heterozygotes for CACNA1C rs10848683 in genetic high-risk individuals was double that in controls (OR=3.15; P=0.00016). For SYNE1 rs214950, higher frequencies of heterozygotes (OR=1.97) and homozygotes for the minor allele (OR=17.89; P=0.00020) were found in the genetic high-risk group than in the control group. In conclusion, polymorphisms in CACNA1C and SYNE1 could confer a greater risk of developing SZ and BD in individuals who are already at high risk because of their family history. This could help identify subjects with a very high genetic risk, in whom early detection and early intervention could lead to better prognosis.

Intrinsic functional connectivity of fronto-temporal networks in adolescents with early psychosis

Adults with psychotic disorders have abnormal connectivity of fronto-temporal networks. However, whether these abnormalities are present in adolescents with early psychosis has not been fully assessed. One-hundred and thirty-nine adolescents aged 12–18 underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging. Following motion correction, data were available for 44 participants with a psychosis risk syndrome, 34 patients with a first episode psychosis (FEP) and 35 healthy controls. Independent component analysis was performed to assess functional networks showing a fronto-temporal scope; this identified a language and a salience network. Mean fractional anisotropy was measured in clusters showing between-group differences in intrinsic functional connectivity (iFC). For the language network, there was a group effect within the right middle/inferior frontal gyrus, explained by reduced iFC in patients with an FEP relative to healthy controls, while in participants with a psychosis risk syndrome values of iFC were intermediate. In this region, values of iFC were positively correlated with mean fractional anisotropy in patients with an FEP. No group differences were observed in the salience network. Reduced iFC of the language network, in association with disrupted white matter microstructure, may characterize FEP during adolescence.

Improvement in cognitive biases after group psychoeducation and metacognitive training in recent-onset psychosis: a randomized crossover clinical trial

Metacognitive training (MCT) improves cognitive biases in psychosis. We aimed to explore whether the effectiveness of the combination of psychoeducation and MCT group treatments on cognitive biases differed if the combination was started by psychoeducation or by MCT. Fourty-nine stable patients with a recent-onset psychosis were randomized to two different sequences: MCT + psychoeducation vs psychoeducation + MCT. Cognitive biases, psychopathology symptoms, insight and functioning were assessed. Cognitive biases and depressive symptoms improved with both group interventions, without differential effects between both sequences. Our study suggests that MCT and psychoeducation are useful in improving cognitive biases and depressive symptoms in recent-onset psychosis.