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1.
J Affect Disord ; 207: 136-140, 2017 Jan 01.
Article En | MEDLINE | ID: mdl-27721187

BACKGROUND: Dysfunctions in the intrinsic clocks are suggested in patients with depressive disorders. The cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2) proteins modulate circadian rhythms in a cell and influence emotional reactions and mood in an individual. The protein kinase C delta binding protein (PRKCDBP, or CAVIN3), similar to the serum deprivation response protein (SDPR, or CAVIN2), reduces metabolic stability of the PER2-CRY2 transcription factor complex that plays a role in the circadian rhythm synchronization. Our aim was to study SDPR, PRKCDBP, CRY1 and CRY2 genetic variants in depressive disorders. METHODS: The sample included 5910 Finnish individuals assessed with the Munich-Composite International Diagnostic Interview (M-CIDI) in year 2000. In year 2011, 3424 individuals were assessed again. After genotype quality control, there were 383 subjects with major depressive disorder, 166 with dysthymia, and 479 with depressive disorders (major depressive disorder, dysthymia or both), and 4154 healthy controls. A total of 48 single-nucleotide polymorphisms from SDPR, PRKCDBP, CRY1 and CRY2 genes were analyzed using logistic regression models controlling for age and gender. RESULTS: The earlier reported association of CRY2 variants with dysthymia was confirmed and extended to major depressive disorder (q<0.05). In addition, novel associations of PRKCDBP rs1488864 with depressive disorders (q=0.02) and with major depressive disorder in specific (q=0.007) were found. LIMITATIONS: The number of cases was moderate and coverage of PRKCDB was limited. CONCLUSIONS: CRY2 and PRKCDBP variants may be risk factors of major depressive disorder and provide information for diagnosis.


Cryptochromes/genetics , Depressive Disorder, Major/genetics , Dysthymic Disorder/genetics , Intracellular Signaling Peptides and Proteins/genetics , Adult , Aged , Aged, 80 and over , Carrier Proteins/genetics , Circadian Rhythm/genetics , Female , Genotype , Humans , Male , Middle Aged , Phosphate-Binding Proteins , Polymorphism, Single Nucleotide
2.
J Neural Transm (Vienna) ; 123(11): 1347-1354, 2016 11.
Article En | MEDLINE | ID: mdl-27324805

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dß, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ 2 = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dß CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ 2 = 8.99, df = 2, p = 0.011). The 5-HTR1Dß CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dß polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.


Anxiety Disorders/drug therapy , Anxiety Disorders/genetics , Citalopram/adverse effects , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Selective Serotonin Reuptake Inhibitors/adverse effects , Adolescent , Child , Citalopram/therapeutic use , Dysthymic Disorder/drug therapy , Dysthymic Disorder/genetics , Female , Humans , Male , Pharmacogenomic Variants , Receptor, Serotonin, 5-HT1B/genetics , Receptor, Serotonin, 5-HT2A/genetics , Receptor, Serotonin, 5-HT2C/genetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sex Factors
3.
J Am Acad Child Adolesc Psychiatry ; 51(5): 518-27, 2012 May.
Article En | MEDLINE | ID: mdl-22525958

OBJECTIVE: Identifying risk factors for adolescent depression is an important research aim. Overgeneral autobiographical memory (OGM) is a feature of adolescent depression and a candidate cognitive risk factor for future depression. However, no study has ascertained whether OGM predicts the onset of adolescent depressive disorder. OGM was investigated as a predictor of depressive disorder and symptoms in a longitudinal study of high-risk adolescents. In addition, cross-sectional associations between OGM and current depression and OGM differences between depressed adolescents with different clinical outcomes were examined over time. METHOD: A 1-year longitudinal study of adolescents at familial risk for depression (n = 277, 10-18 years old) was conducted. Autobiographical memory was assessed at baseline. Clinical interviews assessed diagnostic status at baseline and follow-up. RESULTS: Currently depressed adolescents showed an OGM bias compared with adolescents with no disorder and those with anxiety or externalizing disorders. OGM to negative cues predicted the onset of depressive disorder and depressive symptoms at follow-up in adolescents free from depressive disorder at baseline. This effect was independent of the contribution of age, IQ, and baseline depressive symptoms. OGM did not predict onset of anxiety or externalizing disorders. Adolescents with depressive disorder at both assessments were not more overgeneral than adolescents who recovered from depressive disorder over the follow-up period. CONCLUSIONS: OGM to negative cues predicted the onset of depressive disorder (but not other disorders) and depressive symptoms over time in adolescents at familial risk for depression. Results are consistent with OGM as a risk factor for depression.


Depressive Disorder/diagnosis , Depressive Disorder/psychology , Generalization, Psychological , Memory, Episodic , Adolescent , Anxiety Disorders/diagnosis , Anxiety Disorders/psychology , Child Behavior Disorders/diagnosis , Child Behavior Disorders/psychology , Comorbidity , Depressive Disorder/genetics , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Diagnosis, Differential , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Humans , Internal-External Control , Interview, Psychological , Longitudinal Studies , Male , Recurrence , Risk Factors , Wales
4.
Biol Psychiatry ; 71(4): 350-7, 2012 Feb 15.
Article En | MEDLINE | ID: mdl-22030358

BACKGROUND: Studies have examined the interaction of MAOA genotype with childhood maltreatment in relation to depressive symptomatology and alcohol abuse with conflicting findings. Both high- and low-activity allele combinations have been shown to be protective for maltreated children with direction of findings varying by study methodology and participants' sex. METHODS: Participants in a prospective cohort design study involving court-substantiated cases of child abuse and neglect and a matched comparison group were followed up into adulthood and interviewed (N = 802). Eighty-two percent consented to provide blood, 631 gave permission for DNA extraction and analyses, and 575 were included in the final sample. This sample included male, female, white, and nonwhite (primarily black) participants. Symptoms of dysthymia, major depression, and alcohol abuse were assessed using the National Institutes of Mental Health Diagnostic Interview Schedule-III-R. RESULTS: Significant three-way interactions, MAOA genotype by abuse by sex, predicted dysthymic symptoms. Low-activity MAOA genotype buffered against symptoms of dysthymia in physically abused and multiply-maltreated women. Significant three-way interactions, MAOA genotype by sexual abuse by race, predicted all outcomes. Low-activity MAOA genotype buffered against symptoms of dysthymia, major depressive disorder, and alcohol abuse for sexually abused white participants. The high-activity genotype was protective in the nonwhite sexually abused group. CONCLUSIONS: This prospective study provides evidence that MAOA interacts with child maltreatment to predict mental health outcomes. Reasons for sex differences and race findings are discussed.


Alcoholism , Child Abuse , Depressive Disorder, Major , Dysthymic Disorder , Genetic Predisposition to Disease/ethnology , Monoamine Oxidase/genetics , Adult , Alcoholism/ethnology , Alcoholism/genetics , Alcoholism/psychology , Battered Women/psychology , Child , Child Abuse/ethnology , Child Abuse/psychology , Depressive Disorder, Major/ethnology , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/ethnology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Gene-Environment Interaction , Genotype , Humans , Male , Prospective Studies , Racial Groups , Sex Factors , Sex Offenses/ethnology , Sex Offenses/psychology , United States/ethnology
5.
Span J Psychol ; 14(2): 936-43, 2011 Nov.
Article En | MEDLINE | ID: mdl-22059337

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small-vessel disease of the brain that is characterized by headache, recurring lacunar strokes, mood changes and progressive cognitive deterioration. The disease is transmitted with an autosomal dominant pattern and usually starts during midadulthood (at 30-50 years of age). Cognitive deficits in patients with CADASIL develop slowly. The dementia causes frontal-like symptoms and it typically develops after a history of recurrent stroke. We describe three patients from one Spanish family affected by this disease. All three cases underwent comprehensive clinical and neuropsychological examination, and were monitored for seven years. The results obtained in this study describe a) a significant loss of the intelligence quotient (IQ) and noticeable damage to abstract ability (g factor), b) mood and psychopathological disturbances (major depression and dysthymia), and c) a personality with neurotic features.


CADASIL/genetics , CADASIL/psychology , Dementia, Multi-Infarct/genetics , Dementia, Multi-Infarct/psychology , Intelligence/genetics , Mental Disorders/genetics , Mental Disorders/psychology , Personality Disorders/genetics , Personality Disorders/psychology , Adult , Alleles , Chromosome Aberrations , DNA Mutational Analysis , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Exons/genetics , Female , Genes, Dominant/genetics , Genetic Testing , Genotype , Humans , MMPI/statistics & numerical data , Male , Middle Aged , Phenotype , Psychometrics , Psychopathology , Receptor, Notch3 , Receptors, Notch/genetics , Wechsler Scales/statistics & numerical data
6.
Nervenarzt ; 82(9): 1169-77, 2011 Sep.
Article De | MEDLINE | ID: mdl-21264458

BACKGROUND: Previous research about the aetiology of depression has analysed how depression-associated personality traits influence familial transmission. Using the community-based sample of the Greifswald Family Study, we investigated longitudinally to which extent the temperament factor harm avoidance influences the correlation between parent's depression and the depression of their offspring (with regard to possible sex differences). METHODS: To test this familial transmission a structural equation model was conducted with the data of 193 children (mean age 19.5, SD=2.41) and their biological parents. Depression was assessed with structured clinical interviews, and harm avoidance with Cloninger's Temperament and Character Inventory (TCI, JTCI). RESULTS: The harm avoidance scores of the mothers were significantly correlated with the harm avoidance scores of their children, but the correlation of the father's and children's scores did not reach significance. The extent of harm avoidance at the first assessment of the 14-year-old children predicted depression 5 years later. CONCLUSION: These results indicate the importance of personality as a vulnerability marker for developing affective disorders. The results are discussed with respect to prevention programmes for children and parents with depression, especially if they exhibit strongly avoidant or anxious behaviour.


Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Harm Reduction , Temperament , Adolescent , Adult , Aged , Child of Impaired Parents/psychology , Depressive Disorder, Major/prevention & control , Dysthymic Disorder/genetics , Dysthymic Disorder/prevention & control , Dysthymic Disorder/psychology , Female , Health Surveys , Humans , Interview, Psychological , Longitudinal Studies , Male , Mass Screening , Middle Aged , Models, Psychological , Personality Inventory/statistics & numerical data , Psychometrics , Risk Factors , Sex Factors , Young Adult
7.
J Affect Disord ; 125(1-3): 249-55, 2010 Sep.
Article En | MEDLINE | ID: mdl-20226536

BACKGROUND: Genetic variations in FKBP5, BDNF, P2RX7 and CACNA1 are current candidates for involvement in depression. METHODS: The single nucleotide polymorphisms FKBP5:rs1360780, BDNF:rs6265 (Val66Met), P2RX7:2230912 (Gln460Arg) and CACNA1C:rs1006737 were genotyped in DNA from 457 depression cases (major depression, dysthymia, and mixed anxiety depression) and 2286 healthy controls with no symptom of psychopathology. Cases and controls were derived from a large well-characterized longitudinal population-based sample of adult Swedes with data on life situation and life history. Association to depression was analyzed with and without consideration to problems during childhood and negative life events last year. RESULTS: FKBP5:rs1360780 allele T and genotype TT were overrepresented in depression for men. Childhood problems and negative life events (two or more) conferred a risk for depression (OR=2.8, 95% CI: 2.2-3.5 and OR=2.9, 95% CI: 2.4-3.7, respectively). The BDNF:rs6265 Met-allele was overrepresented in depression for women with problems during their childhood. No indication for association to depression was found for P2RX7:2230912 and CACNA1C:rs1006737 without or with consideration of childhood problems or negative life events. LIMITATIONS: The sample size did not allow exclusion of true association to depression at low odds ratios. There was possibly some recall bias of childhood problems. CONCLUSIONS: These data support previous reports on FKBP5:rs1360780 and show a gender difference. Likewise, they support previous reports on BDNF:rs6265 and show involvement of environmental stress. P2RX7:2230912 and CACNA1C:rs1006737 did not have a large or moderate-size effect on depression risk. Further studies are required to estimate the significance of these findings.


Alleles , Anxiety Disorders/genetics , Brain-Derived Neurotrophic Factor/genetics , Calcium Channels, L-Type/genetics , Depressive Disorder, Major/genetics , Dysthymic Disorder/genetics , Genotype , Polymorphism, Single Nucleotide/genetics , Receptors, Purinergic P2X7/genetics , Tacrolimus Binding Proteins/genetics , Adult , Anxiety Disorders/diagnosis , Anxiety Disorders/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Dysthymic Disorder/diagnosis , Dysthymic Disorder/psychology , Epistasis, Genetic/genetics , Female , Genetic Predisposition to Disease/genetics , Humans , Life Change Events , Longitudinal Studies , Male , Middle Aged , Phenotype , Risk Factors , Sex Factors , Social Environment , Young Adult
8.
J Am Acad Child Adolesc Psychiatry ; 49(2): 114-21, 2010 Feb.
Article En | MEDLINE | ID: mdl-20215933

OBJECTIVE: Exposure to suicidal behavior in peers and relatives is thought to increase risk for suicidal behavior in vulnerable individuals, possibly as a result of imitation or modeling. This study examines exposure to suicidal behavior and likelihood of suicide attempt in a high-risk cohort of offspring of a depressed parent. METHOD: A total of 449 offspring of 255 probands with a mood disorder were enrolled in a family study. Probands and offspring were assessed for psychopathology and suicide attempt history, and offspring for suicide exposure. Generalized estimating equations (GEE) and generalized least squares models were used to compare suicide attempt history in exposed and nonexposed offspring as well as characteristics of exposure in exposed offspring suicide attempters and exposed nonattempters. GEE was used to compare exposure occurring before first attempt in attempter offspring and exposure occurring before the same age in matched nonattempter offspring. RESULTS: Offspring reporting exposure to suicidal behavior were four times more likely to report a lifetime suicide attempt compared with unexposed offspring, controlling for age. Suicide attempt status was not associated with age at first exposure, total number or degree (attempt or threat) of exposures, or relationship. Analysis of exposure occurring before age at first suicide attempt found no association between exposure and suicide attempt. CONCLUSIONS: Offspring exposed to suicidal behavior are more likely to report a lifetime suicide attempt than nonexposed offspring. However, when examining the temporal sequence of exposure and attempt, the association is no longer significant, suggesting that imitation is not sufficient explanation.


Bipolar Disorder/psychology , Child of Impaired Parents/psychology , Depressive Disorder, Major/psychology , Depressive Disorder/psychology , Dysthymic Disorder/psychology , Social Environment , Suicide, Attempted/psychology , Suicide/psychology , Adolescent , Adult , Age Factors , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/psychology , Bipolar Disorder/epidemiology , Bipolar Disorder/genetics , Child , Child of Impaired Parents/statistics & numerical data , Comorbidity , Cross-Sectional Studies , Depressive Disorder/epidemiology , Depressive Disorder/genetics , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/genetics , Dysthymic Disorder/epidemiology , Dysthymic Disorder/genetics , Female , Health Surveys , Humans , Male , Middle Aged , Psychotic Disorders/epidemiology , Psychotic Disorders/genetics , Psychotic Disorders/psychology , Risk Factors , Substance-Related Disorders/epidemiology , Substance-Related Disorders/genetics , Substance-Related Disorders/psychology , Suicide/statistics & numerical data , Suicide, Attempted/statistics & numerical data
9.
Psychol Med ; 39(12): 2043-59, 2009 Dec.
Article En | MEDLINE | ID: mdl-19796429

BACKGROUND: The extant major psychiatric classifications DSM-IV, and ICD-10, are atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis would be greatly enhanced by an understanding of risk factors and clinical manifestations. In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. This paper considers the validity of the fourth cluster, emotional disorders, within that proposal. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force, as applied to the cluster of emotional disorders. RESULTS: An emotional cluster of disorders identified using the 11 validators is feasible. Negative affectivity is the defining feature of the emotional cluster. Although there are differences between disorders in the remaining validating criteria, there are similarities that support the feasibility of an emotional cluster. Strong intra-cluster co-morbidity may reflect the action of common risk factors and also shared higher-order symptom dimensions in these emotional disorders. CONCLUSION: Emotional disorders meet many of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster.


Affective Symptoms/classification , Affective Symptoms/diagnosis , Anxiety Disorders/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , International Classification of Diseases , Mood Disorders/classification , Mood Disorders/diagnosis , Somatoform Disorders/classification , Somatoform Disorders/diagnosis , Affective Symptoms/genetics , Affective Symptoms/psychology , Anxiety Disorders/classification , Anxiety Disorders/genetics , Anxiety Disorders/psychology , Comorbidity , Depressive Disorder, Major/classification , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/classification , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Feasibility Studies , Genetic Predisposition to Disease , Humans , Mood Disorders/genetics , Mood Disorders/psychology , Risk Factors , Social Environment , Somatoform Disorders/genetics , Somatoform Disorders/psychology , Temperament
10.
Compr Psychiatry ; 50(5): 477-84, 2009.
Article En | MEDLINE | ID: mdl-19683619

BACKGROUND: Akiskal and Mallya (Psychopharmacol Bull. 1987;23:68-73) proposed criteria defining 4 affective temperaments-hyperthymic, irritable, cyclothymic, and dysthymic. This study aims to develop and validate, using a 3-point rating scale, a short questionnaire that assesses these temperaments. METHODS: The Affective Temperament Questionnaire (ATQ) was administered to a family-based sample of individuals with major depressive disorder (MDD), bipolar disorder (BP), or no mood disorder (N = 378). Factor analyses, internal consistency, and analysis of variance were undertaken to examine the factorial structure and concurrent validity (relative to Axis I mood disorder diagnosis) of the ATQ. Affective Temperament Questionnaire data were evaluated with respect to raw scores and dominant affective temperament. RESULTS: Three factors emerged--hyperthymia, cyclothymia, and dysthymia--which had moderate to high internal consistency. Support for the concurrent validity of ATQ was found, whereby temperament scores and rates of dominant affective temperaments differed with respect to mood disorder diagnosis. Hyperthymia and cyclothymia were more prevalent among individuals with BP than among individuals with MDD or no history of a mood disorder. Dysthymia occurred at a relatively similar rate among individuals with MDD or BP. CONCLUSIONS: Our findings support the use of the ATQ for collecting information regarding affective temperaments and for furthering understanding regarding the links between affective temperament and mood disorders.


Arousal , Cyclothymic Disorder/diagnosis , Dysthymic Disorder/diagnosis , Irritable Mood , Mood Disorders/diagnosis , Personality Assessment/statistics & numerical data , Temperament , Adult , Aged , Bipolar Disorder/diagnosis , Bipolar Disorder/genetics , Bipolar Disorder/psychology , Cyclothymic Disorder/genetics , Cyclothymic Disorder/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Humans , Male , Middle Aged , Mood Disorders/genetics , Mood Disorders/psychology , New Zealand , Phenotype , Psychometrics/statistics & numerical data , Reproducibility of Results
11.
J Clin Child Adolesc Psychol ; 38(1): 36-47, 2009 Jan.
Article En | MEDLINE | ID: mdl-19130356

This study examined expressed emotion in the families of children and adolescents who were (a) in a current episode of Major Depressive Disorder (MDD), (b) in remission from a past episode of MDD, (c) at high familial risk for developing MDD, and (d) low-risk controls. Participants were 109 mother-child dyads (children ages 8-19). Expressed emotion was assessed using the Five Minute Speech Sample, and psychiatric follow-ups were conducted annually. Mothers of children with a current or remitted episode of MDD and at high risk for MDD were more likely to be rated high on criticism than mothers of controls. There were no differences in critical expressed emotion among mothers of children in the current, remitted, or high-risk for depression groups. Higher initial critical expressed emotion was associated with a greater likelihood of having a future onset of a depressive episode in high-risk and depressed participants. Diagnostic groups did not differ in Emotional Overinvolvement.


Depressive Disorder, Major/psychology , Expressed Emotion , Mother-Child Relations , Adolescent , Anxiety Disorders/diagnosis , Anxiety Disorders/genetics , Anxiety Disorders/psychology , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/genetics , Child Behavior Disorders/psychology , Comorbidity , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Genetic Predisposition to Disease/genetics , Genetic Predisposition to Disease/psychology , Humans , Longitudinal Studies , Male , Parenting/psychology , Personality Assessment , Recurrence , Risk Factors
12.
J Affect Disord ; 117(1-2): 30-41, 2009 Sep.
Article En | MEDLINE | ID: mdl-19167093

BACKGROUND: The purpose of this study was to estimate the contribution of genetic, common- and unique environmental factors in the aetiology of unipolar major depression (MD), and to investigate whether the unipolar depressive disorders; MD, atypical depression/depression NOS, dysthymia and depressive adjustment disorder can be viewed as various expressions of an underlying genetic commonality. METHODS: A sample consisting of same-sexed mono- and dizygotic twins was drawn from in- and outpatient hospital registers (N=303). DSM-III-R criteria were assessed by personal interviews. One hundred and forty-three of the probands fulfilled the criteria for one or another unipolar depressive disorder. Cross-tabulations were used to compare concordance rates for MD and different combinations of MD and other unipolar depressive disorders. Correlations in liability and estimations of the heritability (h(2)) with biometrical model fitting were performed. RESULTS: Concordance rates were higher among MZ- than among DZ pairs for both MD and all the different combinations of MD and other unipolar depressive disorders. Cross-concordance between MD and other unipolar disorders was observed. In all instances, except for the situation when MD was considered alone, the correlations in liability among MZ pairs were more than twice the correlations in liability among DZ pairs. The heritability of MD was 0.42, of MD+atypical depression 0.51, of MD+atypical depression+dysthymia 0.45 and of MD+atypical depression+dysthymia+depressive adjustment disorder 0.46. LIMITATION: Probands were not sampled from the general population. Most often the same person interviewed both twins in a pair. CONCLUSION: Unipolar MD is moderately heritable without significant shared family environmental effects. Unipolar depressive disorders taken together are moderately heritable without any detectable shared family environmental effects. The tendency is towards higher heritability estimates for the combined groups compared to MD alone. The study suggests that the disorders in the unipolar depressive spectrum may be different manifestations of the same genetic liability.


Depressive Disorder/genetics , Diseases in Twins/genetics , Genotype , Social Environment , Twins/genetics , Adult , Aged , Aged, 80 and over , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Diseases in Twins/psychology , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Humans , Male , Middle Aged , Registries/statistics & numerical data , Severity of Illness Index , Surveys and Questionnaires , Twins/psychology , Twins, Dizygotic/genetics , Twins, Dizygotic/psychology , Twins, Monozygotic/genetics , Twins, Monozygotic/psychology , Young Adult
13.
J Affect Disord ; 109(1-2): 157-63, 2008 Jul.
Article En | MEDLINE | ID: mdl-18191458

BACKGROUND: There has been growing evidence that temperamental traits, including affective temperaments, are heritable and associated with genetic polymorphisms. The purpose of the present study was to investigate the possible relationship between affective temperaments and the triallelic serotonin transporter gene-linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) polymorphisms in healthy Korean subjects. METHODS: Three hundred thirty-five healthy college students were recruited, and 290 participants with a complete data set (172 males, 118 females) were included in the data analysis. The DNA of the subjects was isolated from whole blood cells, and the 5-HTTLPR and DRD4 variable number of tandem repeats polymorphisms were genotyped using polymerase chain reaction. Participants performed the 110-item version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring five affective temperamental traits. RESULTS: A significant association was found between the DRD4 polymorphism and the cyclothymic and irritable temperaments in male subjects. No significant association was shown between the 5-HTTLPR gene polymorphisms and affective temperaments. LIMITATION: Our data were collected from a specific group of college students and cannot be generalized easily to other non-clinical populations. In addition, Korean version of the TEMPS-A used in this study has not yet been validated in Korean population. CONCLUSIONS: This study showed a possible association between the DRD4 polymorphism and certain affective temperaments in the Korean male population. The clarification of the biological basis of predisposing temperaments such as cyclothymic temperament might help to understand the pathophysiology and mechanisms of mood disorders.


Anxiety Disorders/genetics , Asian People/genetics , Depressive Disorder/genetics , Dysthymic Disorder/genetics , Health Status , Minisatellite Repeats/genetics , Polymorphism, Genetic/genetics , Receptors, Dopamine D4/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Temperament , Adult , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Depressive Disorder/diagnosis , Depressive Disorder/epidemiology , Diagnostic and Statistical Manual of Mental Disorders , Dysthymic Disorder/diagnosis , Dysthymic Disorder/epidemiology , Female , Genotype , Humans , Male , Severity of Illness Index , Surveys and Questionnaires
14.
J Affect Disord ; 108(1-2): 25-32, 2008 May.
Article En | MEDLINE | ID: mdl-18006072

BACKGROUND: The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these "subaffective" forms on their quality of life (QoL). METHODS: The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients ("cases") and 115 comparison subjects without family history of affective illness ("controls"). We used The Mood Disorder Questionnaire to rule out clinical bipolarity. RESULTS: Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic. LIMITATIONS: We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses. CONCLUSIONS: Our findings support the concept of a spectrum of subthreshold affective traits or temperaments - especially for the cyclothymic and anxious - in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in "clinically well" relatives. Overall, our data are compatible with the "endophenotype" and "subaffective" theses for affective temperaments.


Bipolar Disorder/genetics , Mood Disorders/genetics , Phenotype , Psychiatric Status Rating Scales/statistics & numerical data , Temperament , Adult , Anxiety Disorders/epidemiology , Anxiety Disorders/genetics , Anxiety Disorders/psychology , Argentina , Bipolar Disorder/epidemiology , Bipolar Disorder/psychology , Case-Control Studies , Cross-Sectional Studies , Cyclothymic Disorder/diagnosis , Cyclothymic Disorder/epidemiology , Cyclothymic Disorder/genetics , Dysthymic Disorder/epidemiology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Humans , Interpersonal Relations , Irritable Mood , Male , Middle Aged , Mood Disorders/epidemiology , Mood Disorders/psychology , Quality of Life/psychology , Surveys and Questionnaires
16.
J Abnorm Child Psychol ; 35(2): 301-12, 2007 Apr.
Article En | MEDLINE | ID: mdl-17216344

Comorbid conduct problems (CPs) and depression are observed far more often than expected by chance, which is perplexing given minimal symptom overlap. In this study, relations between parental psychopathology and children's diagnostic status were evaluated to test competing theories of comorbidity. Participants included 180 families with an 8-12-year-old child diagnosed with CPs, depression, both conditions, or neither condition. Although no single theory of comorbidity was supported fully, evidence suggested that CPs and depression may be inherited separately. Paternal antisocial characteristics and maternal depression provided independent prediction of both child depression and CPs. However, paternal antisocial behavior moderated the effect of maternal depression on CPs. For children with antisocial fathers, CPs were observed regardless of maternal depression levels. In contrast, a strong relation was observed between CPs and maternal depression for children without antisocial fathers.


Conduct Disorder/genetics , Depressive Disorder/genetics , Antisocial Personality Disorder/epidemiology , Antisocial Personality Disorder/genetics , Antisocial Personality Disorder/psychology , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit and Disruptive Behavior Disorders/epidemiology , Attention Deficit and Disruptive Behavior Disorders/genetics , Attention Deficit and Disruptive Behavior Disorders/psychology , Child , Comorbidity , Conduct Disorder/epidemiology , Conduct Disorder/psychology , Depressive Disorder/epidemiology , Depressive Disorder/psychology , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Fathers/psychology , Female , Genetic Predisposition to Disease/genetics , Humans , Juvenile Delinquency/prevention & control , Juvenile Delinquency/psychology , Longitudinal Studies , Male , Mothers/psychology , Phenotype , Risk Factors , Washington
17.
J Affect Disord ; 99(1-3): 181-9, 2007 Apr.
Article En | MEDLINE | ID: mdl-17049621

BACKGROUND: Depressive personality disorder (DPD) was introduced in DSM-IV as a new category requiring further study. The aim of this study was to estimate genetic and environmental contributions to DPD in a population-based twin sample, and include data on criteria performance, prevalence and diagnostic overlap. METHODS: Axis I and Axis II diagnoses were obtained by structured interviews in a population-based sample of 2794 young adult twins. Statistical analyses included correlation and factor analysis based on polychoric correlation coefficients, and diagnostic overlap applying adjusted odds ratios. Contributions from additive genetic and common and unique environmental influences to the liability to DPD were computed using structural equation modelling, applying a multiple threshold variable. RESULTS: Liability to DPD could best be explained by additive genetic and unique environmental factors, with heritability estimates of 49% (95% CI 0.41-0.57) in females and 25% (95% CI 0.12-0.40) in males. The best-fitting model indicated that some of the genes contributing to DPD differ between men and women. Chronbach's alpha was 0.87. 2.0% of participants fulfilled the criteria for DPD, and overlap was most pronounced for dysthymic disorder and avoidant personality disorder. LIMITATIONS: Low prevalence rates and subsequent inclusion of subthreshold criteria could have influenced parameter estimates, especially in males. CONCLUSIONS: DPD was almost twice as heritable in females as in males, comparable to previous studies on major depression. The proposed criteria showed good measurement properties, and DPD was not completely subsumed within any other disorder.


Depressive Disorder/genetics , Diseases in Twins/genetics , Personality Disorders/genetics , Social Environment , Adult , Cross-Sectional Studies , Depressive Disorder/epidemiology , Depressive Disorder/psychology , Diseases in Twins/epidemiology , Diseases in Twins/psychology , Dysthymic Disorder/epidemiology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Norway , Personality Disorders/diagnosis , Personality Disorders/epidemiology , Personality Disorders/psychology , Risk Factors , Sex Factors
18.
J Affect Disord ; 96(1-2): 1-8, 2006 Nov.
Article En | MEDLINE | ID: mdl-16844230

BACKGROUND: Recent studies have suggested that eating and sleep problems during early childhood may pose as risk factors for mood and anxiety disorders in later life. We aim to study the associations between early childhood sleep and eating problems, specifically high motor activity during sleep and irregularities in sleep/eating schedules, and lifetime history of mood and anxiety disorders. METHODS: We followed up 164 offspring, who were at high and low risk for major depression by virtue of their parental history (at least one parent had Major Depressive Disorder). Target sleep and eating problems were measured using Dimensions of Temperament Survey (DOTS). The offspring were blindly assessed at 3 times over 20 years using a structured diagnostic interview. RESULT: Irregularities in sleeping and eating schedules in childhood (low rhythmicity) was associated with adolescent-onset major depression and anxiety disorder, as well as childhood-onset anxiety disorder. High motor activity level during sleep was associated with both childhood-onset and adolescent-onset dysthymic disorder. Neither childhood sleep nor eating irregularities were associated with adult onset psychopathology. LIMITATIONS: Retrospective reports of childhood sleep and eating patterns were derived from parent-reports. Reported problems may overlap with clinical diagnoses. CONCLUSION: Clinicians should be alerted to parental reports of children's sleep and eating problems suggesting low rhythmicity, as well as high motor activity levels during sleep. These early behaviors may be predictive of subsequent mood and anxiety disorders in childhood and adolescence.


Anxiety Disorders/diagnosis , Depressive Disorder, Major/diagnosis , Dysthymic Disorder/diagnosis , Feeding and Eating Disorders of Childhood/diagnosis , Sleep Wake Disorders/diagnosis , Adolescent , Adult , Age Factors , Anxiety Disorders/genetics , Anxiety Disorders/psychology , Child , Depressive Disorder, Major/genetics , Depressive Disorder, Major/psychology , Dysthymic Disorder/genetics , Dysthymic Disorder/psychology , Feeding Behavior , Feeding and Eating Disorders of Childhood/psychology , Female , Humans , Male , Motor Activity , Personality Assessment , Retrospective Studies , Risk Factors , Sleep Disorders, Circadian Rhythm/diagnosis , Sleep Disorders, Circadian Rhythm/psychology , Sleep Wake Disorders/psychology , Statistics as Topic
19.
Twin Res Hum Genet ; 8(2): 101-7, 2005 Apr.
Article En | MEDLINE | ID: mdl-15901472

Questionnaire-based dimensional measures are often employed in epidemiological studies to predict the presence of psychiatric disorders. The present study sought to determine how accurately 4 dimensional mental health measures, the 12-item General Health Questionnaire (GHQ-12), Neuroticism (EPQ-N), the high positive affect and anxious arousal scales from the Mood and Anxiety Symptoms Questionnaire (MASQ-HPA and MASQ-AA) and a composite of all 4, predicted psychiatric caseness as diagnosed by the University of Michigan Composite International Diagnostic Interview (UM-CIDI). Community subjects were recruited through general practitioners; those who agreed to participate were sent a questionnaire containing the above measures. Subsequently, the UM-CIDI was administered by telephone to 469 subjects consisting of sibling pairs who scored most discordantly or concordantly on a composite index of the 4 measures. Logistic Regression and Receiver Operating Characteristic (ROC) curve analyses were carried out to assess the predictive accuracy of the dimensional measures on UM-CIDI diagnosis. A total of 179 subjects, 62 men and 117 women with an average age of 42 years, were diagnosed with at least one of the following psychiatric disorders: depression, dysthymia, generalized anxiety disorder (GAD), social phobia, agoraphobia and panic attack. The six disorders showed high comorbidity. EPQ-N and the Composite Index were found to be very strong and accurate predictors of psychiatric caseness; they were however unable to differentiate between specific disorders. The results from the present study therefore validated the four mental health measures as being predictive of psychiatric caseness.


Anxiety Disorders/diagnosis , Mental Health , Mood Disorders/diagnosis , Personality Inventory , Adult , Affect , Aged , Aged, 80 and over , Agoraphobia/diagnosis , Agoraphobia/genetics , Anxiety Disorders/genetics , Arousal , Depression/diagnosis , Depression/genetics , Dysthymic Disorder/diagnosis , Dysthymic Disorder/genetics , Female , Forecasting , Humans , Interview, Psychological , Male , Middle Aged , Mood Disorders/genetics , Neurotic Disorders/diagnosis , Neurotic Disorders/genetics , Panic Disorder/diagnosis , Panic Disorder/genetics , Phobic Disorders/diagnosis , Phobic Disorders/genetics , Predictive Value of Tests , Siblings
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