AUTISM Spectrum Disorders and Suicidality

The paper describes the suicidal ideation and behavior in a series of 26 adult psychiatric patients affected by Autism Spectrum Disorders (ASDs), the clinical features and the psychiatric comorbidity of patients presenting suicidal behavior, and the history of suicide or suicide attempt in their relatives. Two (7,7%) patients committed suicide. One (3.8%) patient attempted suicide twice, and one (3.8%) patient self-harmed by cutting his face and one finger of his hand with a razor. Eight (30.8%) patients presented suicidal ideation. Two (7.7%) patients had one relative who had attempted suicide, and two (7.7%) patients had one or more relatives who had committed suicide. Most patients with suicidal behavior or ideation presented psychotic symptoms. Although it is not clear whether the high suicidal risk is related with ASDs per se or with psychotic symptoms, a high index of suspicion is warranted in evaluating suicidal risk in patients affected by ASDs, whatever is their age, psychiatric comorbidity, and setting of visit

Posible especificidad de los síntomas tipo pánico inducidos por inhalantes: a propósito de un caso

La intoxicación aguda por inhalantes produce distintos síntomas psiquiátricos y se ha documentado daño orgánico cerebral por exposición crónica a los mismos. Describimos la aparición de un subgrupo específico de síntomas tipo pánico, tras la exposición a solventes volátiles, en una mujer de 36 años con historia de exposición profesional y adicción a los solventes volátiles que posteriormente desarrolló un trastorno de pánico comórbido con escasa respuesta al tratamiento antidepresivo. La paciente se evaluó mediante la administración del SCL-90-R, el WAIS y el test de Rorschach; también se le realizó RM de medio contraste. No se encontraron datos sólidos de daño cerebral, aunque sus síntomas de ansiedad cumplen criterios para el subtipo neurobiológico de trastorno de pánico no relacionado con miedo a asfixia. Este subgrupo de síntomas de ansiedad se atribuye al mecanismo de acción de los solventes volátiles, es decir, la neurotransmisión gabaérgica

A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine

Background Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Methods Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Results Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65–2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. Conclusions The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels

Genetic basis of psychopathological dimensions shared between schizophrenia and bipolar disorder

Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity. Genome-wide analyses were performed at gene and gene set level, while 148 genome-wide significant loci previously associated with SCZ and/or BP were investigated. Each sample was analyzed separately then a meta-analysis was performed. SH3GL2 and CLVS1 genes were associated with suicidal ideation in SCZ (p = 5.62e-08 and 0.01, respectively), the former also in the meta-analysis (p = .01). SHC4 gene was associated with depressive symptoms severity in BP (p = .003). A gene set involved in cellular differentiation (GO:0048661) was associated with substance disorder comorbidity in the meta-analysis (p = .03). Individual loci previously associated with SCZ or BP did not modulate the phenotypes of interest. This study provided confirmatory and new findings. SH3GL2 (endophilin A1) showed a role in suicidal ideation that may be due to its relevance to the glutamate system. SHC4 regulates BDNF-induced MAPK activation and was previously associated with depression. CLVS1 is involved in lysosome maturation and was for the first time associated with a psychiatric trait. GO:0048661 may mediate the risk of substance disorder through an effect on neurodevelopment/neuroplasticity

Correction to: Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer's disease

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Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies