Long-term effects of preterm birth on large-scale brain organization

Being born preterm (< 37 weeks of gestation)increases the risk for several psychiatric disorders, cognitive impairments, and academic underachievement. It is hypothesized that this is due to perinatal brain injury and subsequent alterations in brain development. Structural and functional magnetic resonance imaging allows the identification of such brain abnormalities in-vivo. Accordingly, previous MRI studies have shown that preterm Born infants, children and adolescents demonstrate both structural and functional alterations when compared to their term born peers. However, it is unclear whether such changes persist into adulthood. Therefore, the present doctoral Thesis aimed to investigate the long-term effects of preterm birth on large-scale brain organization. Study I: in 95 preterm and 83 full-term Born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial Patterns of intrinsic functional connectivity (iFC) in ongoing blood oxygenation level–dependent activity. We found widespread iFC differences that overlapped and correlated with aberrant regional gray matter volume in subcortical and temporal areas. Overlapping changes were predicted by the degree of prematurity and neonatal medical complications. The second study investigated functional brain organization in 73 adults born very preterm and/or with very low birth weight (VP/VLBW), and 73 termborn controls, while participants were involved in a verbal N-Back paradigm with varying workload. Although behavioral performance was comparable between groups, VP/VLBW adults showed significantly stronger deactivations of posterior default mode network regions during the most demanding 2-back condition. Our results suggest long-term effects of preterm birth on both structural and functional brain organization and imply compensatory brain activity as a mechanism to help overcome functional deficits.Eine Frühgeburt (d.h. Geburt vor der 37. Schwangerschaftswoche) erhöht das Risiko für psychiatrische Erkrankungen, kognitive Defizite und schwächere akademische Leistungen. Es wird vermutet, dass dies auf perinatale Hirnschädigungen und nachfolgende Veränderungen in der Gehirnentwicklung zurückzuführen ist. Die strukturelle und funktionelle Magnetresonanztomographie ermöglicht es solche Gehirnveränderungen in-vivo darzustellen. Frühere MRT-Studien haben gezeigt, dass frühgeborene Säuglinge, Kinder und Jugendliche sowohl strukturelle als auch funktionelle Unterschiede im Vergleich zu reifgeborenen Gleichaltrigen aufweisen. Jedoch ist unklar, ob solche Veränderungen bis ins Erwachsenenalter bestehen. Das Ziel der vorliegenden Doktorarbeit war es daher, die langfristigen Auswirkungen einer Frühgeburt auf die Gehirnorganisation im Erwachsenenalter zu untersuchen. Zu diesem Zweck wurden in der ersten Studie strukturelle und Ruhe-fMRT Daten von 95 frühgeborenen und 83 reifgeborenen Erwachsen erhoben und mittels Voxel-basierter Morphometrie und „Independent Component Analysis“ analysiert. Bei frühgeborenen Erwachsenen zeigten sich ausgedehnte Veränderungen in der funktionellen Konnektivität intrinsischer Hirnnetzwerke, die mit subkortikalen und temporalen Veränderungen im Volumen der grauen Substanz überlappten und korrelierten. Überlappende Veränderungen wurden durch den Grad der Frühgeburtlichkeit und das Ausmaß an perinatalen medizinischen Komplikationen vorhergesagt. Die zweite Studie untersuchte die funktionelle Gehirnorganisation von 73 Erwachsenen, die sehr frühgeboren und/oder ein sehr geringes Geburtsgewicht (SF/SGG) hatten, und 73 reifgeborenen Kontrollen, während diese ein verbales N-Back Paradigma mit variierendem Schwierigkeitsgrad absolvierten. Beide Gruppen meisterten die Aufgabe gleich gut. Jedoch zeigten die SF/SGG Erwachsenen während der schwierigsten 2-back Bedingung eine signifikant stärkere Deaktivierung von Regionen, die zum posterioren „default mode“ Netzwerk gezählt werden. Unsere Ergebnisse lassen langfristige Effekte einer Frühgeburt auf die strukturelle und funktionelle Gehirnorganisation im Erwachsenenalter vermuten und deuten an, dass kompensatorische Gehirnaktivität ein möglicher Mechanismus ist, um funktionelle Defizite auszugleichen

Long-term effects of preterm birth on large-scale brain organization

Being born preterm (< 37 weeks of gestation)increases the risk for several psychiatric disorders, cognitive impairments, and academic underachievement. It is hypothesized that this is due to perinatal brain injury and subsequent alterations in brain development. Structural and functional magnetic resonance imaging allows the identification of such brain abnormalities in-vivo. Accordingly, previous MRI studies have shown that preterm Born infants, children and adolescents demonstrate both structural and functional alterations when compared to their term born peers. However, it is unclear whether such changes persist into adulthood. Therefore, the present doctoral Thesis aimed to investigate the long-term effects of preterm birth on large-scale brain organization. Study I: in 95 preterm and 83 full-term Born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial Patterns of intrinsic functional connectivity (iFC) in ongoing blood oxygenation level–dependent activity. We found widespread iFC differences that overlapped and correlated with aberrant regional gray matter volume in subcortical and temporal areas. Overlapping changes were predicted by the degree of prematurity and neonatal medical complications. The second study investigated functional brain organization in 73 adults born very preterm and/or with very low birth weight (VP/VLBW), and 73 termborn controls, while participants were involved in a verbal N-Back paradigm with varying workload. Although behavioral performance was comparable between groups, VP/VLBW adults showed significantly stronger deactivations of posterior default mode network regions during the most demanding 2-back condition. Our results suggest long-term effects of preterm birth on both structural and functional brain organization and imply compensatory brain activity as a mechanism to help overcome functional deficits.Eine Frühgeburt (d.h. Geburt vor der 37. Schwangerschaftswoche) erhöht das Risiko für psychiatrische Erkrankungen, kognitive Defizite und schwächere akademische Leistungen. Es wird vermutet, dass dies auf perinatale Hirnschädigungen und nachfolgende Veränderungen in der Gehirnentwicklung zurückzuführen ist. Die strukturelle und funktionelle Magnetresonanztomographie ermöglicht es solche Gehirnveränderungen in-vivo darzustellen. Frühere MRT-Studien haben gezeigt, dass frühgeborene Säuglinge, Kinder und Jugendliche sowohl strukturelle als auch funktionelle Unterschiede im Vergleich zu reifgeborenen Gleichaltrigen aufweisen. Jedoch ist unklar, ob solche Veränderungen bis ins Erwachsenenalter bestehen. Das Ziel der vorliegenden Doktorarbeit war es daher, die langfristigen Auswirkungen einer Frühgeburt auf die Gehirnorganisation im Erwachsenenalter zu untersuchen. Zu diesem Zweck wurden in der ersten Studie strukturelle und Ruhe-fMRT Daten von 95 frühgeborenen und 83 reifgeborenen Erwachsen erhoben und mittels Voxel-basierter Morphometrie und „Independent Component Analysis“ analysiert. Bei frühgeborenen Erwachsenen zeigten sich ausgedehnte Veränderungen in der funktionellen Konnektivität intrinsischer Hirnnetzwerke, die mit subkortikalen und temporalen Veränderungen im Volumen der grauen Substanz überlappten und korrelierten. Überlappende Veränderungen wurden durch den Grad der Frühgeburtlichkeit und das Ausmaß an perinatalen medizinischen Komplikationen vorhergesagt. Die zweite Studie untersuchte die funktionelle Gehirnorganisation von 73 Erwachsenen, die sehr frühgeboren und/oder ein sehr geringes Geburtsgewicht (SF/SGG) hatten, und 73 reifgeborenen Kontrollen, während diese ein verbales N-Back Paradigma mit variierendem Schwierigkeitsgrad absolvierten. Beide Gruppen meisterten die Aufgabe gleich gut. Jedoch zeigten die SF/SGG Erwachsenen während der schwierigsten 2-back Bedingung eine signifikant stärkere Deaktivierung von Regionen, die zum posterioren „default mode“ Netzwerk gezählt werden. Unsere Ergebnisse lassen langfristige Effekte einer Frühgeburt auf die strukturelle und funktionelle Gehirnorganisation im Erwachsenenalter vermuten und deuten an, dass kompensatorische Gehirnaktivität ein möglicher Mechanismus ist, um funktionelle Defizite auszugleichen

Patients with Borderline Personality Disorder Not Participating in an RCT: Are They Different?

Background: Despite the notion that randomized controlled trials are regarded as the gold standard in psychotherapy research, questions about their generalizability have been raised. This paper focuses on the differences between participants and eligible nonparticipants of a randomized controlled trial for patients with borderline personality disorder (BPD). Sampling and Methods: One hundred forty-two patients were screened, and 122 were found eligible for study participation. Out of these, 64 patients (52.5%) gave informed consent and were included in the study. Results: The 58 eligible nonparticipants showed a lower level of functioning (global assessment of functioning score), had a history of more outpatient treatment attempts and were living alone more often. Regarding acute symptoms and severity of BPD as indexed by suicide attempts, inpatient treatments, substance abuse and history of trauma, no differences between the groups could be detected. Moreover, participants showed significantly more eating disorders, whereas nonparticipants presented more affective and anxiety disorders. Conclusions: The results indicate that lower psychosocial functioning and comorbid affective and anxiety disorders decrease BPD patients' willingness to participate in an RCT. Copyright (C) 2010 S. Karger AG, Base

Insular dysfunction reflects altered between-network connectivity and severity of negative symptoms in schizophrenia during psychotic remission

Schizophrenia is characterized by aberrant intrinsic functional connectivity (iFC) within and between intrinsic connectivity networks (ICNs), including the Default Mode- (DMN), Salience- (SN), and Central Executive Network (CEN). The anterior insula (AI) of the SN has been demonstrated to modulate DMN/CEN interactions. Recently, we found that the dependence of DMN/CEN interactions on SN's right AI activity is altered in patients with schizophrenia in acute psychosis and related to psychotic symptoms, indicating a link between aberrant AI, DMN, CEN, and psychosis. However, since structural alterations of the insula are also present during psychotic remission and associated with negative symptoms, impaired AI interaction might be relevant even for psychotic remission and corresponding symptoms. Twelve patients with schizophrenia during psychotic remission (SR) and 12 healthy controls were assessed using resting-state fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed ICNs including DMN, SN, and CEN. Scores of iFC within (intra-iFC) and between (inter-iFC) distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Intra-iFC was altered in patients SN, DMN, and CEN, including decreased intra-iFC in the left AI within the SN. Patients' inter-iFC between SN and CEN was increased and correlated with the severity of negative symptoms. Furthermore, decreased intra-iFC of the left AI correlated with both severity of negative symptoms and increased inter-iFC between SN and CEN. Our result provides first evidence for a relationship between AI dysfunction and altered between-network interactions in schizophrenia during psychotic remission, which is related to the severity of negative symptoms. Together with our previous results, data suggest specific SN/DMN/CEN reorganization in schizophrenia with distinct insular pathways for distinct symptom dimensions

Psychoeducation: A Basic Psychotherapeutic Intervention for Patients With Schizophrenia and Their Families

Psychoeducation was originally conceived as a composite of numerous therapeutic elements within a complex family therapy intervention. Patients and their relatives were, by means of preliminary briefing concerning the illness, supposed to develop a fundamental understanding of the therapy and further be convinced to commit to more long-term involvement. Since the mid 1980s, psychoeducation in German-speaking countries has evolved into an independent therapeutic program with a focus on the didactically skillful communication of key information within the framework of a cognitive-behavioral approach. Through this, patients and their relatives should be empowered to understand and accept the illness and cope with it in a successful manner. Achievement of this basic-level competency is considered to constitute an “obligatory-exercise” program upon which additional “voluntary-exercise” programs such as individual behavioral therapy, self-assertiveness training, problem-solving training, communication training, and further family therapy interventions can be built. Psychoeducation looks to combine the factor of empowerment of the affected with scientifically founded treatment expertise in as efficient a manner as possible. A randomized multicenter study based in Munich showed that within a 2-year period such a program was related to a significant reduction in rehospitalization rates from 58% to 41% and also a shortening of intermittent days spent in hospital from 78 to 39 days. Psychoeducation, in the form of an obligatory-exercise program, should be made available to all patients suffering from a schizophrenic disorder and their families

An analysis of MRI derived cortical complexity in premature-born adults : regional patterns, risk factors, and potential significance

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain’s basic geometry of cortical organization in prematurity

Housing situation and healthcare for patients in a psychiatric centre in Berlin, Germany: a cross-sectional patient survey

OBJECTIVE: To determine the housing situation among people seeking psychiatric treatment in relation to morbidity and service utilisation. DESIGN: Cross-sectional patient survey. SETTING: Psychiatric centre with a defined catchment area in Berlin, Germany, March-September 2016. PARTICIPANTS: 540 psychiatric inpatients including day clinics (43.2% of all admitted patients in the study period (n=1251)). MAIN OUTCOME MEASURES: Housing status 30 days prior the interview as well as influencing variables including service use, psychiatric morbidity and sociodemographic variables. RESULTS: In our survey, 327 participants (68.7%) currently rented or owned an own apartment; 62 (13.0%) reported to be homeless (living on the street or in shelters for homeless or refugees); 87 (18.3%) were accommodated in sociotherapeutic facilities. Participants without an own apartment were more likely to be male and younger and to have a lower level of education. Homeless participants were diagnosed with a substance use disorder significantly more often (74.2%). Psychotic disorders were the highest among homeless participants (29.0%). Concerning service use, we did neither find a lower utilisation of ambulatory services nor a higher utilisation of hospital-based care among homeless participants. CONCLUSIONS: Our findings underline the need for effective housing for people with mental illness. Despite many sociotherapeutic facilities, a concerning number of people with mental illness is living in homelessness. Especially early interventions addressing substance use might prevent future homelessness

Sequelae of premature birth in young adults

Background and Purpose Qualitative studies about the abnormalities appreciated on routine magnetic resonance imaging (MRI) sequences in prematurely born adults are lacking. This article aimed at filling this knowledge gap by (1) qualitatively describing routine imaging findings in prematurely born adults, (2) evaluating measures for routine image interpretation and (3) investigating the impact of perinatal variables related to premature birth. Methods In this study two board-certified radiologists assessed T1-weighted and FLAIR-weighted images of 100 prematurely born adults born very preterm (VP <32 weeks) and/or at very low birth weight (VLBW <1500 g) and 106 controls born at full term (FT) (mean age 26.8 ± 0.7 years). The number of white matter lesions (WML) was counted according to localization. Lateral ventricle volume (LVV) was evaluated subjectively and by measurements of Evans’ index (EI) and frontal-occipital-horn ratio (FOHR). Freesurfer-based volumetry served as reference standard. Miscellaneous incidental findings were noted as free text. Results The LVV was increased in 24.7% of VP/VLBW individuals and significantly larger than in FT controls. This was best identified by measurement of FOHR (AUC = 0.928). Ventricular enlargement was predicted by low gestational age (odds ratio: 0.71, 95% CI 0.51–0.98) and presence of neonatal intracranial hemorrhage (odds ratio: 0.26, 95% CI 0.07–0.92). The numbers of deep and periventricular WML were increased while subcortical WMLs were not. Conclusion Enlargement of the LVV and deep and periventricular WMLs are typical sequelae of premature birth that can be appreciated on routine brain MRI. To increase sensitivity of abnormal LVV detection, measurement of FOHR seems feasible in clinical practice

Decreased BOLD fluctuations in lateral temporal cortices of premature born adults

Lasting volume reductions in subcortical and temporal-insular cortices after premature birth suggest altered ongoing activity in these areas. We hypothesized altered fluctuations in ongoing neural excitability and activity, as measured by slowly fluctuating blood oxygenation of restingstate functional MRI (rs-fMRI), in premature born adults, with altered fluctuations being linked with underlying brain volume reductions. To investigate this hypothesis, 94 very preterm/very low birth weight (VP/VLBW) and 92 full-term born young adults underwent structural and rsfMRI data acquisition with voxel-based morphometry and amplitude of low-frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF was reduced in lateral temporal cortices, and this reduction was positively associated with lower birth weight. Regions of reduced ALFF overlapped with reduced brain volume. On the one hand, ALFF reduction remained after controlling for volume loss, supporting the functional nature of ALFF reductions. On the other hand, ALFF decreases were positively associated with underlying brain volume loss, indicating a relation between structural and functional changes. Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices. These results demonstrate long-term impact of premature birth on ongoing BOLD fluctuations in lateral temporal cortices, which are linked with brain volume reductions. Data suggest permanently reduced fluctuations in ongoing neural excitability and activity in structurally altered lateral temporal cortices after premature birth

The association of children’s mathematic abilities with both adults’ cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults’ IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children’s mathematic abilities and adults’ fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults’ IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children’s mathematic abilities may represent potential neurocognitive targets for early intervention