Suicide and other Violent Death Cases in Norwegian Peacekeeping Forces

U populaciji bivših norveških jedinica u sklopu UN-a koje su služile u UNIFIL-u (United Nations Interim Forces in Lebanon = Privremene snage UN-a u Libanonu) u razdoblju 1978.-1991. utvrđen je 43 postotni porast smrtnosti zbog samoubojstva i 28 postotni porast smrtnosti zbog drugih načina nasilne smrti. Ovi su nalazi pridonijeli razvoju strategija za sprečavanje samoubojstva u norveškim jedinicama pri UN-u. Strategije sprečavanja samoubojstva u norveškim jedinicama pri UN-u prije misije usmjerene su na samopomoć, pomoć drugovima i odgovornost vođa. Na ratištu u središtu su pažnje krizne intervencije. Po završetku misije, identificirane su grupe visokog rizika u svrhu postupaka sustavnog praćenja. Sadašnji planovi za poboljšanje postojeće strategije sprečavanja samoubojstva usmjereni su na razvoj postupaka individualnog snimanja prilagođenijih muškoj simptomatologiji, a sadašnje istraživanje usmjereno je na ispitivanje počinjenih samoubojstava i drugih načina nasilne smrti norveških veterana UN-a.In a population of former Norwegian UN personnel serving in UNIFIL (United Nations Interim Forces in Lebanon) in the period 1978-1991, was found a 43% increased mortality of suicide and a 28% increase in the mortality of other violent death. These findings have contributed to the development of suicide prevention strategies targeting Norwegian UN personnel. Suicide prevention strategies in the Norwegian UN forces before the mission focus on self-help, buddy aid and leader responsibilities. In theatre focus is put on crisis interventions. After completing the mission, high risk groups are identified for systematic follow-up procedures. Current plans for improvement of the existing suicide prevention strategy focus on development of individual screening procedures better adapted to male symptomatology, and current research targets investigations of committed suicides and other violent deaths amongst Norwegian UN veterans

Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation

Scandinavian Star : Erfaringer og helse hos overlevende og etterlatte etter 26 år

Background Scandinavian Star was a car and passenger ferry on route between Oslo, Norway and Frederikshavn, Denmark. During the night of April 7th, 1990, a fire broke out, which resulted in the death of 159 people. The police investigation concluded that the ship was set on fire by one or more arsonists. To date, the fire remains an unsolved crime. The aftermath has been ridden by controversies, and the ship owners and Norwegian authorities have been criticized. In 2015, The Norwegian Parliament appointed an independent commission with the mandate to evaluate several aspects of the Scandinavian Star case. As part of their work, the commission gave the Norwegian Centre for Violence and Traumatic Stress Studies the assignment to perform a systematic investigation of the survivors and the bereaved, focusing on traumatic exposure, what types of assistance they had received and their evaluation of this assistance, as well as current health, work participation, and well-being. The direct victims of this tragedy, both the survivors from the ship and the bereaved families, were involved in an extremely traumatic event. Exposure to adverse and traumatic events increases the risk for later health problems. In this report, we will describe the experiences of the survivors and the bereaved, with a focus on their recollection of what happened during the event, how they have perceived the support from the public health care system, what their own situation was like following the disaster, and their views on the political aftermath. We have also investigated health consequences as well as factors associated with current health. Methods Information letters with a description of the study and an invitation to participate were sent to the survivors and the bereaved. We performed face-to-face interviews during the autumn of 2016, 26 years after the fire. The survivors included both passengers and employees at the ship. Some survivors also lost someone they knew in the fire. The bereaved included individuals who were not present on the ship, but who lost someone close. In total, 193 individuals participated in the study, including 98 survivors and 95 bereaved, resulting in a response rate of 60% for both groups. Results Exposure Many of the 98 survivors were exposed to danger during the fire. Three out of four survivors reported that they had been in areas of the ship with heavy smoke, and about half had experienced dangerous situations in the lifeboats. One out of five thought they were going to die. More than one third heard cries for help or saw someone seriously injured or killed. One in four survivors lost someone they knew to the fire. Among the 95 bereaved participants, who were not on board the ship, 81 had lost a close family member: a spouse, one or several children, one or both parents, or siblings. The majority lost more than one close person to the fire. About one out of four bereaved participants also had surviving relatives or friends on board the ship. Memories and centrality Participants’ memories of this event were experienced as vivid and many could easily re-experience what happened. For many participants the fire had become highly central to their life story. The fire was also central for their understanding of the world and their personal identity. For example, one out of four survivors and more than half of the bereaved “fully agreed” that the fire changed their life forever. The aftermath Looking back to the first two years following the event, four out of ten reported that they had mental health problems and one out of four that they had somatic problems related to the fire. Almost half had accompanying difficulties with their daily life level of functioning. Among those who reported impaired functioning, one in four perceived that they never had regained their pre-fire level of functioning. The majority of the participants reported a lack of trust in the police investigations, and felt that the Norwegian authorities had shown little interest or support for those affected by the fire. Most participants reported satisfaction with the support they had received from their local communities. The general trust in the police and the justice system was significantly lower in the participants, compared to a general population sample. Trust in the police and the justice system was associated with the degree of trust in the authorities’ handling of the Scandinavian Star tragedy, and was also related to current mental health and perceived social support. Shame and guilt About one out of four reported that they had been worried about what others might think about them, and that they have had bothersome thoughts that they should have done something differently when it happened or to prevent it from happening. Support systems Overall, negative opinions about the support were more prevalent than positive ones. The majority did not receive assistance without requesting it themselves, and they did not feel that they were taken good care of. About half felt they were not given sufficient time to talk with professionals. The most positive evaluations concerned the arrangement of a commemoration trip to Copenhagen and the Scandinavian Star Support group’s outreach program. Concerning the overall experience with the public health and support systems, negative evaluations were predominant among participants. More than half considered the support and treatment not at all or hardly satisfactory. One in three reported that they missed proactive outreach. Many participants underlined the need for long-term follow-up as well as assistance to children or support in parental roles. Work absence and current level of functioning About half of the participants reported to have had at least one lengthy absence from work during the years following the fire. Many participants attributed this absence to the consequences of the fire. About one in four had minor or major problems with their current level of daily functioning, which they attributed to the consequences of the fire. The participants’ self-rated mental health trajectories When looking back, participants reported to have had a low level of mental health problems in the period preceding the fire, which had increased dramatically at one month after the fire. From that time, the participants described a gradual process of recovery. Bereaved described a slower improvement compared to survivors. The current level of mental health problems remained higher than the low level reported before the fire. The participants’ evaluation of long-term mental health problems related to the fire More than one third of the survivors, and almost half of the bereaved, reported that the fire had resulted in long-term mental health problems. Current health and life satisfaction More than one out of four scored above a clinical cutoff for either posttraumatic stress reactions or anxiety/depression. One in five bereaved reported a current impairment in social, occupational or other important areas of functioning due to grief reactions. Only a few fulfilled the criteria for complicated grief. Participants had an increased level of anxiety/depression, and a lower level of social support, compared to a general population sample. About half of the participants had a high level of life satisfaction, yet one in five had a low or very low life satisfaction. Factors associated with mental and physical health Social support and barriers to social support were strongly associated with current mental and physical health. That is, individuals with a high level of perceived social support, and low barriers to seeking social support, had less mental and somatic health problems. Shame and guilt feelings related to what had happened, as well as centrality of the event, were also associated with current mental health. Conclusions and implications 26 years after the disaster, the majority of survivors and bereaved had good health and a high level of life satisfaction. However, for many, the fire has had severe consequences. Even today, the affected group shows a disproportional burden of psychological health problems. Social factors, such as high perceived social support and a low level of social support barriers, seemed to be of particular importance for current mental health. The lack of confidence in the Norwegian authorities’ handling of the disaster might have contributed to a reduced general trust in the police and the justice system. This low level of trust was associated with impaired mental health and social relationships. Negative experiences or views regarding the early support and later treatment were predominant. Proactive outreach services are necessary post disaster, and these should last longer than has previously been assumed. Because social factors are of importance for mental health, interventions should target social relationships. For outreach services to be useful, specialized mental health care must be available when needed. Time does not heal all wounds. Despite all the years that have passed, many participants still remembered the event as if it happened yesterday. After a while, there is often an expectation that life should move on. But for some, life will never be the same, and it will take time to adjust to a new reality.

Scandinavian Star : Erfaringer og helse hos overlevende og etterlatte etter 26 år

Background Scandinavian Star was a car and passenger ferry on route between Oslo, Norway and Frederikshavn, Denmark. During the night of April 7th, 1990, a fire broke out, which resulted in the death of 159 people. The police investigation concluded that the ship was set on fire by one or more arsonists. To date, the fire remains an unsolved crime. The aftermath has been ridden by controversies, and the ship owners and Norwegian authorities have been criticized. In 2015, The Norwegian Parliament appointed an independent commission with the mandate to evaluate several aspects of the Scandinavian Star case. As part of their work, the commission gave the Norwegian Centre for Violence and Traumatic Stress Studies the assignment to perform a systematic investigation of the survivors and the bereaved, focusing on traumatic exposure, what types of assistance they had received and their evaluation of this assistance, as well as current health, work participation, and well-being. The direct victims of this tragedy, both the survivors from the ship and the bereaved families, were involved in an extremely traumatic event. Exposure to adverse and traumatic events increases the risk for later health problems. In this report, we will describe the experiences of the survivors and the bereaved, with a focus on their recollection of what happened during the event, how they have perceived the support from the public health care system, what their own situation was like following the disaster, and their views on the political aftermath. We have also investigated health consequences as well as factors associated with current health. Methods Information letters with a description of the study and an invitation to participate were sent to the survivors and the bereaved. We performed face-to-face interviews during the autumn of 2016, 26 years after the fire. The survivors included both passengers and employees at the ship. Some survivors also lost someone they knew in the fire. The bereaved included individuals who were not present on the ship, but who lost someone close. In total, 193 individuals participated in the study, including 98 survivors and 95 bereaved, resulting in a response rate of 60% for both groups. Results Exposure Many of the 98 survivors were exposed to danger during the fire. Three out of four survivors reported that they had been in areas of the ship with heavy smoke, and about half had experienced dangerous situations in the lifeboats. One out of five thought they were going to die. More than one third heard cries for help or saw someone seriously injured or killed. One in four survivors lost someone they knew to the fire. Among the 95 bereaved participants, who were not on board the ship, 81 had lost a close family member: a spouse, one or several children, one or both parents, or siblings. The majority lost more than one close person to the fire. About one out of four bereaved participants also had surviving relatives or friends on board the ship. Memories and centrality Participants’ memories of this event were experienced as vivid and many could easily re-experience what happened. For many participants the fire had become highly central to their life story. The fire was also central for their understanding of the world and their personal identity. For example, one out of four survivors and more than half of the bereaved “fully agreed” that the fire changed their life forever. The aftermath Looking back to the first two years following the event, four out of ten reported that they had mental health problems and one out of four that they had somatic problems related to the fire. Almost half had accompanying difficulties with their daily life level of functioning. Among those who reported impaired functioning, one in four perceived that they never had regained their pre-fire level of functioning. The majority of the participants reported a lack of trust in the police investigations, and felt that the Norwegian authorities had shown little interest or support for those affected by the fire. Most participants reported satisfaction with the support they had received from their local communities. The general trust in the police and the justice system was significantly lower in the participants, compared to a general population sample. Trust in the police and the justice system was associated with the degree of trust in the authorities’ handling of the Scandinavian Star tragedy, and was also related to current mental health and perceived social support. Shame and guilt About one out of four reported that they had been worried about what others might think about them, and that they have had bothersome thoughts that they should have done something differently when it happened or to prevent it from happening. Support systems Overall, negative opinions about the support were more prevalent than positive ones. The majority did not receive assistance without requesting it themselves, and they did not feel that they were taken good care of. About half felt they were not given sufficient time to talk with professionals. The most positive evaluations concerned the arrangement of a commemoration trip to Copenhagen and the Scandinavian Star Support group’s outreach program. Concerning the overall experience with the public health and support systems, negative evaluations were predominant among participants. More than half considered the support and treatment not at all or hardly satisfactory. One in three reported that they missed proactive outreach. Many participants underlined the need for long-term follow-up as well as assistance to children or support in parental roles. Work absence and current level of functioning About half of the participants reported to have had at least one lengthy absence from work during the years following the fire. Many participants attributed this absence to the consequences of the fire. About one in four had minor or major problems with their current level of daily functioning, which they attributed to the consequences of the fire. The participants’ self-rated mental health trajectories When looking back, participants reported to have had a low level of mental health problems in the period preceding the fire, which had increased dramatically at one month after the fire. From that time, the participants described a gradual process of recovery. Bereaved described a slower improvement compared to survivors. The current level of mental health problems remained higher than the low level reported before the fire. The participants’ evaluation of long-term mental health problems related to the fire More than one third of the survivors, and almost half of the bereaved, reported that the fire had resulted in long-term mental health problems. Current health and life satisfaction More than one out of four scored above a clinical cutoff for either posttraumatic stress reactions or anxiety/depression. One in five bereaved reported a current impairment in social, occupational or other important areas of functioning due to grief reactions. Only a few fulfilled the criteria for complicated grief. Participants had an increased level of anxiety/depression, and a lower level of social support, compared to a general population sample. About half of the participants had a high level of life satisfaction, yet one in five had a low or very low life satisfaction. Factors associated with mental and physical health Social support and barriers to social support were strongly associated with current mental and physical health. That is, individuals with a high level of perceived social support, and low barriers to seeking social support, had less mental and somatic health problems. Shame and guilt feelings related to what had happened, as well as centrality of the event, were also associated with current mental health. Conclusions and implications 26 years after the disaster, the majority of survivors and bereaved had good health and a high level of life satisfaction. However, for many, the fire has had severe consequences. Even today, the affected group shows a disproportional burden of psychological health problems. Social factors, such as high perceived social support and a low level of social support barriers, seemed to be of particular importance for current mental health. The lack of confidence in the Norwegian authorities’ handling of the disaster might have contributed to a reduced general trust in the police and the justice system. This low level of trust was associated with impaired mental health and social relationships. Negative experiences or views regarding the early support and later treatment were predominant. Proactive outreach services are necessary post disaster, and these should last longer than has previously been assumed. Because social factors are of importance for mental health, interventions should target social relationships. For outreach services to be useful, specialized mental health care must be available when needed. Time does not heal all wounds. Despite all the years that have passed, many participants still remembered the event as if it happened yesterday. After a while, there is often an expectation that life should move on. But for some, life will never be the same, and it will take time to adjust to a new reality.

Scandinavian Star : Erfaringer og helse hos overlevende og etterlatte etter 26 år

Background Scandinavian Star was a car and passenger ferry on route between Oslo, Norway and Frederikshavn, Denmark. During the night of April 7th, 1990, a fire broke out, which resulted in the death of 159 people. The police investigation concluded that the ship was set on fire by one or more arsonists. To date, the fire remains an unsolved crime. The aftermath has been ridden by controversies, and the ship owners and Norwegian authorities have been criticized. In 2015, The Norwegian Parliament appointed an independent commission with the mandate to evaluate several aspects of the Scandinavian Star case. As part of their work, the commission gave the Norwegian Centre for Violence and Traumatic Stress Studies the assignment to perform a systematic investigation of the survivors and the bereaved, focusing on traumatic exposure, what types of assistance they had received and their evaluation of this assistance, as well as current health, work participation, and well-being. The direct victims of this tragedy, both the survivors from the ship and the bereaved families, were involved in an extremely traumatic event. Exposure to adverse and traumatic events increases the risk for later health problems. In this report, we will describe the experiences of the survivors and the bereaved, with a focus on their recollection of what happened during the event, how they have perceived the support from the public health care system, what their own situation was like following the disaster, and their views on the political aftermath. We have also investigated health consequences as well as factors associated with current health. Methods Information letters with a description of the study and an invitation to participate were sent to the survivors and the bereaved. We performed face-to-face interviews during the autumn of 2016, 26 years after the fire. The survivors included both passengers and employees at the ship. Some survivors also lost someone they knew in the fire. The bereaved included individuals who were not present on the ship, but who lost someone close. In total, 193 individuals participated in the study, including 98 survivors and 95 bereaved, resulting in a response rate of 60% for both groups. Results Exposure Many of the 98 survivors were exposed to danger during the fire. Three out of four survivors reported that they had been in areas of the ship with heavy smoke, and about half had experienced dangerous situations in the lifeboats. One out of five thought they were going to die. More than one third heard cries for help or saw someone seriously injured or killed. One in four survivors lost someone they knew to the fire. Among the 95 bereaved participants, who were not on board the ship, 81 had lost a close family member: a spouse, one or several children, one or both parents, or siblings. The majority lost more than one close person to the fire. About one out of four bereaved participants also had surviving relatives or friends on board the ship. Memories and centrality Participants’ memories of this event were experienced as vivid and many could easily re-experience what happened. For many participants the fire had become highly central to their life story. The fire was also central for their understanding of the world and their personal identity. For example, one out of four survivors and more than half of the bereaved “fully agreed” that the fire changed their life forever. The aftermath Looking back to the first two years following the event, four out of ten reported that they had mental health problems and one out of four that they had somatic problems related to the fire. Almost half had accompanying difficulties with their daily life level of functioning. Among those who reported impaired functioning, one in four perceived that they never had regained their pre-fire level of functioning. The majority of the participants reported a lack of trust in the police investigations, and felt that the Norwegian authorities had shown little interest or support for those affected by the fire. Most participants reported satisfaction with the support they had received from their local communities. The general trust in the police and the justice system was significantly lower in the participants, compared to a general population sample. Trust in the police and the justice system was associated with the degree of trust in the authorities’ handling of the Scandinavian Star tragedy, and was also related to current mental health and perceived social support. Shame and guilt About one out of four reported that they had been worried about what others might think about them, and that they have had bothersome thoughts that they should have done something differently when it happened or to prevent it from happening. Support systems Overall, negative opinions about the support were more prevalent than positive ones. The majority did not receive assistance without requesting it themselves, and they did not feel that they were taken good care of. About half felt they were not given sufficient time to talk with professionals. The most positive evaluations concerned the arrangement of a commemoration trip to Copenhagen and the Scandinavian Star Support group’s outreach program. Concerning the overall experience with the public health and support systems, negative evaluations were predominant among participants. More than half considered the support and treatment not at all or hardly satisfactory. One in three reported that they missed proactive outreach. Many participants underlined the need for long-term follow-up as well as assistance to children or support in parental roles. Work absence and current level of functioning About half of the participants reported to have had at least one lengthy absence from work during the years following the fire. Many participants attributed this absence to the consequences of the fire. About one in four had minor or major problems with their current level of daily functioning, which they attributed to the consequences of the fire. The participants’ self-rated mental health trajectories When looking back, participants reported to have had a low level of mental health problems in the period preceding the fire, which had increased dramatically at one month after the fire. From that time, the participants described a gradual process of recovery. Bereaved described a slower improvement compared to survivors. The current level of mental health problems remained higher than the low level reported before the fire.<img src="file:///page24image960" /> The participants’ evaluation of long-term mental health problems related to the fire More than one third of the survivors, and almost half of the bereaved, reported that the fire had resulted in long-term mental health problems. Current health and life satisfaction More than one out of four scored above a clinical cutoff for either posttraumatic stress reactions or anxiety/depression. One in five bereaved reported a current impairment in social, occupational or other important areas of functioning due to grief reactions. Only a few fulfilled the criteria for complicated grief. Participants had an increased level of anxiety/depression, and a lower level of social support, compared to a general population sample. About half of the participants had a high level of life satisfaction, yet one in five had a low or very low life satisfaction. Factors associated with mental and physical health Social support and barriers to social support were strongly associated with current mental and physical health. That is, individuals with a high level of perceived social support, and low barriers to seeking social support, had less mental and somatic health problems. Shame and guilt feelings related to what had happened, as well as centrality of the event, were also associated with current mental health. Conclusions and implications 26 years after the disaster, the majority of survivors and bereaved had good health and a high level of life satisfaction. However, for many, the fire has had severe consequences. Even today, the affected group shows a disproportional burden of psychological health problems. Social factors, such as high perceived social support and a low level of social support barriers, seemed to be of particular importance for current mental health. The lack of confidence in the Norwegian authorities’ handling of the disaster might have contributed to a reduced general trust in the police and the justice system. This low level of trust was associated with impaired mental health and social relationships. Negative experiences or views regarding the early support and later treatment were predominant. Proactive outreach services are necessary post disaster, and these should last longer than has previously been assumed. Because social factors are of importance for mental health, interventions should target social relationships. For outreach services to be useful, specialized mental health care must be available when needed. Time does not heal all wounds. Despite all the years that have passed, many participants still remembered the event as if it happened yesterday. After a while, there is often an expectation that life should move on. But for some, life will never be the same, and it will take time to adjust to a new reality.

Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation

Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation