Lithium: a key to the genetics of bipolar disorder

Since the 1950s, lithium salts have been the main line of treatment for bipolar disorder (BD), both as a prophylactic and as an episodic treatment agent. Like many psychiatric conditions, BD is genetically and phenotypically heterogeneous, but evidence suggests that individuals who respond well to lithium treatment have more homogeneous clinical and molecular profiles. Response to lithium seems to cluster in families and can be used as a predictor for recurrence of BD symptoms. While molecular studies have provided important information about possible genes involved in BD predisposition or in lithium response, neither the mechanism of action of this drug nor the genetic profile of bipolar disorder is, as yet, completely understood

LITHIUM MUTAGENICITY

ESCOLA PAULISTA MED,RUA BOTUCATU 740-3,BR-04023900 São Paulo,BRAZILESCOLA PAULISTA MED,RUA BOTUCATU 740-3,BR-04023900 São Paulo,BRAZILWeb of Scienc

BIPOLAR DISORDER FOLLOWING A LEFT BASAL-GANGLIA STROKE

ESCOLA PAULISTA MED,DEPT PSIQUIAT,RUA BOTUCATU,740-3 ANDAR,BR-04023900 São Paulo,BRAZILESCOLA PAULISTA MED,DEPT PSIQUIAT,RUA BOTUCATU,740-3 ANDAR,BR-04023900 São Paulo,BRAZILWeb of Scienc

Which are the recent clinical findings regarding the association between depression and suicide?

OBJECTIVE: Suicide is one of the leading causes of mortality worldwide, especially among young subjects. Suicide is considered the outcome of a multidimensional and complex phenomenon, which is a result of the interaction between several factors. The association between psychopathology and suicide has been extensively investigated. Major depression plays an important role among the psychiatric diagnoses associated with suicide. This finding seems to be confirmed by different study designs, and in distinct populations. The present paper aims to briefly review the recent findings regarding the suicide-related clinical features of depression. Moreover, strategies for suicide prevention were also reviewed. REVIEW: Recent references were identified and grouped in order to illustrate the main contributions about depression and suicide. Briefly, the literature review stresses the high prevalence of major depression among subjects presenting suicide behaviors. Psychopathological traits, such as aggression and impulsivity play a relevant role in triggering suicidal behaviors. Strategies for suicide prevention were also reviewed in Brazil and internationally. In general, detection and treatment are effective in reducing suicide rates. CONCLUSION: Studies regarding suicide behaviors have had a pragmatic approach, and generated a large body of evidence about correlates of suicide. However, these studies have not been able to provide a consistent theoretical explanation for this phenomenon. The recent adoption of modern strategies represents a possibility of enhancing the research capability of such studies. In order to be clinically useful, findings should make it possible to deepen the understanding over the experience of a suicidal person, as well as to design specific strategies for prevention and treatment in population subgroups.OBJETIVO: Suicídio é uma das maiores causas de mortalidade ao redor do mundo, especialmente entre indivíduos jovens. Suicídio é considerado o desfecho de um fenômeno complexo e multidimensional, e decorrente da interação de diversos fatores. A associação entre psicopatologia e suicídio tem sido largamente estudada. Dentre os diagnósticos psiquiátricos associados a suicídio, depressão maior se destaca sobremaneira. Tais achados parecem ser confirmados em diferentes desenhos metodológicos e em distintas populações. Este artigo visa a revisar sucintamente as contribuições recentes acerca das características clínicas da depressão que se encontram vinculadas a casos de suicídio. Destacam-se também os esforços de prevenção, no sentido de, ao se detectar e tratar casos de depressão em serviços gerais de saúde, diminuir o risco de suicídio. REVISÃO: Referências recentes foram identificadas e agrupadas com o intuito de ilustrar as principais contribuições acerca da interface entre depressão e suicídio. Brevemente, a revisão de literatura aberta aponta para a grande prevalência do diagnóstico de depressão maior entre os casos de comportamento suicida. Traços psicopatológicos de agressão e impulsividade parecem exercer um papel relevante no desencadeamento de atos suicidas. Estratégias de prevenção foram também revisadas nos contextos internacional e brasileiro. De modo geral, a detecção e tratamento de depressão são capazes de reduzir as taxas de suicídio. CONCLUSÃO: No campo da pesquisa sobre comportamento suicida, os estudos têm tido caráter pragmático e produziram um panorama de fatores claramente associados ao suicídio, sem, no entanto, oferecer uma amarração teórica consistente para os achados. A crescente adoção de modernas técnicas traz uma ampliação das possibilidades de investigação. Para serem clinicamente úteis, os novos conhecimentos devem possibilitar um olhar mais profundo no mundo de uma pessoa suicida, bem como a adoção de estratégias específicas de tratamento e de prevenção que fossem mais eficientes para subgrupos populacionais.S18S2

Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides

International audienceLong non-coding RNAs (lncRNAs) are an emerging class of regulatory RNA that may be implicated in psychiatric disorders. Here we performed RNA-sequencing in the rostral anterior cingulate cortex of 26 depressed suicides and 24 matched controls. We first performed differential lncRNA expression analysis, and then conducted Weighted Gene Co-expression Network Analysis (WGCNA) to identify co-expression modules associating with depression and suicide. We identified 23 differentially expressed lncRNAs (FDR < 0.1) as well as their differentially expressed overlapping and antisense protein-coding genes. Several of these overlapping or antisense genes were associated with interferon signaling, which is a component of the innate immune response. Using WGCNA, we identified modules of highly co-expressed genes associated with depression and suicide and found protein-coding genes highly connected to differentially expressed lncRNAs within these modules. These protein-coding genes were located distal to their associated lncRNAs and were found to be part of several GO terms enriched in the significant modules, which include: cytoskeleton organization, plasma membrane, cell adhesion, nucleus, DNA-binding, and regulation of dendrite development and morphology. Altogether, we report that lncRNAs are differentially expressed in the brains of depressed individuals who died by suicide and may represent regulators of important molecular functions and biological processes

Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides

International audienceThe nociceptin/orphanin FQ (N/OFQ)-Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration

Suicide and no axis I psychopathology

BACKGROUND: It is unclear why approximately 10% of suicide completers seem to be psychiatrically normal. To better understand this issue, we studied suicide completers without an axis I diagnosis and compared them, on measures of psychopathology other than axis I, to normal controls and suicide cases with axis I psychopathology. METHODS: 168 suicide cases were examined by way of a psychological autopsy with the best possible informant. Sixteen cases did not meet criteria for an axis I diagnosis; each of these cases was then age and gender matched to 52 suicide completers with an axis I disorder and 110 normal controls. RESULTS: Fourteen of sixteen suicide cases without an axis I diagnosis had detectable abnormalities that were more similar to the axis I diagnosed suicide group than to a living group. Both suicide groups were similar in the total number of past suicide attempts, the total number of individuals with an axis II disorder, and similar scores on measures of impulsive-aggressive behaviors. CONCLUSIONS: These findings suggest that most of the individuals who committed suicide and appeared psychiatrically normal after a psychological autopsy may probably have an underlying psychiatric process that the psychological autopsy method, as commonly carried out, failed to detect

Braz J Psychiatry

International audienc

Suicide attempts and non-suicidal self-harm: a national prevalence study of young adults

Background: There are few prevalence studies of suicide attempts (SAs) and non-suicidal self-harm (NSSH). Aims: This study aimed to estimate the prevalence of thoughts of NSSH, suicidal thoughts, NSSH and SAs among 18-34 year olds in Scotland for the first time. Method: We interviewed a representative sample of young adults from across Scotland. Results: 3508 young people were interviewed. 11·3% and 16·2% reported a lifetime history of SAs and NSSH, respectively. The first episode of NSSH tended to precede the first SA by about two years. Age of onset of NSSH and SA was younger in females. Earlier age of onset was associated with more frequent NSSH/SA. Women are significantly more likely to report NSSH and SA compared to men. Conclusion: One in 9 young people has attempted suicide and 1 in 6 has engaged in NSSH. Clinicians should be vigilant as SAs and NSSH are relatively common