A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders

Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including obsessive-compulsive disorder, panic disorder, major depressive disorder, bipolar disorder, schizophrenia and Alzheimer's disease. As the search for patterns of inheritance and candidate genes of these complex disorders continues, we review relevant findings from quantitative genetic studies and outline the main challenges for the field of psychiatric genetics to focus on in order to more definitively establish the underpinnings of genetic and environmental influences of adult psychopathology.     

Family,twin and adoption studies of severe mental disorders in sub-Saharan Africa: a scoping review

Social Psychiatry and Psychiatric Epidemiology - The traditional genetic epidemiological studies are necessary to improve accurate risk communication to service users and their families. This...     

The contribution of failing adult hippocampal neurogenesis to psychiatric disorders

PURPOSE OF REVIEW: Failing adult neurogenesis is increasingly considered a factor in the pathogenesis and course of psychiatric disorders. The level of evidence in favor of such hypotheses varies, but disturbed cellular plasticity in the hippocampus may be a common aspect of several neuropsychiatric diseases. RECENT FINDINGS: This review covers the literature from mid-2006 to the end of 2007. We discuss studies and theoretical papers dealing with the contribution of adult neurogenesis to dementias and neurodegeneration, major depression, schizophrenia, and alcohol and drug abuse. Of these disorders, most progress has recently been made with schizophrenia for which, in contrast to the other conditions, suggestive genetic evidence exists (e.g. Disc1, Npas3). SUMMARY: Failing adult hippocampal neurogenesis may not explain major depression, addiction or schizophrenia, but contributes to the hippocampal aspects of the disease. We propose that the key to a more thorough understanding of this contribution will come from increased knowledge on the functional relevance of new neurons in the hippocampus and better clinical data relating to symptoms possibly related to such function. Research on the molecular basis of adult hippocampal neurogenesis may help to explain how hippocampal aspects of these disorders develop.     

Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder

Juvenile bipolar disorder (JBD) has been a subject of significant research and debate. Phenotypic differences between JBD and adult-onset bipolar disorder have led researchers to question whether or not similar neuropathologic mechanisms will be found. While much is known about the genetic and environmental contributions to the adult-onset phenotype, less is known about their contributions to JBD. Here, we review family, twin, adoption, and molecular genetic studies of JBD. Behavioral genetic data suggest both genetic and environmental contributions to JBD, while molecular genetic studies find linkage to age of onset of bipolar disorder to chromosomes 12p, 14q, and 15q. Additionally, changes associated with symptom age of onset have been recently reported in the brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK3-beta) genes. We contend that further progress in discovering the precise genetic and environmental contributions to JBD may depend on advances in phenotypic refinement, an increased appreciation of comorbid conditions, and more investigation of the longitudinal course of the disorder.     

Family, twin, and adoption studies of bipolar disease

Bipolar disease features states of severe depression that usually fluctuate with at least one episode of intense elation or mania. It is a disorder that has been thought for some time to have a heritable component. The lifetime prevalence of bipolar disease in the general population is approximately 1%. In contrast, family studies have shown the approximate lifetime risk of a first-degree relative of a bipolar proband to be 5% to 10%. Moreover, studies of monozygotic twins show that their risk of contracting the disease is as much as 75 times greater than that for the general population. In addition, adoption studies have demonstrated that biological relatives of bipolar patients are substantially more likely to have the disorder than are adoptive relatives.     

A review of herbal medicines for psychiatric disorders

OBJECTIVE: This review examines herbs commonly used for psychiatric symptoms-St. John's wort, kava, ginkgo biloba, and valerian. METHODS: MEDLINE was searched for articles related to the use of herbs in psychiatry published after 1990. A secondary search examined sources cited in articles obtained from the MEDLINE search. RESULTS: Of nine controlled and standardized trials of St. John's wort, five showed the herb's superiority to placebo, and four found no differences in effectiveness when compared with antidepressant drugs. The pharmacologically active components are not known. Several double-blind, placebo-controlled trials have demonstrated the anxiolytic efficacy of kava, but these studies had ill-defined patient populations, small sample sizes, and short treatment duration. All but one of 40 controlled trials of ginkgo extracts in the treatment of dementia found clinically significant improvement in memory loss, concentration, fatigue, anxiety, and depressed mood. Most studies of gingko had poorly defined patient populations and small sample sizes and used nonstandard measures. A recent well-designed multicenter study showed significantly less decline in cognitive function among patients with dementia receiving gingko. Valerian has been shown to decrease sleep latency and nocturnal awakenings and improve subjective sleep quality, but placebo effects were marked in some studies, and in some cases the beneficial effects were not seen until two to four weeks of therapy. CONCLUSIONS: Although evidence of the efficacy of herbal preparations in treating psychiatric conditions is growing, translating the results of efficacy studies into effective treatments for patients is hampered by the chemical complexity of the products, the lack of standardization of commonly available preparations, and the paucity of well-controlled studies.     

The prevalence of psychiatric disorders in epilepsy: a critical review of the evidence

Psychopathology has long been associated with epilepsy and should not be overlooked as it could exacerbate the epilepsy itself and impair the health-related quality of life of sufferers. A higher prevalence of psychiatric disorders has frequently been demonstrated amongst patients with epilepsy compared both with the general population and with individuals presenting neurological or non-neurological conditions. This review critically evaluates selected studies on the prevalence of psychiatric disorders in epilepsy patients compared with the general population and controls. Heterogeneity exists across the research methodologies, therefore further research, using less selected groups, should be undertaken to allow valid comparisons and the identification of more precise prevalence rates.     

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context

The human leukocyte antigen (HLA) is a complex genetic system that encodes proteins which predominantly regulate immune/inflammatory processes. It can be involved in a variety of immuno-inflammatory disorders ranging from infections to autoimmunity and cancers. The HLA system is also suggested to be involved in neurodevelopment and neuroplasticity, especially through microglia regulation and synaptic pruning. Consequently, this highly polymorphic gene region has recently emerged as a major player in the etiology of several major psychiatric disorders, such as schizophrenia, autism spectrum disorder and bipolar disorder and with less evidence for major depressive disorders and attention deficit hyperactivity disorder. We thus review here the role of HLA genes in particular subgroups of psychiatric disorders and foresee their potential implication in future research. In particular, given the prominent role that the HLA system plays in the regulation of viral infection, this review is particularly timely in the context of the Covid-19 pandemic.     

Reading disability, immune disorders and non-right-handedness: twin and family studies of their relations.

Geschwind and colleagues discussed associations among learning disorders, immune disorders and non-right-handedness. In this study, we examined the associations between reading disability (RD) and both immune disorders (ID) and non-right-handedness (NRH) in family and twin samples (total N = 1731 cases) identified through an RD proband. We also conducted co-segregation analyses to ascertain the degree to which NRH, ID and RD were biologically related. There was little evidence for an overall association between RD and NRH. There was not convergent evidence across all four samples for an association between RD and ID, although we did find an association between RD and ID in two of four samples. Nor was there strong support for a subtype where RD and NRH, or RD and ID, co-segregate in families. These data suggest that the associations postulated by Geschwind and colleagues are not robust in RD samples, although we cannot completely rule out the possibility of an RD plus ID subtype.     

Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies

CONTEXT: There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used. OBJECTIVE: To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data. DATA SOURCES: We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches. STUDY SELECTION: Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment. DATA SYNTHESIS: By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.     

Temperament and psychiatric disorder: the genetic contribution to behaviour in childhood

The studies stemming from the New York longitudinal study of temperament in childhood are summarised and conceptual difficulties and problems arising from them are described. An alternative model of temperament provided by Buss and Plomin is also considered. Finally, a new typology of temperament is proposed. It is based on the suggestion that ordinary, non-pathological behaviours, in extreme form, can be viewed as manifestations of emotional disorder, hyperactivity and antisocial disorder. Empirical evidence derived both from twin studies and from epidemiological investigations is put forward to support this view.     

Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies

There is a longstanding association between substance-use disorders (SUDs) and the psychological construct of impulsivity. In the first section of this review, personality and neurocognitive data pertaining to impulsivity will be summarised in regular users of four classes of substance: stimulants, opiates, alcohol and 3,4-methylenedioxymethamphetamine (MDMA). Impulsivity in these groups may arise via two alternative mechanisms, which are not mutually exclusive. By one account, impulsivity may occur as a consequence of chronic exposure to substances causing harmful effects on the brain. By the alternative account, impulsivity pre-dates SUDs and is associated with the vulnerability to addiction. We will review the evidence that impulsivity is associated with addiction vulnerability by considering three lines of evidence: (i) studies of groups at high-risk for development of SUDs; (ii) studies of pathological gamblers, where the harmful consequences of the addiction on brain structure are minimised, and (iii) genetic association studies linking impulsivity to genetic risk factors for addiction. Within each of these three lines of enquiry, there is accumulating evidence that impulsivity is a pre-existing vulnerability marker for SUDs.     

Childhood psychiatric disorders and young adult crime: a prospective, population-based study

OBJECTIVE: While psychopathology is common in criminal populations, knowing more about what kinds of psychiatric disorders precede criminal behavior could be helpful in delineating at-risk children. The authors determined rates of juvenile psychiatric disorders in a sample of young adult offenders and then tested which childhood disorders best predicted young adult criminal status. METHOD: A representative sample of 1,420 children ages 9, 11, and 13 at intake were followed annually through age 16 for psychiatric disorders. Criminal offense status in young adulthood (ages 16 to 21) was ascertained through court records. RESULTS: Thirty-one percent of the sample had one or more adult criminal charges. Overall, 51.4% of male young adult offenders and 43.6% of female offenders had a child psychiatric history. The population-attributable risk of criminality from childhood disorders was 20.6% for young adult female participants and 15.3% for male participants. Childhood psychiatric profiles predicted all levels of criminality. Severe/violent offenses were predicted by comorbid diagnostic groups that included both emotional and behavioral disorders. CONCLUSIONS: The authors found that children with specific patterns of psychopathology with and without conduct disorder were at risk of later criminality. Effective identification and treatment of children with such patterns may reduce later crime.     

A systematic review of off-label uses of memantine for psychiatric disorders

Recent data points to glutamatergic dysfunction in mood disorders, anxiety disorders, obsessive-compulsive disorder, and schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts at the N-methyl-d-aspartate receptor, has been used off-label for various psychiatric disorders. Although promising, the available data for the use of memantine in these disorders is limited. Given this data, the routine use of memantine for depression, schizophrenia, obsessive-compulsive disorder, substance abuse, pervasive developmental disorders, bipolar disorder, and binge eating disorder cannot be recommended at this time.     

常见精神障碍的分子遗传学研究回顾和展望

精神障碍是一大类常见疾病,其不仅给家庭和社会带来沉重的经济负担,还经常威胁社会的安全与稳定.多数精神障碍的病因及发病机制至今未明,学术界普遍认为,遗传因素在精神障碍发病过程中发挥重要的作用,其遗传模式不符合孟德尔遗传规律,属于多因素复杂疾病(complex disease),即由多个微效基因协同并与环境因素共同作用导致的疾病.