Personality dimensions harm avoidance and self-directedness predict the cortisol awakening response in military men

To account for individual differences in vulnerability for stress-related disorders, studies have examined the relationship between hypothalamic-pituitary-adrenal (HPA) axis functioning and personality. The present study examined the relationship between the free fraction of cortisol in saliva after awakening and personality as measured with Cloninger's Temperament and Character Inventory [Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., Wetzel, R.D., 1994. The Temperament and Character Inventory (TCI): A Guide to its Development and Use. Washington University, Center for Psychobiology of Personality, St. Louis, MO] in 107 healthy male soldiers. Harm avoidance explained 9% of variance in cortisol levels after awakening (AUCG), and harm avoidance and self-directedness predicted 10% of variance in mean cortisol increase. The cortisol awakening response (CAR) was lower in participants with low scores on harm avoidance, and mean cortisol increase after awakening was higher in soldiers high on self-directedness and harm avoidance. These results show that the CAR is related to personality and that it can be used to examine individual differences in HPA (re)activity.     

Malignancy of recurrent, early-onset major depression: a family study.

Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (> or = 2 episodes), early-onset (< or = 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members.     

Borderline personality disorder characteristics in young adults with recurrent mood disorders: a comparison of bipolar and unipolar depression

BACKGROUND: In young adults it can be difficult to differentiate between an early bipolar illness and borderline personality disorder. There are considerable areas of clinical overlap between cyclothymic temperament, bipolar-spectrum disorders and borderline characteristics. The aim of this study was to measure borderline characteristics in young adults during an index depressive episode and to compare three diagnostic groups: DSM-IV bipolar affective disorder (BPAD); bipolar spectrum disorder (BSD); and DSM-IV recurrent major depressive disorder (MDD). METHODS: Eighty-seven young adults with a current episode of major depression and at least one previous episode of depression were recruited from consecutive referrals to a psychiatric clinic. Diagnoses were based on the Structured Clinical Interview for DSM-IV (SCID-1) and recently proposed structured diagnostic criteria for BSD. All patients also completed the borderline questions from the screening questionnaire of the International Personality Disorders Examination (IPDE). RESULTS: Diagnostically, the cohort of 87 patients divided into three groups: 14 with BPAD; 27 with BSD; and 46 with MDD. None of the subjects fulfilled DSM-IV or ICD-10 diagnostic criteria for personality disorder and all three groups were well matched in terms of age, gender distribution, ethnicity, socioeconomic and educational status, age at onset of illness, and severity of index depressive episode. Both of the bipolar-depressed groups reported significantly higher median levels of borderline characteristics than the MDD group (p<0.0001). Three of the borderline characteristics emerged as potentially useful in differentiating bipolar depression from unipolar depression: 'I've never threatened suicide or injured myself on purpose' (sensitivity=0.93; positive predictive value [PPV]=56.7); 'I have tantrums or angry outbursts' (sensitivity 0.66; PPV=65.6%); and 'Giving in to some of my urges gets me into trouble' (sensitivity=0.76; PPV=59.6%). LIMITATIONS: All of the subjects were recruited from a university health service clinic and as such are unlikely to be representative of patients from more diverse socio-economic backgrounds. No structured diagnostic assessment of personality disorder was administered. The diagnostic criteria for BSD are not yet fully validated. CONCLUSIONS: Young adults with bipolar depression exhibit significantly higher levels of borderline personality pathology than those with unipolar depression. Those borderline screening questions that reflect cyclothymic characteristics or depressive mixed states may be of practical use to clinicians in helping to differentiate between bipolar depression and unipolar depression in young adults.     

Prevalence, course, and comorbidity of insomnia and depression in young adults

STUDY OBJECTIVES: (1) To describe the prevalence and prospective course of insomnia in a representative young-adult sample and (2) to describe the cross-sectional and longitudinal associations between insomnia and depression. DESIGN: Longitudinal cohort study. SETTING: Community of Zurich, Switzerland. PARTICIPANTS: Representative stratified population sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The Zurich Study prospectively assessed psychiatric, physical, and sleep symptoms in a community sample of young adults (n=591) with 6 interviews spanning 20 years. We distinguished 4 duration-based subtypes of insomnia: 1-month insomnia associated with significant distress, 2- to 3-week insomnia, recurrent brief insomnia, and occasional brief insomnia. The annual prevalence of 1-month insomnia increased gradually over time, with a cumulative prevalence rate of 20% and a greater than 2-fold risk among women. In 40% of subjects, insomnia developed into more chronic forms over time. Insomnia either with or without comorbid depression was highly stable over time. Insomnia lasting 2 weeks or longer predicted major depressive episodes and major depressive disorder at subsequent interviews; 17% to 50% of subjects with insomnia lasting 2 weeks or longer developed a major depressive episode in a later interview. "Pure" insomnia and "pure" depression were not longitudinally related to each other, whereas insomnia comorbid with depression was longitudinally related to both. CONCLUSIONS: This longitudinal study confirms the persistent nature of insomnia and the increased risk of subsequent depression among individuals with insomnia. The data support a spectrum of insomnia (defined by duration and frequency) comorbid with, rather than secondary to, depression.     

Impaired dynamic cerebral autoregulation in young adults with mild depression

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18–35 years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty-three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression.     

The high prevalence of bipolar spectrum disorders in young adults with recurrent depression: toward an innovative diagnostic framework

BACKGROUND: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. METHODS: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off > or =8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. RESULTS: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. LIMITATIONS: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi's BSD construct. CONCLUSIONS: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile.     

Symptoms of depression among adolescents and young adults

The authors evaluated the depressive symptomatology of 26 adolescent and 27 young adult, hospitalized patients meeting Research Diagnostic Criteria for Major Depressive Disorder. Few differences were found between these two groups with regard to either symptoms or subtypes of depression. Overall, these data indicate that Major Depressive Disorder can be easily identified in younger samples using established criteria. We also report a particularly high percentage of endogenous subtype among our patients. The RDC endogenous subtype of depression among younger inpatients may be more frequent than generally realized.     

Psychiatric treatment seeking and psychosocial impairment among young adults with depression

BACKGROUND: We report data on 1-year prevalence and comorbidity of depression, related impairment, treatment need, and psychiatric treatment among young adults. METHODS: A sample of young urban adults (n=245) mean age 21.8 years was screened from a baseline population of 706 high-school students and given a semistructured clinical interview to evaluate 12-month prevalence of depression, psychosocial functioning according to DSM-IV GAF scale, need for psychiatric treatment, and use of mental health services. RESULTS: One in 10 young adults suffered from depression with associated psychosocial impairment, the female-to-male-ratio being approximately 2:1. Most depressive disorders were comorbid with other DSM-IV disorders, depression usually occurring secondary to other disorders. Comorbidity was related to impairment, treatment need, and treatment contacts. Less than half of the depressed young adults had ever contacted mental health services, and less than one-third reported treatment contacts during the index episode. Males were less likely than females to report previous treatment contacts or intention to refer to mental health services for their problems, but treatment contacts during the index episode were reported equally often by both sexes. CONCLUSIONS: A minority of the severely depressed young adults with associated impairment had sought treatment. Except for subjects with dysthymia, no gender difference emerged in treatment contact rates during the 12-month depression episode. Comorbidity showed important clinical implications by its relation to severity of depression and treatment contacts.     

Genetic segregation analysis of recurrent, early-onset major depression: evidence for single major locus transmission

Coordinated efforts are now underway to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders. These studies have focused on recurrent, early-onset MDD (RE-MDD), thought to be the most familial form of this disorder. The goal of this study was to conduct a complex segregation analysis of recurrent MDD and other major mood disorders aggregating in families identified by probands with RE-MDD. Eighty-one families were identified through probands over the age of 18 who met criteria for recurrent (> or =2 episodes), early-onset (< or =25 years), nonpsychotic, unipolar MDD (RE-MDD) and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best-estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Segregation analyses were performed using the REGD routine in S.A.G.E. release 4.0. The segregation analysis of recurrent MDD supported a sex-independent Mendelian codominant model. Analysis of major mood disorders supported a sex-independent Mendelian dominant model. Interestingly, inclusion of spousal residual correlations provided better fitting models for recurrent MDD but not the broader phenotype of major mood disorders. Unlike unipolar MDD, the lifetime prevalence of bipolar I disorder in this sample of families did not exceed the reported population prevalence [Zubenko et al., 2001]. Our results suggest that a major locus contributes to the expression of recurrent MDD and possibly other major mood disorders within families identified by probands with RE-MDD. Due to the limitations of the segregation analysis model, our results cannot address whether the same major locus is segregating across families in our sample or whether multiple major loci are involved (genetic heterogeneity). The absence of aggregation of bipolar I disorder in these families strongly suggests that while the genetic determinants of unipolar and bipolar disorders may overlap, they are not identical. Our findings illustrate the advantage of employing families identified by probands with RE-MDD in studies designed to detect susceptibility loci for unipolar MDD and related disorders.     

A comparison of the familiality of chronic depression in recurrent early-onset depression pedigrees using different definitions of chronicity

BACKGROUND: The study of chronicity in the course of major depression has been complicated by varying definitions of this illness feature. Because familial clustering is one component of diagnostic validity we compared family clustering of chronicity as defined in the DSM-IV to that of chronicity determined by an assessment of lifetime course of depressive illness. METHODS: In 1750 affected subjects from 652 families recruited for a genetic study of recurrent, early-onset depression, we applied several definitions of chronicity. Odds ratios were determined for the likelihood of chronicity in a proband predicting chronicity in an affected relative. RESULTS: There was greater family clustering of chronicity as determined by assessment of lifetime course (OR=2.54) than by DSM-IV defined chronic major depressive episode (MDE) (OR=1.93) or dysthymic disorder (OR=1.76). In families with probands who had preadolescent onset of MDD, familiality was increased by all definitions, with a much larger increase observed for chronicity by lifetime course (ORs were 6.14 for lifetime chronicity, 2.43 for chronic MDE, and 3.42 for comorbid dysthymic disorder). Agreement between these definitions of chronicity was only fair. LIMITATIONS: The data used to determine chronicity were collected retrospectively and not blindly to relatives' status, and assessment of lifetime course was based on global clinical impressions gathered during a semi-structured diagnostic interview. Also, it can be difficult to determine whether individuals with recurrent major depressive episodes who frequently experience long periods of low grade depressive symptoms meet the strict timing requirements of DSM-IV dysthymic disorder. CONCLUSIONS: An assessment of lifetime symptom course identifies a more familial, and thus possibly a more valid, type of chronic depression than the current DSM-IV categories which are defined in terms of particular cross-sectional features of illness.     

Sleep quality in young adults with very low birth weight--the Helsinki study of very low birth weight adults

Objective To assess the relationship between very low birthweight (VLBW; <1,500 g) and quality and amount of sleep inyoung adults. Methods We compared 89 VLBW and 78 term-born19- to 26-year-old adults, by actigraphy and the Basic NordicSleep Questionnaire. Results There were no group differencesin sleep quality or amount (p's >.15), although VLBW adultswent to bed on average 36 min earlier (95% confidence interval6–66 min). Shorter gestational age was related to longersleep latency both within VLBW (standardized regression coefficientβ = –.36, p =.040) and term-born adults (β =–.25, p =.029). Conclusion Adults with VLBWhad similar quality and amount of sleep as those born at term,although VLBW adults went to bed earlier, suggesting an advancedsleep phase. Within each group, a lower gestational age wasrelated to a longer sleep onset.     

Lower resting cardiac autonomic balance in young adults with current major depression

Research on cardiac autonomic function in major depressive disorder (MDD) has predominantly examined cardiac vagal control and adopted a model of reciprocal autonomic balance. A proposed bivariate autonomic continuum uses cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) models, derived from normalized values of respiratory sinus arrhythmia and pre‐ejection period, to more adequately index patterns of autonomic control. The purpose of this study was to assess resting levels of CAB and CAR among young adults with and without a current diagnosis of major depression. One hundred forty‐two young adults (n = 65 MDD, n = 77 healthy controls; 20.8 ± 2.6 years) completed a structured diagnostic interview, cardiovascular assessment, and a maximal aerobic fitness test. The findings revealed that CAB, but not CAR, significantly predicted current MDD status (OR = 0.70, 95% CI [0.53, 0.93]), an effect that remained after controlling for aerobic fitness and body mass index. Although CAB was found to be a significant predictor of current MDD status among a sample of young adults, there remained substantial variation in autonomic control that was not captured by the traditional model of reciprocal autonomic balance.     

Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression.

We previously described the results of a genome-wide linkage survey for genetic loci that influenced the development of unipolar mood disorders in 81 families identified by individuals with Recurrent, Early-Onset, Major Depressive Disorder (RE-MDD) [Zubenko et al. 2003b; Am J Med Genet (Neuropsychiatr Genet) 123B:1-18]. In the current study, we extended this linkage analysis by including the history of a suicide attempt as a covariate to identify chromosomal regions that harbor genes that influence the risk of this behavior in the context of mood disorders. This approach identified six linkage peaks with maximum multipoint DeltaLOD scores that reached genome-wide adjusted levels of significance (2p, 5q, 6q, 8p, 11q, and Xq). Four of these (2p, 6q, 8p, and Xq) exceeded the criterion for "highly-significant linkage" (genome-wide adjusted P < 0.001) recommended by Lander and Kruglyak [1995; Nat Genet 11:241-246]. The strongest evidence for linkage was observed in analyses employing affected relative pairs (ARPs) with the most severe and disabling Mood Disorders: Depression Spectrum Disorder and RE-MDD. The highest DeltaLOD score that emerged from this linkage analysis, 5.08, occurred for ARPs with Depression Spectrum Disorder at D8S1145 (37.0 cM, 18.2 Mbps, P < 0.0001) at cytogenetic location 8p22-p21. Significant linkage results on Xq arose from analyses of ARPs with RE-MDD at DXS1047 (143 cM, 127.8 Mbps, DeltaLOD = 3.87, P < 0.0001), a finding that may contribute to the higher rate of suicide attempts among women than men. These findings provide evidence for suicide risk loci that are independent of susceptibility loci for Mood Disorders, and suggest that the capacity for suicide risk loci to affect the development of suicidal behavior depends on the psychiatric disorder or subtype with which they interact.     

High prevalence of Helicobacter pylori in the Alaska native population and association with low serum ferritin levels in young adults

Iron deficiency anemia is a common public health problem in the Alaska Native population. Yet, a clear etiology has eluded researchers for decades. Previous studies suggested a link between Helicobacter pylori infection, gastrointestinal blood loss due to hemorrhagic gastritis, and generalized iron deficiency anemia in adult Alaska Natives. Therefore, we examined the association between the prevalence of H. pylori-specific immunoglobulin G (IgG) and serum ferritin levels, a marker of iron deficiency. A random sample of 2,080 serum samples from Alaska Native residents drawn between 1980 and 1986 from residents in 13 regions was selected, and the samples were stratified by age, sex, and region. Overall, 75% were positive for H. pylori-specific IgG. The rate of H. pylori seropositivity increased with age; by age 14 years, 78% of the residents were positive. There were no gender differences in H. pylori seropositivity. However, marked regional differences were observed. Serum ferritin levels of <12 ng/ml were found most commonly among persons <20 years of age and among women of childbearing age. A significant association between low serum ferritin levels and prevalence of H. pylori-specific IgG was found, particularly for people aged less than 20 years. H. pylori may be a factor contributing to the iron deficiency anemia in the Alaska Native population.     

Genome survey for susceptibility loci for recurrent, early-onset major depression: results at 10cM resolution

Recurrent (two or more episodes), early-onset (first episode at < or = 25 years) major depressive disorder (RE-MDD) is a strongly familial condition (lambda(first-degree relatives) = 8) whose malignant effects have a significant negative impact on the health and longevity of patients and their family members. The goal of this study was to identify candidate susceptibility loci that influence the development of RE-MDD. We completed a systematic survey of the human genome, conducted at an average resolution of 10 cM, for the identification of simple sequence tandem repeat polymorphisms (SSTRPs) that target susceptibility genes for RE-MDD by virtue of linkage disequilibrium. The efficiency of our association study was enhanced by genotyping pools of DNA from 100 adults with RE-MDD and 100 adult controls who had no personal or family history of mental disorders. Both groups included equal numbers of Caucasian men and women and were matched as closely as possible for age and ethnicity. Allelic associations with RE-MDD were observed for 19 of the 387 SSTRPs in the CHLC Human Screening Set/Weber Version 9. Sixteen of the 19 candidate susceptibility loci revealed significant allelic associations with RE-MDD in men (n = 7) or women (n = 9), but not in both sexes. Evidence for both risk and protective alleles was detected. Two of the candidate susceptibility loci reside within several Mb of loci previously reported-megabases to be linked to "comorbid alcoholism and depression" in families of individuals with alcoholism and to a broadly defined affected phenotype that included recurrent major depression in the families of patients with bipolar disorder. Although it has been suggested that the genes that influence risk for MDD in the two sexes may not be entirely the same, the results of our study suggest that sex specificity of susceptibility loci for RE-MDD may be the rule rather than the exception. The observed preponderance of sex-specific susceptibility loci for RE-MDD suggests that there may be important differences in the molecular pathophysiology of RE-MDD in men and women. Alternatively, our findings may reflect the existence of sex-specific differences in the molecular mechanisms that determine resilience to endogenous or environmental depressogenic stimuli.     

Effects of a secondary task on obstacle avoidance in healthy young adults

Research on attention and gait stability has suggested that the process of recovering gait stability requires attentional resources, but the effect of performing a secondary task on stability during obstacle avoidance is poorly understood. Using a dual-task paradigm, the present experiment investigated the extent to which young adults are able to respond to a secondary auditory Stroop task (requiring executive attentional network resources) concurrently with obstacle crossing during gait when compared with performing unobstructed walking or sitting (control task). Our results demonstrated that as the level of difficulty in the postural task increased, there was a significant reduction in verbal response time from congruent to incongruent conditions in the auditory Stroop task, but no differences in gait parameters, indicating that these postural tasks require attention, and that young adults use a strategy of modulating the auditory Stroop task performance while keeping stable gait performance under the dual-task situations. Our findings suggest the existence of a hierarchy of control within both postural task (obstacle avoidance requires the most information processing resources) and dual-task (with gait stability being a priority) conditions.     

Linkage and association analysis of chromosomal regions containing genes related to neuroendocrine or serotonin function in families with early-onset,recurrent major depression

Recurrent unipolar depression with an early age of onset is a severe form of unipolar depression that has both genetic and environmental components. We genotyped the members of 16 families identified by probands with early onset (⩽25 years), recurrent unipolar, major depression for 38 simple sequence tandem repeat polymorphisms (SSTRPs) from chromosomal regions containing 12 genes involved in neuroendocrine or serotonergic functioning. Pairwise linkage analysis was performed with the software package FASTLINK. The affected phenotype was defined four ways, and both dominant and recessive models of depression were analyzed. Seven SSTRPs showed lod scores >1.00 at θ values between 0.10–0.20. The members of an additional 18 families were genotyped for these seven SSTRPs, and the complete sample of 34 families was evaluated using lod score analysis, affected pedigree member linkage analysis, and within-family association analysis. Evidence for linkage between D11S929 and affective illness remained positive, necessitating the analysis of four additional SSTRPs within 3 cM of D11S929. After all confirmatory analyses were completed, no evidence suggestive of linkage remained between any of the 38 SSTRPs and the affected phenotypes. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:443–449, 1998. © 1998 Wiley-Liss, Inc.