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Personality and substance use disorders: II. Alcoholism versus drug use disorders.

The relationship between personality and substance use disorders was investigated in a community-based sample of 638 individuals who were alcoholic and/or had a drug use disorder, and 1,530 individuals who did not have a substance use disorder. Personality was assessed by the Multidimensional Personality Questionnaire; substance use diagnoses were based on standard criteria as assessed by interview. Data were analyzed using a 3-factor (Gender x Alcoholism x Drug Use Disorder) multivariate analysis of variance. The significant alcoholism main effect was associated primarily with negative emotionality, whereas the significant drug use disorder main effect was associated primarily with constraint. No significant interactions with gender were observed. These findings suggest that the elevated levels of behavioral disinhibition observed with alcoholic individuals may be attributable to a subset of alcoholic individuals who also abuse drugs other than alcohol.

Adult↗

Axis I and axis II disorders as predictors of prospective suicide attempts: findings from the collaborative longitudinal personality disorders study.

This study examined diagnostic predictors of prospectively observed suicide attempts in a personality disorder (PD) sample. During 2 years of follow-up, 58 participants (9%) reported at least 1 definitive suicide attempt. Predictors that were examined include 4 PD diagnoses and selected Axis I diagnoses (baseline and course). Multivariate logistic regression analyses indicated that baseline borderline personality disorder (BPD) and drug use disorders significantly predicted prospective suicide attempts. Controlling for baseline BPD diagnosis, proportional hazards analyses showed that worsening in the course of major depressive disorder (MDD) and of substance use disorders in the month preceding the attempt were also significant predictors. Therefore, among individuals diagnosed with PDs. exacerbation of Axis I conditions, particularly MDD and substance use, heightens risk for a suicide attempt.

Adult↗

Disorder as harmful dysfunction: a conceptual critique of DSM-III-R's definition of mental disorder.

The Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) operationally defines disorder essentially as "statistically unexpectable distress or disability." This definition is an attempt to operationalize 2 basic principles: that a disorder is harmful and that a disorder is a dysfunction (i.e., an inability of some internal mechanism to perform its natural function). However, the definition fails to capture the idea of "dysfunction" and so fails to validly distinguish disorders from nondisorders, leading to invalidities in many of DSM-III-R's specific diagnostic criteria. These problems with validity are traced to DSM-III-R's strategies for increasing reliability.

Humans↗

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium.

Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases.

Amino Acid Sequence↗

Comparison of obsessive-compulsive disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders using a structured clinical interview.

Increasing attention has been paid to the possibility that a range of disorders, the putative obsessive-compulsive spectrum disorders (OCSDs), may share overlapping phenomenological and neurobiological features with obsessive-compulsive disorder (OCD). The development of a structured clinician-administered interview for the putative OCSDs (SCID-OCSD) is described. This instrument was used to investigate differences between OCD patients with a comorbid putative OCSD and OCD patients without a comorbid putative OCSD. A sample of 85 adult patients (38 men and 47 women) presenting for treatment of OCD was interviewed with the SCID-OCSD. OCD patients without comorbid putative OCSDs (n = 36) were compared to patients with comorbid OCSDs (n = 49) in terms of demographic features, clinical characteristics, and associated comorbidity with other non-OCSD DSM-IV axis I disorders. Of the OCD patients, 57.6% currently met criteria for at least one putative OCSD and 67.1% had a lifetime history of at least one comorbid OCSD. The OCSDs with the highest prevalence rates were compulsive self-injury (22.4%), compulsive buying (10.6%), and intermittent explosive disorder (10.6%). There was a significantly larger proportion of women in the group with comorbid OCSDs. Although the two groups did not differ in terms of severity of OCD symptoms, the group with comorbid OCSDs had significantly more obsessions and compulsions. The two groups did not differ significantly in terms of associated psychopathology other than OCSDs. We conclude that the SCID-OCSD provides clinicians and researchers with an instrument for the diagnosis of putative OCSDs. Our findings suggest that putative OCSDs have a relatively high prevalence rate in OCD patients. In addition, OCD patients with comorbid OCSDs differ with regard to certain demographic and clinical features. Further research, particularly genetic and neuroimmunological work, may ultimately be useful in validating the obsessive-compulsive spectrum.

Adult↗

Tic disorders and obsessive-compulsive disorder: is autoimmunity involved?

The precise cause of tic disorders and paediatric obsessive-compulsive disorder (OCD) is unknown. In addition to genetic factors, autoimmunity may play a role, possibly as a sequela of preceding streptococcal throat infections in susceptible children. Here we review the most recent findings, from July 2003 onwards, with regard to a possible relationship between tics/OCD and autoimmunity. Evidence about an intriguing correlation between streptococcal infections and tic disorders and OCD is accumulating. Specific criteria have been outlined for paediatric autoimmune disorders associated with streptococcal infections (PANDAS), but autoimmunity may also be involved in tic disorders and/or OCD in general. Anti-basal ganglia auto-antibodies are an important potential indicator of autoimmunity. Although the lack of a standardized methodology makes comparisons of findings difficult, new data has emerged pointing to the possible involvement of specific auto-antigens. Earlier findings of increased D8/17 B cell expression as a putative susceptibility marker could not be replicated, possibly due to instability of the D8/17-binding antibody. Although PANDAS patients have been reported to improve after therapeutic plasma exchange, and antibiotics may prevent symptom exacerbations, immune-based treatments should not be routinely given. In future studies, demonstrating the pathogenetic significance of anti-basal ganglia antibodies in animals is a major challenge to draw any firm conclusions about a role for autoimmunity. Future longitudinal studies should be aimed at assessing the precise relationship between symptom exacerbations, infections, and immune parameters, possibly along with gene expression profiles.

Animals↗

Working memory impairments in children with attention-deficit hyperactivity disorder with and without comorbid language learning disorders.

Our objectives were to examine whether children with attention-deficit hyperactivity disorder (ADHD) are impaired on one or more components of working memory (WM) independent of comorbid language learning disorders, and whether WM impairments are more strongly related to symptoms of inattention than to symptoms of hyperactivity-impulsivity. Four groups of children participated: ADHD (n = 62); ADHD+RD/LI (n = 32); RD/LI (n = 15); and a typically developing comparison group (n = 34). Four simple and brief measures of WM were used that varied in modality (auditory-verbal; visual-spatial) and processing demands (temporary storage versus manipulation of information). Children with ADHD without comorbid language learning disorders exhibited deficits in visual-spatial storage and verbal and visual-spatial central executive (C.E.) functions that were independent of comorbid psychiatric disorders. Children with language learning disorders, regardless of comorbidity with ADHD, exhibited impairments in both verbal and spatial storage as well as C.E. domains of WM. Symptoms of inattention, but not symptoms of hyperactivity/impulsivity, predicted performance on verbal and visual-spatial C.E. measures independent of age, verbal cognitive ability, and reading and language performance. Findings are consistent with data implicating neuropsychological impairments in ADHD. The dimensional results are also consistent with prior research demonstrating the neuropsychological impairments are more strongly associated with the inattention symptom dimension than with the hyperactive-impulsive dimension.

Attention Deficit Disorder with Hyperactivity↗

Influence of age and tic disorders on obsessive-compulsive disorder in a pediatric sample.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous disorder with emerging data suggesting that age of onset and/or the presence of tics may define clinically important subgroups. OBJECTIVE: This study set out to evaluate the impact of age and tic disorders on the symptom profile in a pediatric sample of patients with OCD ascertained from a specialty clinic. METHODS: Eighty children with OCD (50 boys, 30 girls) were assessed for symptom type, severity, age of onset, presence of a tic disorder, and functional status. Each child's most impairing obsessions and compulsions were identified and compared by age category (above and below the age of 11 years) and according to the presence or absence of a tic disorder. RESULTS: The mean age of the sample was 11.1 +/- 3.19 years (range 4-18 years). The most common obsessions reported were contamination and worries about harm. Common compulsions included washing and rituals to prevent harm. The only significant differences across age groups were the percentage of religious worries and slightly higher severity of obsessions in the adolescent age group (p < 0.05). The presence of tics was associated with increased frequency of repetitive behavior unrelated to harm avoidance (p < 0.05). Children without a history of tics were more likely to describe incidents of contamination, washing, and repetitive request for reassurance (p < 0.05 for each). CONCLUSION: In this convenient sample of clinically ascertained children, there were few phenotypic differences in children above or below the age of 11 years. Differences in the distribution of OCD symptoms according to the presence or absence of tics, which has been documented in adult samples, were evident in this sample.

Adolescent↗

Childhood-onset obsessive-compulsive disorder and tic disorders: case report and literature review.

A subgroup of childhood-onset obsessive-compulsive disorder (OCD) and tic disorders has been found to have a postinfectious autoimmune-mediated etiology. Clinical observations and systematic investigations have shown that a subgroup of children with OCD and/or tic disorders have the onset and subsequent exacerbations of their symptoms following infections with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and the temporal association between symptom exacerbations and GABHS infections. The proposed poststreptococcal inflammatory etiology provides a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin. A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma exchange were effective in reducing neuropsychiatric symptom severity (40 and 55% reductions, respectively) for a group of severely ill children in the PANDAS subgroup. Further research is required to determine why the treatments are helpful and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal symptom exacerbations.

Anti-Bacterial Agents↗

Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders.

Over a 5-yr period, 19 adults presented to our sleep disorders center with histories of involuntary, nocturnal, sleep-related eating that usually occurred with other problematic nocturnal behaviors. Mean age (+/- SD) at presentation was 37.4 (+/- 9.1) yr (range 18-54); 73.7% of the patients (n = 14) were female. Mean age of sleep-related eating onset was 24.7 (+/- 12.9) yr (range 5-44). Eating occurred from sleep nightly in 57.9% (n = 11) of patients. Chief complaints included excessive weight gain, concerns about choking while eating or about starting fires from cooking and sleep disruption. Extensive polysomnographic studies, clinical evaluations and treatment outcome data identified three etiologic categories for the sleep-related eating: (a) sleepwalking (SW), 84.2% (n = 16); (b) periodic movements of sleep (PMS), 10.5% (n = 2) and (c) triazolam abuse (0.75 mg hs), 5.3% (n = 1). DSM-III Axis 1 psychiatric disorders (affective, anxiety) were present in 47.4% (n = 9) of the patients, and only two patients had a daytime eating disorder (anorexia nervosa), each in remission for 3-7 yr. Nearly half of all patients fulfilled established criteria for being overweight, based on the body mass index. Onset of sleep-related eating was linked directly to the onset of SW, PMS, triazolam abuse, nicotine abstinence, chronic autoimmune hepatitis, narcolepsy, encephalitis or acute stress. In the SW group, 72.7% (8/11) of patients had nocturnal eating and other SW behavior suppressed by clonazepam (n = 7) and/or bromocriptine (n = 2) treatment. Both patients with PMS likewise responded to treatment with combinations of carbidopa/L-dopa, codeine and clonazepam. Thus, sleep-related eating disorders can generally be controlled with treatment of the underlying sleep disorder.

Adolescent↗

Obsessions with aggressive content emerging during the course of panic disorder: a different subtype of obsessive-compulsive disorder?

We report the clinical and therapeutic features of three patients with an obsessive-compulsive syndrome that emerged during the course of panic disorder. The DSM-IV criteria for panic disorder places central attention on the patient's phobic responses to the panic attacks and their perceived consequences. These phobic responses may develop into a syndrome that closely resembles obsessive-compulsive disorder (OCD) but typically responds to conventional anti-panic approaches. Our cases suggest that patients with OCD should be probed for an underlying panic disorder. This 'panic disorder-related subtype of OCD' may be associated with an excellent treatment response and increased rates of remission.

Adult↗

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders, substance use, and substance use disorders in preadolescent and adolescent offspring.

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.

Adolescent↗

Risk of substance use disorders in adolescents with bipolar disorder.

OBJECTIVE: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. METHOD: Probands with DSM-IV BPD (n=57, mean age +/- SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. RESULTS: Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or =13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi1=9.3, p=.002). CONCLUSIONS: These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder.

Adolescent↗

A controlled trial of methylphenidate in adults with attention deficit/hyperactivity disorder and substance use disorders.

AIMS: Attention deficit/hyperactivity disorder (ADHD) is common among adult patients with substance use disorders. The benefits of treating ADHD in these patients are uncertain and the prescription of psychostimulants is disputed, because of the risk of abuse. This study examined the short-term effectiveness of methylphenidate treatment for ADHD in adults with substance use disorders. DESIGN: Double-blind, placebo-controlled, multiple cross-over (A-B-A-B design) comparative trial of methylphenidate versus placebo. SETTING: In-patient addiction treatment facility. PARTICIPANTS: Twenty-five patients with ADHD who were receiving in-patient treatment for various substance use disorders. INTERVENTION: During the course of 8 weeks, each participant completed two phases of placebo and two phases of active medication treatment, in a fixed low-dosage schedule (up to 0.6 mg/kg/day). Abstinence was maintained during the study. MEASUREMENTS: The outcome measure was ADHD symptomatology, as measured with the ADHD rating scale-IV. The results were compared using MANOVA repeated measures. FINDINGS: Nineteen of the 25 patients completed the trial. A significant reduction in ADHD symptoms was observed in the first week in both conditions. The positive response to active treatment (nine patients; 36%) was not significantly higher than that to placebo (five patients; 20%). CONCLUSIONS: In this small pilot study, the effect of low-dose methylphenidate in adult ADHD patients with concomitant substance use disorders is limited. ADHD symptoms in adults were susceptible to a distinct short-term placebo response.

Adult↗

Posttraumatic stress disorder in patients with bipolar disorder: a review of prevalence, correlates, and treatment strategies.

OBJECTIVES: In this article, we review the evidence for, and implications of, a high rate of comorbid posttraumatic stress disorder (PTSD) in individuals with bipolar disorder. METHODS: We reviewed studies providing comorbidity data on patients with bipolar disorder, and also examined the PTSD literature for risk factors and empirically supported treatment options for PTSD. RESULTS: Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. Risk factors for PTSD that are also characteristic of bipolar samples include the presence of multiple axis I disorders, greater trauma exposure, elevated neuroticism and lower extraversion, and lower social support and socio-economic status. CONCLUSIONS: These findings are discussed in relation to the cost of PTSD symptoms to the course of bipolar disorder. Pharmacological and cognitive-behavioral treatment options are reviewed, with discussion of modifications to current cognitive-behavioral protocols for addressing PTSD in individuals at risk for mood episodes.

Bipolar Disorder↗

Acute treatment outcomes in patients with bipolar I disorder and co-morbid borderline personality disorder receiving medication and psychotherapy.

OBJECTIVE: Patients suffering from both bipolar I disorder and borderline personality disorder (BPD) pose unique treatment challenges. The purpose of this matched case-control study was to compare acute treatment outcomes of a sample of patients who met standardized diagnostic criteria for both bipolar I disorder and BPD (n = 12) to those who met criteria for bipolar I disorder only (n = 58). METHOD: Subjects meeting criteria for an acute affective episode were treated with a combination of algorithm-driven pharmacotherapy and weekly psychotherapy until stabilization (defined as four consecutive weeks with a calculated average of the 17-item version of the Hamilton Rating Scale for Depression and Bech-Rafaelsen Mania scale totaling < or = 7). RESULTS: Only three of 12 (25%) bipolar-BPD patients achieved stabilization, compared with 43 of 58 (74%) bipolar-only patients. Two of the three bipolar-BPD patients who did stabilize took over 95 weeks to do so, compared with a median time-to-stabilization of 35 weeks in the bipolar-only group. The bipolar-BPD group received significantly more atypical mood-stabilizing medications per year than the bipolar-only group (Z = 4.3, p < 0.0001). Dropout rates in the comorbid group were high. CONCLUSIONS: This quasi-experimental study suggests that treatment course may be longer in patients suffering from both bipolar I disorder and BPD. Some patients improved substantially with pharmacotherapy and psychotherapy, suggesting that this approach is worthy of further investigation.

Adult↗

DSM-III symptom disorders (Axis I) and personality disorders (Axis II) in an outpatient population.

Type and prevalence of Axis I and Axis II disorders (DSM-III) were assessed in a sample of 298 consecutive psychiatric outpatients. The instruments used were SCID and SIDP. About half of the Axis I diagnoses consisted of different subgroups of depression. Most patients had more than one diagnosis, anxiety being the second most common disorder. Eighty one percent of the subjects met the criteria for a personality disorder diagnosis; half of them obtained more than one Axis II diagnosis. Personality disorder was more common among men than among women. Avoidant and dependent personality disorders constituted the most frequent diagnoses.

Adult↗

Acute and transient psychotic disorder: comorbidity with personality disorder.

A study sample of 51 patients with acute and transient psychotic disorder (ATPD) (ICD-10) is presented. The findings suggest that, in hospital settings, ATPD is a non-frequent condition with onset in early adult life and most often associated with female sex, good premorbid social functioning and no or minor/moderate psychosocial stressors. The DSM-IV criteria distribute the patients into three diagnostic categories: schizophreniform disorder (41%), brief psychotic disorder (33%) and psychotic disorder not otherwise classified (25%). A high prevalence (63%) of personality disorders (PD) is revealed after recovery from the psychotic episode. The ATPD is not related to any specific PD, and in a substantial minority (37%) of cases no PD is found. The unspecified category is by far the most frequent PD in patients with ATPD. The sample will be followed up and reassessed.

Acute Disease↗