Genetic Epidemiology of Major Depression: Review and Meta-Analysis

Sullivan, Patrick F.; Neale, Michael C.; Kendler, Kenneth S.

doi:10.1176/appi.ajp.157.10.1552

Cited by 2,740 publications

(1,984 citation statements)

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“…However, the extant evidence more clearly points to a role for genetic influences. Twin studies of depression indicate that depression in general is transmitted through genetic and non-shared environmental influences (Sullivan, Neale, & Kendler, 2000), and studies of the transmission of recurrent depression in particular also indicate that recurrent depression is transmitted through a combination of genetic and non-shared environmental influences, with little evidence of shared environmental influence (Kendler, Neale, Kessler, Heath, & Eaves, 1992). However, there has been some evidence that, once a recurrent course of depression is established, shared environmental factors may influence the number of episodes one has (Kendler et al, 1992).…”

Section: Family History Of Psychopathologymentioning

confidence: 99%

“…That is, individuals with more than one episode of depression may also have earlier ages at onset, more severe episodes, more comorbid disorders, and a stronger family history of psychopathology. It is also conceivable that all of these clinical picture variables reflect an underlying genetic vulnerability to the recurrent type of depression, particularly given the likely genetic transmission of recurrent depression (Kendler et al, 1992;Sullivan et al, 2000;Zubenko et al, 2002). Earlier age at onset, more severe early episodes of depression, greater comorbidity, and greater family history of psychopathology may all reflect an underlying genetic predisposition to the more severe recurrent type of depression.…”

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confidence: 99%

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Risk for recurrence in depression

Burcusa

Iacono

2007

Clinical Psychology Review

816

648

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Depression is a highly recurrent disorder with significant personal and public health consequences. Prevention of recurrence would be extremely desirable, and thus researchers have begun to identify risk factors that are specific to recurrence, which may be different from risk factors for first-onset of depression. Methodological issues in this area of research are briefly reviewed (e.g., the various definitions of "recurrence" and "depression"), followed by a review of studies on specific risk factors, including demographic variables (gender, socio-economic status, marital status), clinical variables (age at first onset, number of prior episodes, severity of first/index episode, comorbid psychopathology), family history of psychopathology, and psychosocial and psychological variables (level of psychosocial functioning, cognitions, personality, social support, and stressful life events). In addition, scar theories are evaluated for their potential to explain how these variables and recurrent depression are linked. Our review suggests that recurrent depression reflects an underlying vulnerability that is largely genetic in nature and that may predispose those high in the vulnerability not only to recurrent depressive episodes, but also to the significant psychosocial risk factors that often accompany recurrent depression.Major depressive disorder is one of the most common forms of psychopathology, one that will affect approximately one in six men and one in four women in their lifetimes . It is also usually highly recurrent, with at least 50% of those who recover from a first episode of depression having one or more additional episodes in their lifetime, and approximately 80% of those with a history of two episodes having another recurrence (American Psychiatric Association, 2000;Kupfer, Frank, & Wamhoff, 1996;Post, 1992). Once a first episode has occurred, recurrent episodes will usually begin within five years of the initial episode (Belsher & Costello, 1988;Lewinsohn, Clarke, Seeley, & Rohde, 1994), and, on average, individuals with a history of depression will have five (Kessler & Walters, 1998) to nine (Kessler, Zhao, Blazer, & Swartz, 1997) separate depressive episodes in their lifetime.Due to the fact that depression can be so recurrent, it can have significant personal and public health consequences. For example, one meta-analysis found that the suicide rate among those with depression is approximately twenty times higher than the rate for the general population (Harris & Barraclough, 1997). In addition, a study of over 3000 adolescents and young adults found that 90% of those with recurrent depression reported "very much" impairment, limiting work productivity and social interactions, and 40% sought professional help as a result (Wittchen, Nelson, & Lachner, 1998). Depression can also have a significant economic impact due to decreased productivity in affected individuals (Klerman & Weissman, 1992); in 1996 the annual direct (e.g., visits to doctors, pharmaceutical costs) and indirect (e.g., time...

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Section: Family History Of Psychopathologymentioning

confidence: 99%

mentioning

confidence: 99%

Risk for recurrence in depression

Burcusa

Iacono

2007

Clinical Psychology Review

816

648

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“…1 Alterations in serotonergic function are implicated in the pathogenesis of major depression and in the diathesis for suicidal behavior. 2,3 Since genetic factors can contribute causally to both major depression and the proclivity to commit suicide 4,5 and since the serotonergic system is partially regulated by genetic factors, 6,7 candidate genes for both major depression and suicidal behavior could involve the serotonergic system. Although levels of serotonin and/or its main metabolite 5-hydroxyindoleacetic acid are reported to be low in suicides, 8 we find that neuronal tryptophan hydroxylase-2, the rate-limiting serotonergic biosynthetic isoenzyme, is elevated in the dorsal raphe nuclei of depressed suicides at both the transcript 9 and protein levels.…”

Section: Introductionmentioning

confidence: 99%

Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression

et al. 2008

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Impaired brain serotonin neurotransmission is a potential component of the diathesis of major depression. Tryptophan hydroxylase-2 (TPH2), is the rate limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and a cause of impaired serotonin transmission. Here, we identify a novel TPH2 short isoform with truncated catalytic domain expressed in human brainstem, prefrontal cortex, hippocampus and amygdala. An exploratory study of 166 Caucasian subjects revealed association with major depression or suicide of a novel single nucleotide polymorphism (SNP) g.22879A > G located in exon 6 of this short isoform. This SNP and additional SNPs were discovered through a systematic characterization of the genetic architecture of the TPH2 gene for further genetic and functional investigations of its relationship to major depression and other psychopathology.

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“…Genetic factors influence vulnerability to depression (Sullivan et al, 2000), but no specific genes have been definitively implicated. One promising approach is to determine whether variations in specific (candidate) genes are associated not with disease per se, but with traits, such as personality factors, that are themselves associated with risk for the disorder (Lander and Schork, 1994;Stoltenberg and Burmeister, 2000).…”

Section: Introductionmentioning

confidence: 99%