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The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia.

The paper discusses the application of fMRI in combination with neuropsychology to neurodevelopmental psychiatric disorders, exemplified on the case of attention deficit hyperactivity disorder (ADHD) in comparison with schizophrenia. The view is presented that ADHD, rather than being a compound of unrelated co-existing deficits, is a pervasive disorder of impulsiveness, which manifests at the motor, emotional, social and cognitive domain. Neuropsychology needs to refine the psychological measurements of these impulsivity symptoms and, in combination with fMRI, provide new insights into the interrelationship between brain and dysfunction and its bi-directional causalities. The suitability of the dynamic technique of functional MRI to assess the dynamic nature of developmental neuropsychiatric disorders is discussed. Brain activation can inform about strategy and compensatory mechanisms at a neuroanatomical level, which are not observable at a psychological level, providing insight into the underlying neurocognitive mechanisms of psychiatric disorders. Data are presented and discussed on opposing neurocognitive activation patterns for patients with ADHD and those with schizophrenia while performing a stop task. Comparisons between patient groups will be essential to address the specificity of neurocognitive mechanisms corresponding to specific neurodevelopmental psychiatric disorders.

Aging↗

Personality disorders do not influence the results of cognitive and behavior therapy for obsessive compulsive disorder.

This study examined whether categorical or dimensional personality disorder variables affected treatment outcome in a sample of 52 patients with obsessive compulsive disorder who followed a standardized cognitive behavior therapy program. Treatment consisted of 12 weekly sessions and was completed by 43 patients. The Structured Clinical Interview for DSM-III-R personality disorders (SCID-II) was taken before the start of treatment by an independent rater. The treatment outcome measures included questionnaires and a Behavioral Assessment Test. Measurements were taken before and after treatment, and at 1 and 6 month follow-up tests. After the first follow-up test, further treatment was provided if clinically indicated. Neither categorical, nor dimensional personality disorder variables affected treatment outcome significantly. The inclusion of drop-outs in the analyses, did not change these results. Therefore, patients with obsessive compulsive disorder and concomitant personality disorder pathology should not be excluded from cognitive or behavior therapy for their obsessive compulsive complaints. Attributing therapy failure to concomitant Axis II pathology should be approached with caution.

Adolescent↗

Prevalence of personality disorders among combat veterans with posttraumatic stress disorder.

Many combat veterans with PTSD have co-occurring symptoms of other forms of psychopathology; however, there have been limited studies examining personality disorders among this population. The few extant studies typically have assessed only two or three personality disorders or examined a small sample, resulting in an incomplete picture and scope of comorbidity. This study assessed all DSM-III-R personality disorders in 107 veterans in a specialized, inpatient unit. Using the Structured Clinical Interview for DSM-III-R Personality Disorders, 79.4% of the participants were diagnosed with at least one personality disorder: 29.9% received only one diagnosis, 21.5% had two, 15.9% had three, and 12.1% had four or more. The most frequent single diagnoses were Avoidant (47.2%), Paranoid (46.2%), Obsessive-Compulsive (28.3%), and Antisocial (15.1%) personality disorders.

Cluster Analysis↗

PTSD and comorbid psychotic disorder: comparison with veterans diagnosed with PTSD or psychotic disorder.

Symptoms of posttraumatic stress disorder (PTSD), psychosis, general psychopathology, role functioning, violence potential, and cognitive and emotional aspects of psychotic states were compared in three groups of veterans. Groups were defined on the basis of their DSM-IV diagnoses: Psychotic disorder and war-related PTSD, war-related PTSD without psychotic symptoms, and psychotic disorder without PTSD. Veterans with PTSD and a comorbid psychotic disorder showed significantly higher levels of positive symptoms of psychosis, general psychopathology, paranoia, and violent thoughts, feelings, and behaviors than the other two groups. These data show that patients with comorbid PTSD and psychotic disorder show levels of cognitive, emotional, and behavioral disturbance that far exceed the levels of disturbance seen in patients with PTSD without psychosis or in patients with psychotic disorder.

Adult↗

[Transcranial magnetic stimulation in child and adolescent psychiatry: excitability of the motor system in tic disorders and/or attention deficit hyperactivity disorders].

Motor system excitability can be investigated in vivo by means of single and paired pulse transcranial magnetic stimulation (TMS). Whereas the cortical silent period reflects the general degree of inhibitory mechanisms mainly within the sensorimotor loop, intracortical excitability measures the focused degree of inhibitory and facilitatory mechanisms within the motor cortex. In child and adolescent psychiatric disorders with uncontrollable motor behavior such as tics in tic disorder or motoric hyperactivity in attention deficit hyperactivity disorder (ADHD), different dysfunctional patterns of motor system excitability could be demonstrated compared to age-matched healthy controls: (1) In tic disorder, a shortened cortical silent period was observed, providing evidence of deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. (2) In ADHD, a decreased intracortical inhibition was found, probably reflecting deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In order to investigate neurophysiological aspects of comorbidity, (3) motor system excitability was also measured in children with combined ADHD and tic disorder. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence of additive effects at the level of motor system excitability. These decreased inhibitory mechanisms within the entire sensorimotor loop and especially the motor cortex could be essential neurobiological substrates of the deficient inhibitory motor control and regulation, respectively, in tic disorder and ADHD.

Adolescent↗

[Aetiology and life-course of conduct disorder in childhood: risk factors for the development of an antisocial personality disorder].

OBJECTIVES: Conduct disorders are among the most common disorders encountered in child and adolescent psychiatry. They represent a heterogeneous group of disorders, each with a different psychopathology and a different life-course. While antisocial behaviour is only transient in some children, others show increasing criminal behaviour and delinquency, and some even develop an antisocial personality disorder. METHODS: This review presents substantial biological and psychosocial factors, as well as their interaction in the aetiology of conduct disorders. Changes in autonomic responsiveness are emphasized. RESULTS: Especially young children with conduct problems seem to be at greater risk for persistent and more widespread antisocial behaviour. Some of these children have emotional disturbances similar to those of psychopathic individuals. CONCLUSIONS: In order to prevent a negative course of the disorder, the relevance of primary care for children at high risk for antisocial behaviour is emphasized. In this context, the application of psychophysiological methods might be useful, in order to identify these children at an early stage.

Adolescent↗

Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nation-wide cohort study in Denmark.

OBJECTIVE: To investigate whether breast cancer patients have increased incidence of psychiatric admission with affective disorders, anxiety disorders, or non-natural mortality compared with the general female population. METHOD: Register-linkage between nation-wide registries: The Danish Psychiatric Central Register, The Danish Cancer Registry, and The Danish National Register of Causes of Death. A total of 61 709 women registered with primary invasive breast cancer between 1970 and 1993 were included and 356 023 person-years were accrued. RESULTS: The standardized incidence ratio of first-ever psychiatric admission with affective disorder was 1.49 (95% CI: 1.35-1.63) and with anxiety disorder 1.25 (95% CI: 1.06-1.46). The standardized non-natural mortality ratio during the first year after breast cancer diagnosis was 1.54 (95% CI: 1.27-1.87). All analyses were adjusted for age, calendar period, and place of residence. CONCLUSION: Breast cancer patients have significantly increased incidence of psychiatric admission with affective disorders, anxiety disorders, and non-natural mortality.

Adolescent↗

Eating disorder or disordered eating? Non-normative eating patterns in obese individuals.

Binge eating disorder (BED) and night eating syndrome (NES) are putative eating disorders frequently seen in obese individuals. Data suggest that BED fulfills criteria for a mental disorder. Criteria for NES are evolving but at present do not require distress or functional impairment. It remains unclear whether BED and NES, as they are currently defined, are optimally useful for characterizing distinct patient subgroups. We propose that a distinction be made between "eating disorders" and "non-normative" eating patterns without associated distress or impairment. Although non-normative eating patterns may not be considered mental disorders, they may be very important in terms of their impact on body weight and health. More precise behavioral and metabolic characterization of subgroups with eating disorders and non-normative eating behaviors has important implications for understanding the etiology, pathophysiology, and treatment of obesity. Ultimately, better understanding of the many pathways to increased energy intake may lead to targeted strategies for prevention of overweight and obesity in at-risk individuals and populations.

Bulimia↗

Positron emission tomography of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without borderline personality disorder.

Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.

Adult↗

Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders?

The fatty acid compositions of red blood cell (RBC) phospholipids from a patient with autistic spectrum disorder (ASD) had reduced percentages of highly unsaturated fatty acids (HUFA) compared to control samples. The percentage of HUFA in the RBC from the autistic patient was dramatically reduced (up to 70%) when the sample was stored for 6 weeks at -20 degrees C. However, only minor HUFA reductions were recorded in control samples stored similarly, or when the autistic sample was stored at -80 degrees C. A similar instability in RBC HUFA compositions upon storage at -20 degrees C has been recorded in schizophrenic patients. In a number of other neurodevelopmental conditions, including attention deficit hyperactivity disorder (ADHD) and dyslexia, reduced concentrations of RBC HUFA have been recorded. The extent and nature of these aberrations require further assessment to determine a possible common biochemical origin of neurodevelopmental disorders in general. To facilitate this, a large scale assessment of RBC fatty acid compositions in patients with ASD, and related disorders, should be performed as a matter of urgency. Supplementing cells in culture with the tryptophan metabolite indole acrylic acid (IAA) affected the levels of cellular HUFA and prostaglandin production. Indole acroyl glycine (IAG), a metabolite of IAA excreted in urine, is found in high concentrations in patients with neurodevelopmental disorders including ASD, ADHD, dyslexia, Asperger's syndrome and obsessive compulsive disorder.

Asperger Syndrome↗

Sleep disorders and daytime sleepiness in children with attention-deficit/hyperactive disorder.

STUDY OBJECTIVES: Children with attention-deficit/hyperactive disorder (ADHD), in spite of being hyperactive, still benefit from treatment with stimulant medications. We hypothesized that children with ADHD are in fact sleepy during the day, and we sought to test it objectively. DESIGN: Single blind comparative study SETTING: University medical center PARTICIPANTS: Thirty-four children with a previous diagnosis of ADHD (mean age +/- SD, 12.4 +/- 4.6 years) and 32 matched controls (mean age, 12.0 +/- 3.6 years). INTERVENTIONS: N/A. MEASUREMENTS: All participants underwent a full-night polysomnographic study followed by a multiple sleep latency test (MSLT). RESULTS: Sleep latency, total sleep time, and sleep efficiency were comparable between the groups, yet children with ADHD were significantly sleepier during the day than those in the control group (mean MSLT score of 21.9 +/- 5.5 minutes versus 27.9 +/- 2.0 minutes, P < .005). Of the children with ADHD, 17 (50%) had signs of sleep-disordered breathing, compared with 7 of the control group (22%, P < .05). Five of the ADHD group had periodic limb movements during sleep (15%) versus none in the control group. Children without sleep-disordered breathing or periodic limb movements during sleep had the lowest nocturnal sleep efficiency and total sleep time. CONCLUSIONS: We conclude that children with ADHD demonstrate objective daytime somnolence, which may explain the beneficial effects of treatment with stimulant medications. Primary sleep disorders, especially sleep-disordered breathing and periodic limb movement disorder, should be looked for in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Autistic disorder and post-traumatic stress disorder.

The present case study examined an adolescent boy who initially was evaluated at our clinic and was found to meet DSM-III-R criteria for autistic disorder. After placement in a residential school using Daily Life Therapy for autistic disorder, the subject reported being physically abused by a staff member. Additional psychiatric evaluation revealed post-traumatic stress disorder (PTSD) including symbolic anxiety and repetition of the trauma. The diagnosis of PTSD should be considered in children with autistic disorder and other severe developmental disorders who have experienced physical and sexual abuse. Furthermore, parents, professionals, educators, and child care workers struggle with emotional reactions to children with severe developmental disorders and may have difficulty accepting the reality of the child rather than the fantasy of the "wished-for child." The disappointment of this fantasy and the equating of the child's weaknesses as one's own may lead to personal devaluation and increase the risk of abusive behavior.

Autistic Disorder↗

A 5-year follow-up study of generalized anxiety disorder and panic disorder.

To examine the course and outcome of subjects with generalized anxiety disorder (GAD) and panic disorder, we compared 64 patients with GAD and 68 patients with panic disorder who had participated in drug treatment studies and were interviewed an average of 5 years earlier. At baseline GAD subjects were significantly older, had an earlier onset, and longer duration of illness than panic subjects. GAD subjects also had less severe symptoms. At follow-up, diagnostic stability was observed for both GAD and panic disorder. Significantly fewer GAD subjects achieved full remission at follow-up (18% vs. 45%, p < .01). Subjects with GAD were significantly less anxious at baseline than the panic disorder comparison group, but at follow-up there were few significant differences between groups on most severity of illness variables. This change was due in great part to improvement in the panic disorder group with a concomitant lack of change in the GAD group.

Adult↗

Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor).

BACKGROUND: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. METHODS: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. RESULTS: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. CONCLUSIONS: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Adolescent↗

HIV risk behavior among psychiatric outpatients: association with psychiatric disorder, substance use disorder, and gender.

People living with a mental illness are disproportionately vulnerable to human immunodeficiency virus. The current study sought to examine the influence of psychiatric disorder, substance use disorder, and gender on risky sexual behavior in this vulnerable population. Participants were 228 female and 202 male outpatients (66% mood disorder, 34% schizophrenia), each of whom took part in a Structured Clinical Interview for the DSM-IV and a comprehensive assessment of sexual risk behavior. Univariate and multivariate analyses tested a priori hypotheses. The results indicated that risk behavior was more frequent among patients diagnosed with a mood disorder (compared with those diagnosed with schizophrenia) or a substance use disorder (compared with those without a comorbid disorder) or both. We recommend routine human immunodeficiency virus risk screening and risk reduction programs for this vulnerable population.

Adult↗

Substance use disorders: Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases, tenth edition (ICD-10).

AIMS: Two major nomenclatures, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases, tenth edition (ICD-10), currently define substance use disorders for broad audiences of users with different training, experience and interests. A comparison of these definitions and their implications for DSM-V and ICD-11 has not been available. METHODS: The background for the dependence concept and abuse, harmful use, withdrawal, substance-induced disorders and remission and other substance-related conditions is reviewed. Reliability evidence is presented, as is validity evidence from approaches including psychometric, genetic and animal studies. The relevance of the DSM-IV and ICD-10 compared to alternative systems (e.g. the Addiction Severity Index) is considered. RESULTS: Reliability and psychometric validity evidence for substance dependence is consistently strong, but more mixed for abuse and harmful use. Findings on the genetics of alcohol disorders support the validity of the dependence concept, while animal studies underscore the centrality of continued use despite negative consequences to the concept of dependence. While few studies on substance-induced disorders have been conducted, those published show good reliability and validity when elements of DSM-IV and ICD-10 are combined. CONCLUSIONS: Dependence in DSM-V and ICD-11 should be retained, standardizing both criteria sets and adding a severity measure. The consequences of heavy use should be measured independently of dependence; add cannabis withdrawal if further research supports existing evidence; conduct further studies of the substance-induced psychiatric categories; standardize their criteria across DSM-V and ICD-11; develop a theoretical basis for better remission criteria; consider changing substance 'abuse' to substance 'dysfunction disorder'; and conduct clinician education on the value of the diagnostic criteria.

Alcoholism↗

What characterizes substance abusers who commit suicide attempts? Factors related to Axis I disorders and patterns of substance use disorders. A study of treatment-seeking substance abusers in Norway.

OBJECTIVE: The frequency of suicide attempts and clinical characteristics of attempters among poly-substance abusers and alcoholics were examined. METHODS: A consecutive sample (n = 260) of in- and outpatients from two Norwegian counties were assessed by Composite International Diagnostic Interview (Axis I disorders), Millon's Clinical Multiaxial Inventory (Axis II disorders) and the Norwegian National Client Assessment Form. When analysing the association between suicide attempters and the range of predictor variables, logistic regression analysis was conducted. RESULTS: Almost half (47%) of the sample reported lifetime suicide attempts; significantly more frequently in poly-substance abusers (58%) than alcoholics (38%). A substance use disorder with duration of >or=15 years and an early onset (<18 years of age) were independently associated with being a suicide attempter after controlling for Axis I disorders. In addition, eating disorders, agoraphobia and major depression were strongly and independently associated with being a suicide attempter. CONCLUSION: Attempts at preventing suicidal behaviour should not ignore the suicide risk among poly-substance abusers. In addition, prevention of suicidal behaviour demands a treatment programme focusing concomitantly on both addictive behaviour and comorbid psychiatric disorders.

Activities of Daily Living↗

Response to hyperventilation and 5.5% CO2 inhalation of subjects with types of specific phobia, panic disorder, or no mental disorder.

OBJECTIVE: This study tested the hypothesis that compared to other DSM-IV specific phobia types, situational specific phobias have more in common with panic disorder and agoraphobia. METHOD: Responses to hyperventilation and CO2 inhalation were compared across groups of patients with the four main DSM-IV specific phobia types, a group with panic disorder, and a group of comparison subjects with no anxiety disorder (N = 15 per group). RESULTS: Although these challenges have been shown previously to distinguish patients with panic disorder from other groups, no groups differed significantly in their responses to hyperventilation. In addition, whereas the patients with panic disorder responded more to the CO2 challenge than did the normal subjects, the specific phobia groups did not differ from one another or from the other groups on most measures. For the few CO2 measures on which specific phobia groups differed, patients with situational and natural environment phobias showed the greatest response. CONCLUSIONS: Overall, these findings provided only limited support for the hypothesis that situational specific phobias are related to panic disorder.

Adolescent↗