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Suicidal ideation, deliberate self-harm behaviour and suicide attempts among adolescent outpatients with depressive mood disorders and comorbid axis I disorders.

OBJECTIVE: We aimed to analyse and compare prevalence and associated clinical features of suicidal ideation, self-harm behaviour with no suicidal intent and suicide attempts among adolescent outpatients with depressive mood disorders with or without comorbidity. METHOD: A sample of 218 consecutive adolescent outpatients aged 13-19 years with depressive mood disorders was interviewed using K-SADS-PL for DSM-IV Axis I diagnoses. They filled out self-report questionnaires assessing depressive and anxiety symptoms. Suicidal behaviour was assessed by K-SADS-PL suicidality items. RESULTS: Half of the subjects reported suicidal ideation or behaviour. There was no difference in prevalence of suicidal behaviour between non-comorbid and comorbid mood disorder groups. Multivariate logistic regression analyses produced the following associations: (1) suicidal ideation with self-reported depressive symptoms and poor psychosocial functioning, (2) deliberate self-harm behaviour with younger age and poor psychosocial functioning, and (3) suicide attempts with self-reported depressive symptoms and poor psychosocial functioning. CONCLUSIONS: Depressed mood disorders, whether comorbid or not, are associated with suicidal ideation and suicide attempts. Diagnostic assessment should be supplemented by self-report methods when assessing suicidal behaviour in depressed adolescents.

Adolescent↗

Auditory P300 does not differentiate borderline personality disorder from schizotypal personality disorder.

The P300 response to an auditory two-tone discrimination task has previously been reported to have prolonged latency and reduced amplitude in schizophrenia and borderline personality disorder. In this study, P300 was recorded from 23 subjects with borderline personality disorder, 12 subjects fulfilling criteria for both borderline and schizotypal personality, and 11 subjects with schizotypal personality. The mean P300 latency was similar in each of these groups and was significantly longer than in 32 patients with neuroses and other personality disorders and 74 nonpatient controls. These findings suggest that borderline and schizotypal patients share a similar abnormality in auditory stimulus evaluation and question whether or not these disorders are separate.

Adolescent↗

A comparison of DSM-III personality disorders in panic/agoraphobia and obsessive-compulsive disorder.

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (161 with agoraphobia) and 51 patients meeting DSM-III criteria for obsessive-compulsive disorder (OCD) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess axis II personality disorders and traits. The results showed that the personality profiles were similar between the two diagnostic groups and that the major personality characteristics identified in panic/agoraphobic patients, e.g., avoidant, dependent, histrionic, and borderline, were more pronounced in patients with OCD. These findings support our earlier suggestion of a nonspecific link between panic disorder/agoraphobia and personality disorder (PD)/traits.

Adult↗

Delimitation of generalized anxiety disorder: clinical comparisons with panic and major depressive disorders.

We compared 40 outpatients with "pure" generalized anxiety disorder (GAD) with 152 panic disordered patients with varying degrees of phobic avoidance, and 241 primary major depressives with single and recurrent episodic patterns. Despite sociodemographic and symptomatologic overlaps with these comparison groups, GAD emerged as a relatively distinct disorder, characterized by chronic low-grade symptomatology with observed anxiety at interview, as well as nausea, headache, tension, and insomnia. These anxious "traits," which appear to be part of the habitual self of the patient, are subject to fluctuation over time, and may form the temperamental substrate or precursor of panic and other anxiety and depressive disorders.

Adult↗

Personality trait differences in boys and girls with clinical or sub-clinical diagnoses of conduct disorder versus antisocial personality disorder.

This study tested differences in personality traits measured by the Multidimensional Personality Questionnaire (MPQ) in a community sample of adolescents with definite or probable conduct disorder (CD) diagnoses that did not progress to a diagnosis of antisocial personality disorder (ASPD) by early adulthood (n=43), those with definite or probable ASPD that persisted into early adulthood (n=68), or controls with neither a CD nor an ASPD diagnosis (n=716) to examine whether antisocial behaviour disorders that differed in course were associated with differences in personality traits. As expected, boys and girls with ASPD were significantly different from controls on constraint, and those with ASPD were significantly lower on constraint than those with only CD. The results suggest that individual differences in certain personality traits may contribute to differences in the type of antisocial behaviour disorder that emerges and thereby to the course of antisocial behaviour.

Adolescent↗

Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: a familial risk analysis.

BACKGROUND: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the 1533 first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly higher rates of ADHD compared with controls (4.6%; p < or = .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a significantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype.

Adolescent↗

Obsessing/worrying about the overlap between obsessive-compulsive disorder and generalized anxiety disorder in youth.

In the treatment of anxious youth, children's symptom presentations cannot always be readily distinguished as indicative of obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD). Following a definition and brief description of the phenomenology, epidemiology, and treatment of OCD and GAD in youth, consideration is given to factors that contribute to the proximity of the two disorders. In an effort to better understand the distinctive and overlapping features of these neighboring disorders, we review (a) obsessions and worry, with reference to process, form, content, and metacognitive beliefs, and (b) the literature on pathological worry and covert compulsions. Studies from the adult literature are considered throughout, and the absence of related work with samples of youth, within a developmental framework, is highlighted. Suggestions for future research are offered.

Adolescent↗

Brain metabolic changes associated with predispotion to onset of major depressive disorder and adjustment disorder in cancer patients--a preliminary PET study.

OBJECTIVES: To explore neurobiological risk factors for major depressive disorder (MDD) and adjustment disorder in cancer patients by examining regional brain metabolism before psychiatric manifestation using positron emission tomography and by prospectively observing depressive and anxiety symptoms. METHOD: Cancer patients who showed no psychiatric symptoms when they underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were followed up for one year using the Hospital Anxiety and Depression Scale (HADS). Fourteen patients who showed high HADS scores and 14 patients who showed low HADS scores were assessed by a psychiatrist 2 years after the PET scan and grouped into the deterioration group (n=10) and the no-change group (n=9). 18F-FDG PET images were analyzed to examine the difference in local brain glucose metabolism between the two groups. RESULTS: The deterioration group showed a decreased glucose metabolism in the right medial frontal gyrus (BA6) and an increased glucose metabolism in the right posterior cingulate (BA29), right anterior cingulate (BA25), left subcallosal gyrus (BA25), and left caudate compared with the no-change group. CONCLUSION: Cancer patients who later developed MDD or adjustment disorder showed regional brain metabolic changes. These regions may be associated with vulnerability to the onset of MDD or adjustment disorder in cancer patients.

Adjustment Disorders↗

Language disorder in schizophrenia as a developmental learning disorder.

Receptive language disorder in schizophrenia is hypothesized to represent a learning disorder that involves a neurodevelopmental etiology. It is argued that a preexisting developmental language disorder may characterize a subset of schizophrenia patients. A primary deficit in the temporal dynamics of brain function is assumed to cause receptive language disorder in schizophrenia. This hypothesized core deficit includes both disturbance in the processing of rapid, sequential information and disruptions to patterns of brain activation and synchronization. These timing deficits may alter the way associative connections are formed and/or accessed in semantic memory. It is suggested that abnormalities in second-messenger pathways of subcortical-cortical circuitry offer an etiological nexus for language dysfunction in schizophrenia and developmental dyslexia.

Brain↗

Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment.

BACKGROUND: Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms. AIM: To examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder. METHODS: Seventy-nine patients were randomized to integrated treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to psychotic disorder. RESULTS: In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk=4.47, (confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk=0.36 (confidence interval 0.16-0.85)). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment compared to 48.3% for patients randomized to standard treatment. CONCLUSION: Integrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.

Adult↗

Two-phase treatment of panic disorder and posttraumatic stress disorder with associated personality features resulting from childhood abuse: case study.

The treatment of a women diagnosed with panic disorder with Agoraphobia and posttraumatic stress disorder and maladaptive personality features resulting from childhood sexual and physical abuse is described. The treatment consisted of nine sessions of cognitive behavior therapy (CBT) for Panic Disorder with Agoraphobia and nine sessions of implosive therapy (IT) for Posttraumatic Stress Disorder. CBT decreased scores on the clinical scales of the Personality Assessment Inventory (PAI), but did not reduce revised Impact of Event Scale (IES) scores, or Dimensional Assessment of Personality Problems-Basic Questionnaire (DAPP-BQ). IT decreased scores on the IES and the DAPP-BQ, and further reduced scores on the PAI. The results are discussed with regard to Levis' (1985) implosive theory of psychopathology, which suggests that psychopathology can be explained by Pavlovian conditioning of serial cues and instrumentally conditioned avoidance responses.

Child↗

The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia.

BACKGROUND: There is strong evidence for the presence of a deficit in cortical gamma aminobutyric acid (GABA) neurotransmission in schizophrenia. In this investigation we have used the calcium binding proteins (CBPs) parvalbumin (PV), calretinin (CR), and calbindin-D28K (CB) as markers of these neuronal populations, and have characterized their pattern and density in schizophrenia, bipolar disorder (BPD), and major depressive disorder (MDD). METHODS: We examined the anterior cingulate cortex (ACC) in four groups of 15 brains each from subjects with schizophrenia, MDD, and BPD, and from control subjects. Using immunocytochemistry to identify these distinct neuronal populations, we quantified their areal density and spatial pattern organization. RESULTS: There were reductions in the density of CB-labeled neurons in layer 2 in schizophrenia (34%; p =.04) and BPD (33%; p =.05) compared with control subjects; however, after correction for multiple comparisons these findings no longer attained formal statistical significance. We observed no differences in the density of the neuronal populations labeled by CR or PV in any layer of the cortex in any disorder compared with control subjects. There was increased clustering among PV-labeled neurons in BPD compared with control subjects but no significant differences in the spatial organization of the other neuronal subpopulations in any disorder. CONCLUSIONS: The study provides some support for the presence of a deficit in GABAergic neurons in schizophrenia and shows that these changes are not specific to schizophrenia. The findings indicate that there may be a pathophysiological condition, shared by subjects with schizophrenia and BPD, which operates to selectively reduce the number or protein expression of CB-immunoreactive neurons.

Adult↗

An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder.

BACKGROUND: Despite the increasing recognition of comorbid attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) in adults, there are no prospective trials of pharmacological agents to treat ADHD in these patients. Given the efficacy of bupropion for ADHD in adults, as well as its use in the management of bipolar depression, we studied the tolerability and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD. METHODS: This was an open, prospective, 6-week trial of bupropion SR (up to 200 mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I) (10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic agents (mood stabilizers and antipsychotics) at baseline were included in the study. We used standardized psychiatric instruments for diagnosis and outcome. Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for ADHD and the ADHD symptom checklist. RESULTS: Of 36 patients entered (75% male, mean age 34 years), 30 patients (83%) completed the protocol. At end point (last observation carried forward [LOCF]) compared to baseline, treatment with bupropion SR resulted in significant reductions in the ADHD symptom checklist (-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001). Bupropion was associated with reductions in ratings of mania and depression. CONCLUSIONS: The results from this open study of adults with ADHD plus BPD suggest that sustained-release bupropion may be effective in treating ADHD in the context of a lifetime diagnosis of BPD, without significant activation of mania. Further controlled trials are warranted.

Adult↗

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics.

BACKGROUND: A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus. METHODS: Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277). RESULTS: Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS: Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.

Antibodies, Bacterial↗

No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism.

BACKGROUND: The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc). METHODS: Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Alc randomly selected from a Finnish alcoholic population in which an association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. RESULTS: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in 1 OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Alc, or suicidality. CONCLUSION: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated.

Alcoholism↗

Association between panic disorder, major depressive disorder and celiac disease: a possible role of thyroid autoimmunity.

OBJECTIVE: To evaluate the association between celiac disease and specific anxiety and depressive disorders and to identify potential common pathogenetic links, with particular regard to thyroid function and autoimmunity. METHODS: Cases included 36 adult celiac patients, 25 females and 11 males, aged 18-64 years. Controls comprised 144 healthy subjects matched by sex and age with no clinical evidence or family history of celiac disease. Diagnosis of celiac disease was made on the basis of clinical history and serological criteria. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview, according to DSM-IV criteria. Thyroid was evaluated by palpation, echography and measurement of serum-free thyroid hormones (FT4, FT3), thyroid-stimulating hormone (TSH) and antithyroid autoantibodies (anti-TPO). RESULTS: Compared to controls, a significantly higher number of celiac patients met criteria for lifetime [15 (41.7%) versus 30 (29.8%), P < .01] and 6-month [7 (19.4%) versus 9 (6.2%), OR = 3.2, chi(2) = 5.2, P < .05] major depressive disorder (MDD) and lifetime [5 (13.9%) versus 3 (2.1%), P < .001] and 6-month [3 (8.1%) versus 2 (1.4%), P < .05] panic disorder (PD). Anti-TPO prevalence was significantly higher in celiac patients than in the control group (11/36 = 30.5% versus 14/144 = 9.7%, P < .001). A higher frequency of PD and MDD was found in celiac patients with positive anti-TPO when compared to negative anti-TPO patients (4/11 = 36.4% PD in TPO+ versus 1/25 = 4% PD in TPO-, P < .01; 9/11 = 81.8% MD in TPO+ versus 6/25 = 9.5% MD in TPO-, P < .01). CONCLUSION: Patients affected by celiac disease tend to show a high prevalence of PD and MDD and association with subclinical thyroid disease appears to represent a significant risk factor for these psychiatric disorders.

Adolescent↗

Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood.

BACKGROUND: In children, exacerbations of tics and obsessive symptoms may occur after infection with group A beta-haemolytic streptococci. If post-streptococcal autoimmunity is the cause of the exacerbations, then children might respond to immunomodulatory treatments such as plasma exchange or intravenous immunoglobulin (IVIG). We studied whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms. METHODS: Children with severe, infection-triggered exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including Tourette syndrome, were randomly assigned treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (saline solution given in the same manner as IVIG). Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, tics, anxiety, depression, and global function. FINDINGS: 30 children entered the study and 29 completed the trial. Ten received plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma exchange groups showed striking improvements in obsessive-compulsive symptoms (mean improvement on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%], respectively), anxiety (2.1 [31%] and 3.0 [47%] improvement on National Institute of Mental Health anxiety scale), and overall functioning (2.9 [33%] and 2.8 [35%] improvement on National Institute of Mental Health global scale). Tic symptoms were also significantly improved by plasma exchange (mean change on Tourette syndrome unified rating scale of 49%). Treatment gains were maintained at 1 year, with 14 (82%) of 17 children "much" or "very much" improved over baseline (seven of eight for plasma exchange, seven of nine for IVIG). INTERPRETATION: Plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. Further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies.

Adolescent↗

Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype?

BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.

Adolescent↗