Intact thalamic microstructure in asymptomatic relatives of schizophrenia patients with high genetic loading

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

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Magnetic resonance relaxometry in monozygotic twins discordant and concordant for schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2004.11.004 ◽

2005 ◽

Vol 20 (1) ◽

pp. 41-44 ◽

Cited By ~ 4

Author(s):

Filip Spaniel ◽

Vit Herynek ◽

Tomas Hajek ◽

Monika Dezortova ◽

Jiri Horacek ◽

...

Keyword(s):

Magnetic Resonance ◽

Globus Pallidus ◽

Relaxation Times ◽

Monozygotic Twins ◽

T2 Relaxation ◽

T1 Relaxation ◽

Significant Prolongation ◽

Healthy Control ◽

Genetic Loading ◽

Mz Twins

AbstractT1 and T2 relaxation times were examined in four pairs of monozygotic (MZ) twins discordant and concordant for schizophrenia with low and high genetic loading for the illness and five healthy control MZ twin pairs. Patients with schizophrenia (n = 11) showed significant prolongation in T1 relaxation times in the globus pallidus (GP) bilaterally (P < 0.005, Bonferroni corrected) when compared to 14 healthy MZ twins.

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The role of maternal infectious diseases during pregnancy in the etiology of schizophrenia in offspring

European Psychiatry ◽

10.1017/s0924933800005241 ◽

1992 ◽

Vol 7 (4) ◽

pp. 147-152 ◽

Cited By ~ 15

Author(s):

G Stöber ◽

E Franzek ◽

H Beckmann

Keyword(s):

Infectious Diseases ◽

Equal Proportion ◽

Second Trimester ◽

Diagnostic Systems ◽

Chronic Schizophrenics ◽

Causative Factors ◽

The Central Nervous System ◽

Genetically Determined ◽

Genetic Loading

SummaryIn 55 chronic schizophrenics, the occurrence of infectious diseases during their mothers’ pregnancies was investigated. Different psychiatric diagnostic systems were compared. Infections were reported by the mothers of familial and sporadic DSM III-R schizophrenics in equal proportion. However, applying Leonhard's classification, the frequency of infections was found to be significantly increased in ‘systematic’ schizophrenia (mainly exogenously induced in the view of Leonhard) compared to ‘unsystematic’ schizophrenia (mainly genetically determined according to Leonhard's findings). Most of the infections occurred during the second trimester (nine out of 13). Thus, in the ‘systematic’ forms of schizophrenia (low genetic loading), maternal infections in this crucial period of neurodevelopmenl would appear to be important causative factors in the cytoarchitectural deviance delected in the central nervous system of schizophrenics.

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Maternal infectious diseases during pregnancy and obstetric complications in the etiology of distinct subtypes of schizophrenia: further evidence from maternal hospital records

European Psychiatry ◽

10.1016/0924-9338(96)80332-4 ◽

1995 ◽

Vol 10 (7) ◽

pp. 326-330 ◽

Cited By ~ 10

Author(s):

E Franzek ◽

G Stöber

Keyword(s):

Infectious Diseases ◽

Maternity Hospital ◽

Obstetric Complications ◽

Perinatal Complications ◽

Hospital Records ◽

Maternal Recall ◽

Genetic Loading ◽

Relationship Of ◽

The Relationship ◽

Good Agreement

SummaryOn the basis of 24 maternity hospital records, the current study investigated the validity of maternal recall and the relationship of maternal infections during pregnancy and obstetric complications (OCs) to different diagnostic subgroups of endogenous psychoses on which we reported previously in this journal. Maternal recall showed good agreement to maternity hospital records in the Lewis and Murray scale (ϑ = 0.74). With regard to infectious diseases during pregnancy maternal recall and records showed a weaker, but also good correlation (ϑ = 0.18). Psychoses with low genetic loading had more OCs than psychoses with high genetic loading. Maternal infectious diseases, especially during the fourth or fifth month of gestation, were significantly allocated to Leonhard's systematic schizophrenias. Data from maternity hospital records support our report that infectious diseases during midgestation and further perinatal complications seem to be important etiologic factors in systematic forms of schizophrenia without marked familial loading.

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Disturbed thalamocortical connectivity in unaffected relatives of schizophrenia patients with a high genetic loading

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867418824020 ◽

2019 ◽

Vol 53 (9) ◽

pp. 889-895 ◽

Cited By ~ 7

Author(s):

Kang Ik K Cho ◽

Minah Kim ◽

Youngwoo Bryan Yoon ◽

Junhee Lee ◽

Tae Young Lee ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Orbitofrontal Cortex ◽

First Episode ◽

Healthy Controls ◽

Degree Relative ◽

Episode Psychosis ◽

Weighted Magnetic Resonance Imaging ◽

White Matter Connectivity ◽

Genetic Loading

Objectives: Alterations in thalamocortical anatomical connectivity, specifically the connection between the orbitofrontal cortex and thalamus, have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. The connectivity of the thalamocortical white matter in unaffected relatives of schizophrenia patients was compared to that of healthy controls. Methods: The unaffected relative group was defined as asymptomatic family members who had at least one first-degree relative with schizophrenia and one or more other affected first- to third-degree relatives. A total of 35 unaffected relatives and 34 healthy controls underwent diffusion-weighted and T1-weighted magnetic resonance imaging to examine the white matter connectivity between the thalamus and orbitofrontal cortex using probabilistic tractography. Results: After controlling for age and sex, the unaffected relatives exhibited significantly reduced fractional anisotropy values for the left thalamo-orbitofrontal tract compared to that of healthy controls, F(1, 65) = 6.93, p = 0.011, effect size partial η2 = 0.10. However, there was no association between the Genetic Liability Score and fractional anisotropy in the left thalamo-orbitofrontal tracts. Conclusion: Our findings in the unaffected relatives of schizophrenia patients, which are in line with the alterations reported in schizophrenia, first-episode psychosis and clinical high risk for psychosis, highlight a possible genetic contribution to the proposed biomarker of altered thalamocortical connectivity.

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Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.bp.105.016998 ◽

2006 ◽

Vol 189 (4) ◽

pp. 337-345 ◽

Cited By ~ 61

Author(s):

Stephen J. Glatt ◽

William S. Stone ◽

Stephen V. Faraone ◽

Larry J. Seidman ◽

Ming T. Tsuang

Keyword(s):

High Risk ◽

Social Development ◽

Personality Traits ◽

Adolescent And Young Adult ◽

Control Group ◽

First Degree Relatives ◽

High Genetic Risk ◽

Genetic Loading ◽

And Control ◽

Opposite Gender

BackgroundEvaluation of individuals at high genetic risk of schizophrenia is a powerful method for identifying precursors of the illness.AimsTo identify aspects of personality, psychopathology and social development that differentiate high-risk and control individuals.MethodAdolescent and young-adult first-degree relatives (n=35) of people with schizophrenia or schizoaffective disorder and a control group (n=55) were compared on 36 measures at baseline of a longitudinal study Measures differentiating high-risk and control participants were related to four genetic loading indices.ResultsHigh-risk participants older than 17 years showed more physical anhedonia, less positive involvement with peers and more problems with peers, siblings and the opposite gender. Older high-risk individuals also were less cooperative, less self-directed and less reward-dependent. Problems with peers and the opposite gender, as well as reward dependence, were related linearly to genetic loading.ConclusionsAlterations in personality traits and social development are present in high-risk individuals, and may be markers for genetic liability toward the illness.

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Regional cortical thinning in subjects with high genetic loading for schizophrenia

Schizophrenia Research ◽

10.1016/j.schres.2012.08.028 ◽

2012 ◽

Vol 141 (2-3) ◽

pp. 197-203 ◽

Cited By ~ 33

Author(s):

Min Soo Byun ◽

June Sic Kim ◽

Wi Hoon Jung ◽

Joon Hwan Jang ◽

Jung-Seok Choi ◽

...

Keyword(s):

Cortical Thinning ◽

Genetic Loading

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Multidimensional assessment of impulsivity in schizophrenia, bipolar disorder, and major depressive disorder: testing for shared endophenotypes

Psychological Medicine ◽

10.1017/s0033291716000131 ◽

2016 ◽

Vol 46 (7) ◽

pp. 1497-1507 ◽

Cited By ~ 21

Author(s):

R. G. Fortgang ◽

C. M. Hultman ◽

T. G. M. van Erp ◽

T. D. Cannon

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Sensation Seeking ◽

Behavioral Measure ◽

Clinical Feature ◽

Major Depressive ◽

Genetic Overlap ◽

Stop Signal Reaction Time ◽

Genetic Loading

BackgroundImpulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis.MethodWe focused on five subfacets of impulsivity: self-reported attentional, motor, and non-planning impulsivity, self-reported sensation seeking, and a behavioral measure of motor inhibition (stop signal reaction time; SSRT). We examined these facets within and across disorder proband and co-twin groups, modeled heritability, and tested for endophenotypic patterning in a sample of twin pairs recruited from the Swedish Twin Registry (N = 420).ResultsWe found evidence of moderate to high levels of heritability for all five subfacets. All three proband groups and their unaffected co-twins showed elevations on attentional, motor, and non-planning impulsivity. Schizophrenia probands (but not their co-twins) showed significantly lower sensation seeking, and schizophrenia and bipolar disorder probands (but not in their co-twins) had significantly longer SSRTs, compared with healthy controls and the other groups.ConclusionsAttentional, motor, and non-planning impulsivity emerged as potential shared endophenotypes for the three disorders, whereas sensation seeking and SSRT were associated with phenotypic affection but not genetic loading for these disorders.

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Depression in young adults

Advances in Psychiatric Treatment ◽

10.1192/apt.10.1.4 ◽

2004 ◽

Vol 10 (1) ◽

pp. 4-12 ◽

Cited By ~ 13

Author(s):

Daniel J. Smith ◽

Douglas H. R. Blackwood

Keyword(s):

Young Adults ◽

Age At Onset ◽

Term Outcome ◽

Long Term Outcome ◽

Bipolar Spectrum Disorders ◽

Spectrum Disorders ◽

Atypical Presentations ◽

Genetic Loading ◽

First Time

Depression, as a heterogeneous collection of disorders, is likely to include subgroups that are more genetic in origin. In common with other neuropsychiatric disorders such as schizophrenia, Alzheimer's disease and Huntington's disease, earlier age at onset in depression is associated with higher genetic loading and poorer long-term outcome. Adolescents and young adults with depression are also at high risk of developing a bipolar illness. This article reviews depressive illnesses that occur for the first time in adolescence and young adulthood. Case studies are used to discuss atypical presentations and the evolving concept of bipolar-spectrum disorders.

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