| 1. |
- Berg, Venla, et al.
(author)
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Parental alcohol and drug abuse and offspring mortality by age 10 : a population-based register study
- 2022
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In: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 32:6, s. 933-938
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Journal article (peer-reviewed)abstract
- BACKGROUND: Parental substance abuse (SA) of alcohol and drugs is associated with offspring mortality, including sudden infant death syndrome (SIDS), in infancy, but research on cause-specific mortality and mortality in later childhood is scarce.METHODS: Using population-based register data on all births in Sweden in 1973-2013 (N = 4.2 million) and Cox regressions, we examined the associations of mother's and father's SA registered between 2 years before and 12 years after the child birth with offspring all-cause and cause-specific mortality in infancy and childhood.RESULTS: Parental SA was associated with increased offspring all-cause and natural-cause mortality in infancy, but not in the neonatal period, and with external-cause mortality in ages 1-9. Risk of SIDS was 130-280% higher in infants with parental SA compared to infants with no parental SA. Adjusting for parental socioeconomic and immigrant status and severe psychiatric disorders, paternal SA was associated with 66% higher mortality due to communicable diseases and infections in infancy, and both maternal and paternal SA were associated with 40-174% higher mortality due to accidents in infancy and in ages 1-9. The associations between parental SA and offspring mortality were similar for male and female offspring.CONCLUSIONS: Child mortality is rare in contemporary Sweden, and parental SA has variable associations with elevated offspring mortality throughout the first 10 years of life, excluding the neonatal period, which is indicative of insufficient recognition of children at risk. Preventive measures should be long-term and targeted to both parental and offspring behaviour.
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| 2. |
- Khemiri, Lotfi, et al.
(author)
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Association of parental substance use disorder with offspring cognition : a population family-based study
- 2020
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In: Addiction. - : Blackwell Publishing. - 0965-2140 .- 1360-0443. ; 115:2, s. 326-336
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Journal article (peer-reviewed)abstract
- AIMS: To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors.DESIGN: A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins).SETTING AND PARTICIPANTS: A total of 3 004 401 people born in Sweden between 1951 and 1998.MEASUREMENTS: The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses.FINDINGS: In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors.CONCLUSIONS: There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
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| 3. |
- Khemiri, Lotfi
(author)
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Cognitive deficits in alcohol use disorder : etiology and treatment
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Alcohol use disorder (AUD) is a psychiatric disorder characterized by a loss of control over drinking, tolerance, withdrawal and negative psychological, physical and social consequences due to excessive alcohol consumption. Even though not explicitly stated in the diagnostic criteria, it is well known that patients with AUD also exhibit impaired cognitive function, e.g., elevated impulsive behavior and deficits in executive functions such as response inhibition, attention and working memory. The aim of this thesis was twofold: First, to investigate the etiology of cognitive deficits in AUD. Second, to investigate if cognitive deficits in AUD can be a potential target for treatment. Study I was a large-scale population-based epidemiological study of approximately 3 million unique individuals based on Swedish national registries. We investigated the effect of family history across all forms of substance use disorders (SUD), including AUD, on general cognitive ability in offspring. The exposure was defined as having a parent with SUD and the outcomes were cognitive test score at conscription and final school grades in compulsory school. At the population level, parental SUD increased the risk of lower cognitive ability in offspring, after adjusting for several covariates such as age, sex, psychiatric co-morbidity and socioeconomic status. However, when analyzing offspring to sibling-pairs discordant for SUD, the strength of this association was reduced with increasing genetic relatedness in the sibling-pairs (half siblings, full siblings, monozygotic twins). These findings suggest that the observed association between parental SUD and lower cognitive ability in offspring can partly be explained by shared genetic factors between SUD and cognitive ability. Study II was a case-control study which further examined the association between AUD and cognitive function, by investigating whether the cognitive profile of people with family history of AUD is more similar to AUD patients than people with no such family history. The study recruited AUD patients (n = 106) and healthy controls (HC; n = 90), who were then further subdivided into AUD family history positive (FH+) and negative (FH-). All subjects underwent psychiatric evaluation and an extensive neuropsychological test battery assessing different aspects of impulsive behavior, decision making, attention, memory and emotion. FH+ and AUD patients had similar levels of elevated self-rated impulsivity, reduced future planning capability and longer emotional recognition latency compared to FH-, while no differences were found for other cognitive outcomes. These findings strengthen the notion that specific aspects of the cognitive profile associated with AUD, can be partly genetically influenced traits, elevating the risk for AUD. Other cognitive disturbances in AUD on the other hand may to a higher degree depend on non-genetic factors such as alcohol intake. Study III and IV were based on a randomized placebo-controlled trial of a novel pharmacological agent, namely the monoamine stabilizer (-)-OSU6162 (OSU). The aims of the studies were to investigate the treatment effect and possible moderating effect of baseline impulsivity, of OSU on craving (study III) and cognitive function (study IV). Patients with AUD (n = 56) were randomized to receive either 14 days of OSU treatment or placebo. The treatment protocol included weekly visits to the clinic and a final test day where they performed a laboratory craving experiment. The patients also underwent neuropsychological testing at baseline and on the final test day. Study III found that OSU treatment reduced alcohol-induced craving, and the greatest treatment effect was observed for patients with higher baseline levels of impulsivity. Study IV found that OSU had no short-term negative effect on any assessed cognitive domain, while improving future planning capacity, emotional recognition latency and divergent thinking. Collectively, these findings suggest that OSU may have beneficial clinical treatment effects in AUD on both craving and cognition, but larger randomized controlled trials are needed to replicate these preliminary findings. Study V was a randomized controlled trial to investigate the effect of working memory training in AUD on drinking, working memory and transfer effects to other cognitive functions. Patients with AUD (n = 50) were randomized to 5 weeks of active computerized working memory training or control training, and came for weekly follow-up visits to the clinic to report drinking and craving. Neuropsychological testing was performed at baseline and after study completion. Active working memory training improved verbal working memory performance, but no significant effect was found for drinking, craving or any of the other assessed cognitive domains. The results did not provide support for working memory training as a sole treatment for AUD, but future studies could consider combining it with pharmacological or psychological treatments. In summary, the current thesis demonstrated that cognitive deficits observed in AUD are in part due to shared genetic factors between AUD and cognitive function. These cognitive deficits may include impulsive behavior, capacity for future planning and emotional recognition. The treatment studies illustrate that cognitive outcomes can indeed be utilized as predictors of treatment response as well as potential treatment targets.
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| 4. |
- Khemiri, Lotfi, et al.
(author)
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Parental substance use disorder and risk of intellectual disability in offspring in Sweden : a national register study
- 2023
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In: eClinicalMedicine. - London : Elsevier. - 2589-5370. ; 63
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Journal article (peer-reviewed)abstract
- Background: Intellectual disability (ID) is a disorder with unknown aetiology in many cases. Maternal alcohol use is a known risk factor for ID, but less is known about the importance of maternal and paternal substance use disorder (SUD) and risk of ID in offspring.Methods: Data from multiple nationwide registers were used to create a cohort of children born from January 01, 1978 to December 31, 2002. All participants were born in Sweden, had available parental identification information and did not emigrate or die before age 12 (n = 1,940,820). Logistic regression modelling was performed with exposure defined as having a parent who received any SUD diagnosis, including alcohol use disorder (AUD) and drug use disorder (DUD). The outcome was registration of diagnosis of any form of ID. First, we analysed the risk of ID if parental SUD was registered prior to childbirth with stepwise adjustment of multiple covariates. Second, the effect of timing of SUD diagnosis in relation to childbirth was analysed.Findings: Of 37,410 offspring with parental SUD registered prior to birth, 3.0% (n = 1110) had any form of ID compared to 1.2% (n = 23,168) of those 1,903,410 individuals without parental SUD prior birth. Parental SUD prior birth was associated with an increased risk of any form of ID (Odds Ratio [OR]: 2.3 [2.2-2.5]), with ORs similar for maternal (OR: 2.3 [2.1-2.5]) and paternal SUD (OR: 2.3 [2.1-2.5]). These ORs were reduced but remained statistically significant after adjusting for parental education, migration, psychiatric comorbidity, and co-parent SUD (OR parental SUD: 1.6 [1.5-1.8]; OR maternal SUD: 1.4 [1.2-1.5]; OR paternal SUD: 1.6 [1.5-1.7]). Parental SUD was associated with increased risk of ID in offspring irrespective of timing of diagnosis, but if mothers or fathers were diagnosed with AUD during pregnancy (OR maternal AUD: 5.0 [3.1-8.2]; OR paternal AUD: 2.8 [2.2-3.6]), the risk was significantly greater than if the AUD diagnosis was first registered after childbirth (OR maternal AUD: 1.9 [1.8-2.0]; OR paternal AUD: 1.6 [1.6-1.7]).Interpretation: Both paternal and maternal SUD were associated with an increased risk of ID in offspring, with greatest risk observed when AUD was diagnosed during pregnancy. Possible mechanisms may involve shared genetic and environmental factors, including toxic effects from alcohol intake. These findings have clinical implications in suggesting that parental SUD in either parent represents a possibly modifiable risk factor to consider when developing prevention, diagnostics and treatment programs for children with ID.
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| 5. |
- Khemiri, Lotfi, et al.
(author)
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Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients
- 2016
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.
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| 6. |
- Virtanen, Suvi, et al.
(author)
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Association of selective serotonin reuptake inhibitor (SSRI) treatment with acute substance misuse outcomes
- 2022
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In: Addiction. - : Blackwell Publishing. - 0965-2140 .- 1360-0443. ; 117:1, s. 234-242
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed medications for patients with anxiety/depression. These patients often have problems with substance use, but it remains unclear whether the risk of substance misuse is influenced by SSRI treatment. We aimed to determine whether SSRI treatment is associated with a decreased risk of acute substance misuse-related outcomes.DESIGN: Cohort study following individuals through Swedish nationwide registers between July 2005 and December 2013 and comparing the risk of substance misuse outcomes during periods on- versus off-treatment within the same individual.SETTING: Swedish general population.PARTICIPANTS: Individuals with a new dispensed prescription of SSRIs between July 2006 and December 2013, and an ICD-10 diagnosis of anxiety/depressive disorder before the first treatment initiation. The cohort included 146,114 individuals (60.7% women).MEASUREMENTS: Substance misuse outcomes included ICD-10 diagnoses of acute intoxications (F10.0-F19.0), accidental poisonings by alcohol or drugs (X41-X42, X45-X46), and substance-related criminal offenses.FINDINGS: The absolute rate of substance misuse increased sharply before the onset of SSRI treatment and decreased after treatment initiation. Stratified Cox regression models showed an elevated risk (hazard ratio (HR)=1.70, 95% confidence interval (CI): 1.62-1.78) of substance misuse outcomes during a 1-month period preceding treatment initiation, compared with the reference period of more than 1 month before treatment start. The on-treatment estimates (1-30 days [HR=1.29, 95% CI: 1.23-1.37], 31-120 days [HR=1.30, 95% CI: 1.24-1.35], and >120 days [HR=1.24, 95% CI: 1.18-1.30] after treatment initiation) were consistently lower than the 1-month pre-treatment estimate, but still elevated compared with the reference period.CONCLUSIONS: For people with anxiety/depression, the risk of substance misuse appears to be particularly elevated right before initiating selective serotonin reuptake inhibitor (SSRI) treatment, which may reflect the emergence or worsening of substance use problems concurrently with anxiety/depression. SSRI treatment appears to be associated with a lower risk of substance misuse compared with the 1-month period preceding treatment initiation, but causality remains uncertain.
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