Deficits in visual processing are well established in schizophrenia. However, there is conflicting evidence about whether these deficits start before the formation of percepts because visual processing studies in schizophrenia have typically examined the processing of consciously registered stimuli. In this study, we used nonconscious color priming to evaluate the very early visual processing stages in schizophrenia. Nonconscious and conscious color priming was assessed in 148 schizophrenia patients and 54 healthy control subjects. In both conditions, subjects identified the color of a ring preceded by a disk (prime) in the same color (congruent) or a different color (incongruent). The ring rendered the disk invisible in the nonconscious condition (SOA of 62.5 ms) or did not mask the disk (SOA of 200 ms) in the conscious condition. Schizophrenia patients exhibited a color priming effect (longer reaction times in the incongruent vs. congruent trials) that was similar to healthy controls in both the nonconscious and conscious priming conditions. Healthy controls had a significantly larger priming effect in the nonconscious vs. conscious condition, but patients did not show a significant difference in priming effects between the two conditions. Our results indicate that schizophrenia patients do not have deficits at the nonconscious, pre-perceptual stages of visual processing, suggesting that the feed forward sweep of information processing (from retina to V1) might be intact in schizophrenia. These results imply that the well-documented visual processing deficits in this illness likely occur at later, percept-dependent stages of processing.
schizophrenia; visual processing; color priming; nonconscious; feed forward
Insight/delusionality of beliefs is an important dimension of psychopathology across psychiatric disorders. This construct is of increasing interest in obsessive-compulsive and related disorders, including obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD). Even though OCD and BDD are considered closely related, no prior study has compared these disorders across a range of categories of global insight (excellent, good, fair, poor, absent/delusional), and only one study has compared these disorders on individual components of insight. Using the reliable and valid Brown Assessment of Beliefs Scale (BABS), this study examined insight/delusionality of OCD- or BDD-related beliefs in 211 individuals with primary OCD versus 68 individuals with primary BDD. In both disorders, levels of insight spanned the full range, from excellent to absent (i.e., delusional beliefs). However, the distribution of BABS scores across insight categories differed significantly by disorder, with the majority of OCD subjects showing excellent or good insight, and the majority of BDD subjects showing poor or absent insight. Compared to OCD subjects, BDD subjects had significantly poorer insight both overall (total BABS score) and on all individual BABS items. BABS score was significantly correlated with BDD and OCD severity, but in regressions it accounted for only 21% of the variance in OCD and 28% in BDD. In summary, both global insight and its individual components are poorer in BDD than in OCD, which has implications for research and clinical care, as well as understanding of the relationship between these disorders. Disorder severity is associated with but not equivalent to insight/delusionality.
obsessive-compulsive disorder; body dysmorphic disorder; delusional disorder; insight; delusions
There is evidence that major depressive disorder (MDD) is associated with increased peripheral markers of oxidative stress. To explore oxidation and antioxidant response in MDD, we assayed human dermal fibroblast cultures derived from skin biopsies of age-, race-, and sex-matched individuals in depressed and normal control groups (n=16 each group), cultured in glucose and galactose conditions, for relative protein carbonylation (a measure of oxidative stress), glutathione reductase (GR) expression, and total glutathione concentration. In control-group fibroblasts, galactose induced a significant increase from the glucose condition in both protein carbonylation and GR. The cells from the MDD group showed total protein carbonylation and GR expression in the glucose condition that was significantly higher than control cells in glucose and equivalent to controls in galactose. There was a small decrease in protein carbonylation in MDD cells from glucose to galactose and no significant change in GR. There was no difference in total glutathione among any of the groups. Increased protein carbonylation and GR expression, cellular responses to oxidative stress induced by galactose in control fibroblasts, are present in fibroblasts derived from MDD patients and are not explainable by reduced GR or total glutathione in the depressed patients. These studies support the role of oxidative stress in the pathophysiology of MDD. Further confirmation of these findings could lead to the development of novel antioxidant approaches for the treatment of depression.
human dermal fibroblasts; oxidative stress; glutathione; glutathione reductase; protein carbonylation; major depression
Understanding the beliefs that protect individuals against suicide can help to enhance suicide prevention strategies. One measure of suicide non-acceptability is the Moral Objections to Suicide (MOS) subscale of the Reasons for Living Inventory (RFLI). This study examined the MOS and suicidal ideation of White, Black, and Hispanic individuals with mood disorders. We expected minority individuals to have stronger objections to suicide.
804 White (588), Black (122) and Hispanic (94) participants with DSM-IV diagnoses of MDD or Bipolar Disorder were administered the Scale for Suicide Ideation, the Reasons for Living Inventory and several measures of clinical distress.
Higher suicidal ideation was modestly correlated with lower MOS scores overall (r=0.15, p=.001). Among Blacks however the relationship was inverted: despite having higher suicidal ideation than Whites or Hispanics, Blacks reported the least accepting attitudes toward suicide.
These results suggest that attitudes regarding the acceptability of suicide may be independent of suicidal ideation.
suicide acceptability; risk factor; protective factor; reasons for living; ethnicity; moral objections to suicide
Moral and religious objections to suicide (MOS) are reported to be associated with less suicidal behavior in depressed patients, and are proposed to act as a protective factor against suicidal behavior. It is unclear whether MOS are a protective factor against suicide attempt per se, or if this effect is mediated through other variables.
Depressed inpatients (n = 265) reporting low or high MOS were compared on history of suicidal behaviour, demographic and clinical characteristics.
Patients with low MOS had significantly more lifetime suicide attempts, were more often without religious affiliation, had greater depression severity, hopelessness and trait impulsivity, less anxiety and fewer reasons for living. Logistic regression revealed that lower MOS was independently associated with suicide attempt.
Moral and religious objections to suicide may serve as a protective factor against suicidal acts given their unique association with less suicidal behavior in depressed inpatients.
Suicide; Moral objections; Protective factors
Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown.
We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function (“disposition index”, DI) by intravenous glucose tolerance test.
At baseline, groups (risperidone: n = 28; olanzapine: n = 31) were overweight or obese by body mass index (risperidone: 28.4 ± 5.4, olanzapine: 30.6 ± 7.0 kg/m2). Both drugs induced weight gain (p < 0.004). Total adiposity was increased by olanzapine at 6 weeks (p = 0.0006) and by both treatments at 24 weeks (p < 0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p < 0.003). SI did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and SI, we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p < 0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p = 0.033), indicating inadequate pancreatic compensation for insulin resistance.
This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.
Risperidone; Olanzapine; Schizophrenia; Diabetes; Minorities
Acute alcohol use is an important risk factor for attempted and completed suicide. We evaluated the effect of acute alcohol intake on the lethality of suicide attempts to test the hypothesis that acute alcohol intoxication is associated with more lethal suicide attempts. This retrospective study included 317 suicide attempters enrolled in mood disorders protocols. Demographic and clinical parameters were assessed. The use of alcohol at the time of the most lethal suicide attempt was determined. On the basis of their responses participants were classified into three groups: participants who reported “Enough alcohol intake to impair judgment, reality testing and diminish responsibility” or “Intentional intake of alcohol in order to facilitate implementation of attempt” were included in the group “Alcohol” (A); participants who reported “Some alcohol intake prior to but not related to attempt, reportedly not enough to impair judgment, reality testing” were included in the group “Some Alcohol” (SA); and participants who reported “No alcohol intake immediately prior to attempt” were included in the group “No Alcohol” (NA). Lethality of the most lethal suicide attempts was higher in the A group compared to the SA and NA groups. Prevalence of patients with alcohol use disorders was higher in the A group compared to the SA and NA groups. SA participants reported more reasons for living and lower suicide intent scores at the time of their most lethal suicide attempt compared to the A and NA groups. Acute alcohol use increases the lethality of suicide attempts in individuals with mood disorders.
Alcohol intoxication; Alcohol use disorders; Mood disorders; Suicide; Lethality
Lifetime prevalence rates of psychopathology vary a great deal depending on whether they are estimated from cross-sectional or prospective longitudinal studies, with the former yielding significantly lower rates. Such findings, however, come from comparisons of separate studies from different countries and cohorts. Here, we compare lifetime rates of psychopathology between a community sample of individuals assessed on multiple occasions to their siblings who completed only a single diagnostic evaluation. Data come from the Oregon Adolescent Depression Project. We included 442 original participants who completed four prospective diagnostic assessments over the course of fifteen years, and 657 of their siblings who completed a single lifetime assessment. Comparisons of rates of depressive, bipolar, anxiety, and substance use disorders were made using survival analysis. We found that rates of depressive disorders, specifically major depressive disorder, were elevated among individuals who completed multiple diagnostic assessments relative to individuals who completed a single lifetime assessment. We did not find significant differences in rates of aggregate anxiety, bipolar, or substance use disorders. Within a single cohort, cross-sectional surveys appear to underestimate the lifetime rates of major depression relative to prospective, longitudinal designs. This suggests that disorders with an episodic course may be under-reported in cross-sectional surveys. Rates of anxiety, bipolar, and substance use disorders did not differ across assessment methods. To further evaluate method effects on lifetime estimates of psychopathology, future work may benefit from comparing rates of retrospectively- and prospectively-derived diagnoses in individuals who are repeatedly assessed over a lengthy follow-up period.
assessment; psychopathology; prevalence; epidemiology
Understanding variations in disease presentation in men and women is clinically important as differences may reflect biological and sociocultural factors and have implications for selecting appropriate prevention and treatment strategies. The aim of this study was to investigate clinical and cognitive differences in treatment-seeking people with pathological gambling as a function of gender.
Materials and methods
501 adult subjects (n=274 [54.7%] females) with DSM-IV pathological gambling presenting for various clinical research trials over a 9-year period were assessed in terms of sociodemographics and clinical characteristics. A subset (n=77) had also undertaken neuropsychological assessment with the Stop-signal and set-shift tasks.
PG in females was associated with significantly worse disease severity, elevated mood and anxiety scores, and history of affective disorders, later age of study presentation, later age of disease onset, and elevated risk of having a first-degree relative with gambling or alcohol problems. These findings were of small effect size (0.20–0.35). Additionally, PG in females was associated with proportionately more non-strategic gambling with medium effect size (0.61). In contrast, PG in males was associated with significantly greater lifetime history of alcohol use disorder and any substance use disorder (small effect sizes 0.22–0.38); and slower motoric reaction times (medium effect size, 0.50). Response inhibition and cognitive flexibility were similar between the groups.
These data suggest that important differences exist in the features of pathological gambling in women and men. Findings are of considerable relevance to clinicians and in terms of targeted treatments.
gender; impulse control disorders; gambling; cognition; addiction; phenomenology
This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) in prison substance use treatment with MDD to group interpersonal psychotherapy (IPT) or to an attention-matched control. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD.
major depressive disorder; prison; women; substance use disorder
Major depressive disorder and bipolar spectrum disorders are debilitating conditions associated with severe impairment. The presence of co-occurring social phobia can make the clinical course of these disorders even more challenging. To better understand the nature of social anxiety in the context of ongoing mood disorders, we report the results of exploratory factor analyses of the Social Phobia Spectrum Self-Report Instrument (SHY), a 162-item measure designed to capture the full spectrum of manifestations and features associated with social anxiety experienced across the lifespan. We examined data from 359 adult outpatients diagnosed with major depressive disorder and 403 outpatients diagnosed with a bipolar spectrum disorder. The measure was divided into its two components: the SHY-General (SHY-G), reflecting general social anxiety features, and the SHY-Specific (SHY-S), reflecting anxiety in specific situations. Exploratory factor analyses were conducted for each using tetrachoric correlation matrices and an unweighted least squares estimator. Item invariance was evaluated for important patient subgroups. Five factors were identified for the SHY-G, representing general features of social anxiety: Fear of Social Disapproval, Childhood Social Anxiety, Somatic Social Anxiety, Excessive Agreeableness, and Behavioral Submission. Seven specific-situation factors were identified from the SHY-S: Writing in Public, Dating, Public Speaking, Eating in Public, Shopping Fears, Using Public Restrooms, and Unstructured Social Interactions. The identified dimensions provide clinically valuable information about the nature of the social fears experienced by individuals diagnosed with mood disorders and could help guide the development of tailored treatment strategies for individuals with co-occurring mood disorders and social anxiety.
Internet gaming addiction (IGA) is increasingly recognized as a widespread disorder with serious psychological and health consequences. Diminished white matter integrity has been demonstrated in a wide range of other addictive disorders which share clinical characteristics with IGA. Abnormal white matter integrity in addictive populations has been associated with addiction severity, treatment response and cognitive impairments. This study assessed white matter integrity in individuals with internet gaming addiction (IGA) using diffusion tensor imaging (DTI). IGA subjects (N=16) showed higher fractional anisotropy (FA), indicating greater white matter integrity, in the thalamus and left posterior cingulate cortex (PCC) relative to healthy controls (N=15). Higher FA in the thalamus was associated with greater severity of internet addiction. Increased regional FA in individuals with internet gaming addiction may be a pre-existing vulnerability factor for IGA, or may arise secondary to IGA, perhaps as a direct result of excessive internet game playing.
internet addiction; internet gaming addiction; diffusion tensor imaging; thalamus; white matter; reward system
Recent studies have implicated brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression and the activity of antidepressant drugs. Serum BDNF levels are lower in depressed patients, and increase in response to antidepressant medication. However, how BDNF responds to different classes of antidepressant drugs is unknown. We assessed serum BDNF levels in 21 patients with major depressive episode treated with sertraline, escitalopram, or venlafaxine and 20 healthy controls. Serum samples were collected between 10 a.m. and 12 p.m. at baseline, 5 weeks, and 6 months of treatment. BDNF levels were measured via immunoassay. The severity of symptoms and response to treatment were assessed by the Hamilton rating scales for depression (HRSD). Baseline serum BDNF levels were significantly lower in depressed patients compared to controls. Sertraline increased BDNF levels after 5 weeks and 6 months of treatment. Venlafaxine increased BDNF levels only after 6 months. Escitalopram did not affect BDNF levels at either time point. A significant negative association was found between percentage increase in BDNF levels and percentage decreased in HRSD scores after 6 months of treatment. In conclusion, these results suggest that different antidepressant drugs have variable effects on serum BDNF levels. This is true even though the three different drugs were equally effective in relieving symptoms of depression and anxiety.
brain-derived neurotrophic factor (BDNF); neuroadaptation; depression; sertraline; venlafaxine; escitalopram
Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N=66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night’s Sleep (N=20) or continuous daytime Wake (N=23), or a 2-hr delay of continuous wake in the Morning (N=11) or Evening (N=12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning.
Sleep; Extinction; Spider Phobia; Fear Conditioning; Exposure Therapy
The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use. We examined the rate of substance use and the risk of substance use on mortality risk over a 4–10 year period in 762 people with psychotic disorders. Deceased patients were identified from the Social Security Death Index and the Maryland Division of Vital Records. Substance use was defined as regular and heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime substance use, with co-morbid cannabis and alcohol use occurring most commonly. Out of 762 subjects, 62 died during follow up. In a Cox model, predicted mortality risk was higher in age group 35–55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p=0.005) in a survival model. Alcohol use was not predictive of mortality. We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments. Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.
psychotic disorders; substance use; cannabis; alcohol; mortality
Interest in commonly co-occurring depression and disruptive behavior disorders in children has yielded a small body of research that estimates the prevalence of this comorbid condition and compares children with the comorbid condition and children with depression or disruptive behavior disorders alone with respect to antecedents and outcomes. Prior studies have used one of two different approaches to measure comorbid disorders: 1) meeting criteria for two DSM or ICD diagnoses or 2) scoring .5 SD above the mean or higher on two dimensional scales. This study compares two snapshots of comorbidity taken simultaneously in the same sample with each of the measurement approaches. The Developmental Pathways Project administered structured diagnostic interviews as well as dimensional scales to a community-based sample of 521 11-12 year olds to assess depression and disruptive behavior disorders. Clinical caseness indicators of children identified as “comorbid” by each method were examined concurrently and 3-years later. Cross-classification of adolescents via the two approaches revealed low agreement. When other indicators of caseness, including functional impairment, need for services, and clinical elevations on other symptom scales were examined, adolescents identified as comorbid via dimensional scales only were similar to those who were identified as comorbid via DSM-IV diagnostic criteria. Findings suggest that when relying solely on DSM diagnostic criteria for comorbid depression and disruptive behavior disorders, many adolescents with significant impairment will be overlooked. Findings also suggest that lower dimensional scale thresholds can be set when comorbid conditions, rather than single forms of psychopathology, are being identified.
classification; comorbid conditions; depression; disruptive behavior disorders; adolescent
Social anhedonia is a promising vulnerability marker for schizophrenia-spectrum pathology. Prior research has demonstrated that individuals with psychometrically-defined social anhedonia show a range of “schizophrenia-like” neurocognitive abnormalities. However, this research is limited in that it is based largely on the study of college students. The present article reports findings from a longitudinal study of social anhedonia recruited from a community sample. As part of this study, a neurocognitive battery was administered at baseline and at three-year follow-up sessions to participants with (n = 78) vs. without (n = 77) social anhedonia. Additional measures of global functioning and schizotypal, schizoid and paranoid schizophrenia-spectrum symptoms were also administered. Across groups, subjects showed significant improvement in neurocognitive functioning over time. Compared to controls, at follow-up, individuals with social anhedonia showed significantly poorer attentional vigilance and simple processing speed, but failed to evidence impairments in immediate or delayed verbal memory, immediate or delayed visual memory, visual or verbal working memory, olfaction or executive abilities. At follow-up, within the social anhedonia group, schizoid (and to a lesser extent, schizotypal) symptom severity was associated with a range of neurocognitive impairments. Neurocognitive impairments were generally not associated with paranoid symptoms or global functioning. Baseline neurocognitive performance was not significantly predictive of follow-up symptom severity or functioning. Collectively, these findings suggest that neurocognitive dysfunctions only characterize a subset of individuals with social anhedonia.
Social anhedonia; schizophrenia; schizotypy; prodrome; risk; neurocognitive; neuropsychological
Suicidal ideation and attempts are a major public health problem. Research has identified many risk factors for suicidality; however, most fail to identify which suicide ideators are at greatest risk of progressing to a suicide attempt. Thus, the present study identified predictors of future suicide attempts in a sample of psychiatric patients reporting suicidal ideation. The sample comprised 49 individuals who met full DSM-IV criteria for major depressive disorder and/or dysthymic disorder and reported suicidal ideation at baseline. Participants were followed for 10 years. Demographic, psychological, personality, and psychosocial risk factors were assessed using validated questionnaires and structured interviews. Phi coefficients and point-biserial correlations were used to identify prospective predictors of attempts, and logistic regressions were used to identify which variables predicted future attempts over and above past suicide attempts. Six significant predictors of future suicide attempts were identified – cluster A personality disorder, cluster B personality disorder, lifetime substance abuse, baseline anxiety disorder, poor maternal relationship, and poor social adjustment. Finally, exploratory logistic regressions were used to examine the unique contribution of each significant predictor controlling for the others. Co-morbid cluster B personality disorder emerged as the only robust, unique predictor of future suicide attempts among depressed suicide ideators. Future research should continue to identify variables that predict transition from suicidal thoughts to suicide attempts, as such work will enhance clinical assessment of suicide risk as well as theoretical models of suicide.
suicide; depression; risk factors; longitudinal design; Cluster B personality disorders
To examine the prevalence and correlates of comorbid anxiety disorders among individuals with bipolar disorders (BP) and their association with prospectively ascertained comorbidities, treatment, and psychosocial functioning.
As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for BP-I (n=1172) and BP-II (n=428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart.
Sixty percent of individuals with BP had at least one lifetime comorbid anxiety disorder. Individuals with BP and anxiety disorders shared lifetime risk factors for major depressive disorder and had prospectively more depressive and manic/hypomanic episodes, suicidal ideation, suicide attempts, and more treatment seeking than those without anxiety. During the follow-up, higher incidence of panic disorder, drug use disorders, and lower psychosocial functioning were found in individuals with BP with versus without anxiety disorders.
Anxiety disorders are prospectively associated with elevated BP severity and BP-related mental health service use. Early identification and treatment of anxiety disorders are warranted to improve the course and outcome of individuals with BP.
anxiety; bipolar disorder; outcome; comorbidity
Previous research has found a longitudinal relationship between sleep problems and suicidal behavior while controlling for depression and other important covariates in a high risk sample of adolescents and controls. In this paper, we replicated this longitudinal relationship in a national sample and examined whether the relationship was partially mediated by depression, alcohol-related problems and other drug use.
Study participants were 6504 adolescents from the National Longitudinal Study of Adolescent Health (ADD HEALTH).
In bivariate analyses, sleep problems (i.e., having trouble falling asleep or staying asleep) at Wave 1 were associated with suicidal thoughts and suicide attempts at Waves 1, 2, and 3 (W1, 2 and 3). In multivariate analyses, controlling for depression, alcohol problems, illicit drug use, and important covariates such as gender, age, and chronic health problems, sleep problems at a previous wave predicted suicidal thoughts and suicide attempts at a subsequent wave. In mediation analyses, W2 depression significantly mediated the effect of W1 sleep problems on W3 suicide thoughts. Moreover, W2 suicidal thoughts also significantly mediated the effect of W1 sleep problems on W3 suicidal attempts.
Sleep problems appear to be a robust predictor of subsequent suicidal thoughts and attempts in adolescence and young adulthood. Having trouble falling sleeping or staying asleep had both direct and indirect effects (via depression and suicidal thoughts) on suicidal behavior. Future research could determine if early intervention with sleep disturbances reduces the risk for suicidality in adolescents and young adults.
Sleep problems; Suicidal thoughts; Suicide attempts; Adolescence
Although adolescents frequently engage in a variety of risky behaviors, much remains unknown about the specific etiologies of such tendencies. Candidate genetic variants, such as the COMT Val158Met polymorphism, may be related to risk-taking propensity, particularly as this variant is linked to functional enzymatic differences influencing dopamine function in regions including the prefrontal cortex. The present study aimed to examine the COMT Val158Met variant in relation to risk taking propensity in a community sample of youth. As part of a larger longitudinal study on adolescent risk behaviors, 223 youths (average age 11.3 years) from the metropolitan Washington D.C. area completed a measure of risk-taking propensity, the Balloon Analogue Risk Task-Youth Version (BART-Y), and provided saliva samples for DNA extraction and genotyping. Results indicate that females, but not males, who are carriers of the COMT158Met allele had higher risk-taking propensity scores on the BART-Y compared to Val homozygotes. Analyses were also conducted in the 111 European American participants, and results were consistent with those of the full sample analyses. This study represents the first investigation of a genetic substrate of risk-taking propensity, measured by a behavioral task, in youth. Results should be taken as quite preliminary, given the small sample. Implications are discussed.
Risk taking; BART; COMT Val158Met; Dopamine; Adolescents
Both theory and empirical evidence support possible associations between two candidate genetic polymorphisms (SLC6A4 5-HTTLPR l/s and COMT Val158Met – rs4680 variants) and emotion-regulation difficulties. One particular form of emotion-regulation difficulty, distress intolerance, has been measured using a behavioral assessment in youth; data indicate a relationship with poor psychological functioning. No prior study has investigated genetic influences on emotion-regulation difficulties in youth. As part of a larger longitudinal study on adolescent risk behaviors, 218 10-14 year-old youths from the metropolitan Washington, D.C., area completed a measure of distress intolerance, the Behavioral Indicator of Resilience to Distress (BIRD), and provided saliva samples for DNA extraction and genotyping. Results indicate that those with one or two copies of the s allele of the 5-HTTLPR polymorphism were more likely to perform poorly on the task (i.e., choose to quit) than were those homozygous for the l allele. Participants who were Val allele carriers of the COMT Val158Met polymorphism were also more likely to quit the task compared to Met homozygotes. A summative risk allele score was created to combine the two polymorphisms, and each risk allele was associated with a 1.75 fold increased likelihood of quitting the task. Exploratory analyses revealed that emotional abuse moderated the relationship between the 5-HTTLPR and BIRD performance, as well as the genetic risk allele and the BIRD. This is the first investigation of genetic predictors of a behavioral measure of tolerance to distress. Results suggest that distress tolerance is at least partially regulated by specific genetic variants. Implications are discussed.
COMT; 5-HTTLPR; Distress Tolerance
Patients (30–50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication.
Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5–3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ≤10 on the Montgomery–Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire.
Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = .011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ≤ 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone.
Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.
Antidepressants; Antipsychotic; Clinical drug studies; Mood disorders – unipolar
Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, however underlying neural circuitry contributing to the comorbidity remain understudied. Our aim was to investigate functional brain circuitry during working memory in a group of participants who meet criteria for both disorders (ADHD+BPD), and to explore the relationship of symptoms of each disorder to brain function. We used fMRI to image brain activity in 18 male adults with both ADHD and BPD, and 18 healthy control participants matched one-to-one on age, sex, and handedness, while they performed a sequential letter n-back task. We investigated differences in activation between these groups, and also correlations of brain activity during the task to symptoms of ADHD and BPD independently. We found significant hypoactivity in the subjects with ADHD+BPD vs. controls across frontal and parietal regions, and further, found that BPD and ADHD symptoms related to activity in anatomically distinct regions that were respectively characterized by activation and suppression during task. We conclude that comorbid ADHD+BPD is associated with alterations across anterior and posterior nodes of the working memory network, and symptoms of each disorder are related to anatomically and functionally distinct brain regions.
fMRI; Bipolar Disorder; ADHD; Working Memory; Executive Function; Default Mode Network