Subthreshold Syndromes Research Articles

Developmental transitions to psychopathology: are there prodromes of substance use disorders?

One of the conceptual difficulties faced by developmental psychopathologists is the plethora of terms for “things that predate the full manifestation of a psychiatric disorder.” We have causes, vulnerabilities, susceptibilities, antecedents, risk factors, exposures, precursors, sub-threshold syndromes, and, of course, prodromes, the subject of this Annual Review. So we must first be clear as to what the word “prodrome” means, and how it differs from other terms for predictors. Merriam-Webster’s dictionary defines a “prodrome” as a “premonitory symptom of disease,” and “premonitory” as “giving warning.” Conflating these two, we define a prodrome as a “symptom or sign that gives warning that a disease is present prior to the full manifestation of that disease.” A review of medical dictionaries on the web shows consistent references to a prodrome as “An early symptom indicating the onset of an attack or disease”; “a premonitory clinical sign; a clinical sign indicating the onset of a disease”; “a symptom, often noted prior to monitoring and diagnosis that may signal the beginning of a disease”, or “the earliest phase of a developing condition or disease.”(http://medical-dictionary.thefreedictionary.com). Wikipedia provides an example: “…a prodrome is an early non-specific symptom (or set of symptoms) that might indicate the start of a disease before specific symptoms occur. For example fever, malaise, headache and anorexia (lack of desire to eat) frequently occur in the prodrome of many infective disorders“. There is an important objection to the “non-specificity” clause in the Wikipedia definition, because there are some highly specific prodromes. We are thinking here of, for instance, the auras of migraine and epilepsy. In both cases, these are actually symptoms of the pathological process underlying the disorders that appear before the most characteristic and florid symptoms (headaches and seizures respectively), but that sometimes occur without those more florid symptoms following. Indeed, medication in the aural phase of migraine is used to preempt the headaches. An intermediate example is the “bulls-eye” rash of Lyme disease, which may or may not be observed in its characteristic form prior to the onset of the full disease. Interest in prodromes of psychiatric disorders has been revived recently by work to intervene at the prodromal phase of first-onset psychosis (reviewed inOlsen, 2005). The key point here is that a prodrome is consistently defined as a manifestation of the disease itself, but non-specificity is not a necessary part of the definition of a prodrome.

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors

BackgroundThe Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as sociodemographic and somatic characteristics of the sample.MethodsAll 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was collected on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree relatives, whereas the collection of DNA and plasma samples was already part of the original CoLaus survey.ResultsA total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam.ConclusionDespite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders.

Validity and reliability of the Structured Clinical Interview for Depersonalization–Derealization Spectrum (SCI-DER)

This study evaluates the validity and reliability of a new instrument developed to assess symptoms of depresonalization: the Structured Clinical Interview for the Depersonalization-Derealization Spectrum (SCI-DER). The instrument is based on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well as clinical and subsyndromal manifestations. Items of the interview include, in addition to DSM-IV criteria for depersonalization, a number of features derived from clinical experience and from a review of phenomenological descriptions. Study participants included 258 consecutive patients with mood and anxiety disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5% generalized anxiety disorder; 2.7% patients were also diagnosed with depersonalization disorder. A comparison group of 42 unselected controls was enrolled at the same site. The SCI-DER showed excellent reliability and good concurrent validity with the Dissociative Experiences Scale. It significantly discriminated subjects with any diagnosis of mood and anxiety disorders from controls and subjects with depersonalization disorder from controls. The hypothesized structure of the instrument was confirmed empirically.

The generalized anxiety spectrum: prevalence, onset, course and outcome

Generalized anxiety disorder (GAD) is generally considered to be a chronic condition, waxing and waning in severity; however prospective investigation of the course of GAD in community samples is lacking. This study seeks to fill that gap, by identifying the whole spectrum of generalized anxiety syndromes, sub-typing them according to their duration and frequency of occurrence, and evaluating their long-term course and outcome in the community. The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 years at first interview) by six interviews over a period of 20 years (1979-1999). GAD syndromes were defined by DSM-III symptom criteria without applying any exclusion criteria. A spectrum of generalized anxiety was defined by duration: 6 months (DSM-IV), 1 month (DSM-III), < or = 2 weeks (with weekly occurrence over one year), and anxiety symptoms. From 1978 (screening) to 1999 the annual presence of symptoms and treatment was assessed. Persistence of anxiety was defined by the almost daily presence of symptoms over the previous 12 months. The annual incidence of DSM-III GAD increased considerably between the ages of 20 and 40. The average age of onset of symptoms was 15.6 years; in 75% of cases it occurred before the age of 20. 75 of 105 DSM-III GAD cases had at least one follow-up. At their individual last follow-up, 12 of those 75 subjects (16%) were re-diagnosed as having GAD, 22 (29%) manifested subthreshold syndromes or anxiety symptoms, while 39 cases, the majority, (52%) were symptom-free; 5 of the 12 re-diagnosed GAD cases were persistent (corresponding to 7% of all 75 initial GAD cases). In their twenties they were treated at some time in 6% of all years, but in their thirties this figure rose to 12%. At their individual last follow-up 26% of 6-month GAD subjects and 22% of 1-month GAD subjects were still being treated. Treated vs. non-treated subjects did not differ in terms of gender but did differ in severity, persistence and in comorbidity with bipolar-II disorder, social phobia, obsessive-compulsive syndromes and substance-use disorders. Results are based on a relatively small sample and cannot be generalized to adults aged over 40 years. The course of DSM-III-defined GAD may not be chronic, as previously suggested, but mainly recurrent with intervening symptom-free periods of recovery in about half of cases. Over a period of 20 years there was more improvement than progression within the anxiety spectrum.

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS)

BackgroundDSM-IV identifies three stress response disorders (acute stress (ASD), post-traumatic stress (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement.MethodsThis paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Study participants, enrolled at 6 Italian Departments of Psychiatry, included consecutive patients with PTSD (N = 48), CG (N = 44), and controls (N = 48).ResultsWe showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions.ConclusionThese results support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations.

Gender Similarities and Differences in Antisocial Behavioral Syndromes among Injection Drug Users

Studies report that more female substance users meet the adult antisocial behavioral (AASB) criteria of antisocial personality disorder (ASPD) without having conduct disorder. We assessed gender and antisocial syndrome (ASPD vs. AASB) effects jointly on multiple outcomes in injection drug users. More males had ASPD (40%) and more females had AASB (67%). After adjusting for gender, the ASPD group was consistently more severe, indicating discriminative validity for the diagnosis. However, the AASB group reported substantial pathology, signifying AASB as an important sub-threshold antisocial syndrome. Antisocial behavior might be described as a distribution, with AASB and ASPD defined by increasingly extreme points.

Co‐occurrence of anxiety and depressive disorders in a community sample of older people: results from the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study)

Few population-based studies have examined the whole range of subthreshold syndromes and disorders of anxiety and depression in older people. To investigate the co-occurrence of anxiety and depressive syndromes in older people. Associations between these conditions and personal and environmental factors are examined. MRC CFAS included 13,004, age 65 years and above, who completed the initial screening interview. A stratified random subsample of 2,640 participated in the assessment interview where the Geriatric Mental State Examination (GMS) was administered. The AGECAT diagnostic system was used to generate subthreshold and disorder-level of anxiety and depression as well as the combination of these into eight syndromes categories plus a group without any of the syndromes categories. Prevalences, unadjusted and adjusted odds ratios are calculated for the syndrome categories in relation to cross-sectional personal and environmental factors, and odds ratios of subthreshold and disorders level are estimated. The overall prevalence of anxiety and depressive disorders are 3.1% and 9.7% respectively. The overall prevalence of either anxiety or depressive disorder (anxiety disorder with subthreshold depression, mixed anxiety and depressive disorder with subthreshold anxiety) where they overlapped is 8.4%. The highest Odds Ratios unadjusted and adjusted for age and gender, of anxiety and depressive disorders and significant for trend are found for increasing disability. Disability has a strong relationship with all the co-morbid syndrome categories. In all analyses women showed significant higher estimates than men. Our study demonstrated high estimates where anxiety and depression occurred in parallel both as disorders and as subthreshold syndromes.

Public Health Shifts Focus To Preventing Chronic Illness

Public Health Shifts Focus To Preventing Chronic Illness

Psychische Auswirkungen von Stalking auf Männer und Frauen

Using data from the Mannheim stalking study, the present report analyses gender differences with regard to various mental health indicators and potential mediator effects of stalking victimization. Furthermore, we were interested in whether the impact of stalking on mental health was comparable for men and women. The study included a postal survey of 675 community residents on the experience of intruding harassment and on mental health indicators. In the Patient Health Questionnaire (PHQ-D, Lowe et al. 2001), women scored higher on most of the subscales (depression, anxiety, somatic complaints, stress, psychosocial impairment) than men. Furthermore, more women fulfilled criteria for at least one threshold or subthreshold mental disorder syndrome according to DSM-IV, and more women were under psychotropic medication. However, the identified associations were completely mediated by the higher prevalence of stalking victims in women. In contrast, the associations of stalking victimization with poor mental health, psychosocial functioning, and use of medication were largely comparable across gender.

A comparative study of nonspecific depressive symptoms and minor depression regarding functional impairment and associated characteristics in primary care

Background Milder forms of depression are highly prevalent in the clinical setting as well as in primary care. However, it is still unclear whether there are distinguishable groups among the various subthreshold syndromes and to what extent they are associated with impairment, thus requiring treatment. Therefore, the study aimed at comparing the degree of impairment in 2 groups of subthreshold depressive patients (nonspecific and minor depressive) with nondepressive patients and with major depressive patients. Another aim of the study was to evaluate the spectrum hypothesis of depressive syndromes. Sampling and methods A sample of 619 primary care patients was studied using the self-administered Patient Health Questionnaire (PHQ). After defining subthreshold depressive syndromes on a criterion basis, frequencies, sociodemographic factors, and impairment of nondepressive, subthreshold depressive, and major depressive patients were compared. Results Nonspecific depressive symptoms (NDS) were diagnosed in 9.1% of the study subjects and minor depression in 6.2%. Subjects with subthreshold depressive disorders did not differ from each other or from subjects with major depression regarding sociodemographic risk factors such as age, sex, or marital status. Yet, a continually increasing impairment from NDS to minor depression to major depression could be found. Moreover, the investigated groups differed with regard to the severity index. Conclusions The results of the study are in accordance with the spectrum hypothesis of depressive syndromes ranging from NDS to minor depression to major depression. Patients with subsyndromal depression showed significant functional impairment to the extent that at least some of these patients probably had a disorder requiring treatment.

Maladaptive core beliefs and eating disorder symptoms

This study compared maladaptive core beliefs of eating-disordered groups (full and subthreshold syndrome) and healthy controls and investigated the association between eating disorder symptoms and core beliefs. Participants were compared on self-report measures of core beliefs (YSQ) and eating disorder psychopathology (BITE). Anorexia nervosa (AN; both subtypes) and bulimia nervosa (BN) patients had significantly more core beliefs than healthy controls. Binge eating disorder (BED) patients had intermediate scores between AN and BN on the one hand and healthy controls on the other hand. No correlation was found between core beliefs and frequency of binge eating. Frequency of vomiting, laxative misuse and fasting was positively associated with all domains of core beliefs. Patients with eating disorders have some core beliefs which are not directly related to eating, weight or shape. Frequency of purging and fasting behaviors is associated with more severe maladaptive core beliefs. Our data demonstrate the importance of identifying purging and fasting as significant clinical markers.

The mood spectrum: improving the diagnosis of bipolar disorder

Although the distinction between bipolar and unipolar disorders served our field well in the early days of psychopharmacology, in clinical practice it is apparent that their phenotypes are only partially described by current diagnostic classification systems. A substantial body of evidence has accrued suggesting that clinical variability needs to be viewed in terms of a broad conceptualization of mood disorders and their common threshold or subthreshold comorbidity. The spectrum model provides a useful dimensional approach to psychopathology and is based on the assumption that early-onset and enduring symptoms shape the adult personality and establish a vulnerability to the subsequent development of Axis-I disorders. To obtain a clearer understanding of the depressive phenotype, it is pivotal that we increase our detection of hypomanic symptoms so that clinicians can better distinguish bipolar II disorder from unipolar depression. Diagnostic criteria sensitive to hypomanic symptoms have been identified that suggest bipolar II disorder is at least as prevalent as major depression. Moreover, the comorbidities of these illnesses are very different and alcoholism in particular appears to be a greater problem in bipolar II disorder than in unipolar depression. Structured clinical interviews and patient self-report questionnaires have also successfully identified the presence of hypomanic symptoms in patients with unipolar disorder and support the concept of a spectrum of bipolar illness. In conclusion, the importance of subthreshold syndromes should not be underestimated as failure to recognize bipolar spectrum disorder could delay treatment and worsen prognosis.

The psychotic spectrum: validity and reliability of the Structured Clinical Interview for the Psychotic Spectrum

This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.

Partial posttraumatic stress disorder revisited

Background: It is thought that the decision rule for a positive diagnosis of Posttraumatic Stress Disorder (PTSD) may be too restrictive, leaving too many victims of a trauma out in the cold for care, compensation, etc. Several authors have proposed the concept of Subthreshold or Partial PTSD (PPTSD). This concept considers that a subject may present a number of symptoms below threshold for criteria C or D (subthreshold syndromes) and may even present without any symptom for one or more of the criteria B, C and D (partial syndromes). Method: Data have been collected by means of the Composite International Diagnostic Interview (CIDI) PTSD-module, in a group exposed to two different traumatic events (130 fire victims and 55 car accident victims). The syndrome patterns has been assessed by means of hierarchical class analyses. Each of the criteria B, C and D has been analyzed separately, showing the symptom patterns as hierarchically order clusters. Results: Depending on the threshold used for criterion C (i.e. 3 or 2 symptoms), 18.4 and 22.7% of the subjects respectively satisfy the criteria for PTSD. 8.7% of the subjects show subthreshold syndromes. 60.7% of the subjects show partial syndromes and 16.7% of the subjects have partial syndromes while fulfilling criterion F, i.e. a clinically significant impairment in functioning. Conclusions: The results show a considerable number of partial and subthreshold syndromes. It is argued that subthreshold syndromes and partial syndromes, which fulfill criterion F, should be regarded as specific nosological categories or as specified PTSD subcategories, i.e. subsyndromal or partial PTSD.

Syndrome profiles in alcoholism and panic disorder with or without agoraphobia: An explorative family study

It is proposed that alcoholism and panic disorder/agoraphobia demonstrate in part common genetic and environmental origins. Shared subthreshold symptom patterns in the parents' generation could confirm the proposed genetic role in alcoholism and panic disorder/agoraphobia, even if the parents do not fulfil the diagnostic criteria for a primary psychiatric diagnosis. This is the first family study of exploratively analyzing subthreshold symptoms in both disorders. The authors investigated families with panic disorder/agoraphobia and/or alcoholism with the Munich-Composite International Diagnostic Interview (M-CIDI). We documented the diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and subdivided the answers of the probands into 16 subthreshold diagnostic groups comprising 259 single items. We found statistically significant correlations of subthreshold syndrome profiles in the parents of patients with panic disorder/agoraphobia and alcoholism. The presented method of analyzing syndrome profiles in a family study seems to be a possibility to demonstrate references to genetic links between patients and parents in anxiety- and alcohol-related disorders.

Clinical significance and comorbidity of subthreshold depression and anxiety in the community.

This report examines: 1) the magnitude of co-occurrence of threshold and subthreshold-level depression and anxiety in the community, and 2) the relationship between comorbidity and the diagnostic level of depression and anxiety and their clinical correlates. A community sample of 591 subjects was interviewed prospectively five times across 15 years from the ages of 20-35. The diagnostic interview allowed the assignment of diagnoses according to DSM-III criteria and operational definitions of subthreshold syndromes. 1) Comorbidity between depression and anxiety was more frequent when one syndrome reached threshold level; 2) comorbidity at both the threshold and subthreshold diagnostic levels was associated with symptom severity, disability and treatment, whereas the diagnostic level was associated with disability and suicidal attempts. The systematic association between comorbidity across diagnostic threshold levels of anxiety and depression with clinical correlates suggests the importance of a more dimensional approach to their classification.

One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample.

Several studies of representative populations have reported prevalence rates of DSM-III and DSM-III-R generalized anxiety disorder (GAD); however, no community study has examined the effect of the stricter DSM-IV criteria on prevalence estimates and patterns of comorbidity. Furthermore, past studies based on "lifetime" symptom assessments might have led to upper-bound 1-year and point prevalence estimates. Data is presented from a national representative sample study of 4,181 adults in Germany, 18-65 years old, who were interviewed for DSM-IV disorders with the 12-month version of the Munich-Composite International Diagnostic Interview. The prevalence rate of strictly defined, 12-month threshold DSM-IV GAD was estimated to be 1.5%; however, 3.6% of respondents presented with at least subthreshold syndromes of GAD during the past 12 months. Higher rates of worrying and GAD were found in women (worrying 10%, GAD 2.7%) and in older respondents (worrying 9.3%, TAD 2.2%). Taking into account a wider scope of diagnoses than previous studies, a high degree of comorbidity in GAD cases was confirmed: 59.1% of all 12-month GAD cases fulfilled criteria for major depression, and 55.9% fulfilled criteria for any other anxiety disorder. In conclusion, prevalence and comorbidity rates found for DSM-IV GAD are not substantially different from rates reported for DSM-III-R GAD. The minor differences in our findings compared to previous reports are more likely attributable to differences in study methodology rather than changes in diagnostic criteria for DSM-IV.

Symptomatic and syndromal anxiety and depression.

The diagnosis of anxiety disorders and major depression can be reliably made based on signs and symptoms. However there are significant limitations to the current system of classification including overlapping criteria, high comorbidity, and the issue of subthreshold syndromes. The literature on treatment response documents that selective serotonin reuptake inhibitors are effective in the treatment of the various anxiety disorders, including when comorbid major depression is present. The literature also suggests that tricyclic antidepressant medications have superior benefits over selective serotonin reuptake inhibitors in major depression. Examination of the functional anatomy of the fear and reward systems may shed light on the underlying processes in the anxiety and depressive disorders. Such an approach points out the importance of addressing avoidance behaviors, which may be more responsive to cognitive behavioral treatments than pharmacological agents.

Onset of Obsessive-Compulsive Disorder: Premorbid Conditions and Prodromal Phase

This article focuses on the clinical onset of obsessive-compulsive disorder (OCD), specifically addressing the age of onset, gradual and acute onset, and whether there are some types of premorbid conditions or a prodromal phase that predispose individuals to the onset of OCD. Clinical and epidemiological studies have come to different conclusions regarding age at onset as well as regarding differences between the sexes. Data gleaned from research to date have demonstrated a relationship between OCD and obsessive-compulsive personality disorder (OCPD), although OCPD does not appear to be the more prevalent personality disorder among patients with OCD. Preliminary research has suggested that Axis I disorders may predispose individuals to OCD onset; however, the significance of this relationship remains to be clarified. Evidence of the association between OCD and subthreshold obsessive-compulsive syndrome suggests that these disorders lie on a continuum of severity, with some cases developing OCD while others do not.

S-10-5 - Psychotropic drugs use in patients with anxious or depressive disorders vs subthreshold syndromes

Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.