Effectiveness of a Cognitive Behavioral Weight Management Intervention in Obese Patients with Psychotic Disorders Compared to Patients with Non-Psychotic Disorders or No Psychiatric Disorders: Results from a 12-month, Real-World Study

Objective—Studies of behavioral weight loss intervention in psychotic patients are sparse and its efficacy compared to other obese patients is unknown. Therefore, we compared the effect of a cognitive-behavioral weight loss intervention in obese subjects with psychotic disorders, other psychiatric diagnoses and without psychiatric disorders. Methods—12-month, naturalistic study of weekly group or individual cognitive-behavioral weight management in 222 consecutively enrolled obese patients (body mass index (BMI): 43.7±9.6) with psychotic-spectrum disorders (PSD, n=47), other psychiatric disorders (OPD, n=49) and no psychiatric disorder (NPD, n=126). Results—PSD patients had greater treatment persistence (48.9%) and longer treatment duration (8.7±4.4 months) than OPD (22.4%, 5.4±4.3 months) and NPD (22.2%, 4.9±4.7 months) patients (p’s\u3c.01, number-needed-to-treat (NNT)=3). In last-observation-carried-forward analyses, PSD patients had greater percent baseline weight loss at 12 months (5.1±9.3%) than OPD and NPD patients (2.7±5.5% and 2.4±6.3%); greater percent BMI loss at 9 and 12 months than both groups (p’s\u3c.05), and greater BMI loss at 9 months (2.1±3.5) and 12 months (2.3±4.1) than NPD patients (1.1±2.3 and 1.2±2.4). Furthermore, weight loss ≥5%, occurred in 42.6% of PSD patients vs. 18.4% and 23.0% in OPD and NPD patients (p’s\u3c.01, NNT=5 and 6). The strongest weight loss predictor was treatment duration (β=.51–.54, p\u3c.001). Attrition was predicted by NPD (p=.001) and OPD group status (p=.036), lower proportion of group sessions (p=.002), higher depression (p=.028), and lower baseline BMI (p=0.030). Conclusions—Psychosis-spectrum disorder patients had greater weight loss than other obese patients. Non-adherence and depression should be targeted to enhance weight loss success

Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines

Abstract Background To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. Methods We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP) and fibrinogen levels. The cytokines IL-6, TNF-α, IFN-γ, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR). T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. Results Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. Conclusion Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a significant degree, mediated by low grade systemic inflammation. These data support the need for further adolescent studies to explore these associations.</p

Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain : A Systematic Review and Meta-analysis

Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples ( n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2–20, n = 81–2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ ADRA2A ], Adrenoceptor Beta 3 [ ADRB3 ], Brain-Derived Neurotrophic Factor [ BDNF ], Dopamine Receptor D2 [ DRD2 ], Guanine Nucleotide Binding Protein [ GNB3 ], 5-Hydroxytryptamine (Serotonin) Receptor 2C [ HTR2C ], Insulin-induced gene 2 [ INSIG2 ], Melanocortin-4 Receptor [ MC4R ], and Synaptosomal-associated protein, 25kDa [ SNAP25 ]) were significantly associated with antipsychotic-related weight gain ( P -values < .05–.001). SNPs in ADRA2A , DRD2 , HTR2C , and MC4R had the largest effect sizes (Hedges’ g ’s = 0.30–0.80, ORs = 1.47–1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1–2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets

Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis.

Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values &lt; .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets