Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

The effects on children of depressed mothers' remission and relapse over 9 months.

BACKGROUND: The high rate of depression among children of depressed mothers is well known. Suggestions that improvement in maternal acute depression has a positive effect on the child have emerged. However, data on the mechanisms of change have been sparse. The aim was to understand how remission and relapse in the mother might explain the changes in the child's outcome. METHOD: Participants were 76 depressed mothers who entered into a medication clinical trial for depression and 135 of their eligible offspring ages 7-17 years. The mothers and children were assessed at baseline and periodically over 9 months by independent teams to understand the relationship between changes in children's symptoms and functioning and maternal remission or relapse. The main outcome measures were, for mothers, the Hamilton Depression Rating Scale (HAMD), the Social Adjustment Scale (SAS) and the Parental Bonding Instrument (PBI) and, for children, the Children's Depression Inventory (CDI), the Columbia Impairment Scale (CIS), the Multidimensional Anxiety Scale for Children (MASC) and the Children's Global Assessment Scale (CGAS). RESULTS: Maternal remission was associated with a decrease in the child's depressive symptoms. The mother's subsequent relapse was associated with an increase in the child's symptoms over 9 months. The effect of maternal remission on the child's improvement was partially explained by an improvement in the mother's parenting, particularly the change in the mother's ability to listen and talk to her child, but also reflected in her improvement in parental bonding. These findings could not be explained by the child's treatment. CONCLUSIONS: A depressed mother's remission is associated with her improvement in parenting and a decrease in her child's symptoms. Her relapse is associated with an increase in her child's symptoms.

Neuronal generators of posterior EEG alpha reflect individual differences in prioritizing personal spirituality.

Prominent posterior EEG alpha is associated with depression and clinical response to antidepressants. Given that religious belief was protective against depression in a longitudinal study of familial risk, we hypothesized that individuals who differed by strength of spiritual beliefs might also differ in EEG alpha. Clinical evaluations and self-reports of the importance of religion or spirituality (R/S) were obtained from 52 participants, and again at 10-y followup when EEG was measured. EEG alpha was quantified using frequency PCA of current source densities (CSD-fPCA). Participants who rated R/S as highly important at initial assessment showed greater alpha compared to those who did not. Those who rated R/S important in both sessions showed greater alpha than those who changed their ratings. EEG differences were particularly well-defined for participants with lifetime depression. Findings extend the view of alpha as a marker for affective processes, suggesting an association with the ontogenesis of spirituality.

Religiosity and resilience in persons at high risk for major depression.

BACKGROUND: Few studies have examined religiosity as a protective factor using a longitudinal design to predict resilience in persons at high risk for major depressive disorder (MDD). METHOD: High-risk offspring selected for having a depressed parent and control offspring of non-depressed parents were evaluated for psychiatric disorders in childhood/adolescence and at 10-year and 20-year follow-ups. Religious/spiritual importance, services attendance and negative life events (NLEs) were assessed at the 10-year follow-up. Models tested differences in relationships between religiosity/spirituality and subsequent disorders among offspring based on parent depression status, history of prior MDD and level of NLE exposure. Resilience was defined as lower odds for disorders with greater religiosity/spirituality in higher-risk versus lower-risk offspring. RESULTS: Increased attendance was associated with significantly reduced odds for mood disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring; however, odds were significantly lower in offspring of non-depressed parents than in offspring of depressed parents. In analyses confined to offspring of depressed parents, those with high and those with average/low NLE exposure were compared: increased attendance was associated with significantly reduced odds for MDD, mood disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and increased importance was associated with significantly reduced odds for mood disorder (by 74%) only in offspring of depressed parents with high NLE exposure. Moreover, those associations differed significantly between offspring of depressed parents with high NLE exposure and offspring of depressed parents with average/low NLE exposure. CONCLUSIONS: Greater religiosity may contribute to development of resilience in certain high-risk individuals.

The role of fear and anxiety in the familial risk for major depression: a three-generation study.

BACKGROUND: The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression. METHOD: Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD. RESULTS: In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns. CONCLUSIONS: These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.

Parents concordant for major depressive disorder and the effect of psychopathology in offspring.

BACKGROUND: Concordance for major depressive disorder (MDD) between parents could happen for different reasons. Regardless of the origin and the frequency of the concordance, the effect on offspring of having two parents affected with MDD may be serious. The sex of the affected parent and offspring may also be a important risk factor for MDD in offspring. METHODS: We examined the increased risk of psychopathology among offspring of the four parental mating groups: both parents affected with MDD (N = 53); only mother affected (N = 31); only father affected (N = 65); and, neither parents affected (N = 33). Parents and offspring were assessed by direct interview, conducted blind and independently of each other. RESULTS: Among the four parental mating groups, offspring of both parents affected had the highest risk of MDD, anxiety disorder and alcohol dependence, and the earliest age of onset for MDD. There were two exceptions: the highest risk of conduct disorder and of drug dependence was in the groups where only the father was affected and where only the mother was affected, respectively. Mother's MDD was a stronger predictor of MDD in male compared to female offspring. Father's MDD was a stronger predictor of MDD in female compared to male offspring. CONCLUSION: Having two parents with MDD increases the risk of psychiatric disorders in offspring. A clear dose-response relationship between the number of affected parents and psychiatric disorders in offspring was observed. The sex of the affected parent and of the offspring is important in determining the risk to offspring. For an examination of the risk to psychopathology in offspring, diagnosis status of both parents should be considered.

Psychiatric disorders in the relatives of probands with prepubertal-onset or adolescent-onset major depression.

OBJECTIVE: To determine whether the familial risk of major depressive disorder (MDD) varies with either onset, recurrence, or continuity of MDD in adulthood in prepubertal- compared with adolescent-onset probands. METHOD: Seventy-six prepubertal-onset MDD, 59 adolescent-onset MDD, and 78 never psychiatrically ill probands were assessed as children or adolescents and were evaluated 10 to 15 years later as adults, by an independent team that was blind to the initial diagnoses. At follow-up, psychiatric disorders among 731 of their first-degree relatives were assessed using direct interviews and family history methods by investigators who were blind to the clinical status of the probands. RESULTS: Both prepubertal- and adolescent-onset MDD were significantly associated with a family history of MDD. The familial rates of MDD and other psychopathology did not vary between the 2 groups. For prepubertal-onset MDD, family history was significantly associated with recurrence and nonsignificantly associated (trend) with continuity into adulthood. In contrast, there was no association between a family history of MDD and either recurrence or continuity into adulthood of adolescent-onset MDD. CONCLUSIONS: Prepubertal- and adolescent-onset MDD are both associated with a family history of MDD, but only in prepubertal-onset MDD is familial loading associated with recurrence and continuity of MDD into adulthood.

Psychiatric disorders and impairment in the children of opiate addicts: prevalances and distribution by ethnicity.

This study examined rates of psychiatric disorders and impairment in 283 children, aged 6 to 17, of 69 Caucasian, 45 African-American, and 47 Hispanic-American methadone maintenance patients. Children were evaluated by direct and/or parental interview with the K-SADS-E. Final DSM-III-R diagnoses and Global Assessment Scale (C-GAS) were assigned by best estimate. Substantial lifetime prevalences of mood (21%), anxiety (24%) and disruptive disorders (30%), school problems (37%), and global impairment (C-GAS < 61) (25%) were observed in the children of opiate-dependent patients. There were few differences between ethnic groups. Effects of proband gender and major depression and their interactions with ethnicity on risk for childhood psychopathology were also examined. The results suggest children of patients in treatment for opiate dependence from diverse ethnic groups are at risk for psychopathology. Programs for early detection and intervention should be devised and evaluated.

Brief screening for family psychiatric history: the family history screen.

BACKGROUND: Brief screens to collect lifetime family psychiatric history are useful in clinical practice and for identifying potential families for genetic studies. METHODS: The Family History Screen (FHS) collects information on 15 psychiatric disorders and suicidal behavior in informants and their first-degree relatives. Since each question is posed only once about all family members as a group, the administrative time is 5 to 20 minutes, depending on family size and illness. Data on the validity against best-estimate (BE) diagnosis based on independent and blind direct interviews on 289 probands and 305 relatives and test-retest reliability across 15 months in 417 subjects are presented. RESULTS: Agreement between FHS and BE diagnosis for proband and relative self-report had median sensitivity (SEN) of 67.6 and 71.1 respectively; median specificity (SPC) was 87.6 and 89.4, respectively. Marked decrease in SEN occurred when a single informant (the proband) reported on a relative (median, 37.5); however, median SPC was 95.8. Use of more than 1 informant substantially improved SEN (median, 68.2), with a modest reduction in SPC (median, 86.8). Test-retest reliability across 15 months resulted in a median kappa of 0.56. CONCLUSIONS: The FHS is a promising brief screen for collecting lifetime psychiatric history on an informant and/or first-degree relatives. Its validity is best demonstrated for major depression, anxiety disorders, substance dependence (alcohol and drug dependence), and suicide attempts. It is not a substitute for more lengthy family history if more detail on diagnosis is required.

Selecting early onset MDD probands for genetic studies: results from a longitudinal high-risk study.

Recent studies have found high rates of familial aggregation of major depression (MDD) in relatives of depressed children coming for treatment, leading investigators to suggest that probands for genetic studies of MDD should be selected from samples of depressed children being brought for treatment. Implicit in this recommendation is the assumption that childhood and adult depression are similar disorders. This assumption in turn implies that children with prepubertal or adolescent onset depression are at high risk for having recurrent episodes of MDD that continue into adulthood. The data supporting this latter hypothesis, however, is limited and contradictory. In this article we report results from a high-risk longitudinal family study in which we explored the recurrence and continuity into adulthood of prepubertal or adolescent onset MDD in offspring who were at high or low risk for MDD, by virtue of their parental depression status. One hundred eighteen offspring from 55 families in which one or more parents had MDD and 50 offspring from 21 families in which neither parent had MDD were followed for more than 10 years (all offspring were 20 years or older at the end of follow-up time) and blindly reassessed using a semistructured diagnostic instrument. Offspring with childhood/adolescent onset MDD were at significantly greater risk for recurrence in adulthood (after age 25) as compared with offspring without an onset of childhood/adolescent MDD, if they had a history of parental MDD. In contrast, among offspring without a history of parental MDD, those with childhood/adolescent onset MDD were at no greater risk for continuing to have MDD in adulthood (after age 25) than those without childhood/adolescent onset MDD. Moreover, there was a trend for offspring with childhood/adolescent onset MDD to be at greater risk for recurrence after age 25 if they had a history of parental MDD, as compared with offspring without a history of parental MDD (60 vs. 18%). We conclude that childhood/adolescent onset MDD is a heterogeneous disorder, with family history of MDD appearing to define a subtype of childhood/adolescent onset MDD that is recurrent and continues into adulthood. Our findings suggest that caution should be exercised in selecting depressed children and adolescents brought for treatment as probands in genetic studies of early onset MDD. A conservative strategy would be to select only those depressed children and adolescents with a family history of MDD and reassess the treated sample as they mature, ensuring that they go on to have MDD in adulthood. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:93-101, 2000

Risk/protective factors among addicted mothers' offspring: a replication study.

There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.

Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood.

OBJECTIVE: To extend findings from several independent reports of an association between maternal smoking during pregnancy and attention-deficit hyperactivity disorder, conduct disorder, and substance abuse in the offspring. METHOD: This is a 10-year longitudinal study of offspring assessed at 3 points in time into adulthood. Fifty offspring of mothers who reported smoking at least 10 cigarettes almost daily during pregnancy and 97 offspring of mothers who reported never smoking during pregnancy were studied. Psychiatric diagnosis in offspring was assessed blind to parental diagnosis. RESULTS: There was a greater than 4-fold increased risk of prepubertal-onset conduct disorder in boys and a greater than 5-fold increased risk of adolescent-onset drug dependence in girls whose mothers smoked 10 or more cigarettes almost daily during pregnancy. These findings could not be explained by maternal substance abuse during pregnancy, parental psychiatric diagnosis, family risk factors, prenatal and early developmental history of offspring, postnatal maternal smoking, or smoking in the offspring. CONCLUSIONS: Maternal smoking during pregnancy may have a long-term effect on specific psychopathology in offspring. The underlying pathophysiology of nicotine on the fetus requires study. The findings suggest the importance of programs aimed at smoking prevention and cessation in women during pregnancy.

Self-esteem and depression: ten year follow-up of mothers and offspring.

OBJECTIVE: The association between maternal bonding style, offspring low self-esteem and offspring depression status was assessed by maternal depression status. SUBJECTS: Sixty mothers and 137 offspring were independently assessed over the course of a ten year follow-up study. METHOD: Assessments included the Schedule for Affective Disorders and Schizophrenia (SADS-LA), Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS), the Coopersmith Self-Esteem Inventory (CSEI) and the Parental Bonding Instrument (PBI). RESULTS: Among daughters of mothers with a history of depression, maternal affectionless-control was associated with daughter low self-esteem which was associated with daughter depression at ten year follow-up. Among daughters of mothers without a history of depression, maternal affectionless-control was not associated with daughter low self-esteem, which was not associated with daughter depression at ten year follow-up but which was associated with a history of childhood depression. None of these associations were found to be significant among sons. LIMITATIONS: As self-esteem was not measured at ten year follow-up, among offspring the stability of self-esteem could not be assessed, nor could the association between adult self-esteem and adult depression. CONCLUSION: Clinical presentation of low self-esteem in girls should be assessed in the context of maternal depression status.

Depressed adolescents grown up.

CONTEXT: Major depressive disorder (MDD) that arises in adolescence impairs functioning and is associated with suicide risk, but little is known about its continuity into adulthood. OBJECTIVE: To describe the clinical course of adolescent-onset MDD into adulthood. DESIGN AND PARTICIPANTS: Prospective case-control study. Seventy-three subjects had onset of MDD based on systematic clinical assessment during adolescence (Tanner stage III-V) and 37 controls had no evidence of past or current psychiatric disorders, and also were assessed in adolescence (assessment years: 1977-1985). Follow-up was conducted 10 to 15 years after the initial assessment by an independent team without knowledge of initial diagnosis (follow-up years: 1992-1996). SETTING: Cases were identified at Columbia Presbyterian Hospital, New York City, NY; controls were recruited from the community. MAIN OUTCOME MEASURES: Suicide and suicide attempts, psychiatric diagnoses, treatment utilization, and social functioning. RESULTS: Clinical outcomes of adolescent-onset MDD into adulthood compared with control subjects without psychiatric illness include a high rate of suicide (7.7%); a 5-fold increased risk for first suicide attempt; a 2-fold increased risk of MDD, but not other psychiatric disorders; an increased occurrence of psychiatric and medical hospitalization; and impaired functioning in work, social, and family life. Thirty-seven percent of those with adolescent MDD survived without an episode of MDD in adulthood vs 69% of the control participants (relative risk, 2.2 [95% confidence interval, 1.0-4.7; P<.05]). CONCLUSION: There is substantial continuity, specificity, morbidity, and potential mortality from suicide into adulthood in adolescent-onset MDD patients. Now that empirically based guides to their treatment are becoming available, early identification and treatment seems warranted.

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study.

OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. METHOD: Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. RESULTS: Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.

Prevalence of suicide ideation and suicide attempts in nine countries.

BACKGROUND: There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data. METHODS: Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand. RESULTS: The lifetime prevalence rates/100 for suicide ideation ranged from 2.09 (Beirut) to 18.51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0.72 (Beirut) to 5.93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married. CONCLUSIONS: While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.

Children with prepubertal-onset major depressive disorder and anxiety grown up.

BACKGROUND: The continuity in adulthood of major depressive disorder (MDD) first arising before puberty is largely unknown. This information could guide early treatment and clarify the appropriateness of including children with MDD in genetic studies. METHODS: Eighty-three subjects with onset of MDD, 44 subjects with anxiety disorder and no MDD, and 91 subjects with no evidence of past or current psychiatric disorders were assessed by two psychiatrists before puberty (Tanner stage < III) and were evaluated 10 to 15 years later as adults by an independent team without knowledge of the initial diagnosis. RESULTS: The clinical outcome of children with prepubertal-onset MDD in adulthood includes a high risk of suicide attempts (nearly 3-fold compared with normal controls and 2-fold compared with children with anxiety) and bipolar disorder. Compared with controls, both the children with MDD and those with anxiety went on to have increased risk of substance abuse and conduct disorder but not other disorders, increased use of longterm psychiatric and medical services, and overall impaired functioning. Children with prepubertal-onset MDD with a recurrence of MDD during follow-up had higher rates of MDD in their first-degree relatives. CONCLUSIONS: There is high morbidity in clinically referred children with prepubertal-onset MDD and anxiety, but continuity and specificity of MDD or anxiety disorder in adulthood is less clear. Caution is warranted in selecting clinically referred children with prepubertal-onset MDD for inclusion in genetic studies unless they have a family history of MDD and recurrence of MDD over time.