Effectiveness of Briefer Coping-Focused Psychotherapy for Common Mental Complaints on Work-Participation and Mental Health: A Pragmatic Randomized Trial with 2-Year Follow-Up.

Purpose The aim of this study was to assess short and long-term effectiveness of brief coping-focused psychotherapy (Brief-PsT) compared with short-term psychotherapy (Short-PsT) on work-participation (WP) and mental health. Both treatments were preceded by group education. Methods All participants were on, or at risk of, sick leave due to common mental complaints. Patients were selected for inclusion in this study based on levels of self-reported symptoms ('some' or 'seriously affected') of anxiety and depression. They were randomized to Brief-PsT (n = 141) or Short-PsT with a more extended focus (n = 143). Primary outcome was the transition of WP-state from baseline to 3 months follow-up. In addition, WP at 12 and 24 months follow-up were assessed. The secondary outcome, clinical recovery rate (CR-rate) was obtained from the Beck Depression and Beck Anxiety Inventories, at 2-year follow-up. In addition, self-reported mental health symptom severity, self-efficacy, subjective health complaints and life satisfaction were assessed. Results At 3 months follow-up, the increase in WP was significantly greater in Brief-PsT than in Short-PsT (p = 0.039). At 3 months, 60% in Brief-PsT and 51% in Short-PsT was at work, partial or full. Thereafter, these differences diminished, 84% and 80% were at work at 2-year follow up. The 2-year follow-up of the secondary outcome measurements was completed by 53% in Brief-PsT and 57% in Short PsT. CR-rate was significantly greater in Brief-PsT compared with the Short-PsT (69% vs. 51%, p = 0.024). Furthermore, there was a greater reduction in the number of subjective health complaints in Brief-PsT (4.0 vs. 1.9 p = 0.012). All other measurements favoured Brief-PsT as well, but did not reach statistical significance. Conclusions Brief coping-focused psychotherapy added to group education for persons with depression or anxiety complaints seemed more effective in enhancing early work participation compared with additional short-term psychotherapy of standard duration with more extended focus. Clinical recovery rate and decline of comorbid subjective health complaints at 2-year follow-up were also in favour of the brief coping-focused program.

Education, training, and practice among nordic neuropsychologists. Results from a professional practices survey.

OBJECTIVE: To investigate sociodemographic characteristics, clinical and academic training, work setting and salary, clinical activities, and salary and job satisfaction among practicing neuropsychologists in four Nordic countries. METHODS: 890 neuropsychologists from Denmark, Finland, Norway, and Sweden participated in an internet-based survey between December 2013 and June 2015. RESULTS: Three-fourths (76%) of the participants were women, with a mean age of 47 years (range 24-79). In the total sample, 11% earned a PhD and 42% were approved as specialists in neuropsychology (equivalent to board certification in the U.S.). Approximately 72% worked full-time, and only 1% were unemployed. Of the participants, 66% worked in a hospital setting, and 93% had conducted neuropsychological assessments during the last year. Attention deficit hyperactivity disorder, learning disability, and intellectual disability were the most common conditions seen by neuropsychologists. A mean income of 53,277 Euros was found. Neuropsychologists expressed greater job satisfaction than income satisfaction. Significant differences were found between the Nordic countries. Finnish neuropsychologists were younger and worked more hours every week. Fewer Swedish neuropsychologists had obtained specialist approval and fewer worked full-time in neuropsychology positions. Danish and Norwegian neuropsychologists earned more money than their Nordic colleagues. CONCLUSION: This is the first professional practice survey of Nordic neuropsychologists to provide information about sociodemographic characteristics and work setting factors. Despite the well-established guidelines for academic and clinical education, there are relevant differences between the Nordic countries. The results of the study offer guidance for refining the development of organized and highly functioning neuropsychological specialty practices in Nordic countries.

Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder.

Ellis-van Creveld syndrome, an autosomal recessively inherited chondrodysplastic dwarfism, is frequent among Old Order Amish of Pennsylvania. Decades of longitudinal research on bipolar affective disorder (BPAD) revealed cosegregation of high numbers of EvC and Bipolar I (BPI) cases in several large Amish families descending from the same pioneer. Despite the high prevalence of both disorders in these families, no EvC individual has ever been reported with BPI. The proximity of the EVC gene to our previously reported chromosome 4p16 BPAD locus with protective alleles, coupled with detailed clinical observations that EvC and BPI do not occur in the same individuals, led us to hypothesize that the genetic defect causing EvC in the Amish confers protection from BPI. This hypothesis is supported by a significant negative association of these two disorders when contrasted with absence of disease (P=0.029, Fisher's exact test, two-sided, verified by permutation to estimate the null distribution of the test statistic). As homozygous Amish EVC mutations causing EvC dwarfism do so by disrupting sonic hedgehog (Shh) signaling, our data implicate Shh signaling in the underlying pathophysiology of BPAD. Understanding how disrupted Shh signaling protects against BPI could uncover variants in the Shh pathway that cause or increase risk for this and related mood disorders.

Neuropsychological test profiles in schizophrenia and non-psychotic depression.

OBJECTIVE: The study examined to what degree schizophrenia is characterized by a neuropsychological (NP) test profile specific in shape and level compared with depression and normal functioning. METHOD: Fifty-three patients with schizophrenia, 45 with non-psychotic depression, and 50 normals were assessed with a comprehensive NP test battery and clinical instruments. NP test scores were factor analyzed into seven composite scores. RESULTS: Schizophrenia patients performed significantly below normals across all seven composite scores, whereas depression patients were impaired in two. Verbal memory was most impaired. Sixty-two percent of schizophrenia patients were moderately or severely impaired, the corresponding figure for depression was 28%. Impairment was moderately associated with IQ level and clinical symptom load in schizophrenia, but not in depression. CONCLUSION: Schizophrenia is characterized by deficits across a wide range of NP functions. Thirty-eight percent of the patients are within normal limits. A mild and limited NP disturbance is apparent in depression.

Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed.

OBJECTIVE: On a group level depression is related to hypercortisolism and to psychomotor retardation, executive dysfunction and memory impairment. However, intra-group heterogeneity is substantial. Why some are impaired while others remain in the normal range, is not clear. The present study aims at discerning the relative contribution of present symptom severity and hypercortisolism to impairment in the three domains of cognition. METHOD: Morning saliva cortisol was measured in 26 subjects with recurrent major depression prior to a neuropsychological examination with tests known to be sensitive to cognitive impairment in depression. RESULTS: Cortisol level correlated with executive dysfunction and post-encoding memory deficits, but not with processing speed. Depression level correlated with processing speed. These patterns remained significant after controlling for confounders through partial correlations. CONCLUSION: The association between cortisol and cognition is not an artifact of psychiatric symptom load. High level of saliva cortisol is associated with aspects of cognition that can be dissociated from psychomotor retardation, which is dependent on symptom load.

General psychopathology is more important for executive functioning than diagnosis.

OBJECTIVE: Impaired executive functioning (EF) has often been reported in patients with major depression or schizophrenia. We hypothesize that the variance in EF is more affected by level of general psychopathology than by diagnosis. METHOD: Forty-three patients with major depression and 47 with schizophrenia were included. EF was measured with Wisconsin Card Sorting Test, Stroop Colour Word Test, Paced Auditory Serial Addition Test, Digits Backwards and Controlled Oral Word Association Test. The level of general psychopathology was measured with Brief Psychiatric Rating Scale - Expanded and Positive and Negative Syndrome Scale, the General psychopathology subscale. RESULTS: The level of general psychopathology predicted more of the variance in EF than diagnosis. In multivariate analyses, the effect of general psychopathology on EF was more robust for adjustment for diagnosis than vice versa. CONCLUSION: Future research on cognitive functioning in psychiatric patients should include level of general psychopathology to avoid overemphasising effects of diagnoses.

Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable.

Attention profile in schizophrenia compared with depression: differential effects of processing speed, selective attention and vigilance.

OBJECTIVE: The aim of the study is to investigate whether subjects with schizophrenia and major depression display attention deficits for different reasons. METHOD: Subjects with schizophrenia (n = 53), recurrent major depression (n = 50) and normal controls (n = 50) were administered with 11 measures of processing speed, selective attention and vigilance. Indices of basal speed, speeded attention, non-speeded attention and vigilance were computed. RESULTS: Both clinical groups were impaired on all chronometric tests. The schizophrenic subjects were also more impaired on speeded attention compared with basal processing speed. Only the schizophrenics were impaired on the non-speeded measures of selective attention. Compared with the schizophrenics, the depressives showed a decrement in vigilance. CONCLUSION: Reduced performance on attention tests in major depression is because of a non-specific speed reduction and loss of vigilance consistent with lack of effort. In addition to generally impaired processing speed, the schizophrenic subjects exposed a deficit in selective attention, indicating executive dysfunction.

A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome (EvC; MIM 225500) is an autosomal recessive chondrodysplastic dwarfism. Thus far, the identified mutations in the EVC gene located on chromosome 4p16 have only accounted for illness in a small proportion of affected individuals. In this report we describe a novel gene, EVC2, that is mutated in an Ashkenazi individual with EvC syndrome. Our findings demonstrate for the first time that the heterogeneity observed in this disorder is not solely the result of mutations in a single gene.

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories.

OBJECTIVE: A priority for research on manic-depressive or bipolar I disorder (BPI) for children and adolescents has been to search for early predictors of the illness. METHOD: Medical record data were reviewed and systematically coded for a sample of 58 adult patients (32 males/26 females) with confirmed diagnoses of BPI to identify prodromal features and possible patterns of symptoms from the Amish Study. RESULTS: The most frequently reported symptoms included episodic changes in mood (depressed and irritable) and energy plus anger dyscontrol, with no significant gender differences. A progression of ages is seen for the most commonly reported symptoms prior to age 16. The time interval was 9 to 12 years between appearance of the first symptoms and onset of a documented BPI syndrome. CONCLUSIONS: The data suggest testable hypotheses about specific symptoms and behaviors that may be useful for the early detection of children at highest risk for developing manic-depressive disorder.

Evidence for genetic transmission of thyroid peroxidase autoantibody epitopic "fingerprints".

Autoimmune thyroid disease is characterized by the tendency to cluster in families and by IgG class autoantibodies to antigens such as thyroid peroxidase (TPO). The epitopes recognized by polyclonal serum autoantibodies can be quantitatively fingerprinted using four recombinant human TPO autoantibodies (expressed as Fab) that define A and B domain epitopes in an immunodominant region. To determine whether these fingerprints are genetically transmitted, we analyzed fingerprints of 63 members of 7 multiplex Old Order Amish families and 17 individuals from 4 Hashimoto thyroiditis families. Inhibition of serum autoantibody binding to [125I]TPO by the recombinant Fab was used to assess recognition of the TPO immunodominant region (4 Fab combined) and recognition of domain A or B (individual Fab). Complex segregation analysis was performed using a unified model (POINTER). For the 4 Fab combined inhibition phenotype, the no transmission model was rejected (chi2(4) = 20.67; P < 0.0032), and the most parsimonious model includes a major gene effect. More importantly, evidence for genetic transmission was obtained for the phenotype defined by the ratio of inhibition by subdomain Fab B1:B2. Thus, for this ratio (reflecting recognition of the B domain), the no transmission model was rejected chi2(4) = 63.59; P < 0.000008). Moreover, the polygenic hypothesis could be rejected, but not the major locus hypothesis, suggesting that major genes might be involved in familial transmission of this trait. In conclusion, our findings suggest that autoantibody recognition of the TPO immunodominant region and the TPO B domain is genetically transmitted. These data may open the way to the identification by candidate analysis or positional cloning of at least one gene responsible for the development of Hashimoto's thyroiditis.

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

Genetic linkage study of bipolar disorder and the serotonin transporter.

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter.

A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish.

The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) interspersed with periods of depression. Manic-depressive illness afflicts about one percent of the population, and if untreated, is associated with an approximately 20% risk of suicide. Twin, family and adoption studies provide compelling evidence for a partial genetic aetiology, but the mode(s) of inheritance has not been identified. Nonetheless, the majority of genetic linkage studies have assumed classical mendelian inheritance attributable to a single major gene. Although segregation analyses have yielded inconsistent results (with most studies rejecting a single locus inheritance model), the best single gene model is dominant inheritance if only BPI is considered. Reported linkages of bipolar affective disorder on chromosomes 11, 18, 21 and X have been difficult to substantiate, and additional studies are required for replication or exclusion of these regions. We now present the results of our genome-wide linkage analyses that provide evidence that regions on chromosomes 6, 13 and 15 harbour susceptibility loci for bipolar affective disorder, suggesting that bipolar affective disorder in the Old Order Amish is inherited as a complex trait.

Complex segregation analyses of old order Amish families ascertained through bipolar I individuals.

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation analyses of Old Order Amish families. The analyses were performed on 1) the total set of 42 families including 689 relatives, 2) a subset of 19 families consisting of those kindreds sharing common ancestors within three generations that contained 333 relatives, and 3) a subset of 23 more distantly related families with 356 relatives. When all 42 families were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme used in the analysis. An autosomal dominant mode of inheritance could be rejected when relatives with bipolar I, atypical bipolar, major depressive disorder, and hypomania were included as affected. When analyses included only the subset of families more closely related, an autosomal dominant inheritance model was found to be consistent with transmission of BP I disorder. It was not possible to distinguish between other transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distantly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic.

Initial report of a genome search for the affective disorder predisposition gene in the old order Amish pedigrees: chromosomes 1 and 11.

Family data have suggested that some forms of major affective disorder are genetic. Certain of the Old Order Amish pedigrees have a familial form of the disease. In this report we present the results of genetic analyses under autosomal dominant mode of transmission with reduced penetrance and three different disease hierarchies. The pedigrees were genotyped with 28 markers from chromosome 1 and 23 markers from chromosomes 11. None of the markers result in a significantly positive lod score.

A linkage study of distal chromosome 5q and bipolar disorder.

There are well-established abnormalities of hypothalamic-pituitary-adrenal (HPA) axis and beta 2 adrenergic receptor function in affective disorders. The genes for the glucocorticoid receptor (GRL) and the beta 2 adrenergic receptor (ADRB2) have been cloned and mapped to distal chromosome 5q. In this study, we have examined polymorphisms of these two candidate genes and other nearby markers for linkage to bipolar disorder in Amish pedigree 110 and three large Icelandic pedigrees. These loci were tested for linkage in two-point and multipoint analyses using a model of autosomal dominant transmission with age-dependent reduced penetrance. Two-point analyses revealed a maximum LOD score of 1.14 at theta = 0.20 from GRL. Linkage could be excluded to ADRB2, as well as to three nearby anonymous markers, D5S207, D5S70, and D5S119. Analyses of another anonymous marker, D5S36, were inconclusive. Multipoint analyses excluded linkage to a 55 cM region including the interval between D5S207 and D5S36 and flanking regions, with the exception of a 7 cM interval between GRL and ADRB2. Despite the intriguing positive LOD score obtained with GRL, linkage to bipolar disorder could not be demonstrated in the region examined.

A genetic linkage study of bipolar disorder and 13 markers on chromosome 11 including the D2 dopamine receptor.

Chromosome 11 is a region of great interest in the search for genes for bipolar disorder. Although an initial report of linkage to 11p15 was not replicated in numerous subsequent studies, the remainder of the chromosome contains a variety of interesting candidate genes and regions. These include the D2 dopamine receptor and the site of a chromosomal translocation that has been reported to be associated with bipolar disorder. As part of a systematic survey of the genome for markers linked to bipolar disorder, we have examined 13 markers on chromosome 11 in three large Icelandic families and Amish pedigree 110. No clear evidence of linkage was obtained. The highest lod score was found at D11S29 (lod = 1.63 at theta = 0.1), which is in the general region of the reported translocation breakpoints. However, this lod is not statistically significant, and its meaning is further mitigated by strongly negative lods in two nearby flanking markers. Linkage to the D2 dopamine receptor locus was strongly excluded (lod = -4.02 at theta = 0.0). In two-point analyses, linkage to bipolar disorder could be excluded to eight of the 13 markers. Multipoint analyses, similarly, failed to reveal any evidence of linkage.