High Risk For Affective Disorders Research Articles

Weighing poor immunometabolic health in relatives for severity of affective symptoms: A study of patients with depressive and anxiety disorders and their siblings

BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands’ immunometabolic health on siblings’ psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. ResultsIn siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. ConclusionsOur findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.

Associations Between Parental Mood and Anxiety Psychopathology and Offspring Brain Structure: A Scoping Review.

A family history of mood and anxiety disorders is one of the most well-established risk factors for these disorders in offspring. A family history of these disorders has also been linked to alterations in brain regions involved in cognitive-affective processes broadly, and mood and anxiety disorders specifically. Results from studies of brain structure of children of parents with a history of mood or anxiety disorders (high-risk offspring) have been inconsistent. We followed the PRISMA protocol to conduct a scoping review of the literature linking parental mood and anxiety disorders to offspring brain structure to examine which structures in offspring brains are linked to parental major depressive disorder (MDD), anxiety, or bipolar disorder (BD). Studies included were published in peer-reviewed journals between January 2000 and July 2021. Thirty-nine studies were included. Significant associations between parental BD and offspring caudate volume, inferior frontal gyrus thickness, and anterior cingulate cortex thickness were found. Associations were also identified between parental MDD and offspring amygdala and hippocampal volumes, fusiform thickness, and thickness in temporoparietal regions. Few studies have examined associations between parental anxiety and high-risk offspring brain structure; however, one study found associations between parental anxiety symptoms and offspring amygdala structure, and another found similar associations with the hippocampus. The direction of grey matter change across studies was inconsistent, potentially due to the large age ranges for each study and the non-linear development of the brain. Children of parents with MDD and bipolar disorders, or elevated anxiety symptoms, show alterations in a range of brain regions. Results may further efforts to identify children at high risk for affective disorders and may elucidate whether alterations in specific brain regions represent premorbid markers of risk for mood and anxiety disorders.

Occupational status and hospitalisation for mental disorders: findings from Friuli Venezia Giulia region, Italy, 2008–2017

Purpose: To investigate to which extent occupational status, and job titles, were associated with types of hospitalisations and psychiatric diagnoses among inpatients of Friuli Venezia Giulia Region, Italy.Methods: Cross-sectional study based on 10 years register data (2008–2017) on 2929 subjects hospitalised in General Hospital Psychiatric Units. Odds ratios (OR) of hospitalisations and psychiatric diagnoses for occupational status and job titles were calculated by logistic regression analysis.Results: Employed were at lower risk of urgent and involuntary hospitalisation. The risk of urgent hospitalisation was higher for affective, organic or other disorders, while all psychiatric diagnoses were at lower risk of involuntary hospitalisation than psychosis. Using white collars as reference category, army showed a higher risk for urgent hospitalisation (OR = 2.3) and affective disorders (OR = 1.9). A higher risk for affective disorders was found in managers (OR = 2.0). Blue collars were at higher risk for alcohol and substance abuse (OR = 1.7).Conclusions: Employment was protective for urgent and involuntary hospitalisations and severe diagnoses. Hospitalisation for affective disorders was more likely in managers, army, and for substances abuse in blue collars. More research is needed to assess the association between specific occupational groups and involuntary hospitalisation.KeypointsEmployment was shown to be a protective factor for both urgent and involuntary hospitalisations and diagnosis of severe mental disorder.Managers, police and military forces were at higher risk of being hospitalised for affective disorders, while blue collars were at higher risk of hospitalisation for alcohol and substances abuse.Future research would benefit from a better analysis on the association between more specific occupational groups and hospitalisation for psychiatric disorders, with a particular focus on involuntary treatment.Further research is needed to compare the risk of hospitalisation for mental disorders in temporary or permanent position, according to recent international changes in labour market and its impact on mental health.

MISOPHONIA, EMOTIONAL DYSREGULATION AND AFFECTIVE DISORDERS: A PRELIMINARY STUDY

Background Misophonia is characterized by aversive reactivity to repetitive and pattern based auditory (and sometimes visual) stimuli1. When faced with stimuli, misophonia sufferers demonstrate autonomic nervous system arousal, accompanied by heightened emotional reactivity. Sufferers describe extreme irritation, the desire to get away from the stimuli (or flee), anger, feelings of helplessness, being overwhelmed, and aggressive urge with physiological reactions including hypertonia, diaphoresis and tachycardia2. Some studies have found comorbidity with psychiatric disorders. However, most of these studies used small samples and very few experimental methodologies3. Despite the paucity of empirically based and large sample studies it is important to study the relationship between affective disorders and their symptoms because people with misophonia suffer from a high level of emotional distress. The purpose of this study is to identify possible overlapping characteristics between misophonia and affective disorders based on DSM-5 and ICD-10 diagnoses. Despite the idiopathic nature of the disorder the small but emerging body of literature begins to contribute to a better understanding of its underlying mechanisms, illuminate nosology, and translate into appropriate treatment methods. Objective The current study identifies (a) the possible relationship between Misophonia and affective disorders (b) if there is any difference between the severity of misophonia in male and female patients. Methods and materials 86 misophonic patients (female=54, mean age= 46.28, SD=1.57) with no history of active substance abuse within 6 months, no prior treatment of any kind, who were free of hormonal and psychotropic medication were recruited in our study. We evaluated the diagnosis of misophonia with A-MISO-S and diagnosis of affective disorders with the M.I.N.I International Neuropsychiatric Interview. Out of 86 patients, 36 participants were excluded from the study due to incomplete questionnaires or unwillingness to continue. Results Among N=50 misophonic patients (major depression = 11, melancholic depression= 5, dysthymia= 11, suicidality= 10, manic= 3, panic disorder= 8, agoraphobia= 5, social phobia= 7, obsessive compulsive disorder= 14, post traumatic stress disorder= 15). Misophonia was associated with MDD (U= 76, p= .001), Suicidality (U= 67, p=.001), OCD (U= 115, p= .002) and PTSD (U=142.5, p=.008) as well as the positive correlation between severity of misophonia and MDD (rs= .486, p Conclusion Misophonia is associated with major depression, suicidality, OCD and PTSD. Our findings highlight the importance of recognizing affective comorbidity among misophonic patients. The presence of these varying affective disorders features with misophonia suggests that while Misophonia has unique clinical characteristics that suggest an underlying neurophysiological mechanism, the sufferers are at high risk for affective disorders. Conversely, when assessing patients with affective disorders is important screen for misophonia symptoms. This will assist researchers, clinicians and sufferers to better understand the nature of their symptoms and how they may be interacting. In addition, from this small sample, it appears that women experience more severe misophonic symptoms than men.

Intellectual Functioning in Offspring of Parents with Bipolar Disorder: A Review of the Literature.

Impaired intellectual functioning is an important risk factor for the emergence of severe mental illness. Unlike many other forms of mental disorder however, the association between bipolar disorder and intellectual deficits is unclear. In this narrative review, we examine the current evidence on intellectual functioning in children and adolescents at risk for developing bipolar disorder. The results are based on 18 independent, peer-reviewed publications from 1980 to 2017 that met criteria for this study. The findings yielded no consistent evidence of lower or higher intellectual quotient (IQ) in offspring of parents diagnosed with bipolar disorder. Some tentative evidence was found for lower performance IQ in offspring of bipolar parents as compared to controls. It is recommended that future research examine variability in intellectual functioning and potential moderators. These findings demonstrate the need to examine how intellectual functioning unfolds across development given the potential role of IQ as a marker of vulnerability or resilience in youth at high risk for affective disorders.

Misophonia and affective disorders: The relationship and clinical perspective

Misophonia is characterized by aversive reactivity to repetitive and pattern based auditory stimuli [1]. Misophonic sufferers demonstrate autonomic nervous system arousal, accompanied by heightened emotional distress. Sufferers describe extreme irritation, anger, and aggressive urge with physiological reactions including hypertonia, diaphoresis and tachycardia [2]. Some studies have found comorbidity with psychiatric disorders. However, most of these studies used small samples and few experimental methodologies [3]. This study identifies the possible relationship between misophonia and affective disorders, and any difference between the severity of misophonia in male and female patients. Fifty misophonic patients (female = 25, mean age = 46.28) were evaluated with Amsterdam Misophonia Scale (A-MISO-S) for the diagnosis of misophonia and with the M.I.N.I International Neuropsychiatric Interview for the diagnosis of affective disorders. Among n = 50 misophonic patients, we found major depression (MDD) = 11, melancholic depression = 5, dysthymia = 11, suicidality = 10, manic = 3, panic disorder = 8, agoraphobia = , social phobia = , obsessive compulsive disorder (OCD) = 14, post-traumatic stress disorder (PTSD) = 15. Misophonia was associated with MDD (U = 76, P = .001), suicidality (U = 67, P = .001), OCD (U = 115, P = .002) and PTSD (U = 142.5, P = .008). There was an indication of a significant difference between men and women in severity of misophonia (U = 160.5, P = .002). The presence of these varying affective disorders suggests that the sufferers are at high risk for affective disorders. Investigation of the co-morbidity will assist researchers to better understand the nature of the symptoms and how they may be interacting.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Neural Mechanism and Neurobiological Basis of Harm Avoidance

Harm avoidance is a type of trait anxiety which is defined as a tendency to respond intensely to aversive stimuli signals and to learn to passively avoid punishment. The tendency is associated with ruminating about future outcomes and being careful in uncertain situations as well as facing a higher risk for affective disorders. The neural network involving in harm avoidance includes the network including the frontal lobe, the parietal lobe and the anterior cingulate cortex; the junction between cortex and amygdala and the structural connectivity in white matter pathways. Not only one polymorphism but also the interaction of different polymorphisms can have influence on the harm avoidance. The future research should focus on the association of neural mechanism with neurobiological basis of harm avoidance and the interaction of multiple polymorphisms, inspect the moderating effect of other factors and the relation among the subscale of harm avoidance as well as research other receptor subtypes of serotonin and rehabilitation work of it.

Temperament trait Harm Avoidance associates with μ-opioid receptor availability in frontal cortex: A PET study using [11C]carfentanil

Harm Avoidance is a temperament trait that associates with sensitivity to aversive and non-rewarding stimuli, higher anticipated threat and negative emotions during stress as well as a higher risk for affective disorders. The neurobiological correlates of interindividual differences in Harm Avoidance are largely unknown. We hypothesized that variability in Harm Avoidance trait would be explained by differences in the activity of μ-opioid system as the opioid system is known to regulate affective states and stress sensitivity. Brain μ-opioid receptor availability was measured in 22 healthy subjects using positron emission tomography and [(11)C]carfentanil, a selective μ-opioid receptor agonist. The subjects were selected from a large Finish population-based cohort (N=2075) on the basis of their pre-existing Temperament and Character Scores. Subjects scoring consistently in the upper (10) and lower (12) quartiles for the Harm Avoidance trait were studied. High Harm Avoidance score associated with high μ-opioid receptor availability (i.e. lower endogenous μ-opioid drive) in anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices and anterior insular cortex. These associations were driven by two subscales of Harm Avoidance; Shyness with Strangers and Fatigability and Asthenia. In conclusion, higher Harm Avoidance score in healthy subjects is associated with higher μ-opioid availability in regions involved in the regulation of anxiety as well as in the control of emotions, affective component of pain and interoceptive awareness. The results have relevance in the research of vulnerability factors for affective disorders.

Variants within the GABA transaminase (ABAT) gene region are associated with somatosensory evoked EEG potentials in families at high risk for affective disorders

Depression frequently co-occurs with somatization, and somatic complaints have been reported as a vulnerability marker for affective disorders observable before disease onset. Somatization is thought to result from an increased attention to somatic sensations, which should be reflected in long-latency somatosensory evoked electroencephalogram (EEG) potentials (SSEPs) at the physiological level. Previous studies revealed that SSEPs are altered in depressed patients and suggested late SSEP components as vulnerability markers for affective disorders. Neurotransmitters such as serotonin, γ-aminobutyric acid (GABA) and the neuropeptide substance P may play an important role for both affective disorders and somatosensory processing. Method We investigated the associations between SSEPs and polymorphisms within candidate genes of the serotonergic, GABAergic as well as the substance P system in subjects at high risk for affective disorders. The sample was composed of high-risk families participating in the Munich Vulnerability Study and genetic association analyses were calculated using qfam (family-based association tests for quantitative traits) implemented in PLINK 1.05. We observed significant associations (false discovery rate <0.05) withstanding correction for multiple testing between late SSEP components (response strength 170-370 ms after stimulation) and four single nucleotide polymorphisms within the GABA transaminase (ABAT) gene region coding for a protein responsible for GABA degradation. No effects were found with the classical disease trait approach, suggesting SSEP marker specificity of the observed associations. Our findings point to a possible role of ABAT gene-regulated GABA catabolism for an altered processing of somatosensory stimuli as a potential vulnerability marker for affective disorders.

Long‐term effects of differential early rearing in rhesus macaques: Behavioral reactivity in adulthood

Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP). We tested 22 rhesus monkeys who were either nursery-reared (NR) or reared with their mothers (mother-reared; MR). NR monkeys were inhibited in their behavior compared to MR monkeys, with reduced locomotion and exploratory behaviors. NR animals showed a marginal increase in freezing. Together these findings demonstrate that the consequences of differential infant rearing experience on socioaffective behavior persist into adulthood, with evidence of greater inhibition in NR monkeys.

P03-474 - Affective temperaments, white matter hyperintensities and suicidal risk in patients with mood disorders

IntroductionPatients with white matter hyperintensities (WMHs) may be at higher risk for affective disorders and suicidal behaviour and affective temperaments may play a significant role in mood disorders.Objectives, aims, methodsRecently, we conducted a study in a sample of 247 patients with major affective disorders consecutively admitted as psychiatric inpatients.ResultsWe found that those with higher dysthymia and lower hyperthymia were more likely to have higher BHS scores, more WMHs, higher MINI suicidal risk, and more recent suicide attempts than patients with higher hyperthymia and lower dysthymia. Previously, we have reported that depressive, cyclothymic, irritable and anxious temperaments are risk factors whereas the hyperthymic temperament is a protective factor for suicidal behaviour, at least for suicide attempters. This is in line with recent genetic studies showing that the short allele of serotonin transporter gene promoter (5-HTTLPR) was significantly related to depressive, cyclothymic, irritable and anxious temperaments (but not to the hyperthymic temperament) and individuals with the short allele of the 5-HTTLPR and major affective disorders have more microstructural white matter abnormalities in specific brain regions.ConclusionsIn subjects with mood disorders, some temperament profiles in addition to WMHs presumably play a critical role in the emergence of hopelessness and suicidal behaviour. Differences among temperament profiles associated with WMHs may be used as biological markers for clinically grouping subjects at higher risk both for the emergence of mood disorders and suicidal behaviour (highly lethal suicide attempts) and this may have relevant implications for treatment.

Affective temperamental profiles are associated with white matter hyperintensity and suicidal risk in patients with mood disorders

Background Patients with white matter hyperintensities (WMH) may be at higher risk for affective disorders and suicide. Affective temperaments may play a significant role in mood disorders. This study aimed to evaluate the eventual association between WMH, affective temperaments and suicidal behaviour in major affective disorder. Methods A total of 318 patients with major affective disorders were consecutively admitted as psychiatric inpatient. A total of 247 were included and given, brain magnetic resonance imaging (MRI) and assessed with the Mini International Neuropsychiatric Interview (MINI), the Beck Hopelessness Scale (BHS), the Hamilton Depression Rating Scale (HDRS 17), the Young Mania Rating Scale (YMRS) and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A). Results A total of 48% of patients had periventricular WMH (PWMH) and 39% of them had deep WMH (DWMH). Patients with higher dysthymia and lower hyperthymia (H-DCIA group) were more likely to have higher BHS scores (BHS ≥ 9 = 77% vs. 52%; p > 0.001), more WMH (46% vs. 29%; χ 2 n = 3 = 9.90; p < 0.05), higher MINI suicidal risk (54% vs. 42%; p < 0.05), and more recent suicide attempts (24% vs. 14%; p < 0.05), than patients with higher hyperthymia and lower dysthymia (H-H group). Limitations The small sample size did not allow the generalization of the present findings. Conclusions Differences among temperament groups measured by the TEMPS-A are associated with differences in their MRIs, indicating that different temperament profiles are associated with differences in the subcortical structures of the brain. The implications of the results were discussed.

Polymorphisms within the 4-aminobutyrate aminotransferase gene are associated with long-latency somatosensory potentials in families vulnerable for affective disorders

Depression is known to frequently co-occur with somatic symptoms and data from the Munich Vulnerability Study pointed to somatization as a possible vulnerability marker for affective disorders observable before disease onset. In this context previous studies furthermore revealed long-latency somatosensory evoked potentials (SSEP) to be a potential marker for susceptibility to depressive disorder. Based on this evidence we performed a small family-based association study to investigate genetic associations between long-latency SSEP and polymorphisms within candidate gene regions of somatosensory pathways including the serotonergic, GABAergic as well as the substance P system. The sample was composed of families at high risk for affective disorders who were participating in the Munich Vulnerability Study. We observed significant associations between average SSEP response strength in the long-latency range and polymorphisms within the 3' untranslated region of the 4-aminobutyrate aminotransferase gene coding for a protein responsible for GABA degradation. These findings point to a possible role of GABA catabolism in processing of somatosensory stimuli as well as for bodily misperceptions in connection with vulnerability for affective disorders.

The Munich vulnerability study on affective disorders: premorbid psychometric profile of affected individuals.

We conducted a longitudinal high-risk study to identify psychometric vulnerability markers for affective disorders. We examined 82 healthy subjects [high-risk probands (HRPs)] with at least one first-degree relative suffering from an affective disorder. The premorbid psychometric profile of 20 HRPs who developed a psychiatric disorder during follow-up was compared with the profile of control subjects without personal and family history of psychiatric disorders matched for age and gender. Somatization, complaints (vegetative lability), and perception of strain are increased in HRPs who developed a psychiatric disorder. These alterations were not influenced by the time interval until the onset of the disorder. The premorbid psychometric profile in subjects at high risk for affective disorders is characterized by somatization, complaints, and elevated perception of strain. Together with previous findings our results suggest that these alterations can be regarded as potential vulnerability markers for affective disorders.

Parental attitudes towards early intervention in children at high risk for affective disorders

Background: Parents volunteered to complete surveys on attitudes toward treatment intervention in children at a theoretically high (20–30%) or very high (70%) risk for affective disorders because of an assumed uni-lineal or bi-lineal family history of bipolar illness. Methods: Questions focused on examining at what ages and stage of symptom and syndrome evolution parents would wish their child to begin treatment with different types of therapeutic approaches and clinical trial designs. Sixty percent of the respondents had a personal history of unipolar or bipolar affective disorders. Results: In 156 completed surveys, 83% of parents favored acute medication intervention and 67% favored long-term medication treatment for those children at very high risk at or before the development of severe symptoms (i.e. even prior to meeting full diagnostic thresholds). On the average, parents indicated that they would enter their child in a trial of: two types of psychotherapy at a point in illness evolution between moderate and severe symptoms, two types of open medications between severe symptoms and a definite diagnosis, two blind medications at a definite diagnosis, and a blind trial of placebo and medication after a definite diagnosis but before multiple recurrences of the illness. Parents, primarily on the basis of perceived safety, would allow their children to use medications that have been found to be effective in adults. Limitations: In addition to a number of methodological limitations, responders to the survey were self-selected. Conclusions: The results indicate a willingness on the part of most parents to treat a child at high risk for affective illness early in the course of symptom evolution, even prior to a full syndromic illness or diagnosis. This and other parental views of the risk–benefit and ethical dimensions of early intervention may be helpful in the initiation and design of studies aimed at assessing the efficacy of early interventions in childhood-onset bipolar illness and its prodromes.

The pre-morbid psychometric profile is stable over time in subjects at high familial risk for affective disorders

Background: The pre-morbid personality profile `autonomic lability' (e.g. elevated neuroticism, frequent somatic complaints and increased interpersonal sensitivity) is suggested to be an antecedent of major depression. Recently, we reported that the psychometric profile of healthy first-degree relatives of patients with an affective disorder (so-called high-risk probands; HRPs) was characterized by the personality trait `rigidity' in association with `autonomic lability' and speculated that such a profile might be a potential candidate for a true vulnerability marker for affective disorders. Because one major prerequisite for any valid vulnerability marker is its stability over time, we re-examined our HRPs about four years after index assessment. Methods: Sixteen HRPs from the initial sample ( n=54) participated in the follow-up investigation which, on average, took place 47 months after index assessment. All these HRPs had remained mentally healthy during the follow-up period. Results: The psychometric profile was remarkably stable over the four-year period when considering the total group of the 16 HRPs. On an individual level, similar findings were obtained. Allowing a fluctuation within a narrowly defined `band width', a constancy of the self-ratings was found in 75% of the HRPs, within a broader `band width' this was the case in 88% of the HRPs. Limitations: The power of the present observations appears to be somewhat limited due to the still small sample size of HRPs re-investigated and the fact that the control probands were not yet re-examined. Conclusions: The present follow-up findings in 16 probands at high risk for an affective disorder indicate a sufficient stability of the psychometric profile over time, so that this requirement for a true vulnerability marker is fulfilled.

Vulnerability of Jews to affective disorders

Psychiatric literature over the past 100 years suggests that Jews are at higher risk for affective disorders than numbers of other religious groups. To examine these claims, the authors analyzed data from the National Institute of Mental Health Epidemiologic Catchment Area (ECA) study. In addition, the relationships among gender, alcoholism, and major depression were investigated. The period prevalence and lifetime rates of DSM-III major depression among Jews, Catholics, Protestants, individuals in other religious groups, and individuals with no religious affiliation were examined in the Los Angeles and New Haven, Conn., ECA data. Logistic regression with covariates for site, gender, marital status, and socioeconomic status was used to estimate odds ratios and 95% confidence intervals. The calculated rates, based on the combined data from ECA study waves 1 and 2 for the white population, were weighted according to the 1980 U.S. population census. Female-to-male rate ratios and rates of alcohol abuse/dependence were also obtained. While no differences were found among females, Jewish males had significantly higher rates of major depression than Catholics, Protestants, and all non-Jews combined. Jews had a 1:1 female-to-male ratio for major depression, in contrast to the other religious groups, which approached the universal 2:1 ratio. Rates of alcohol abuse/dependence were inversely related to rates of major depression. The results support only in part the earlier reports that Jews have higher rates of depression. The equal gender distribution of major depression among Jews may be associated with the lower rate of alcoholism among Jewish males.

Pre-morbid psychometric profile of subjects at high familial risk for affective disorder.

Recent observations indicate that a certain pre-morbid personality profile ('autonomic lability', i.e. elevated neuroticism, frequent somatic complaints and increased interpersonal sensitivity) appears to be a valid antecedent of major depression. However, most of these prospective studies used samples drawn from the general population, which limits the power of any observed differences between subjects who developed a depressive disorder during the follow-up period and those who did not. We investigated the psychometric profile of 54 high-risk probands (aged between 18 years and 45 years) without a current or lifetime diagnosis of any psychiatric disorder, but who had first-degree relatives with an affective disorder according to DSM-III-R criteria. Twenty-two control probands, matched for age and gender and without any personal or family history of psychiatric disorders, served as the reference group. As a group, the high-risk probands scored higher than the controls on scales that assessed neuroticism, rigidity, depressive cognitions, vegetative lability and stress. With an individual-orientated approach (cluster analysis), 30 high-risk probands were identified as conspicuous, characterized by elevated rigidity and increased 'autonomic lability'. The remaining 24 high-risk probands showed a psychometric profile very similar to that of the controls. The present findings in 54 probands at high risk for affective disorders not only strongly underline the assumption that the personality trait 'autonomic lability' is a valid antecedent of at least major depression, but also add the personality trait 'rigidity' as a further and potential candidate for a true vulnerability marker for affective disorders.

Are schizoaffective psychoses heterogeneous?: Results of a genetic investigation, II

150 schizoaffective probands and their 1029 first-degree relatives were examined in search of the heterogeneity of the disorder. The sample of probands was split by several criteria. Among the various subgroups the morbidity risk of relatives was analysed as an external criterion for heterogeneity. Female relatives show a higher risk for affective disorders than male relatives. This is true for relatives of male and female index patients. Schizophrenia is equally frequent in male and female relatives. Schizoaffective psychoses take an intermediate position. The further analysis included the following characteristics of the probands: age at first episode, number of episodes, psychopathological subtypes (affective, schizophrenic, undifferentiated: manic, non-manic). None of these criteria proved to distinguish subgroups significantly, therefore, the search for heterogeneity was negative, although some results show a trend to the expected direction.